Pⁿ Blog
The Pⁿ Blog is a forum for opinions, questions, controversies, and instructive discussions across the field of pathology and its relevant subspecialties.
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Friday, May 03, 2013
Virtually every organization in existence has one or more "authoritative" structures with variable power. Pathology has many. There are groups governing training, certification, quality, reporting formats, billing, continuing medical education, and on and on.
On the diagnostic side of pathology a variety of subspecialty groups has been of value in establishing more uniform diagnostic and reporting guidelines for surgical pathology and cytopathology. The World Heath Organization (WHO) conferences and resultant "Blue Books" have been generally useful in codifying tumor diagnosis on a worldwide level and the AJCC has been instrumental in setting staging criteria and, indirectly, report formatting for tumor diagnosis, at least in the United States. But as potentially valuable as these and other "expert" groups can be in codifying our approach to pathology, they are composed of human beings and are not infallible... far from it. Sometimes, in fact, they make decisions that seem downright bone headed.
This shouldn't be totally surprising. Lauren Ackerman used to describe a WHO tumor consensus meeting more or less as follows:
A bunch of variably capable, variably experienced individuals with very large egos come together from all over the world, each with their own agenda and little or no willingness to abandon their preconceptions. They spend most of the day debating whose nomenclature should be adopted for this or that tumor until the dinner hour approaches, thoughts of food and drink intercede, and discussions rapidly degenerate into, "I'll vote for your tumor if you vote for mine.... and let's go to dinner!" Amazingly, most of the time things work out reasonably well, but there are notable exceptions. And blind trust in any authority is NEVER a good idea.
From my personal perspective the following is a very brief, off the top of my head list of what I believe are some recent (and not so recent) examples of muddy thinking by "authorities." You may or may not agree.
1. The 2010 AJCC decision that a single immunohistochemically positive "malignant-appearing" cell in a sentinel lymph node for malignant melanoma constitutes "N1" disease. I don't know where to start with this one. Can you recognize a malignant nucleus when it's covered with brown/red chromogen? Do these patients really have Stage III disease? Wow! Cure rates for Stage III melanoma are going to skyrocket. ...and don't get me started on the value of sentinel lymph nodes for melanoma. Where are the data? At least once a week we review cases for our melanoma clinic in which S100-positive dendritic cells or intra-capsular nevus cells have been interpreted as metastases. In some cases, it's unlikely the original lesion was anything more than an architecturally disordered nevus. There's a LOT more that could be said on this point, but I'll save that for a later blog.
2. The ACS requirement that synoptic reports should be filled out on tumor resections that are devoid of any residual tumor. Lots of words wasted to say, "no tumor seen."
3. The decision to relabel all pancreatic neuroendocrine carcinomas as "pancreatic endocrine tumors." The word "tumor" doesn't even indicate that it's a neoplasm, let alone benign or malignant.
4. The 2002 WHO decision to rename uterine malignant mixed mullerian tumors as "carcinosarcomas." They are sarcomatoid carcinomas, not sarcomas.
5. Multiple overly complex contrived systems for designating thymomas.
6. The decision by the WHO to retain the term "atypical carcinoid tumor" in pulmonary pathology.
...I'm sure you can think of more!
(I could as well, but I'm already late with this blog!)
Tuesday, April 09, 2013
I'll begin this blog with a question. Are patients getting too much medical information without proper context? At my own institution "My Chart" is the tool that patients use to access their medical records on-line. Surgical pathology reports are about to be added to their "My Chart" records, although after a 14-day delay to allow for any corrections, ancillary studies, etc. Are patients really equipped to understand a gross note or microscopic description, let alone a diagnosis? Who are they going to contact when they don't? I'm certainly not in favor of keeping patients in the dark, but if they're going to be given all this (often extraneous) information, who's going to sift it and interpret it for them? And make sure they understand?
The days of an uninformed populace served by a paternalistic medical system are fortunately long gone. Whenever I think about what it was like in those days, I remember a case that I encountered as a resident while rotating at a nearby private hospital. An elderly woman had undergone abdominal surgery for diverticular disease. At the time of surgery a several centimeter mesenteric mass was noted and removed. The specimen was clearly a low-grade neuroendocrine carcinoma involving a mesenteric lymph node but no primary tumor could be found anywhere in the GI tract. On a whim, I went up to talk to the patient after she had recovered from her surgery and asked her if she'd ever had any other surgical procedures. She said that 30 years earlier she'd had part of her thyroid gland removed. I asked her if she remembered what the diagnosis was and she said that her doctor had told her, "Don't worry about it." I dug up the case from our archives and it was a medullary thyroid carcinoma, microscopically identical to the the mesenteric lesion. "Don't worry about it," was paternalistic in the extreme, but it turned out, paradoxically, to be not bad advice. However, I don't recommend this approach, especially in today's world!
Now patients have access to every data point but little or no context in which to place the data and harried physicians have little or no time to explain things properly. Sometimes, in desperation they pass the buck to the pathologist of record, which brings me to my second story. About twice a month I get contacted by a patient or family member trying to understand their pathology, often with a substantial (and understandable!) emotional overlay. Given all the furor about HIPPA regulations and compliance, I don't discuss cases with anyone over the phone, or via e-mail, when I can't positively identify them as properly meriting access to that information.
The latest case involved an adolescent who had undergone a thyroid lobectomy for an encapsulated nodule that the original hospital thought represented an encapsulated follicular variant of papillary carcinoma (FVPC). On review, I interpreted it as a follicular adenoma. The parents were extremely distraught because an original diagnosis of encapsulated FVPC had been now interpreted as benign. Was I SURE of the diagnosis? Had I really changed a cancer (possible death sentence?) diagnosis to a benign one?
Imagine the issues involved in trying to explain this to someone without a medical background who desperately wants to understand. Consider the following points that need to be understood to fully comprehend this particular situation:
1. All cancers are not created equal. Some ARE virtual death sentences, some almost certainly will NOT impact longevity.
2. The diagnosis of FVPC is one of the least reproducible in all of surgical pathology.
3. The biologic behavior of FVPC, especially an encapsulated one, is so close to that of an adenoma that it is virtually impossible to further refine diagnosic criteria without thousands of patient-years of follow up.
4. Overdiagnosing FVPC is undoubtedly common and contributes to the vanishingly low metastatic rate associated with this tumor.
5. Underdiagnosing FVPC may also be common and is unlikely to come back to "bite" the pathologist given the banal nature of this lesion.
6. Any form of papillary thyroid carcinoma, even ones with regional lymph node metastases, has a superb prognosis in children and young adults to the point that they are far more likely to die of other common teenage issues like driving while inebriated or while texting.
For other malignancies a similar list of complicated issues can easily be generated. It's no wonder that harried clinicians try, increasingly, to pass these complex discussions off on anyone and everyone, including their pathologists.
Even the national press and media are woefully ignorant of the basic pathology that they try to report and they have or should have, virtually unlimited access to expert advice. Consider the recent case of the actress Valerie Harper said REPEATEDLY to have inoperable brain cancer as if she had a primary CNS neoplasm. Even the more detailed descriptions that gave the diagnosis of leptomeningeal carcinomatosis treated this as a primary brain lesion. Only a few sites, days later, made the connection that this was, in fact, metastatic disease from a prior lung carcinoma. Lots of information, not so much understanding!
With the advent of molecular/gentic testing for cancer related genes it became abundantly clear that this information should not be conveyed to the patient without adequate counseling. In fact, genetic testing is ONE rare exception to information that's available on "My Chart." I wonder if at least some cancer diagnoses shouldn't fall into the same category? Do we need "cancer counselors?"
Tuesday, March 26, 2013
We have all encountered aberrant bits of tissue (floaters) on microscopic slides and within paraffin tissue blocks. Most of the time these are from obviously different tissue types and pose no diagnostic difficulty, though they often serve for us to remind the gross room and histopathology staff of the importance of scrupulous cleanliness. Sometimes, of course, the aberrant tissue is of the same type as the proper specimen on the slide and things become more difficult. If the floater is only on one slide, it's a little easier to assess that it represents a contaminant, than if it is present in the paraffin tissue block. In the latter case it becomes a matter of evaluating how much this presumed floater matches the rest of the tissue on the slide. For example if the presumed floater is a small fragment of high-grade colonic adenocarcinoma, the rest of the specimen is entirely normal colon, and there was no clinical suspicion of malignancy, then things seem relatively straightforward.
Unfortunately, sometimes it's not that easy. One approach that is often of value is to closely examine the other specimens accessioned, grossed, and processed on the same day. Does the presumed floater closely match any of these cases? Was the original tumor particularly friable and prone to shedding small tumor fragments? Does the fragment make sense in the context of the rest of the specimen and the clinical history? It is rare that some combination of these approaches does not result in confidence that a contaminant does (or does not) exist. In a few instances, though, either repeat biopsy or molecular testing can be performed to sort things out, the choice depending on the ease of the former v. the cost and time for the latter.
The above refers to instances of focal contamination of an otherwise appropriate specimen. A related and potentially more difficult problem is one of COMPLETE specimen mix up. These may be obvious, as when the tissue on the slide and in the paraffin block don't match the specimen designation, or the diagnosis is clinically untenable. As above, comparison with other similarly processed specimens will often reveal the flip side of the mixup. For example the endometrial curetting from a recently pregnant 24 year old shows high-grade serous carcinoma and the endometrial curetting from a 70-year-old woman with bleeding shows a decidual cast. All of us in practice for a reasonable length of time have encountered such cases. At my own institution we have taken considerable pains to educate clinic staff about this problem and, for example, the danger of pre-labelling specimen vials; something that seems like a good, timesaving, idea but is a setup for a mixup.
Recognized tissue errors of contamination or mixup have been noted to occur in about 6% of cases. A reasonable and somewhat unsettling question is, "How often is there a specimen mixup or contamination and we don't even know it?" Until now this question of occult errors has been seldom considered and never directly addressed. However, a recent article in the American Journal of Clinical Pathology (Am J Clin Pathol 2013;139:93-100) addresses just this point based on a large series of 13,000 prostate biopsies for which DNA data and short tandem repeat (STR) analysis were available, comparing the prostate biopsy with a buccal smear from each patient. Cases in which there was any clinical suspicion of a mixup were excluded in order to assess the truly occult rate of error. Rigorous protocols were followed to avoid mixups in the testing itself by using forensic type collection methods, chain of custody, and appropriate retesting.
The authors considered complete specimen mixup as a "type 1" error, and tissue contamination as a "type 2" error. The results indicated that type 1 errors occurred in 0.26% of cases and type 2 errors were three times as common, occurring in 0.67% of cases. Taken together almost 1 in 100 cases had an unrecognized "tissue origin" error. The study did not assess how many of the type 2 errors had the potential for significant clinical impact. All of the type 1 errors had at least this potential. The type 1 error rates could not be correlated with the type of pathology laboratory or clinical setting. The type 2 error rates showed a correlation with the pathology laboratory setting but, as expected, not with the clinical setting.
This study is a fascinating and somewhat unsettling example of applying current molecular technology to address a important patient safety issue.
Wednesday, March 13, 2013
The last few weeks have seen the loss of two more greats in surgical pathology, John Azzopardi and John Batsakis. Although younger readers may not immediately recognize these names, those who trained in the 1970's and 1980's will immediately recognize both as immensely important to our understanding of surgical pathology.
I unfortunately never had the opportunity to meet Dr. Azzopardi. He was born in Malta and spent virtually all of his professional career at the Hammersmith Hospital in London. Although he has primarily been identified for his pioneering monograph on breast pathology, John Azzopardi was the consummate general surgical pathologist and authored exquisitely written papers on many areas of surgical pathology including lung, salivary gland, soft tissue, GI tract, genitourinary tract, and gynecologic tract, as well as numerous other areas. He first identified the deposition of nucleic acids around blood vessels in necrotic small cell carcinomas, a finding for which the term "Azzopardi effect" is now widely used. Juan Rosai noted in 2010 that, "the majority of the papers he has written have become the standard reference for the respective entities." His monograph of breast pathology (Problems in Breast Pathology, 1979) with an emphasis on problematic intraductal and in-situ lesions, was the first cogent treatise on what for many was an almost incomprehensible area of surgical pathology. It served as the foundation for much that followed in this field. As a resident, I read it cover to cover at least twice and came away feeling that, thanks to Dr. Azzopardi, for the first time I now (at least partially) understood breast pathology. Not only did the text explain things in a logical manner, including numerous black and white photomicrographs, but it contained many first time observations that have stood the test of time in breast pathology. Even today, almost 35 years later, many of his histologic descriptions remain umatched, even if a very few of the terms have been changed (ie. "clinging carcinoma" = flat epithelial atypia).
I did have a chance to speak briefly on several occasions with John Batsakis and I found him to be quite approachable, friendly and more than willing to chat with anyone sharing his interest in ENT pathology. Dr. Batsakis began his career at the University of Michigan and ended it as the Chair of Pathology at the M.D. Anderson Cancer Center in Texas. Like Dr. Azzopardi, he was also the author of a seminal text in surgical pathology, this time on head & neck pathology (Tumors of the Head and Neck. Clinical and Pathological Considerations, 2nd ed. 1979). Again, I read his monograph (both the first and second editions) cover to cover and it formed the basis for my understanding and love of this area of pathology. His text was also full of astute observations that have stood the test of time and emphasized the clinical as well as the histopatholgic features of the entities that he described. Because of this, many ENT surgeons, as well as pathologists, found his text to be indispensible. In particular, much of the foundation of our understanding of salivary gland pathology is attributable to Dr. Batsakis and his junior colleagues. When I began work on the 3rd series AFIP fascicle on head and neck pathology, I frequently referred to Dr. Batsakis' text to make certain that I hadn't forgotten to cover an important point. Ever one to utilize new technology without short changing the old, I'm sure that he would be fascinated by what we now know about molecular anomalies in salivary gland neoplasia and the role of HPV and EBV in squamous carcinogenesis in the head and neck.
A much more detailed "In Memorium" for Dr. Azzopardi is already in press in AJSP, and I hope to have one for Dr. Batsakis shortly.
Friday, March 01, 2013
Sorry for the brief hiatus in blog writing! I managed to come down with a couple of back to back URI's, the second of which is still lingering a bit.
I'll be in Baltimore for the first few days of the 2013 USCAP meeting. If you see me, by all means please come up, introduce yourself and let me know about topics you might liked to have discusse here.
I'll return to the "blogosphere" when I get back from Baltimore. Hope to see you there!
Monday, February 11, 2013
This blog is for those of us more "seasoned" pathologists who hold open-ended board certifications from the American Board of Pathology that do not have expiration dates.
Although we might all wish to assume that we will be permanently immune from the issues of SAM's and recertification examinations, the reality is that state agencies and third party payers, including the government, may take an increasingly negative view of such open-ended certifications and require recertification even if the board itself does not. There is a window of opportunity for voluntary recertification by the American Board of Pathology that does not require an examination (though you CAN take one if you wish). However, this window closes on July 1, 2013 and applications should be submitted well before that date. After that date, all recertifications will be accompanied by an examination and appropriate proof of SAMs and CMEs.
The recertification application is somewhat lengthy but straightforward. It can easily be completed in a few hours if you have the appropriate documents reasonably at hand. The basic requirements are that you must currently hold a board certification in AP, CP, or AP/CP, hold a valid medical license in the state in which you primarily practice, and have medical staff privileges with an accredited health care organization. There is an additional requirement for 150 hours of CME during the last three years, 100 hours of which must be category 1 and 80 hours of that must be related specifically to the applicants area of practice. Basically you must demonstrate that you are activey practicing pathology and are in good standing with your affiliated institution.
The fee for voluntary recertification without examination is $1000.00 and the recertification certificate is valid for 10 years. You may reasonably ask what happens to your original open-ended certification if you decide to recertify? The answer is, "nothing." It remains in effect during and more importantly after any recertification expires so you re not stepping outside of the "grandfather" pool by voluntarily recertifying.
Information regarding voluntary recertification and the application itself can be easily found on the American Board of Pathology website ( http://www.abpath.org).
Given the increasing demands of hospital, state and insurance companies with regard to certification, voluntary "exam free" recertification seems to me to head off at least this aspect of potential credentialing problems for the next decade. Most of my senior colleagues at the University of Virginia have elected to take this opportunity while it still exists. The choice, of course, is entirely up to you, but you should at least consider the option now while there is still time.
Thursday, January 31, 2013
In the past I've discussed the importance of viewing minimal prostatic carcinoma, often detected solely on the basis of a PSA-driven biopsy in the proper clinical context and not overtreating these patients, given that much of what we know about the biology of prostate cancer was based on years of experience with clinically detected symptomatic disease in the pre-PSA era. Such information cannot be directly extrapolated to minute foci of carcinoma found with the aid of immunohistochemistry in biopsies based solely on PSA elevations. As we all know, this isn't easy for a variety of reasons including litigation anxiety on the part of the physician, and generalized anxiety on the part of the patient.
There has been a trend in the last few years towards emphasizing the substantial risks and rates of overtreatment for prostatic carcinoma. Recent consensus studies have suggested not performing PSA screening on patients over 70 years of age.
However, a recent article on behalf of the U.S. Preventative Services Task Force published in the prestigious Annals of Internal Medicine (Ann Intern Med 2012;157:120-134) takes things considerably further down the road. The task force is recommending that PSA-based screening not be used in patients REGARDLESS OF AGE! They supported the use of serum PSA only for following post-treatment or post-diagnosis patients to assess for recurrent or progressive disease.
In essence the task force concluded that serum PSA assays in males of any age led to unwarranted therapy and anxiety that greatly outweighed any benefits, given that the great majority of prostatic carcinomas were likely to remain asymptomatic for the natural lifetime of the patient. Needless to say, this is a highly controversial and contentious recommendation not likely to sit well with the urology world. I'm also concerned that this is an overly simplistic "solution" to a much more complex issue that includes issues of test sensitivity and specificity, patient over anxiety, surgeon overtreatment, and pathologist over diagnosis (at least compared to what was called cancer 2 decades ago). As but one example, is it not reasonable to at least follow serum PSA's in patients with strong family histories of prostate cancer? Admittedly I don't know, but I suspect we'll be hearing a lot more on this topic.
Wednesday, January 16, 2013
Lippincott - William & Wilkins has recently released (and had approved by Apple / iTunes), their iPad "App" for the American Journal of Surgical Pathology (AJSP). This App is a huge step towards giving paper-like functionality to an electronic version of the journal. The full text articles are easy to read and can be shared via email or social media. Text size is adjustable with "pinch and zoom" finger movements. Supplemental material is easily accessible. You can store or delete downloaded issues. Browsing is easy with the "Quick View" format, including the ability to quickly scroll through abstract summaries of each article. Archived issues can be easily accessed, as can "publish ahead of print" articles. You are notified, if you wish, when new issues are available.
The App can be downloaded by searching "American Journal of Surgical Pathology" in the iTunes store.
Print may not be dead but it is no longer "king" or the driving force in publishing, and in fact it hasn't been for quite some time. Its role in the publishing world will undoubtedly continue to diminish, perhaps at a rate even faster than we currently imagine. (Trees of the world, rejoice!)
As good as this first generation of the App is, expect some really nice improvements in not too future updates. Additional functionality will include, among other niceties, the ability to highlight text and make annotations in the margins, just as you would do with a printed copy of the journal.
As a byproduct of the focus on the electronic version of the journal, trying to maintain a separate print version with some B&W images if the authors elect not to pay color charges, and a full color electronic version becomes too difficult to continue. Accordingly, effective January 2013 color charges are no long assessed for images in AJSP. (Authors of the world, rejoice!)
Wednesday, January 02, 2013
Happy 2013 to All!
If you're involved in laboratory administration, in a lab of any size, you're undoubtedly aware of the recent re-evaluation of Medicare/Medicaid payments for the 88305 charge code. You may be aware anyway, but if not perhaps this blog will shed a bit of light on this troubling topic.
In summary, the Centers for Medicare/Medicaid Services (CMS) released its new fee schedule on November 1st. Part of this schedule was the result of a review of the high-volume 88305 charge code and a reduction of the reimbusement of the technical component (TC) of this code by 52%! As a small "bone" thrown in our direction, the professional component (PC) reimbursement was increased by a whopping 2%. There are other less drastic cuts as well, but I'll focus on the 88305. More detailed (and rather numbing) discussions can be easily found on the internet.
Given the intense pressure to cut government heath care spending and the fact that the TC of the high-volume 88305 code had not been reviewed since 2000, it's not surprising that it came under close scrutiny. More of the same is undoubtedly coming in future years, with the CMS already announcing that they are targeting the PC of immunohistochemistry evaluations and enhanced cytology procedures (among others) for next year. Pathologists can take some minor solace in the fact that we are not alone, as virtually all medical specialties have been targeted for review and "cost savings." The only beneficiaries of this on-going process are likely to be primary care physicians who have historically been greatly undervalued.
Although it's uncertain if the CMS had this specifically in mind (as opposed to just overall cost reduction), it is clear that the marked reduction in the TC of the 88305 code will have a dramatic effect on small independent and "in house" labs. The historically "generous" TC for the 88305 led many physician groups to form their own pathology laboratories to capture this technical charge. The impetus for that approach has now virtually disappeared. Considerable economy of scale, beyond the reach of many small labs, will be needed to break even on the diminished technical reimbursements for the small biopsies that are the bread and butter of these labs. I suspect that we are about to see a LOT of consolidations of small laboratories in order to achieve viable specimen volumes.
Most (?all) third party payers will undoubtedly all too eagerly follow the CMS lead and reduce their payments as well. Many already have their reimbursements specifically tied to the Medicare fee schedule. Of course, as insurance purchasers, we can all look forward to the third party payers passing these savings on to us in the form of reduced rates! Hah!! Pardon me! I drifted off to Never Never Land there for a second.
Tuesday, December 18, 2012
For several years Lippincott-Williams & Wilkins and its parent organization, Wolters Kluwer Publishing, have sponsored a meeting of its staff and editors to discuss current trends in publishing. This year's meeting was in Philadelphia on November 8th and 9th. The organizers of this symposium are to be congratulated for putting on a fantastic, incredibly well organized and highly informative meeting. There were several large sessions for the entire group, as well as smaller "breakout" sessions dealing with a variety of topics.
The biggest topics this year, perhaps not surprisingly, were electronic publishing and "open access" publishing. With regard to the former, although print is certainly not dead, it is no longer king either. More and more journals consider the on-line electronic version to be the version "of record," rather than the corresponding paper version. What is becoming clear as well is that the on-line version, rather than primarily being accessed through a web browser, is being tailored for access primarily from tablets (read: iPad, and iPad-like) applications (apps). These apps will, as they continue to mature, allow for increasing manipulation of articles by readers, including the ability to archive, highlight, search, annotate and export as the reader's needs require. Journal subscribers will be given the options of "online + print" or "online only" subscriptions with the strong likelihood that the former will decrease substantially over time. Needless to say, now is not a great time to invest in a printing company! Look for the debute of the AJSP tablet "app" in the very near future!
The topic of "open access" publishing is also a very timely, though currently less clear-cut one. As government and other funding agencies around the world increasingly require open access for work that they have supported, publishing houses, societies, and others have struggled with how to maintain quality and (and revenue!) in the face of this new paradigm. There are basically three publishing models to consider. The current standard print model is limited access fee for subcription. In this model, concessions must be made for publications whose funding agencies demand open access, at least after a limited time of private (subscription only) access. At the other extreme are a growing number of on-line only open access journals, many of which have little or no peer review oversight and correspondingly limited reputations as publication sites. Since most promotion and tenure committees take the status of the journals (as measured by the Science Citation Index or similar system) where articles are published into consideration, these journals are not highly sought by authors as homes for their work.
Many publishers are currently favoring a hybrid model of these two. In this system, authors would be given the choice of either standard "subscriber only" access at no cost, or open access for an up front publication fee. Since funded research is likely to be the main driving force for open access, it is likely that publication fees would find their way into grant proposals to cover this expense. Many journals, in fact, currently enforce rather high publications fees even for "subscriber only" publications, though this is not typical in the medical literature where advertising revenues typically partially offset these expenses.
What is clear is that open access is not "free." If quality is to be maintained both in production standards and peer/editorial review, then costs will be generated and these must be recouped either at the reader end, as the current subscriber model dictates, or at the author end, with an up front publication fee. Certainly in our field, advertising revenues will not be sufficient to cover these expenses (pathology is not Facebook).
One of the breakout sessions that I always try to attend is the one dealing with COPE (Committee on Publishing Ethics) recommendations for editors. This international organization has been invaluable to editors for its comprehensive ethical guidelines covering virtually any publishing situation. The session typically consists of a series of 3 or 4 scenarios that the audience is asked to evaluate and decide on the proper course of action.
My favorite this year was the author who suggested two potential reviewers for his manuscript, both well known experts. The journal editor noticed that both proposed reviewers had "funny" e-mail addresses. A little investigation showed that these "funny" addresses reflected back to the author, allowing him to review his own work! Clear-cut fraud but with a certain undeniable amount of ingenuity. Another case dealt with plagerism and the considerable international variation in this concept. In certain parts of the world, to have your work copied, even without attribution, is considered an honor.
Monday, November 26, 2012
On Tuesday, October 30th Dr. Robert E. Scully died at 91 years of age following a stroke. That short sentence conveys a world of loss for our profession. Bob Scully has been called by his academic colleagues around the world, "one of the premier, if not THE premier surgical pathologist of his generation." He had suffered from a number of age-related maladies for the last few years but had remained remarkably in command of his mental faculties until the very end. He was primarily known around the world for his landmark work throughout the broad fields of gynecologic and gonadal pathology. As but one example, he was the absolute world expert on the pathology of intersex gonads. What may be less well known is that he was a superb, world-class general surgical pathologist and the "go to" guy at the Massachusetts General Hospital pathology department for specimens of all types for decades. Yet, in a profession that has no shortage of large egos, Bob Scully was remarkably lacking in one; and if anyone deserved a large ego, he certainly did!
Just as I noted in my comments on Ron Dorfman's death a few months back, Bob Scully was both a gentleman and a gentle man. He was always willing to give credit and aid to his junior faculty, often suggesting that they be given positions of honor or responsibility in lieu of him. The noted gynecologic pathologist Harold Fox once described Dr. Scully as, "modest, welcoming and friendly, treating all, from the most eminent to the most junior, with the same warmth and amicability."
I was privileged and honored to work with Bob for several years on an ASCP workshop and on several ASCP committees, as well as working with him as editor of Diagnostic Surgical Pathology. I cherish the memories of our course together, as well as the after-course dinners and occasional Martini's. I remember him once saying to me that he did his best writing after drinking a Martini. I suspect that was more an example of Bob's wit rather than truth, but his best writing, indeed ALL his writing, was truly the gold standard for all of us, each article a true work of art.
Several decades ago, I had the privilege of traveling around the Yucatan pennisula with Bob and four other United States pathologists who were invited to speak at the Mexican Pathology Association. Bob was the hit of the trip, sprinting up the steps of Mayan ruins far ahead of the rest of us, and waving from the top, chastising us for being so slow. In addition he kept us all laughing on the long car rides with his wonderfully dry sense of humor.
Suffice it to say, we are unlikely to see his equal. He leaves a HUGE legacy of both work and trainees.
Monday, November 12, 2012
With some trepidation, I'd like to discuss a topic that I think has significant implications for our profession, the over use of and over billing for immunohistochemistry stains.
I do not think this is a widespread abuse, but it definitely does exist in isolated practice foci. There's no doubt whatsoever that immunohistochemical stains, properly applied, are one of the most valuable, if not THE most valuable diagnostic tools in our surgical pathology armamentarium. However, it is also clear when viewing cases from other institutions and speaking to colleagues across the country, that a few surgical pathologists are overly and inappropriately "generous" in their application. In some cases this may well be the result of nothing more than a haphazard and not well thought out approach to trying to diagnose a difficult a case. In other instances, however, I suspect a more clear-cut and less noble motive. Why, for example does one need to order a panel of nearly a dozen cytokeratin subtypes on a pleomorphic malignancy before initially determining that the tumor is entirely cytokeratin negative with an appropriate cocktail? Why order a large panel of hematopoietic markers as an initial diagnostic foray before demonstrating positivity or negativity with a CD45 study? Why order basal cell markers on every prostate biopsy? I could go on at length, but I think you get the picture.
The reality is that these abuses constitute a form of inappropriate self-referral. They're coming under increasing scrutiny, and the result may well be some Draconian ruling outside of our control that, for example, may state that no payer will reimburse for more than three immunostains on any given case. Witness the recent radical cut in reimbursement for the technical component of 88305 (and other codes) by the CMS, based on perceived abuses. Even worse, imagine if no immunostains could be ordered without clinician approval.
In order to avoid the above we really need to police ourselves, and soon! This will require developing and using "best practice" algorithms for working up cases needing immunohistochemical studies. My friend and collague Dr. Mark Wick has spent a signficant portion of his career developing such algorithmic approaches to light microscopically undifferentiated tumors. I'm not remotely suggesting that immunostains be ordered one by one, day after day, until the answer is realized, an approach that would add tremendous delay to the diagnosis. Nor am I suggesting that we can or should eliminate cases where, once the diagnosis is known, a shorter immunohistochemical path to the diagnosis becomes obvious. Hindsight is always 20:20! Rather, I'm advocating that staining panels proceed in a logical, one, two or even three-step process from the broader to the more specific markers, instead of "bathing" the specimen up front with huge numbers of markers. And, needless to say, I'm suggesting that immunostains should not be used unless they are truly needed.
Tuesday, October 30, 2012
I'd like to call your attention to the October 2012 issue of Archives of Pathology and Laboratory Medicine, which includes multiple articles from the April 2012 Houston Lung Symposium.
Since the discovery in 2004 of EGFR mutations in lung cancers that confer gefitinib sensitivity, the topic of personalized ("precision medicine") therapies for non-small-cell lung cancers has exploded. Many additional drug-targeted oncogenes have been identified, particularly in adenocarcinomas from never-smokers. It is clear that when properly applied to sensitive tumors these therapies result in dramatic at least initial responses, often with minimal toxic side effects compared to traditional chemotherapy. I do however, have some concerns about the long-term prognosis in these patients given the genetic instability of high-grade carcinomas and their ability to mutate their way around single-point chemotherapy "roadblocks." The trick, as readily acknowledged by the experts is to find those early critical mutations that are "inviolate" and cannot be bypassed by further mutations, if indeed they exist.
As Drs. Cagle and Myers emphasize in their overview article on "Precision Medicine for Lung Cancer," surgical pathologists should embrace these new techniques, but with the assurance that traditional morphologic diagnosis remains the critical initial step in the precision medicine pathway.
As a "bread and butter" diagnostic surgical pathologist I found these articles on this rapidly evolving topic to be interesting and very well written. I have no idea where this is all going to lead, who's going to pay for it, and how efficacious it will ultimately be with regard to long-term survivals or even cures, but initial results are certainly promising.
Also in this issue, and based on the Houston Lung Symposium, are some more traditional articles by world-class experts dealing with the vexing topics of distinguishing mesothelial hyperplasia from mesothelioma, the spectrum of benign mass-forming lesions of the lung, and idiopathic interstitial pneumonias. If the discussions of mutations, translocations, Sanger and next generation sequencing, PCR, etc. begins to make your head spin, as it did mine, you can take refuge in these more conventional and very practical diagnostic reviews.
Wednesday, October 17, 2012
This article deals with pathology having the ability to "leapfrog" the advances made by radiology with regard to establishing "digital pathology." It is an interesting but, I believe, flawed presentation. Part of the discussion deals with the need to predict workflow by linking pathology LIS's with other information systems such that pathologists will know, days ahead, exactly what specimens are coming on any given day and thereby predict and adjust workflow. The major advantage to this over current systems escapes me. The reality is that workflow is amazingly constant in most sizeable pathology practices. Knowing minor variations in the background noise level is unlikely to have any substantive effects on manpower allotments. Moreover, as we all know, patients cancel visits, schedules change at the last minute, cases get bumped for emergency procedures, etc, etc. etc. We currently know what cases are scheduled for in-patient surgery the following day and this allows ample time to pull old material and have it readily available for comparison with any expected frozen sections. There are, however, always unexpected cases and they would be unexpected with or without better electronic record integration. It also seems completely unrealistic to expect that numerous off-site clinics would feed information in this work prediction model in any meaningful fashion.
In sum, although more information is almost always a better thing and it would be nice to have this level of information access, I don't see it as having a major inpact on how we structure our day. I also do not see how it would be paid for.
The second issue is the digitization of pathology slides for diagnosis and storage. Of course, radiology is already 100% digital (at least in most departments) but they have digital images right from the start, achieved by eliminating the silver emulsion film step from their system and resulting in a net savings in time and money. Digital pathology would come as an "add on" at the end of our current system of slide production. As such it would ADD considerable time and expense to the process. Government and third party carriers are not going to pay more for a system that provides no improvements in diagnosis and actually takes longer than the current approach. Digitized pathology slides are NOT the same as digital radiographic images. They must be in color and require multiple levels of focus up and down through the section. The result is EXTREMELY large files and extremely expensive storage costs, even by today's relativlely cheap (and getting cheaper) memory standards.
And the above assumes that diagnoses from digitized slides are at least as good as diagnoses from glass slides. This is by no means clear. It does seem clear that currently at least the diagnostic process is no where near as fast from a digitized slide as from the real thing. In addition, as discussed in an earlier blog, The FDA has labelled digital slide scanners as Class III medical devices and will not allow their use for primary diagnostic purposes until they have been submitted to appropriate (and exhaustive) testing and approval. This process is likely to take a minimum of three years.
So in spite of a great deal of enthusiasm from the pathology informatics crowd, and considerable potential for the future, the needs of digital radiology and digital surgical pathology are quite different and simply not comparable. Although the B&W two-dimensional world of radiology is firmly in the digital age, it will be quite some time (if ever) before the color, partially 3-dimensional world of surgical pathology reaches a similar level. I see no easy way to go directly from biopsy to digitized image without all of the processing, sectioning, glass slide mounting, and staining that we currently employ. Until these steps are eliminated, digital pathology will always be a costly add-on.
Friday, October 05, 2012
OK, here's another blog that has virtually nothing to do with pathology, except that there are an ever-growing number of Iphone/Ipad/Ipod "Apps" that provide increasing access to pathology information. Several new and exciting ones are on the horizon from LWW, but that's a topic for another day.
For several years my cell phone has been an Iphone-4, using AT&T as my service provider. I resisted the urge to upgrade to the 4S because my 2-year contract with AT&T was still in effect and the 4S was not compatible with 4G/LTE data transmission rates. With the advent of the Iphone-5, I had the chance to get a 4G/LTE compatible cell phone and switch from AT&T to Verizon. AT&T may work fine for you, especially if you live in a large urban area, but in the suburban and rural areas of central Virginia it's a mess with frequent loss of signal and dropped calls due to overloaded servers, even when the signal is strong.
The Verizon service plan costs a little more than AT&T and I lost my unlimited "grandfathered" data plan that I had with AT&T, but most of my data transfers are via WiFi so it hasn't been a big issue. The signal strength, coverage areas, and dropped calls are all MUCH better, at least in my area (your "mileage" may vary).
Switching from one sophisticated electronic device (home computer, laptop, smart phone), to another can be a traumatic experience with all sorts of concerns about data loss, lost and forgotten passwords, familiarization with a new device, etc. I've had a few nasty experiences in this regard over the years, and I'm sure you have as well. Happily, this is an area where Apple has almost always excelled, and keeps doing better and better. I downloaded the latest version of Itunes, backed up my old Iphone-4 on both Itunes and Icloud, activated the new Iphone-5 and connected it to Itunes on my computer. I then told Itunes to update my new Iphone with all my "goodies" and went off to eat dinner.
When I returned, presto, the new Iphone-5 had all my apps, passwords, contacts, calendars, music, videos, settings, etc. in place. Many of the Apps even picked up exactly where I had left off with the old Iphone. E-mail accounts, a minor problem I'd had in the past when migrating from an Iphone 3 to 4, were set up perfectly with all the proper settings, passwords, etc. This was the most painless upgrade experience I've ever had!
I had provided Verizon with my AT&T account information and within minutes of activating the new Iphone on Verizon, my AT&T account was shut down and my phone number had been painlessly migrated to the new phone.
What about the phone itself? Well, I'm still learning. There are many incremental but much appreciated improvements. The screen is larger to conform to the widescreen TV aspect ratio of 16:7, allowing better viewing of videos, a feature that I have yet to use. The retina display is noticeably better than the screen on the Iphone-4. The phone is slightly thinner and feels lighter, two features that don't mean a lot to me. When you put the phone in an OtterBox case for protection, the decreased thickness is even less noticable.
When not in WiFi data mode, the Verizon LTE network is MUCH faster on data transfer than the old AT&T 3G system and 4G/LTE, when available should be amazing. Not surprisingly, the higher data transfer comes at the expense of increased battery drain, though this hasn't been a major problem and charging at night seems to be all that's required after a long day's use.
My two most favorite new features are the voice to text system, allowing you to dictate notes, text messages, calendar events, etc. and have them transcribed with amazing accuracy. Beats the heck out of typing on that tiny keyboard. "Siri" is a hoot and undoubtedly the direction of the future in human - computer interfaces. The system is amazingly adept at figuring out what you want and supplying the correct answer. I've just begun to explore this very helpful feature.
I'm told by fairly reliable sources that unlike prior Iphones, which were service provider specific, the Iphone-5 can actually be used with ANY current cellphone provider, with just a change of the SIM memory card. If true, this makes life easier for Apple (only one model), and much easier for the user who wishes to keep their phone but change service providers.
So, should you buy and Iphone-5? Well, if you're happy with your current service provider and have an Iphone-4s or even an Iphone-4, it may not be worth the extra features to you. If you have an Iphone-3 or Iphone-3s, it's definitely time for a change, and if you want to switch services providers, now's the time.
Monday, September 24, 2012
You may remember (or not) that a while back I wrote a blog about how I nearly lost a huge amount of data, including the digital images for the upcoming ENT fascicle, when my external USB hard disk drive (HDD) crashed. Fortunately, the local repair shop was able to extract 99+% of the files. After that, I bought a RAID 1 USB external HDD to store my work data. RAID stands for "redundant array of independent disks" and comes in several subtypes. For maximum data security, I recommend RAID 1 in which there are two drives that are mirror images of each other. If one drive fails, you're notified and can replace it while the system runs normally on the remaining functional drive. The functional drive will then mirror itself onto the replacement drive and nothing is lost.
After my prior near disaster with data loss, when it came time to upgrade my home PC clone computer, I specifed two 1 terrabyte hard drives in a RAID 1 configuration. I'm sure glad I did. Last week the RAID management software indicated that one of my RAID hard drives had failed completely after only about two years of use. The PC functioned perfectly on the remaining drive. I pulled the suspect drive and tested it separately. Sure enough it was completely dead. Ordering a matching replacement drive from Amazon for $89 took about 10 minutes and arrived about four days later. During the interim, the PC functioned perfectly, though I was nervous that the sole remaining disk might crash before I could back it up. Fortunately it didn't.
It was a piece of cake to install the replacement drive and overnight the RAID management software mirrored the functional disk onto it... bingo. I never lost a bit of data thanks to the RAID 1 redundancy. The key of course is to IMMEDIATELY take action when one of the two drives fails.
If you're going to buy a new computer with mechanical hard drives, I STRONGLY recommend that you get a RAID 1 setup. Likewise, for ultimate data security external USB hard drives should also be RAID 1. Mechanical hard drives are not that expensive and the redundancy can be virtually priceless. Like all mechanical devices, it's not a question of if they'll fail. It's purely a question of WHEN. Typical ANNUAL failure rates for hard drives range from 2% to as high as 13%!
The big question currently is the failure rate of increasingly popular solid state (SSD) drives. The natural assumption is that since SSD's have no moving parts they won't fail. That turns out to be quite incorrect. SSD's have finite read/write cycle numbers, though the value is likely to be so high as to seldom cause problems due to "wearing out" the SSD. What is becoming clear, though, is that these drives do fail even though they don't "move." They're susceptible to heat, power surges and component failures. Typically the failure occurs in the file allocation table, which may render the entire disk inoperative. Moreover, it is looking like the failure rates are not too dissimilar from the failure rates of HDD's. The bottom line is that if you think you don't need backup because you have an SSD, you're wrong! ... and you've been warned. My MacBook Air has an SSD, but I back it up with an external USB SSD hard drive using the Mac "Time Machine" software.
Once burned....
Tuesday, September 11, 2012
"Screening is a double-edged sword, sometimes wielded clumsily by the well intended." Grimes & Schultz, Lancet 2002.
All of us who look at breast biopsies for a living are familiar with the BIRADS (or BI-RADS, ie. Breast Imaging Reporting and Data System) system used by mammographers. This system was developed to force mammographers to think in terms of risk stratification and was first utilized in 2000 by the Dutch Institute for Health Care Improvement.
The classification levels are as follows:
0- incomplete,
1- negative,
2-benign findings,
3-probably benign,
4-suspicious abnormality,
5-highly suspicious of malignancy,
6-known biopsy with proven malignancy.
Up to 9% of breast cancer screening mammograms have traditionally been given a BIRADS category of 3, 4 or 5, which implies that something needs further study. Historically, if a mammogram was classified into the BIRADS category 3, it tended to have a very low positive predictive value (2% or less) for carcinoma. A BIRADS category 4 mammogram had a positive predictive value of about 30%, and a category 5 mammogram was almost certainly predictive of breast cancer, with a positive predictive value of about 95%. Because of the low positive predictive value of a BIRADS 3 score, it was typically treated by repeat mammography at 6-month intervals, rather than biopsy.
However, things have definitely changed in the past few years! BIRADS 3 is much less commonly used today. BIRADS 4 and 5 are categories that lead to biopsies, and biopsies give definitive answers quickly, whereas BIRADS 3 leads to a 6-month follow-up mammogram, which leads to some uncertainty and stress for everyone during those 6 months. Both radiologists and patients prefer fast answers rather than waiting 6 months. So..... it has become clear that MANY (MOST?) mammograms that would have been called BIRADS 3 in the past have been inflated to a BIRADS 4 category. This is not a secret by any means, and is documented in lay press on-line discussions of mammography. Because of this approach, as you would have expected, the positive predictive value of a BIRADS 4 score has plummeted to well below the former approximately 30% level. The result, in my humble opinion, is that MANY women are now getting breast biopsies who in the past would have appropriately received only 6-month watchful waiting.
Given that the billed charge for a mammographically directed breast biopsy is approximately $5,000 and there is a high frequency of BIRADS 3, estimated to be up to 7%, in the mammographically studied population, conversion of these cases to BIRADS 4 with biopsy represents a major increase in health care costs, some increase in morbidity, and little or no gain in cancer detection.
There are, of course, two explanations for this phenomenon. One, the more charitable and well intentioned (but misdirected), is as described above. Mammographers are acquiescing to patient's demands and upstaging their BIRADS score to justify immediate biopsy of low-risk lesions, eliminating six months of patient stress and possibly detecting rare cancers "early." The second is less charitable but more obvious. Mammographers benefit significantly from biopsy procedure charges, though I doubt that this factor operates on a conscious level in any individual case. Pathologists benefit as well, but we are not involved in decision to biopsy or not.
When obvious examples of increased, and I believe unwarranted, medical costs like this arise, all I can imagine is that they will ultimately fall under the watchful eye of insurers at both the private and the governmental level, and that this is likely to result in some sort of poorly conceived draconian regulations that will also impact appropriate use of mammographically directed biopsies.
Friday, August 24, 2012
In the not so distant past, pathology residents (and residents in other medical specialties) studying for board exams went to their departmental files to review prior examinee's recollections of board questions. Participants never signed a pledge to not divulge prior questions and in many departments it was expected that you'd contribute to the question bank when you returned from the exam, or be ostracized if you didn't! It's debatable how much this helped other than directing ones attention to areas to be studied since multiple exams were used in each session and the existence of a large and ever-expanding question bank made it highly unlikely that you'd be tipped off to more than a few of the questions on your exam.
When I took the exam over 30 years ago, I don't recall any statement from the board about not divulging question recollections, and we did not sign any statements pledging not to do so. I do recall examinees actively reviewing old questions out in the hallways in plain sight between exam sessions. It may well have been that at that time the exams were always made virtually de novo such that old questions were of very limited value.
Needless to say, the above approach no longer exists (or shouldn't!), and that's definitely a good thing! When signing up for the exam all residents and fellows are now required to sign a document pledging that they agree to not participate in creating, selling, distributing or using remembrances.
At a recent pathology program director’s meeting, Dr Betsy Bennett from The American Board of Pathology discussed the issue of exam "remembrances" and how this is playing out in Pathology. At one pathology board exam, two residents from different institutions were caught with identical remembrances when they checked their materials in the testing room ante chamber. They were dumb enough to have notebooks with clear covers so that the title of Board remembrances was clearly visible without anyone opening any bags or notbooks. Not only may their test be invalidated, but they may not be allowed to retake the boards for a few years (the Board is deliberating this point).
Furthermore, it has been estimated that each test question costs approximately $5,000.00 to produce so the board may be suing the person who created the remembrances for $5,000 x the number of questions. Where that figure comes from is, by the way, unclear since the test committees work as volunteers with only transportation charges paid by the board. I suspect it reflects the considerable operating costs of the ABP amortized across the yearly exams.
If you are in possession of remembrances they should be destroyed immediately. Remember, however, it IS OK to discuss in general what exams were about (or emphasized)but you may not attempt to recreate specific questions and answers.
Monday, August 13, 2012
You can't read any news-related source today without finding a reference to this thing or that thing being a "miracle." It would be hard to think of a more overused word in the English language today, with the obvious exception of "like." "It was like.... and then I like.... " but don't get me started on that horrid misspeak! I hear it a 100+ times a day from my residents. But back to the topic of this blog...
The "miracle" of the day that caught my eye recently was the story in the news of the extremely lucky young woman who was a victim of the Aurora, Colorado shooter and survived a front to back brain penetration by a shotgun pellet with minimal injury because vital structures were missed. The story quotes Dr. Michael Rauzzino, a neurosurgeon at The Medical Center of Aurora who operated on the patient to remove the pellet.
"I would say this is definitely a miracle," he said, while showing an MRI of the patient's brain.
At this point, it's wise to reflect on the primary definition of "miracle:"
1. an event that is contrary to the established laws of nature and attributed to a supernatural cause.
Now as some of you will be quick to point out, there are other second-order definitions of miracle that seem to justify its use for virtually any unusual or wonderous event. Fair enough, but I would argue that the word has been grotesquely over used, and over time the definition has been bent to suit the rampant over usage.
When applied to an unusual or amazing medical outcome it immediately discounts the real science and medical expertise or just dumb luck that went into achieving the result, and instead seems to ascribe the result to some unknown force or devine intervention. That's really unfortunate. Patients don't get better because of true miracles... at least none I'm aware of. They get better (or they don't) because of the natural order of things, coupled with the high quality of medical care that exists today.
I would humbly suggest that the word be reserved for events (if any) that truly defy the laws of nature and not just for wonderful or amazing things. As such, its usage should be limited virtually entirely to religious texts. Walking unaided on (liquid) water, or parting the Red Sea, I freely admit would be true miracles. Events clearly explained by science and luck are not miracles and should not be treated as such...
Of course, I realize the chance of "miracle" being used in a more restrictive and appropriate fashion in the current version of the English language is about the same as my chance of being bitten by a polar bear and a grizzly bear in the same day, or winning the lottery without buying a ticket, but I can still dream!
Friday, August 03, 2012
In my last blog I talked about the considerable value of an internal consensus conference. This blog briefly addresses an important external consensus conference run by the CAP and the ASCCP (American Society for Colposcopy and Cervical Pathology), termed the Lower Anogenital Squamous Terminology Standardization Project, or LAST project for short.
The LAST project has been a two-year effort to unify diagnostic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive carcinomas and to define the appropriate use of biomarkers in this setting. The July 2012 issue of the CAP Today contains an excellent review on this topic. The specific recommendations were also published in the Archives of Pathology and Laboratory Medicine.
The most important recommendations can be divided into three groups:
1. SQUAMOUS INTRAEPITHELIAL NEOPLASIA.
*The group recommended adoption of the Bethesda system of a two-tiered nomenclature, LGSIL and HGSIL, which optionally may be followed by the appropriate -IN three-tier designation (CIN, VIN, VAIN, etc).
2. SUPERFICIALLY INVASIVE SQUAMOUS CELL CARCINOMA (SISCCA).
*Use the term SISCCA for minimally invasive squamous cell carcinomas of the lower anogenital tract that are completely excised and "may be amenable to conservative therapy." (More site-specific details are available elsewhere.)
3. USE OF BIOMARKERS IN HPV-RELATED SQUAMOUS LESIONS.
*Use p16 to help distinguish dysplasia from mimics (atrophy, metaplasia, etc.)
*Use p16 to clarify borderline distinctions (LGSIL v. HGSIL)
*UDo not use p16 for histologically negative, obviously low-grade, or obviously high-grade lesions.
*Consider using p16 in patients with HGSIL Pap smears and apparently "normal" cervical biopsies.
*************
With regard to the first recommendation, the drop from 3-tiered system to a 2-tiered system puts biopsy diagnoses in line with the Bethesda system for cervical cytology. Yet, this approach was the only one in the LAST project that encountered some considerable push-back, mainly from clinicians who were concerned that it might force their hand with regard to treating patients with small foci of CIN II who they, for a variety of reasons, would have preferred to follow. Thus, the note regarding the option for including the 3-tier -IN designation was added as a compromise toward the end of the project.
The project also makes it clear that p16 is currently the best available marker for assisting in defining dysplasia, but that it has a defined role and should not be over used (estimates suggest fewer than 20% of cases, probably much fewer, require p16). In addition, the project saw no need for a panel of markers (Ki67, ProEx C, etc) in this regard.
Tuesday, July 24, 2012
A few months back I wrote about the pluses and substantial minuses associated with going to subspecialty or modified subspeciality signout in surgical pathology. If you missed that one, dig back through the blog postings and check it out. (I would point you to the exact posting with a link, but then you might miss scanning all of the other great posts!) One of the several driving forces behind subspecialty signout is the clinicians' desire to have a trusted expert review their cases. Another is realistic pathologist concerns regarding keeping up with all of the changes in the broad and ever expanding field of surgical pathology.
I won't review the problems associated with subspecialty signout, especially in smaller or medium-sized academic practices, but I would like to briefly discuss what I think is an excellent way to address many of the pressures on surgical pathologists to subspecialize, without actually subspecializing and thus avoiding the associated problems; the institution of a daily consensus conference.
Although we utilize this in a medium-sized academic department, it can work equally well in a multi-person private pathology practice. Here's how it works for us. All available faculty and residents gather around a multiheaded scope with a projection screen at 3:00 in the afternoon. Faculty members sit around the multiheads and residents take any available additional multihead seats or view the cases on the monitor. Faculty on service present the day's problematic or highly interesting cases to the group, with the associated resident providing background history. The presenting faculty member will give his or her thinking about the case and a brief discussion will then take place about the validity of the diagnosis, alternate possibilities, additional studies needed, etc. Each case takes 5 minutes or less and the entire conference typically lasts 30 minutes or less. If more time is required for an individual case, the case is brought back with additional studies or concerned faculty may elect to view the case in more detail on their own scope.
The end point of the case should be a diagnosis that the group can unanimously support. Teaching points are often emphasized to the residents, particularly once diagnostic agreement is reached, but the focus is on making this a working conference directed towards optimizing patient care. Every case presented at the conference has a note attached to the diagnosis that, "This case was reviewed at the daily surgical pathology consensus conference and the group agreed with the diagnosis." Of course, a consensus diagnosis may not be a specific diagnosis as in many problematic cases a specific diagnosis cannot be rendered.
The advantages of this conference are many. To list just a few:
Although resident/fellow teaching is not the primary function of the conference, it is an excellent venue to further residents' education, particularly with regard to real time approaches to problematic cases.
The conference helps refine and unify (as much as is possible) the department's diagnostic criteria for a variety of problematic areas. For example, all Barrett's esophagus cases with any suspicion of dysplasia are reviewed at the conference. This gives the rest of the faculty a chance to hone their dysplasia criteria to closely match those of the departmental GI gurus.
The conference is the perfect forum for discussing the clinical implications of what may seem to pathologists to be minor differences in terminology. As with many institutions, we have a large number of interdepartmental specialty conferences and the pathology faculty member who attends each of these conferences has first hand knowledge, which can be shared with the group, of the current clinical thinking regarding the diagnosis -> therapy paradigm.
The conference provides more than a little medicolegal support by flagging the case as problematic and indicating that it was reviewed by a group of faculty who agreed with the diagnosis. It's hard to argue that standard of care has been violated when a group of half a dozen or more pathologists has agreed with the diagnosis.
The conference is a genuinely enjoyable experience giving everyone the chance to see interesting and challenging cases, swap stories about their day, etc. Try it.... you'll like it.
Friday, July 13, 2012
Those of you involved in education, medical or otherwise, or those simply engaged in hiring new graduates in any profession have undoubtedly noticed that the young adults of today seem noticeably different from those of even five or six years ago. Maybe you thought it was just you, and you were just getting old and turning into the prototypical curmudgeon. After all, berating the younger generation is probably as old as mankind and undoubtedly has a deep psychological underpinning (they're ascending and you're descending). Well, if you're less than ecstatic about the current crop of college graduates, you're not alone.
First, a brief review of the in vogue generational nomenclature is in order. Although there's no universally agreed upon definition, "baby boomers" are generally considered to be the offspring of post-World War II parents .... that's me. The baby boomers' parents were part of the so-called "Greatest Generation" that built much of the country's infrastructure and firmly established the middle class. "Generation X" represents children born of baby boomers and generally begins in the mid-1960's and extends to the early 1980's. "Generation Y," also called the Millenium Generation, represents children born from the mid 1980's onward. These are the folks now in residencies and applying for jobs.
Although generalizations are never more than just that, there are some rather well-defined generalizations about Gen "Y" that impact how they function in a learning or employment environment.
An article in the December 2011 issue of the Journal of Graduate and Medical Education addresses the challenges and potential opportunities of teaching Generation "Y." My comments below are derived in part from this article, laced with my own perceptions. The article and comments are based primarily on children raised in North America and it is unclear to what degree, if any, they apply to children in or from other countries. If you are involved with Gen "Y" as a teacher, boss or older colleague, this is must reading! If you're a member of Gen "Y," read what the world thinks of you.... and please do your best to prove them wrong!
Gen "Y" is the first post-911 generation. Its members were over protected and over scheduled from birth. They were raised by parents who told them they were special and winners for no good reason, other than that they were breathing. Every organized childhood activity likely resulted in a trophy, certificate or prize. The result is a group that has little experience handling failure or criticism and incredibly unrealistic expectations about their prospects for the future.
One study has suggested that Gen "Y" requires a highly structured learning environment, which unfortunately seems to be exactly counter to the current movement in medical education towards "guided self discovery." But it has also been said that Gen "Y" does not like to read or attend lectures. Exactly how they are to assimilate the vast amount of knowledge required to practice medicine is thus unclear, and I suspect many WON'T learn what they should.
Educators and the business world are likely to view Gen "Y" as lazy, unmotivated, unprofessional, and selfish. Not exactly a glowing set of personal qualities, and not exactly the qualities suited to the self-sacrifice, deferred gratification, and long hours necessary to master the field of medicine.
Gen "Y's" often like to form close associations with authority figures just as they did with their parents. The result is that mentoring Gen "Y" is much more like parenting than a traditional teacher - pupil relationship. Gen "Y's" have been taught that their opinions are always valid and OK to share with anyone without regard to organizational hierarchy. They feel free to espouse critical comments to anyone from the cleaning staff to the departmental Chair. Needless to say, dealing with this style of communication can be problematic in a hierachical setting.
The unfortunate reality is that Gen "Y's" seem, as a group, to have a level of immaturity and real world naivete that requires successful program directors in the educational realm and managers in the business world to function "in loco parentis" (in place of parents), with all of the high maintenance efforts that requires. As if the often thankless job of program director weren't hard enough with the ever increasing mounds of paperwork required by accrediting agencies, "parenting" the trainees also requires an additional major commitment in time. Program directors deserve our undying thanks. I hope that they don't undergo "Gen-Y" burn out.
Tuesday, July 03, 2012
While those of us on the central east coast were watching the news last week and feeling horrible for the devastating fire situation in the Colorado area, Nature decided to give us a small taste of chaos as well. On Friday evening, June 29th a huge storm front moved through much of the central Atantic region with straight line (non-tornado) wind gusts approaching 80 MPH.
Although the storm moved through rather rapidly, the damage exceeded that of many hurricanes that have involved the area. Hundreds of thousands are without power in the middle of a 95 - 105 deg.F heat wave. In and around the Charlottesville, Virginia area where I live was particularly hard hit. We have been without power for four days, and are probably looking at four more days before service is restored. Every morning on my drive to work I pass by the tangled, downed power lines near our home, with no evidence of a power crew in sight.
My colleagues at work are forced to live in their basements and shower at work or, if they have access to one, shower with buckets of water from a nearby swimming pool. (In the country, when you have a well, no electricity = no water!) All the food in their refrigerators and freezers has had to be discarded. All of the local hotels are full with folks abandoning their homes to escape the heat. Many of the roads are barely passable due to downed trees.
My family was fortunate enough to escape any structural damage and we have a home generator which supplies enough power to run most of the needed utilities. Although the temperatures and humidity are dangerously high, if this outage had occurred during a hard winter freeze the damage would have been MUCH worse with thousands of home suffering burst water pipes, fires from improper attempts at emergency heating, and likely hypothermic deaths.
Undoubtedly we'll get through this without too much delay and I am in awe of the utility crews who are working around the clock to get things back on-line, but it certainly points to the extreme fragility of the complex technological infrastructure on which we all depend. If you're one of the many who were impacted by this, stay cool and do what you can to help your neighbors! I'll get back to a pathology topic in my next blog!
Wednesday, June 20, 2012
One of the greats of surgical pathology in general and hematopathology in particular, Dr. Ronald Dorfman, died on June 15th after a brief illness. Dr. Dorfman was Emeritus Professor of Pathology at Stanford and one of the founders of the field of Hematopathology. He was born in South Africa and began his pathology career studying Kaposi's sarcoma where, while presenting a paper on this topic, he fell under the scrutiny of Dr. Lauren Ackerman. Dr. Ackerman was the consumate world traveler and when he encountered promising young talent around the world, he eagerly invited them to train with him at Barnes Hospital in St. Louis. The young Dr. Dorfman caught his eye, an invitation was given and accepted, and the rest, as they say, is history.
Dr. Dorfman prospered as a trainee and junior faculty member in St. Louis and in 1968, along with Dr. Richard Kempson, he was recruited to Stanford. Together, he and Dr. Kempson founded a Surgical Pathology service that quickly became and still remains one of the very best in the world. Dr. Dorfman became a world leader in the relatively new subspecialty of Hematopathology, and with Dr. Costan Berard founded the Society for Hematopathology in 1981, in which Dr. Dorfman served as President from 1982 through 1984. He became Emeritus Professor at Stanford in 1993, but still occasionally visited the department to render his opinion on problematic cases, often these were examples of the entity that bears his name, Rosai-Dorfman disease.
Ron Dorfman was a gifted diagnostician, teacher and researcher but those who knew him well were equally impressed by his warmth and his many admirable personal qualities. He was a consummate gentleman and scholar. In honor of his achievements and his contributions to Stanford, his field, and his patients, the Department of Pathology established the Ronald F. Dorfman, MBBCh, FRCPath, Professorship in Hematopathology in 2002, a Chair that is current held by Dr. Roger Warnke.
(parts of the above were abstracted from an e-mail by Drs. Warnke & Galli)
I was fortunate enough to have interacted with Dr. Dorfman on several occasions including a visit to the University of Virginia quite a few years ago when he was visiting professor and astounded us with the depth and breadth of his hematopathology experience. As I recall, for example, he had well over 400 cases of lymphocyte predominant Hodgkin's disease in his personal files! I was also privileged to dine with him on several invited trips to speak at the California Pathology Society or the South Bay Pathology Society. I can only echo what those who knew him much better have said. He was not just an icon in our field, but a true gentlemen in every sense of the word.
Please feel free to contribute your comments or anecdotes regarding this fine man.
Friday, June 08, 2012
Over the last several decades there has been a progressive modification (generally a decrease) in the recommended intervals for Pap smear screening in the general population. Recently, the U.S. Preventive Services Task Force (USPST) published their latest Pap smear screening guidelines in the Annals of Internal Medicine and a multidisciplinary partnership among the American Cancer Society/American Society for Colposcopy and Cervical Pathology/American Society for Clinical Pathology (ACS/ASCCP/ASCP) published their updated guidelines in Ca: A Cancer Journal for Clinicians.
The guidelines were independently derived but are quite similar in their conclusions, a reassuring point for both patients and physicians. In general, they recommend that most patients get screened for cervical cancer no more often than every 3 to 5 years.
Principal recommendations include:
•Women between ages 21 and 65 without risk factors (such as DES exposure or immunodeficiency) should undergo cytologic screening every 3 years.
•Those aged 30 to 65 wishing to extend the screening interval could undergo screening with both cytologic exam and human papillomavirus testing every 5 years.
•Women younger than 21 should not be screened.
•Women older than 65 who have been adequately screened previously should not be screened.
The complete guidelines with comments from the American College of Obstetricians and Gynecologists (ACOG) can be found here:
The following is taken from the ACOG comments (found above) regarding the guideline changes.
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What is new about these guidelines?
This is the first time that USPSTF has recommended the combined use of cervical cytology and high-risk human papillomavirus (HPV) DNA testing (“co-testing”). The previous USPSTF guidelines had indicated that evidence was insufficient to make a recommendation regarding the use of co-testing. USPSTF now recommends that women age 30–65 years should be screened by either cytology every 3 years or co-testing every 5 years.
In contrast, ACS/ASCCP/ASCP finds that co-testing every 5 years is preferred to cytology alone but that cytology alone every 3 years is an acceptable strategy. In choosing to make co-testing the preferred strategy, ACS/ASCCP/ASCP focused on evidence from multiple randomized trials showing that co-testing has improved performance compared with cytology alone. Specifically, co-testing has increased sensitivity for detecting cervical intraepithelial neoplasia grade 3 or greater (CIN3+), and women who have undergone co-testing have a lower risk of CIN3+ and invasive cancer after the first screening round. Because of this improved performance, co-testing can be used for screening at less frequent intervals than cytology alone. In addition, co-testing offers greater risk reduction than cytology alone for adenocarcinoma of the cervix and its precursors.
What is the ACOG's position on these new guidelines?
The College applauds the work of these organizations in integrating the significant new evidence that has become available into the revised guidelines. Each set of recommendations was developed under a separate work plan, with its own policies and procedures for evidence collection and analysis. The very similar recommendations are reassuring because although they were developed independently and by different methodology, they drew on a common evidence base, which was interpreted the same way by different groups of experts. The College encouraged and facilitated collaboration among the groups, urging that consistency of message would benefit American women and the clinicians who care for them. This message was clearly heard.
The College now moves to its final phase of evaluating the recommendations. They will be evaluated by committees that make the College’s recommendations on screening for cervical cancer. Any new guidelines from the College will be published in Obstetrics & Gynecology.
Why do all these organizations—including the College—discourage annual cervical cancer screening?
Cervical cancer is typically slow growing, and most cancers are found in women who have never been screened or who have not been screened in the past 5 years. Recommending less frequent screening for cervical cancer is not new. The ACS has recommended less frequent screening for some women since 1980. The College has made similar recommendations since 1989. Note that the new guidelines from USPSTF and ACS/ASCCP/ASCP are for women at average risk. More frequent testing may be appropriate for women with conditions that place them at an increased risk of cervical cancer, such as immunocompromise or human immunodeficiency virus (HIV) infection.
These recommendations reflect a balance between benefits and harms. Both cervical cytology and testing for high-risk types of HPV DNA can detect cervical cancer and its precursors, but each will detect many abnormalities that will not go on to become cancer. Annual screening with cytology alone has been shown to lead to a very small increase in cancers prevented but greatly increases the number of unnecessary procedures and treatments. The prevalence of transient HPV infections and associated low-grade lesions is high, but most of these will regress within 1 to 2 years. The small fraction of lesions that do not regress will, on average, require many years to progress to cancer. Identifying and treating lesions that will likely regress on their own does not provide a benefit large enough to outweigh the harms. These harms may include anxiety associated with a “positive” cancer screening test, potential stigmatization from the diagnosis of a sexually transmitted infection, discomfort from additional diagnostic and treatment procedures, bleeding from treatment, and, longer term, an increased risk of pregnancy complications such as preterm delivery in women previously treated with excisional procedures for precancerous lesions.
While cost was explicitly not considered in the guideline development, increased testing and treatment clearly has associated cost and may be an additional potential harm for some women. Extending the interval for screening strikes the most appropriate balance between benefits and harms.
As noted in the ACS/ASCCP/ASCP guidelines, no screening test has perfect sensitivity, and preventing all cervical cancer is unrealistic. Even with annual cervical cancer screening, a small risk of cancer would remain after screening.
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In their comments, ACOG is careful to note that not needing a yearly Pap smear does not mean that women should not have yearly physician visits, since the Pap smear is only one small component of a yearly physician evaluation.
Given the current availablity of effective vaccines against HPV, one wonders how this will ultimately figure into Pap screening recommendations as the vaccinated population grows. Will vaccinated patients even need routine Pap smear studies in the absence of any symptomatology? For the moment the recommendations clearly state that vaccination status should NOT affect screening, but we'll see how this changes as the efficacy of the vaccine continues to be documented.
If you're engaged in long-term planning for a pathology department it seems reasonable to assume that Pap smear volume will continue to decrease (assuming a stable patient population base) over the next few years. HPV testing, however, is likely to continue to increase.
Thursday, May 24, 2012
I'm about to leave town for a two-week business/vacation trip "down under," so there will be a delay in my postings until I return. Before departing, though, I thought I'd post a list of common language-related mistakes made by residents (and authors). This list is by no means complete, but deals with some of the more common errors I encounter. I continue to revise this list and present this to our new residents each year.
Hyphens
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Words ending in "ly" are NEVER hyphenated. Hyphens are used with compound adjectives. The topic is admittedly complex. Consult "compound adjectives" in Wikipedia. All of the following are correct:
"poorly differentiated carcinoma"
"well-differentiated carcinoma"
"the carcinoma is well differentiated."
"A 20-year-old man"
"He is 20 years old."
Immunohistochemical stains
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Most immunostains should not be capitalized. The following are correct:
desmin
vimentin
keratin
S100 protein ( not S100 )
CD117 reacts to the protein product KIT, not the RNA, c-kit.
Recognize the difference between a reagent named for the actual antibody and one named for the antigen to which it reacts. One stains "with" and the other stains "for."
Grammatical issues
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"data" is plural, "datum" is singular
"it's" is ONLY a contraction for "it is;" "its" is the possessive of it (no apostrophe)
Don't say, "we feel the diagnosis is.." Feeling is not a cognitive function. Say, "We believe, we consider, we interpret, etc."
Verbs must agree with the subject of the sentence not the noun in a nearby preposition or subordinate clause. The following are correct:
"The author, along with many others," believes that..... (subject "author" -> "believes," not believe).
The noun is "mucus." The adjective is "mucous."
"septa" is plural, "septum" is singular, "septae" is not a word.
"trabecula" is singular, "trabeculae" is plural. Trabeculum is something different.
"reticulin" is the silver-positive material seen with a light microscope. "reticulum" is an ultastructural feature, as in "endoplasmic reticulum."
"exenteration" is the removal of organs. "exhoneration" is a legal pardon.
Pathologists study "direction of differentiation." "Cell of origin" or "histogenesis" can be inferred but not proven.
"Revealed" is an over-used word. Revelations come from deities.
"thyroid," "parathyroid," "pituitary" and "adrenal" are adjectives and should always be followed by "gland." Admittedly, this is often ignored, but it shouldn't be.
"whirled" means to revolve rapidly. "whorled" is a spiraled or twisted pattern (the one you want to use!)
"centrolobular" is in the middle of a lobule. "centrilobular" is not a word.
"bronchioloalveolar" is a form of lung carcinoma. "bronchoalveolar" and "bronchioalveolar" are not correct.
"lumen" is singular. "lumina" is plural (not lumens, which is a measure of brightness).
"human papillomavirus" is correct, NOT "human papilloma virus"
"peri-" means around, as in perilobular "para-" means beside, next to, or near, as in parathyroid
Sentences that begin with "There" still require subject-verb agreement.
"There is" only works if the subject is singular, otherwise it's "There are..."
"There is no jobs".... is not correct! (the subject is "jobs.")
"concerning" means regarding. Tumors are "of concern" for malignancy or "worrisome" for malignancy, but "concerning for malignancy" should be avoided.
"ileum" is part of the small bowel. "ilium" is a bone.
There is only one "nose," which is composed of the left and right "nares" (singular = naris). There is no left nose, thought there is a left side of the nose.
There is only one thyroid gland; it has left and right (and pyramidal) lobes.
The engulfment of lymphocytes in Rosai-Dorfman disease is called "emperipolesis" and not "emperipoiesis."
A "papillary microcarcinoma" is NOT the same as a "micropapillary carcinoma."
.....I'm sure you can think of MANY more common errors.
Wednesday, May 16, 2012
Departments and divisions of pathology, like empires and countries, and most other human endeavors, can, and often do, have their ups and downs. Sometimes the "ups" appear to last indefinitely, and at other times, departments never seem to recover from the "downs." An "up" department has the following characteristics:
1. A variably sized cadre of nationally respected, senior pathologists who maintain the departmental academic reputation, advance the field of knowledge, and support the development of junior faculty and trainees.
2. Adequate time for faculty to pursue academic endeavors
3. Adequate in-house and consultation material for trainees and to serve as the basis for on-going clinicopathologic studies.
4. Appropriate support from the departmental Chair and the hospital heirarchy including adequate salary support, funding for "non-funded" clinicopathologic research, support for academic time off service, nurturing environment for junior faculty, etc.
5. An intelligent and motivated housestaff.
6. A stable and collegial work environment.
7. Long-term planning to account for faculty retirements, changes in workload, etc.
There are, of course, multiple other factors such as the location of the institution. Some places are simply more attractive for raising a family, have reasonable costs of living, low crime, adequate recreational outlets, decent weather, etc. The degree to which faculty will tolerate problems at work is often closely related to their comfort in their off-work environment.
The idea is to have a stable, "buffered" environment in which destructive tipping points can be avoided. When a program is "up" its reputation is such that recruiting top flight junior or even senior level faculty is relatively easy and the program tends to almost effortlessly maintain its status. But this environment is surprisingly fragile. Any perturbation to the system that leads to the departure of just a few critical faculty can create a chain reaction in which the remaining faculty are overworked, feel under appreciated, and increasingly inclined to work elsewhere. Thus, the exodus begins and those who remain work ever harder, and leave at ever increasing rates until the only ones left either are unwilling to depart for personal reasons or unable to find jobs, suggesting that the best and brightest are almost certainly NOT left minding the store.
Once this process starts it often seems to run its inexorable course until the "wheels come off" and the powers that be in the medical center finally become focused on the problem and are forced to act, often due to intolerable clinician complaints about quality of service issues. By now things have gone way too far downhill, but the medical center finally elects to provide support to attempt to remedy the situation.
This usually involves a commercial recruitment campaign in an attempt to hire a nationally known pathologist as the new Chair or Division Director who can (hopefully!) reverse the ever accelerating downward trend. This is no simple feat.
Recruiting an established academic pathologist who wants to take on such a daunting task of rebuilding is difficult or in many instances impossible. Even if successfully recruited, this individual must then lure other usually junior faculty to a "down" department and ask them to initially work long service hours because of diminished staffing, on the promise and charisma of a new director that things will be better "soon." There aren't huge numbers of academic pathologists in the job market and not surprisingly most would much rather go to an "up" department where tangible benefits are readily apparent and they are confident that their careers will advance.
Without naming names there are very few instances in which the revival of a "down" department has been nearly as successful as hoped. The very few successes that come to mind during my career have required the up front recruitment of not one but several nationally known and respected pathologists who know each other, work well together and can form an instant critical mass for the resurrection of the moribund department.
The key of course is to avoid the downturn and associated faculty exodus in the first place and instead maintain a stable, content and productive work force. "Up" departments that can do that will remain "up" for the foreseeable future.
Thursday, May 03, 2012
The following is borrowed, with modification from an article published on MSNBC's web site. Much more information is present at this site.
On April 4th, nine medical societies, including the American Society of Clinical Oncology and the American College of Cardiology, representing nearly 375,000 physicians released guidelines challenging the widely held perception that more health care is better health care. The list includes 45 tests and treatments physicians should no longer automatically order. Each of the nine participating societies submitted five items to the total list of 45. Other medical subspecialties are expected to come forward with additional recommendations.
Dr. Christine Cassel, president of the American Board of Internal Medicine, said the goal is to reduce wasteful spending without harming patients. She suggested some may benefit by avoiding known risks associated with medical tests, such as unnecessary exposure to radiation.
The recommendations come at a time when American health care is undergoing dramatic change. No matter what the Supreme Court decides on President Barack Obama's health overhaul, employers, lawmakers, insurers and many doctors are questioning how the United States spends far more on medical care than any other economically advanced country and still produces mediocre results overall.
The 45 tests and procedures considered to be overused include:
Repeat colonoscopies within 10 years of a first test
Early imaging for most back pain
Brain scans for patients who fainted but didn't have seizures
Antibiotics for mild- to-moderate sinusitis unless symptoms last for seven or more days or worsen
Stress cardiac imaging or advanced non-invasive imaging in the initial evaluation of patients without cardiac symptoms unless high-risk markers are present
PAP smears on women younger than 21 or who have had a hysterectomy for a non-cancer disease
Advanced imaging or bone scans in patients with early-stage breast or low-grade prostate cancer
Bone scan screening for osteoporosis in women younger than 65 or men younger than 70 with no risk factors
Routine cancer screening on dialysis patients with limited life expectancies
Chemotherapy for sickest (terminal) cancer patients
Bioethicist Art Caplan noted the need for doctors to initiate more discussion about testing with their patients. "A lot of testing now done in medicine involves tests that are not especially accurate, tests done solely to protect against the fear of lawsuit and due to hyping of tests by manufacturers, providers and hospitals" says Caplan, professor of medical ethics at the University of Pennsylvania. "Patients need more information on the pros and cons of testing and screening if they are to make truly informed choices consistent with their personal values. Hopefully, this initiative will get that discussion moving."
The full lists are being propagated by an organization called "Choosing Wisely," an initiative of the American Board of Internal Medicine.
Of course, this consortium of medical specialties has no power to enforce any of these guidelines and only time will tell whether this quite logical approach to controlling medical costs will yield detectable results. It may well be an uphill battle against the competing pressures of physician revenue, malpractice fears, and patient demands, as well as other issues.
Friday, April 20, 2012
In my February 16th blog, I discussed a recent NIH consensus conference that concluded that "active surveillance" was appropriate therapy for men with low-grade and low-stage prostate cancer. I also discussed the conference suggestion that these low-grade and low-stage lesions should be called something other than cancer (or carcinoma). Many clinicians view both the conclusion and the suggestion as long overdue. Not everyone agrees of course, but a personal incident last week emphasized to me how much we need to consider what our words mean, both to patients and clinicians.
A colleague of mine, who I consider to be an expert in prostatic gland pathology had signed out two of 12 prostate cores as showing "atypical small acinar proliferation (ASAP)." He had based the distinction from adenocarcinoma on the presence of scattered basal cells around a few of the glands. The case had been sent to another expert in consultation at the patient's request, and he interpreted both cores as showing minimal ( <5% ) prostatic adenocarcinoma, Gleason score 3+3=6. I was asked to review the case and, not surprisingly, I found it to be a totally borderline call.
I would suggest that the following inter-related facts about this and similar cases are true:
1. Seeking additional expert consultation for a diagnosis of either minimal low-grade adenocarcinoma OR ASAP (or equivalent terms) is not only a waste of time and money, it is likely to cause nothing but increased confusion and anxiety.
2. The biologic significance of ASAP and minimal adenocarcinoma is (virtually) identical and the treatment (or more appropriately lack there of) should be identical as well.
3. Basing a clinical decision on the distinction between ASAP and minimal adenocarcinoma shows a fundamental and alarming lack of understanding of the biology of this disease.
4. If a patient or clinician is naive enough to think that this distinction should form the basis for a therapeutic decision, ie. therapy for minimal carcinoma and surveillance for ASAP (in spite of the new guidelines), then when faced with conflicting opinions, it makes no sense whatsoever to go with the more aggressive course, given the considerable morbidity associated with both radiation and prostatectomy and the indolent nature of low-grade / low-stage prostatic carcinoma.
5. There is no reproducible "gold standard" for the distinction between ASAP and minimial carcinoma and if such a standard existed, it would have no clinical meaning. Because of the limited biologic behavior of such lesions, we are unlikely to ever devise a meaningful way to discriminate between them.
6. The NIH consensus committee's suggestion that we find another name for these minimal lesions that does not involve the "C-words" (cancer, carcinoma) is, on balance, a step in the right direction. Perhaps we should simple expand rather than shrink, the use of the ASAP (or similar) designation.
7. Although, the diagnosis of clinically significant prostatic carcinoma is rarely difficult, careers have been made based on clinically insignificant diagnostic ascertions about lesions at the low end of this disease spectrum.
8. There have been many important advancements in our understanding of the variants of prostatic adenocarcinoma, refinements of our grading system, identification of carcinoma mimics, and recognition of pathologic features carrying prognostic weight. However, the trend toward diagnosing low-grade, low-stage carcinoma on smaller and smaller foci has led to widespread patient anxiety and over treatment.
9. As I hope is obvious, the above is a reflection of a much larger general problem in medicine, namely misinformed clinicians (and patients) making radically different treatment decisions based on pathologists "drawing lines" where in fact none exist and using differing terminologies that imply significant biologic differences where none exist. A short list of other similar problem areas would include:
ADH v. low-grade DCIS of the breast
low-grade dysplasia v. indefinite for dysplasia in Barrett's esophagus
severe dysplasia v. intramucosal adenocarcinoma in any GI biopsy
severe dysplasia v. carcinoma-in-situ at any anatomic site
CIN2 v. CIN3 of the cervix
Atypical melanocytic proliferation v. "early" melanoma
....you get the idea!
Monday, April 09, 2012
March 16th was residency match day. At 1:00 pm EDT all across the country fourth year medical students found out where they'll spend the next several years of their training. This year for the first time the non-matching students and the unfilled programs were notified four days before the match results were published. This allowed the unmatched students to more formally pursue an alternate program, eliminating the former one-day "scramble" to find a position.
The algorithm that generates the match list is not overly complicated but over the years I've noticed that quite a few program directors don't seem to fully appreciate how it works. Basically, the system first looks at every student's first choice and compares it to their favored schools first choice. If both are #1, then there's a match and they move on. On the next iteration, it looks at unmatched student's first choices and program's second choices. If there's a space available in the program, then there's a match. This process continues until all of the students' first choices have either been filled or rejected. It then moves to the student's second choices and unfilled programs first choices and repeats the iteration. The process continues until the all the students' choice lists and programs' choice lists have been exhausted.
The result is that students get their highest possible ranked program and programs get their highest possible ranked students. There are a few obvious points to keep in mind.
First, programs should only rank students they consider acceptable and likewise students should only rank acceptable programs.
Second, programs should rank their students in their order of preference without any consideration of their likelihoood of getting (or not getting) a particular student. Ranking the students you think you're most likely to get higher than better students who you think you're unlikely to get does the program no good and may well work to its detriment. There seem to be two reasons why some programs continue to do this. First, it gives them "bragging rights" in that they can say, we filled our match list with our top _ choices!" But they would have gotten no worse than the same residents anyway, and they may well have gotten BETTER residents if they had stuck to the "order of preference." Second, they don't understand how the system works.
This process has been around for a long time and has brought reasonable order and equity to a once completely chaotic system. For several years now, there has been discussion about expanding the matching system to fellowship programs. The current fellowship system is really a "non-system" of individual programs and approaches to filling fellowship positions. Some programs fill their fellowship positions multiple years into the future. Others fill them only relatively late in the process, ie. only shortly before the fellowship begins. As a general rule the more established and confident a program is in its worth, the more it is willing to wait longer for the best possible candidates. Less confident programs are more inclined to take candidates whenever they appear.
All of this creates confusion for fellowship applicants and I would argue does not best serve either the programs or the applicants. The big question is whether a coherent fellowship match can ever be developed that serves the needs of all fellowship programs, regardless of type and "rank" and likewise best serves all applicants. "Lesser" programs, or perhaps better phrased, "less confident programs" are all in favor of a fellowship match. More prestigious programs, those that can afford to wait until the last possible minute to get the best possible applicant, are in favor of the status quo. Reconciling these positions will not be easy and may require a mandate from the ACGME.
Monday, March 26, 2012
A recent article in the "Informed Patient" section of the Wall Street journal is entitled, "What if the doctor is wrong?" It's written by resident Wall Street Journal columnist Laura Landro. Like any good pathologist, I was prepared to hate this article, but it's actually a relatively balanced discussion of this topic. The article begins with the description of a woman with a pelvic mass initially thought to be an ovarian carcinoma, but ultimately determined to be a difficult to diagnose follicular lymphoma. The initial biopsy was interpreted as inconclusive and a subsequent larger biopsy was required for the diagnosis. The (mis)interpretation as probable ovarian carcinoma was based on clinical and radiographic observations, not a pathologic misdiagnosis.
The article then discusses the value of and indications for second opinions, particularly with regard to radiographic and pathologic diagnoses. To its credit the article does not get bogged down regarding nuanced differences in diagnosis (atypical ductal hyperplasia v. intraductal carcinoma, for example), rather it focuses on differences in diagnosis that have important clinical consequences. A number of interesting statistics emerge. For example, more than half of women having mammograms for a decade will have a false positive recall for a repeat screen. A spokesman for M.D. Anderson indicates that for certain high-risk diagnoses such as lymphoma, up to 25% of patients undergo revision of their original outside diagnoses. The article also reviews a study of 742 cancer diagnoses referred for second opinion. 9% had their diagnoses revised. What is unclear is whether these revisions were minor or clinically meaningful. Interestingly, the highest number of revisions (16%) was for the diagnosis of thyroid carcinoma. My suspicion is that this was the result of the overdiagnosis of the follicular variant of papillary carcinoma. The second highest revision rate (11%) was for salivary gland malignancies. I suspect that most of these were minor terminology differences of little if any clinical significance. A spokesman from Hopkins indicated an 8% clinically significant disagreement rate with reviews of outside pathology for patients admitted to their institution.
At the University of Virginia, all patients admitted for outside-diagnosis-based therapy are required to have their outside pathology material reviewed prior to initiation of therapy unless emergent treatment is required or confirmatory biopsy material can be obtained at the time of the therapeutic procedure, but before its initiation. Our own signficant disagreement rate is in the range of 3-6%.
Of course, as the old saying goes, "A man with two watches never knows what time it is." When there are two diagnoses, who's to say which is correct? Being an academic medical center most certainly does not insure infallibility. In our department, descrepant diagnoses on examination of outside material are always reviewed by at least two and sometimes several more concurring pathologists before a differing report is issued.
As the article rightly points out, not all diagnoses require second opinions, and the overuse of this approach can leave patients overwhelmed by conflicting information. Ultimately, patients may be better served if they pick a physician they trust and accept his or her recommendations regarding treatment or the need for second opinions.
The article only touches in passing on the need for and use of internal reviews. In many larger institutions, including my own, this function occurs frequently among my collegues on virtually any diagnostically difficult case, and then occurs more formally when virtually all significant diagnoses are reviewed at corresonding multidisciplinary treatment boards (ENT tumor board, colposcopy board, liver board, thoracic surgery board, gastroenterology board, etc, etc)
Overall, I found this to be a balanced and factual article and I think most pathologists would enjoy reading it. Just don't read the "doctor bashing" comments from the readership. ...but then, I recommend not reading the comments after ANY on-line article. The "signal to noise" ratio there is always extremely low.
Monday, February 27, 2012
The lead article in the January 2012 issue of CAP Today addresses the pending FDA regulation of whole slide imagers (WSI's). The FDA has concluded dthat these devices are "Class III" medical devices, and as such are subject to considerable federal regulation (compared to Class I and II devices). Depending on your perspective, this is either a good thing for patient safety or the death knell for rapid development, certification and deployment of these devices in the United States, with many companies looking elsewhere for testing and validation).
By way of quick review, Class I devices are lowest risk and require no pre-market notification. Your light microscope is, believe it or not, classified as a Class I device. Class II devices are considered "moderate risk" and are usually based on modifications of prior approved devices or techniques. Class III devices are considered "highest risk" and such devices require premarket FDA approval, quality controls, etc. Automated cytology screeners, for example, are Class III devices. The FDA has said that WSI's belong in this category as well.
It seems somewhat surprising, at least to me, that a technique based on standard light microscopy, with microscopes being essentially unregulated, Class I devices, should be given the "highest risk" Class III rating. Although the rationale for that decision may be difficult to fathom, it has, in fact, been made and is highly unlikely to be reversed.
The fact that the FDA has even been reviewing WSI's and has decided to regulate them as "highest risk" Class III devices, may come as a surprise to most end-user pathologists since the topic of regulation is understandably not a major one at trade shows where vendors try to sell these devices. It certainly isn't a topic the vendors themselves are likely to bring up, at least until now.
Although the FDA has been less than specific in discussing their thinking, they have indicated that they have concerns about image quality when compared to standard light microscopy, and the effect of navigating on a computer screen v. moving a slide on a microscope. It is even unclear whether WSI's might be approved for a certain TYPE of specimen or group of diagnoses and not for other types or groups. Might it be approved for small core biopsies and not for big tissue blocks? Might it not be approved for hematologic malignancies, where the diagnosis often requires viewing large areas at relatively high magnification, something that is more difficult with a WSI? At this point, no one knows. Clinical trials comparing the accuracy of WSI's v. traditional microscopy will be difficult to construct and time consuming to perform, but will likely provide the data to answer these questions.
Given the FDA's pace of action in regard to other issues, it's now expected that it may take up to five years for the first devices to be approved in the United States, with Aperio likely to be among the first. Some companies will most likely concentrate their efforts in Europe where the approval process (and subsequent sales) are likely to be much more rapid.
There are many unanswered questions at this early juncture, but it does seem clear that buying and using a WSI for clinical (not research) diagnosis would not be a prudent move at this point in time. If you are currently using a WSI for primary clinical diagnosis, you had better have "state of the art" (whatever that is!) validation policies in effect, and even then your CLIA or CAP inspection is likely to be problematic. Even when these instruments gain approval, their use for diagnosis at a distance will fall under the highly diverse state laws regarding telemedicine. A topic I covered in one of my early blogs, "Down the Telepathology Rabbit Hole."
Thursday, February 16, 2012
In the past here in this blog, I and others have discussed the problem with the nomenclature of in-situ carcinoma, particularly with regard to breast carcinoma. The problems relate both to the difficulty in distinguishing DCIS from atypical hyperplasia, and the fact that the term "carcinoma in situ" applies the "C word" to a lesion that is, in its current state, incapable of acting in a fully malignant fashion. As we noted, in other organ systems, notably the GYN tract, pathologists and gynecologists have gotten away from this problem by switching to the intraepithelial neoplasia terminology.
In the prostate gland, there are similar but not identical problems. The in-situ carcinoma in the prostate has long been labeled with the intraepithelial neoplasia rubric, ie. high-grade prostatic intraepithelial neoplasia" (HGPIN). In fact the term, "carcinoma in-situ" has never been used to any significant degree in this organ. Moreover, since its initial description, the frequency of HGPIN in biopsy specimens has increased markedly with increasing recognition of this lesion, and its biologic significance has correspondingly decreased. As we all know, it is quite common in needle biopsies from older males, and even some younger ones. It's presence as an isolated finding does not typically lead to any definitive therapy. So in respect to in-situ disease, our terminology and approach to the prostate, it can be argued, is appropriate and reality based.
However, the major problems with regard to invasive prostatic carcinoma are, 1. that it is an incredibly prevalent disease that in many instances remains indolent throughout the patient's life, and 2. with the advent of immunohistochemical staining for basal epithelial markers and racemase, we can now detect small 3-5 gland foci of "carcinoma" that would never have been diagnosed as such even a decade ago. These small foci of well-differentiated carcinoma are invasive lesions so the "intraepithelial neoplasia" system isn't at all appropriate. Nonetheless, most of them will do nothing, yet the patient is labelled as having cancer. Many folks, both patients and clinicians have a problem with the concept of clinically irrelevant "cancer." As our former chair of urology used to say, "saying you have a little bit of cancer is like saying you're a little bit pregnant."
Recently, the NIH convened a consensus panel, which concluded that "active surveillance" is an appropriate course of action for men with low-grade and low-stage prostatic carcinoma. This is a welcome and many would argue overdue decision. It gives clinicians who elect to follow their patients with these small lesions important additional support for that decision. The remaining problem, of course, is to get patients to understand that doing nothing for carcinoma is a rational decision. The NIH consensus panel also recognized this problem and suggested that it may well be a mistake to call these low-grade, low-volume lesion "cancer," as this may lead to unnecessary patient anxiety and prompt patients to push for unnecessary treatment.
In a recent editorial in the February issue of The Oncologist entitled, "Call it Cancer," Drs. Bruce Chamner and Matthew Smith from MGH argue for retaining the cancer designation. Their arguments are well constructed and well reasoned, but they do not deal with the fact that the minimum threshold for the diagnosis of prostate cancer in 2012 is not the same as it was in, for example, 1990. Today, that diagnosis may well be based on foci far too small to have been unequivocally diagnosed as carcinoma without the aid of immunohistochemical support that was unavailable until relatively recently. Second, as all pathologists know, prostate cancer is a notably multifocal disease and there is no evidence (nor is there likely to ever be) that such microscopic foci of low-grade carcinoma are themselves the seeds for the development of subsequent, clinically significant cancers. Rather they may simply be markers of limited increased risk.
Unfortunately, the NIH panel did not suggest an alternative terminology for these small foci of "carcinoma" but it is heartening to know that they are well aware of the problem and the need for a better solution. Perhaps these should be called, "glandular neoplasia of low (or uncertain) malignant potential" to borrow again from our gynecologic colleagues.
Monday, February 06, 2012
A few weeks ago, my son-in-law who's a fellow in internal medicine on the west coast sent me this link to an essay by Ken Murray, a retired physician from USC about how doctors choose to control their own deaths. It's a really fascinating and thought-provoking read. Patients don't die the way their doctors often do, but they should!
The first four paragraphs are reprinted here to get your attention:
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Years ago, Charlie, a highly respected orthopedist and a mentor of mine, found a lump in his stomach. He had a surgeon explore the area, and the diagnosis was pancreatic cancer. This surgeon was one of the best in the country. He had even invented a new procedure for this exact cancer that could triple a patient’s five-year-survival odds, from 5 percent to 15 percent, albeit with a poor quality of life. Charlie was uninterested. He went home the next day, closed his practice, and never set foot in a hospital again. He focused on spending time with family and feeling as good as possible. Several months later, he died at home. He got no chemotherapy, radiation, or surgical treatment. Medicare didn’t spend much on him.
It’s not a frequent topic of discussion, but doctors die, too. And they don’t die like the rest of us. What’s unusual about them is not how much treatment they get compared to most Americans, but how little. For all the time they spend fending off the deaths of others, they tend to be fairly serene when faced with death themselves. They know exactly what is going to happen, they know the choices, and they generally have access to any sort of medical care they could want. But they go gently.
Of course, doctors don’t want to die; they want to live. But they know enough about modern medicine to know its limits. And they know enough about death to know what all people fear most: dying in pain, and dying alone. They’ve talked about this with their families. They want to be sure, when the time comes, that no heroic measures will happen; that they will never experience, during their last moments on earth, someone breaking their ribs in an attempt to resuscitate them with CPR (that’s what happens if CPR is done right).
Almost all medical professionals have seen what we call "futile care" being performed on people. That’s when doctors bring the cutting edge of technology to bear on a grievously ill person near the end of life. The patient will get cut open, perforated with tubes, hooked up to machines, and assaulted with drugs. All of this occurs in the Intensive Care Unit at a cost of tens of thousands of dollars a day. What it buys is misery we would not inflict on a terrorist. I cannot count the number of times fellow physicians have told me, in words that vary only slightly, "Promise me if you find me like this that you’ll kill me." They mean it. Some medical personnel wear medallions stamped "NO CODE" to tell physicians not to perform CPR on them. I have even seen it as a tattoo.
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There is much more to this excellent article including a review of how patients, doctors and the system often conspire to bring about such futile, expensive, and often painful end of life care. Even the best intentioned patients can get trapped by the system. Family members often have unrealistic expectations and contribute to the problem. When they say "do everything possible" do they really mean, "do everything possible that's reasonable"?
There's also an excellent discussion of this essay and topic on Time.Com.
I'm told that Dr. Murray's article has "gone viral" on the internet so you may have already seen it, but if you haven't you need to. Share it with your family and friends as well. Bravo to Dr. Murray.
Thursday, January 26, 2012
I was looking at my shelf of bound journals today and remembering that I have a full set of the American Journal of Surgical Pathology starting with the 1st volume in 1977 (the year I started my residency) and ending in 2008. The issues from 2009-today sit, unbound, in an ever-growing pile on my shelf. For continuity sake, part of me wants to continue with the binding, but my more pragmatic side realizes that all this information is readily available online and, after all, "a foolish consistency is the hob goblin of little minds" (or something like that). Not to mention the fact that journal binderies are rapidly becoming nearly extinct. Office pickup and delivery is no longer available and getting journals bound is becoming increasingly expensive. It's difficult or impossible to justify.
Access to information has never been easier. Google often gives better, quicker search results than PubMed. At our unknown conference this morning a reference to large cell calcifying Sertoli cell tumor of the testis, led me to comment that, "I think these can be associated with Peutz-Jeghers syndrome, and another syndrome that I can't remember." A few seconds on Google confirmed this association, as well as one with Carney Complex. Einstein reportedly once said that he could never remember the speed of light, but he knew where he could look it up. He would have LOVED Google!
Against this somewhat rambling background about ever-increasing access to digital-based information, I'd like to refer you to what I think is the beginning of an excellent approach to learning in pathology. If you have an Ipad, Johns Hopkins has developed a beautiful (and free!) application (App) to teach you pancreatic pathology. A brief video explaining this App is available on You Tube The App can be downloaded by going to this web site , or by doing a search for "Johns Hopkins Atlas of Pancreatic Pathology" from the Itunes App on your Ipad. This App is not designed for an Iphone or Ipod. The images are just too big to properly display on such a small screen.
We are just beginning to tap the tremendous potential of Ipads and similar tablet devices as learning tools. I suspect that this is the first of an educational teaching series in pathology from Hopkins as well as others.
Check it out.
Monday, January 16, 2012
Pathologists know a LOT about tumor biology and sometimes what we know calls into serious question practices that are accepted as "standard of care" by our clinician / surgeon colleagues. Getting well-accepted procedures changed often takes a LOT longer than it did to get them accepted in the first place, particularly when (forgive my innately "jaundiced" views here) physician revenues are involved. Indeed, those who call these procedures into question often face considerable ridicule, at least initially (ie. for the first few decades!).
In the late 1800's, Halsted put forth the concept that breast cancer spread linearly and primarily in a direct "crab-like" fashion, and decided that optimal treatment would require en bloc removal of breast, chest wall musculature and axillary tissue. Even though pathologists KNEW for many decades that the life-threatening form of breast cancer spread is not direct extension, but embolic distant metastasis, it took 80 years to convince the (surgery) world that this radical procedure provided no increased benefit over more conservative approaches. This mentality persists even today. Surgeons routinely perform mutilatingly large skin excisions for cutaneous melanomas to assure multi-centimeter free margins. When have you ever seen a patient die of locally uncontrollable cutaneous melanoma? Local control is a non-issue.
Now comes the era of the sentinel lymph node. The concept behind this procedure is as flawed as Halsted's conception of the biology of breast carcinoma. The theory is that cancer spreads linearly, first involving regional lymph nodes, and only after that, spreading to other body sites. Therefore, if the sentinel lymph node is positive, removing adjacent regional lymph nodes can prevent distant spread. We know better. I'll primarily confine my remarks here to sentinel lymph nodes in malignant melanoma, because the biology of melanoma most flagrantly calls this approach into question, but similar arguments can be made for lymphadenectomies based on SLN status at other anatomic sites.
There is widespread agreement that SLN status is a prognostic sign, even for malignant melanoma. However, it is nothing more than a staging element, and not a particularly good one at that. Given the limited options for efficacious non-surgical therapy for melanoma, of what value is this additional bit of prognostic information, and at what cost was it obtained? Large prospective studies with over a thousand patients have made it clear that patients with intermediate depth cutaneous malignant melanoma treated by local excision and removal of isolated lymph nodes only if they are clinically enlarged, have the same prognosis as matched patients undergoing SLN biopsy and completion lymphadenectomy for positive SLN's. Given what we know about the biology of malignant melanoma, namely that it is fully capable of metastasizing widely and hematogenously, completely bypassing lymphatics, very early in its clinical course, this makes perfect sense.
So why are we continuing this approach? Because patients want it? Because it makes surgeons feel like they're doing something for the patient (and generating RVU's)? Because it has become a de facto "standard of care" and not doing it risks medicolegal entanglements? The answer is, of course, all of the above. Breaking this cycle, like eliminating the radical mastectomy will not be easy.
There is a comprehensive discussion of this topic in the December 2011 edition of CAP Today, based on a plenary CAP conference held in 2011 and entitled, "Sentinel Lymph Node Dissection for Melanoma: Is the Standard of Care Ahead of the Evidence?" I strongly recommend it as a scholarly and insightful discussion of this important topic.
Tuesday, January 03, 2012
Happy 2012 to one and all!
I bet that most of you have experienced the following scenario more than once. It happens to me at least once (and usually more often) each year. You get a single specimen jar containing multiple polyps from throughout the large intestine of a patient undergoing routine surveilance colonoscopy. One of the polyps contains either a well-differentiated neuroendocrine carcinoma (carcinoid tumor), an overt adenocarcinoma, or a polyp with at least intramucosal carcinoma. The resultant phone call is usually interesting! Some actually have the temerity to ask, "Which one is it?" ".....ahh, it's the one with the cancer in it!" The chagrined clinician is usually forced to re-endoscope the patient in the hopes that remnants of the offending lesion can be found... They seldom are, placing the clinician in the uncomfortable position of considering a resection from an un-localized lesion, or watchful waiting.
Asking clinicians WHY they put all their polyps in one jar is also an interesting, if somewhat frustrating exercise and often leads to comments like, "I thought they were all benign," or "I was trying to save the patient some money." With regard to the former, the old adage that familiarity breeds contempt seems appropriate. The fact is that experienced endoscopists are very very good at identifying benign polyps, but they are not perfect at it; and every single one will tell you that they've been burned more than once in a variety of different ways. With regard to the "save the patient some money" argument, this works right up until the moment that it doesn't, and then it costs that one patient a LOT of money to figure out what's going on and get appropriate treatment.
I certainly don't advocate putting each polyp in a separate jar, though I do think that large or otherwise suspicious polyps should be submitted separately. It is also reasonable (and prudent) to tatoo any areas where suspicious polyps are removed. In my opinion, a good compromise approach to the submission of multiple endoscopically banal polyps is to submit them according to surgical resection boundaries. Separate specimen jars should be submitted for polyps from the ascending colon, transverse colon, descending colon, and rectosigmoid region. In this fashion, the number of 88305 charges is kept to a reasonable value and, for example, if one of 12 polyps from the ascending colon contains carcinoma, and a surgical resection is planned, the area containing the polyp will be encompassed by the standard partial colectomy procedure. The burden of finding any residual carcinoma then falls to the pathologist.
This seems like an obvious approach to me and I wish that all of my gastroentoenterologist colleagues would follow it.
Monday, December 19, 2011
If you're looking for that last minute holiday gift or just want to treat yourself to a little diversionary reading over the holidays, I would recommend, "Bright-Sided: How Positive Thinking is Undermining America," by Barbara Ehrenreich. This 256 page book, available in paperback is on the New York Times best seller list and deals with an interesting topic that has both medical and non-medical ramifications. In this relatively short book the author debunks the false promises of positive thinking and shows just how widespread this phenomenon is and its effect on all aspects of life. We're told that if we're positive, upbeat, and optimistic, then good things will most certainly come our way. Motivational speakers have made billions of dollars pushing this life approach on the general public. However, when the desired results do not occur, the stage is set for self-blame and denial, sometimes on a national scale.
Fully 91% of the general population believes that attitude affects medical outcomes, even though there are no data to support this belief, and a large volume of data to refute it. How often have we heard that someone "lost their battle with cancer," somehow implying that the individual's fate is dependent on circumstances under their control. If disease is a battle we must "fight" using some internal "weapons" that we can manipulate, then ultimately we will all exit this world as "losers." Not the way we'd like to be remembered!
The author takes this discussion in many different directions and provides some intriguing insights and opinions about the harms caused by this approach, from the Iraq war to the home mortgage meltdown. You may not agree with all of the conclusions, but the book provides LOTS of food for thought.
For a little more detail about the book, the Publishers Weekly review is included below:
From Publishers Weekly
Starred Review. Ehrenreich (Nickel and Dimed) delivers a trenchant look into the burgeoning business of positive thinking. A bout with breast cancer puts the author face to face with this new breed of frenetic positive thinking promoted by everyone from scientists to gurus and activists. Chided for her anger and distress by doctors and fellow cancer patients and survivors, Ehrenreich explores the insistence upon optimism as a cultural and national trait, discovering its symbiotic relationship with American capitalism and how poverty, obesity, unemployment and relationship problems are being marketed as obstacles that can be overcome with the right (read: positive) mindset. Building on Max Weber's insights into the relationship between Calvinism and capitalism, Ehrenreich sees the dark roots of positive thinking emerging from 19th-century religious movements. Mary Baker Eddy, William James and Norman Vincent Peale paved the path for today's secular $9.6 billion self-improvement industry and positive psychology institutes. The author concludes by suggesting that the bungled invasion of Iraq and current economic mess may be intricately tied to this reckless national penchant for self-delusion and a lack of anxious vigilance, necessary to societal survival. (Oct.)
Friday, December 09, 2011
As pathologists, we should never lose sight of what our diagnoses mean, or should mean, to the patients who will carry them. I have touched on this topic, at least tangentially, before but a recent, rather nicely done essay by Gina Kolata in the New York Times reminded me of the importance of our words. In particular, the words "cancer" and "carcinoma" instill the sort of primal, reptilian fear usually associated (at least in susceptible individuals) with things like snakes, spiders, and dizzying heights. The public is in large part unaware or only marginally aware of what a huge spectrum of disease these words encompass, ranging from in-situ lesions and inconsequential invasive lesions like basal cell carcinomas of the skin with virtually no associated mortality to uniformly (and rapidly) fatal tumors such as glioblastoma multiforme and inoperable pancreatic carcinoma.
The essay focuses in part on what I believe is a particularly bad use of these terms, referring to DCIS of the breast as Stage 0 cancer (carcinoma). Are most patients really capable of understanding the significance of this lesion? Or do they hear the words "cancer" or "carcinoma" and none of the modifiers that follow them? Even if they DO understand the meaning of their particular form of cancer at some higher cortical level, does this overpower the primal power of the word? To continue the analogy above, if you're a "snake hater" does your brain really distinguish in a logical, rational fashion between small harmless garden snakes, big harmless black snakes and rattlesnakes? Probably not; you get that same primal fear around any of them. That's the power that the words "cancer" and "carcinoma" have over many (most?).
Does the power of these words contribute to unnecessary treatment, anxiety, medical expense, etc.? I think it does. As the essay points out, gynecologic pathologists addressed this issue with regard to cervical carcinoma in-situ in 1988 and developed the "intraepithelial neoplasia" terminology that eliminates the word "carcinoma" from these in-situ lesions. This terminology has been adopted by others, leading, for example to the "PanIN" system for pancreatic ductal neoplasia. Unfortunately, other specialists have not been so far-sighted or so successful in modifying terminology to better reflect disease. But the tide is slowly turning and quite a few clinicians are beginning to raise this issue. Two years ago and expert panel at the National Institutes of Health said that the word "carcinoma" (cancer) should be eliminated from all in-situ lesions. So far, unfortunately, their advice has gone largerly unheeded. Perhaps in part due to concerns about lack of clinician understanding and even increased medicolegal liability.
There's also a "factoid" in the essay of which I was not aware. Donald Gleason, developer of the Gleason grading system for prostatic carcinoma, was in favor of re-labelling 3+3 prostatic adenocarcinoma as "adenosis" because of its indolent clinical course. Rightly or wrongly, he lost that argument.
The essay is a quick read. It's always refreshing when the lay press delves into a medical issue and gets it more or less exactly right.
Thursday, December 01, 2011
Basal or myoepithelial cell markers are being increasingly utilized to distinguish in-situ from infiltrative lesions. In the prostate, for example, absence of basal cell markers (p63, HMW keratins) are used to help identify infiltrating adenocarcinomas. In the breast, absence of myoepithelial markers (CD10, SMA, p63) fulfills the same purpose. Yet, it is important to understand that there are exceptions in both directions; not everything lacking a normally present basal / myoepithelial layer is invasive, and some invasive lesions with retain this layer.
As an example of the former scenario, back on June 27th of this year, my "image of the week" was an intraductal apocrine lesion of the breast that completely lacked a surrounding myoepithelial layer. The case had been sent for consultation because the initial pathologist was concerned about the absence of a myoepithelial layer and was not aware that this had been described with regard to intraductal apocrine breast proliferations (AJSP 2011;35[2]:202-11). We continue to see cases just like this one in which this rather common "exception to the rule" has caused diagnostic problems.
Other examples that are perhaps better known are adenosis of the prostate and microglandular adenosis of the breast. These lesions may have a markedly attenuated or completely lacking basal cell layer. Thus, this finding per se cannot be used to make a diagnosis of carcinoma in the absence of other (mainly nuclear in the case of prostate) histologic features. Here, I'm setting aside for another day the argument that "adenosis," at least in the prostate gland, might, in fact, be a very low-grade adenocarcinoma.
What happens to the myoepithelial or basal cell layer in these cases is an interesting and unanswered question. Was it never there, or was it there at one time and subsequently became highly attenuated or disappeared altogether, through mechanisms that we don't understand?
What about infiltrative lesions that retain a basal or myoepithelial cell layer? The most obvious example would be an epithelial-myoepithelial carcinoma of the salivary glands. These distinctly biphasic-appearing tumors have a very well-formed outer myoepithelial layer and yet are clearly invasive and metastatic-capable tumors.
A somewhat less obvious example of this phenomenon was encountered in our consultation material very recently, and appeared as last week's "image" case. This was a small mass from the upper-outer quadrant of the breast in an elderly woman that had the classic features of a so-called low-grade adenosquamous carcinoma of the breast. The contributor had done immunohistochemistry for myoepithelial markers (SMA, CD10), and demonstrated abundant myoepithelial cells around the periphery of the tumor cell nests and cords, leading to an incorrect interpretation as a benign sclerosing process. It has, however, been well documented that this particular variant of low-grade breast carcinoma retains a myopepithelial cell layer.
How are these invasive lesion able to retain a myoepithelial layer? Either they are regenerating it by divergent differentiation of neoplastic cells as they invade, or the tumors are somehow recruiting myoepithelial cells from the surrounding stroma. The former scenario is almost certainly at play with regard to epithelial-myoepithelial carcinomas, but other lesions may not be so clear cut.
There are, of course other examples in both directions (benign lesions lacking myoepithelial/basal cells, and invasive malignant lesions retaining them) that defy our general conventions with regard to basal / myoepithelial cells and infiltrative malignancy, but these four will suffice for our purposes here.
The take home message is that virtually every rule has exceptions. When the immunohistochemical findings don't seem to match our pre-conceived notions, a little internet searching can be extremely productive. And by the way, although I used to be a big fan of PubMed on-line searches, my residents have long since convinced me that Google searches are faster and generally more complete, unless you have a specific citation or journal in mind.
Monday, November 21, 2011
I really do try not to be a "grumpy old man!" I'm not usually grumpy and I'm not that old. I just turned 60, which as we all know, the new 40! However, when I look at the radical ways in which medical education is being altered, strikingly for the worse in my opinion, I can't help but be concerned for the future of those of us destined to be under the care of these poorly educated, lacking in the fundamentals, future physicians. Rather than requiring a core knowledge of the basic medical sciences, the new approach seems to be, "don't worry about the details, just get the big picture by guided self-discovery," whatever that is.
Medical schools are clearly abrogating their responsibility to teach core biologic / medical principles. Some schools have acknowledged this and noted that they are now requiring significantly more undergraduate training in the basic sciences before acceptance into medical school. I certainly hope so, because it is abundantly clear that they're no longer getting this material in medical school. How an English major can expect to ever come to grips with the science background necessary to be a physician when it is no longer being taught in the first two years of medical school is quite beyond me.
Even if you come to medical school with a stellar basic science background, you are unlikely to learn the fundamentals of anatomy, histology, and pathology that should underpin a solid medical school education. Indeed, courses with these names no longer exist in most medical schools, being folded into "big picture" courses with names like, "Fundamentals of Human Disease." We see the effects of this all too clearly in our residents. Although we have been fortunate to attract some of the best and brightest into our residency program, these individuals, through no fault of their own, are lacking in the fundamentals of anatomy, histology, and pathology. In fact, I would say that these excellent, highly motivated students of today, almost all AOA members, would fare quite poorly in these subject areas, when matched with the lowest 10% of a medical school class from two decades ago. Pathology is hard enough to learn in 4 years when you enter a program well trained in the basics. It's almost impossible when you begin and are unable tell the dermis from the epidermis on a microscopic slide.
As a side issue, given how little exposure medical students have to gross and microscopic pathology during their training, it's a wonder that ANY of them is attracted to a career in pathology.
When I consider what medical school tuition COSTS today, even for an in-state student in a state-supported school, I can't help but think that they're definitely NOT getting their money's worth!
The argument against all this is to say that although those going into pathology might benefit from more training in these areas, for most physicians it just isn't important. Histology is, after all, "archaic." I know it must be, because a second-year medical student told me so recently!
In 1952, Dr. Robert A. Moore, a well-known pathologist who was then the Dean of the Washington University Medical School in St. Louis published an article in the journal, Academic Medicine entitled, "The Place of Pathology in Medical Education." I wish that this were mandatory reading for new medical students, or more pointedly for those altering medical school curricula. Dr. Moore's point that understanding pathology is pivotal to the ability to think and reason as a physician is right on the mark. If you're interested, and I hope that you are, you can get a PDF of the article at this site.
Tuesday, November 08, 2011
For years, clinical pathologists have had lists of critical laboratory values that trigger a phone call or other immediate contact with the patient's treating physician. These critical values are relatively easy to define for serum analytes. Surgical pathologists have been slower to recognize the need for a codified list of critical diagnoses, in part because of the greater difficulty in constructing such a list. However, for a few years the CAP and other accrediting agencies have been putting ever-increasing emphasis on the need for an institutional list of critical diagnoses that will trigger immediate physician contact, a hierarchical approach to contacting physicians, and a clear-cut way to document these efforts.
The general approach has been that each institution should, in collaboration with its clinician colleagues, formulate their own list of critical diagnoses that will trigger immediate physician contact. The Association of Directors of Anatomic and Surgical Pathology (ADASP) has performed surveys and made recommendations in regard to critical diagnoses lists for surgical pathology (Am J Clin Pathol 2006;125:815). In general, these lists should consist of items, often unexpected, that are likely to have immediate, significant, often life threatening consequences. Examples might include, unexpected infectious agents, particularly in immunocompromised patients; significant disagreements between initial (frozen section, preliminary FNA) and final diagnoses; high-grade transplant rejection, crescentic glomerulonephritis, mesothelial cells in a cardiac biopsy (perforation?) etc. Note that an unexpected diagnosis of malignancy is NOT, a priori, typically a critical diagnosis, though there are exceptions.
In short, a critical diagnosis list is a trigger to contact the treating physician when a significant, immediately clinically significant and typically unexpected finding is encountered. When treating physicians are not available, a contact hierarchy should be available and the key is to document, document, document your efforts in the pathology report.
It is clear that these lists are important and are in fact now mandated for laboratory accreditation. We are currently in the process of updating our own departmantal lists and procedures, and that effort led me to write this blog.
As valuable as these lists are, however, as with most things, there is a potential downside that needs to be minimized. A critical diagnoses list is an important patient safety measure, but it is NOT a substitute for clinician diligence. Our clinical colleagues should not be lulled into thinking that they don't need to search for and read their patients' pathology reports routinely because, "If the diagnosis were important, you'd call me." Many IMPORTANT diagnoses (aren't ALL diagnoses IMPORTANT to the patient??) aren't of immediate clinical consequence and don't merit a critical values trigger. These lists are not for clinician convenience. They should be relatively short.
The other potential downside comes into play when someone forgets to contact a clinician for a critical diagnosis. Perhaps an unsuccessful attempt was made and then not followed up with additional attempts. Perhaps the case falls into a gray zone. Does this constitute a deviation from standard of care and increased medical liability? Probably, but the net effect of these lists is still extremely positive if they are properly constructed, and every effort should be made to make sure they are implemented.
Thursday, October 27, 2011
The internet last week was full of coverage of the trial of Michael Jackson's doctor and "teasers" from the new authorized biography of Steve Jobs. These were two highly talented, incredibly creative individuals with little else in common, except, perhaps, that the death of both may well have been hastened by their celebrity status. In the case of Michael Jackson the story is clear. Surrounded by enablers and "yes men" his life spiralled out of control with seemingly no one to say NO to his ever-increasing, medically dangerous requests. It is never easy to speak truth to power and when the individual in question is your incredibly famous, incredibly wealthy employer, denying their requests, medical or otherwise, requires a level of integrity that many apparently do not possess. The parallels to the life and death of billionaire recluse Howard Hughes are obvious.
Things are more nebulous with regard to Steve Jobs. For most of his illness his medical care was state of the art, but, of his own volition, he delayed treatment of his pancreatic islet cell tumor for at least nine months after diagnosis. Did this delay convert a potentially curable tumor into an uncureable one? Of course, we don't know for sure. I haven't seen his tumor and have no feeling for its growth rate or any other microscopic features. For many islet cell tumors, nine months would NOT affect prognosis, but the delay in therapy is certainly suboptimal, and we know that the final outcome was not good. Because of his stature, were his clinicians a bit less forceful in their treatment recommendations than normal? Or was Steve Jobs' own persona totally responsible for the delay? Did his business successes create a false sense of omniscience or invincibility? Who knows?
Of course you don't have to be Michael Jackson or Steve Jobs to be affected by the "special care" phenomenon. How often have you, as a pathologist, been asked to deviate from the norm in some minor or major fashion because Mr/Ms X is a VIP? These requests usually come in the form a well-meaning request to rush this or that specimen or to make sure that a specific pathologist signs out the case because the person in question is a VIP. I've also been asked by residents if the grossing of a specimen should be handled in some way differently if a patient is a VIP. As an example, I was once asked if a prostate from a VIP with BPH should be entirely embedded and sectioned in levels, "to be certain that we didn't miss any carcinoma." My response was that, "If there were a BETTER way to treat a specimen than our normal procedures, wouldn't it be unethical NOT to treat ALL specimens that way?" And conversely, if our normal way is best then isn't any deviation from normal less than best?
What does seem clear is that special care is often sub-standard care even though it attempts to be just the opposite. When the VIP shows up in the emergency room with an upper GI bleed, the best person to perform the endoscopy is the person normally on call for this procedure who does lots of them routinely, not the chair of surgery or someone less familiar with the procedure who happens to be of higher academic stature but possessing lesser up-to-date skills.
Consider the autopsy of President John F. Kennedy. Instead of allowing the Dallas medical examiner to perform the procedure, the normal approach for every other forensic case at Parkland Hospital, special military personnel were brought from Washington in to handle the "ultimate VIP," and the result was a highly botched procedure leaving forever unanswered questions.
There are many other examples of "people of stature" getting special treatment that turned out to be worse than the normal routes of care. Many VIP's check into hospitals under pseudonyms to protect their identities from prying eyes. Maybe they need pseudonyms (and disguises) to protect themselves from those trying to give them special treatment! OK, that wouldn't really work, but at the very least they should strongly consider telling their clinicians that, "I want the same high quality care that you give everyone else, nothing special."
Monday, October 17, 2011
In one of my earliest blogs I lamented that fact that the history of pathology is in many ways slipping away from us as those who made it, and those who personally knew them depart this world. In particular, I lamented the fact that documenting the personalities of famous pathologists such as Arthur Purdy Stout was becoming increasingly difficult or impossible. Dr. Rosai's excellent edited text, "Guiding the Surgeon's Hand, a History of Surgical Pathology in the United States is a notable oasis in this sea of ignorance. Unfortunately, that text is out of print, but used copies are occasionally available on several web sites.
Against this background comes a new book, marking the two hundredth anniversary of the Massachusetts General Hospital (MGH), and providing the definitive history of the development of pathology at the MGH and Harvard Medical School. The text is edited by Drs. David N. Louis and Robert H. Young with multiple chapter authors. It is entitled, "Keen Minds to Explore Dark Continents of Disease. A history of the pathology services at the Massachusetts General Hospital." The primary title, I must admit, is rather obtuse and suggests a text about the pathogenesis of tropical diseases in Africa, but the subtitle straightens things out nicely. The book is published by MGH and may be a little difficult to obtain (I couldn't find it yet on Amazon), but is well worth it if you're at all interested in the major contributions of MGH faculty toward making us what we are today.
The book includes six general sections: the early years, the Wright years, the Mallory years, the Castleman years, the McCluskey years, and the later years. It also includes individual chapters devoted to the specialized areas of pathology and other chapters representing mini-biographies of some of the true giants in the field including James Homer Wright (note, NO HYPHEN), Tracy Mallory, Benjamin Castleman, Austin Vickery Jr, Robert Scully, and others. What to me makes this book an absolute joy to read is the personal, first-hand style in which most of these giants of the field are described, wherever possible by those who actually knew them very well. Having been fortunate enough to have at least briefly met Drs. Castleman and Vickery, and to have spent considerably more time with the wonderful Bob Scully, the descriptions of these individuals are absolutely "spot on." Here in one place, preserved for those who will never have the opportunity to meet them, are not just the accomplishments, but the personas of these legends in pathology.
The other beauty of this text is the collection, in one place, of several hundred amazing B&W photographs stretching from the mid-1800's until the current time. I can't imagine the time required to hunt these down and identify everyone (or almost everyone, there are a few "unknowns") present. Most of these photographs have not been published for decades and their collection in one place is a treasure. Where else can you find a picture of Ben Castleman with a full head of hair? He's virtually unrecognizable! I certainly hope that graduating MGH residents are given a commemorative copy of this text. The rest of us will have to buy ours!
Thursday, October 06, 2011
When I was in high school I thought that my English classes were a complete waste of my highly valuable adolescent time. Of course, they turned out to be by far the most valuable education that I obtained in high school. Fortunately, I had some very good teachers. In college I took a lot of advanced math classes in preparation for a degree in physics. How I took a turn into medicine is a topic for another time. My math courses included topics like vector analysis, advanced calculus and linear differential equations, all of which I've completely forgotten. Somehow, however, I managed to avoid a basic statistics class. That's something I've regretted for many years.
Basic statistics is an invaluable tool that should be better understood by all medical authors (and readers). The topic is at the foundation of so-called "evidence-based medicine" a concept that is much on vogue in all of medicine. As health care dollars become more difficult to obtain, there will be an ever greater emphasis on providing diagnosis and treatment in the most time and cost efficient manner possible.
Against this background, Dr. Alberto Marchevsky, along with my friend and colleague, Dr. Mark Wick, have edited a concise multi-authored text entitled, "Evidence Based Pathology and Laboratory Medicine," published by Springer. The chapter authors are all well-known experts in their field. Chapter titles from the first half of the book include:
Biostatistics 101
Prognosis and Prediction in Anatomic Pathology
Power Analysis and Sample Sizes in Pathology Research
Meta-analysis: A Statistical Method to Integrate Information Provided from Different studies
Decision Analysis and Decision Support Sytems in Anatomic Pathology
...and many others.
The second half of the book is devoted to solutions offered to pathology and laboratory medicine using an evidence-based approach. Topics here include, among others:
Evidence-based approach to interpreting and integrating pathology literature.
Evaluating and reducing diagnostic errors using an evidence-based approach.
Evidence-based practices in applied immunohistochemistry.
Evidence-based pathology in molecular diagnostics.
As an example of the insights provided, have you ever wondered how many cases it would take to validate and refine our criteria for distinguishing an encapsulated follicular variant of papillary carcinoma from a follicular adenoma? Both, have extremely good prognoses, and because of this one would need approximately 120,000 patients followed for at least 10 years each to fully sort out the morphologic distinctions. Needless to say, this is unlikely to ever happen.
This book is an extremely well done, thought provoking series of treatises on how to interpret medical literature and improve pathology practices. Each chapter stands as an essentially independent topic, and the book can be "cherry picked" or read straight through. Since one of the editors and several of the authors are good friends, I might be accused of bias in recommending this book, but I really believe it is an excellent treatment of an extremely timely topic.
See if you agree, and please post your comments.
Monday, September 26, 2011
In the July issue of AJSP is an article that I co-authored dealing with high-grade non-intestinal adenocarcinomas of the sinonasal region. Far from representing a distinct entity, this is actually a surprisingly heterogeneous group of neoplasms, as the article illustrates. The topic of sinonasal adenocarcinomas is one that has held my attention for many years. These tumors can be broadly divided into intestinal-type neoplasms and non-intestinal / non-salivary neoplasms.
The intestinal-type tumors are highly diverse in their own right. At one extreme are lesions that are virtually indistinguishable from normal intestinal mucosa, complete with resorptive, goblet, Paneth, and argentaffin cells, as well as an underlying muscularis mucosae. Although one may be tempted to consider such lesions as heterotopias, they are recurring, locally destructive proliferations. Death has resulted when such lesions invaded the intracranial cavity.
At the other extreme are intestinal-type tumors composed of highly malignant enteric-type glands or signet-ring cells, often with abundant extracellular mucin pooling. Although very locally aggressive, the metastatic rate from such tumors is not as high as would be expected for similar-appearing colonic tumors.
In between, are intestinal-type proliferations that, although obviously neoplastic, more closely resemble exophytic colonic adenomas than overt colonic carcinomas. These tumors are also locally agressive with a prognosis somewhat intermediate between that of the two extremes. In our experience this pattern is the most common of the intestinal-type lesions.
Not surprisingly, the intestinal-type tumors show considerable immunohistochemical overlap with their colonic "cousins" including staining for CDX2 and appropriate MUC's. There are, at most, only minor immunohistochemical differences (generally lower level of CEA expression, and higher number of chromogranin-postive cells) when compared to colonic neoplasms.
Intestinal-type adenocarcinomas were recognized several decades ago as being strongly associated with environmental exposure to hardwood dusts, particularly in the woodworking industry in the United Kingdom, but also in the United States. Other environmental dusts, including leather dusts in the shoemaking industry have also been implicated. Environmental regulations appear to have greatly reduced these industry-related tumors.
The other broad category of sinonasal adenocarcinomas consists of tumors noted primarily for what they are NOT, the non-intestinal / non-salivary adenocarcinomas. These can also be divided broadly into low-grade and high-grade tumors, though it seems likely that with better understanding further subdivisions of each group will be possible.
The low-grade tumors are a rather incompletely characterized group of indolent neoplasms. Some appear to arise in pre-existent respiratory epithelial adenomatoid hamartomas (REAH's). These tumors have limited local destructive potential and virtually no metastatic potential. Where to draw the line between a benign but exhuberant glandular proliferation and a low-grade adenocarcinoma is problematic. Also problematic is the distinction from salivary-type neoplasms such as acinic cell carcinomas.
The paper in the July issue of AJSP is the first detailed description of a series of high-grade non-intestinal (and non-salivary) sinonasal adenocarcinomas. Nine cases had a blastomatous appearance resembling the glands in so-called teratocarcinosarcoma. Six cases had a more apocrine appearance, but did not resemble conventional salivary gland carcinomas. Six additional cases has a non-specific but poorly differentiated appearance with occasional micropapillary structures, and the remaining 3 cases had unique features that could not be categorized with the other tumors. Several of the tumors appeared to arise in Schneiderian papillomas. A quick perusal of the figures should provide convincing evidence of the heterogeneity of this group of neoplasms.
Clearly this is a fertile area for additional study.
Thursday, September 15, 2011
Many pathology journals have discontinued case reports, but we have continued to publish a limited number in AJSP. A while back I wrote a blog about what constitutes a good case report. It is decidedly more than a "funny lesion in a funny place." The bar for acceptance is high with fewer than 5% of submissions accepted. Yet, I have been reluctant to categorically dismiss case reports because occasionally they provide valuable information or make intriguing points.
The September issue of AJSP (Am. J. Surg. Pathol. 35:1413-1418, 2011) contains a case report by Jalas and colleagues that clearly fits into the latter category. The authors describe a 75-year-old woman who, 13 years earlier, had a malignant melanoma removed from her upper back. She presented with a right axillary mass showing two distinctly different juxtaposed components, a moderately differentiated adenocarcinoma and a malignant melanoma. Both components reacted immunohistochemically in quite distinct and expected ways. The melanoma component was positive for S100 protein and Melan-A and interestingly showed some patchy positivity for cytokeratin. The adenocarcinomatous component was negative for melanoma markers but strongly positive for cytokeratin, CDX-2 and Ber-EP4. The latter two were negative in the melanoma component.
Given the above findings, along with the histologic features described in the text, any rational surgical pathologist would normally conclude that they were looking at a collision tumor and alert the clinicians to find the occult gastrointestinal adenocarcinoma primary. In this case, an extensive clinical and radiographic evaluation failed to turn up a primary source.
Then the fun began. The authors performed DNA sequencing and comparative genomic hybridization (CGH), and found that both tumor components contained identical NRAS Q61K mutations and had highly similar CGH profiles, including gains in 1q and losses of 1p, 4, 9, and 10, all archetypical of malignant melanoma. The NRAS mutation was also present in the initial melanoma as a somatic mutation and was not present in the patient's normal tissues. The inescapable conclusion was that the adenocarcinoma divergently differentiated from the previous malignant melanoma. Needless to say, without the compelling molecular evidence the authors present, this would be a very hard conclusion to "swallow."
Although it seems likely that this is an extremely rare occurrence, the fact is, without molecular studies such as this in each instance of an apparent occult second primary, we don't really know the frequency of this phenomenon. I like this case report because it ties in nicely with one of my pet peeves, namely that pathologists often confuse differentiation with histogenesis or cell of origin. Immunohistochemistry is great for documenting differentiation, and almost invariably corroborates the H&E impression - if it looks like a gastrointestinal carcinoma it will almost always immunolabel like one. Immunohistochemistry says nothing about histogenesis.
This case has, indirectly, a few nice "take home" messages.
1. When all rational explanations have been exhausted it is time to examine the seemingly irrational ones.
2. Malignancies, especially high-grade ones, are genetically labile and not constrained to "breed true" or follow our preconceived rules for their behavior.
3. Given enough time and enough genetically labile mitotic divisions, every malignant tumor may eventually give rise divergently to every other malignant tumor.
4. Immunohistochemistry is a tool for studying differentiation, NOT cellular origin.
5. Molecular techniques are powerful tools when applied to answer the proper questions.
Wednesday, September 07, 2011
Several of my blogs have dealt with various forms of bad medicine. Most recently in "Cancer Hope or Hype?" I presented an example of documented fraud in chemotherapy sensitivity and resistance assays. Labs providing these assays have sprung up like weeds on a wet spring day and many naive patients and clinicians have been swayed by their claims, in spite of a lack of documented efficaciousness. We frequently get requests from our clinicians and patients to perform these highly expensive tests. Refusal to comply, even when accompanied by a carefully thought out rational reason, usually leads to something resembling a childhood temper tantrum accompanied by a string of derogatory comments ranging from, "you guys are so backward," to "you're killing my patient."
Undoubtedly, many of you have been confronted with exactly this scenario, and you may well have buckled to the strident demands and sent appropriate materials off for the favored assay de jour. In many instances your department may then have been forced to "eat" the exorbitant charges when neither the patient's insurance carrier, the patient or (heavens no!) the requesting physician would cover the charges.
Well, guess what? The American Society of Clinical Oncologists (ASCO) has just given you an extremely powerful bit of ammunition for your refusal to order these highly expensive and highly questionable (resisting the urge to use the word "worthless" here) tests. In the August 20th issue of the Journal of Clinical Oncology, ASCO has published its "Clinical Practice Update on the Use of Chemotherapy Sensitivity and Resistance Assays (CSRAs)." This paper is a short, well-written tribute to evidence-based medicine. If you're in a hurry, here's the bottom line:
"The use of CSRAs to select chemotherapeutic agents for individual patients is not recommended outside of the clinical trial setting. Oncologists should make chemotherapy treatment recommendations based on published reports of clinical trials and a patient’s health status and treatment
preferences."
Importantly, this is EXACTLY the same recommendation that the ASCO group reached in 2004! That's right, in the last seven years, despite a huge number of reports and hype, there has been NO CONVINCING EVIDENCE that these studies are clinically efficacious on a case by case basis.
This report deserves a bit more attention, and can be quickly read if you've got the time. In brief, at the request of the ASCO leadership, the eight authors of this study began with a review of over 11,000 abstracts published in the English language literature between December 1, 2003 and May 31 2010 and dealing with human clinical oncology. Search terms including "controlled trial, "meta-analysis," "guidelines," and "review," wittled this group down to only 21 articles that were reviewed in detail. Included in this group were five randomized clinical trials, which are reviewed in the text. The raw data from this study, including the search guidelines, are available as an on-line data supplement
It should be noted that the authors confined their review to in vitro assays using viable tumor cells, analogous to bacterial antibiotic sensitivity and resistance assays that measure growth inhibition in the presence of an antibiotic diffusion gradient. These are generally considered the most direct (and potentially most valid) assays for assessing tumor cell sensitivity and resistance. The authors did not review assays performed on non-viable tumor tissues by immunohistochemistry, gene expression or transcript profiling. I can't help but wish that the authors had specifically addressed these forms of CSRAs as well, yet you should note that the guidelines make no distinction with regard to the manner in which the CSRA is performed. If direct tumor cell sensitivity and resistance assays are not efficacious on case by case basis, the authors seem to conclude (rightly, I believe), that more indirect assays should not influence treatment either.
Print out some copies of this paper and keep them handy. In all likelihood you'll need them.
Wednesday, August 24, 2011
I was sitting at my microscope yesterday at 1:50 pm, looking at a problematic breast case with a colleague. Suddenly things got REALLY interesting as a shallow, magnitude 5.8 - 5.9 quake with an epicenter only about 25 miles away struck.
We've had minor earthquakes in central Virginia at least half a dozen times in my 30+ years of living here, but this one was really memorable. The building shook considerably for at least 30 seconds with growing amplitude for the first 15 seconds. Books were dislodged from shelves, pictures were rendered crooked, but there was virtually no structural damage. Amazingly, because of its shallow location and the nature of the east coast crust, the quake was felt from Atlanta to Canada. In Washington, D.C. and New York City, it was strong enough to raise considerable 911-related angst. At the epicenter in Mineral, VA, several buildings were damaged and 100+ miles away the Washington Cathedral lost several spires.
In my particular location on the 4th floor of a well-insulated building, I couldn't really hear the earthquake, although prior smaller ones in Virginia experienced outdoors or in less insulated locations have sounded distinctly like a locomotive passing close by.
One of my friends was standing in a huge dirt field 11 miles from the epicenter with a several mile vista in every direction. He reported seeing a "ripple" in the ground move at great speed toward him, under him and then rapidly retreat into the distance. Wow! That would have made a great video for the evening news!
Subsequent to the main quake there have been multiple after shocks, some of which have been quite audible, but fortunately much smaller in magnitude.
Now no doubt those of you on the geologically active west coast are chuckling about all the evacuations and near panic stimulated by this (to you) minor event. I've seen the humorous pictures of the "massive devastation" (yogurt cups and lawn chairs turned on their sides) posted by west coasters to poke fun at us. They really ARE rather funny. In reality, though, even the west coast sees a 5.8 quake only ever other year or so, and quakes on the east coast tend to be shallow and spread much farther without attenuation. It's all about what you're used to.
In the east, we're getting ready to hunker down for another 3-4 magnitude hurricane. The east coast takes these more or less in stride. We've been incredibly lucky the last few years. Ever seen someone in L.A. drive in the rain? You'd think the roads were covered with Wesson oil. I can't imagine what they'd do in snow. Like I said, it's all in what you're used to.
Monday, August 15, 2011
There was an interesting exposé in an issue of the New York Times last month dealing with a promising technique in personalized cancer chemotherapy that turned out to be completely worthless. And this is unlikely to be an isolated incident.
Using patterns of gene expression to detect and tailor cancer treatment has turned into a huge "cash cow" and companies are springing up like weeds on a wet Spring day, offering great promise (at high price) that often is not backed by solid scientific research and in some instances may be based on downright fraudulent work.
The FDA has generally avoiding enforcing regulations on these new labs, and naive clinicians and patients have been flocking to them to get costly information that often is of no (or even erroneous) clinical value.
The case highlighted in the NY Times article began when a Duke University researcher, Dr. Anil Potti (several GREAT name-related puns come immediately to mind!), published a series of articles, the first in Nature Medicine, on complex gene signatures to determine appropriate cancer chemotherapy regimens. When others began reviewing the data from these studies they found both careless and inexplicable errors. Subsequently, the Cancer Letter reported that Dr. Potti had falsified his résumé, wrongly claiming among other things, that he was a Rhodes Scholar. Ultimately, his four papers on gene profiling were retracted and he resigned from Duke University. In short, his career was flushed down his last name (sorry, couldn't resist). A private company set up to sell his "cancer tests" was disbanded, but not before quite a few patients had received costly and worthless results and gone on to die of their diseases. As you can imagine, lawsuits are pending.
This is certainly another stain on the Duke University research record and those of you who have been around for a while will remember the famous Duke "B72.3" debacle from a few decades ago. There have been others. Not that I have anything against Duke.... well maybe I still do a little, since I found my interview for their MD-PhD program MANY years ago to be one of the most bizarre experiences in my life... but I suspect that this problem is multi-institutional, and the larger the research program the more likely there is, by mass effect, to be a "bad egg" falsifying data. In short, large institutions risk becoming victims of their own success. As the article noted, successful research labs have become so large that it is impossible for one person, even a conscientious senior PI, to fully comprehend everything that is going on. Given the pressure to produce, fraud becomes very easy under these circumstances.
Even if all of the other cancer gene profiling tests that seem to spring up daily are not overtly fraudulent, they are in most instances NOT backed by solid clinical trial results, or they provide costly information that can be obtained much more simply by other means. Clearly this in an area where the FDA NEEDS to step in to prevent false hope, improper care, and spiraling health care costs devoid of patient benefit.
Friday, August 05, 2011
With apologies to Ray Bradbury, 133 deg.F is the approximate temperature at which our favorite histology embedding medium, aka paraffin melts. There is some variation in melting point, depending on the formulation and additives. For the past several weeks much of the country has experienced temperatures at or over 100 deg.F in the shade for multiple days in a row. (Still don't believe in climate change?) If it's 100 deg.F in the shade, imagine what the temperature reaches when a package is left out in the sun, in the trunk of a car, or in the back of a delivery truck. You can probably guess where this is going.
During this triple digit heat wave, we have received multiple consult cases in which the paraffin blocks had completely melted.... not just stuck together, but melted to the point where all of the paraffin and tissue formed a large solidified puddle in the bottom of the package. Sorting these out was extremely difficult. It was impossible, of course, to determine which bit of tissue went with which labelled holder. More alarming was the fact that after re-embedding the tissue seems to have lost or dramatically altered its immunohistochemical viability. In short, immunohistochemical stains didn't work properly at all.
In 30+ years, I've never experienced anything quite like this. We used to store paraffin blocks in the un-air conditioned attic of the old residents' quarters here at U.Va. and even under those adverse conditions, the blocks seldom did more than stick together. But then these were times when temperatures slightly over 90 deg.F in central Virginia were considered REALLY HOT and one could look forward to only a handful of such days in a typical summer.
We were initially concerned that our hospital loading dock, where all packages are mandated to arrive, was somehow leaving these items out in the sun, but some quick checks made it clear that the problem wasn't occurring on our end. What did seem to be the case, however, was that material sent by 2-day economy or other slower routes of shipping was MUCH more likely to show melting than cases sent by overnight express when the temperatures were presumably lower. Items shipped overnight also travel by air and at 30,000+ feet it's really cool, even now! Items shipped by ground routes were invariably a mess.
So we seem to find ourselves in the almost ludicrous situation of having environmental summer temperatures that routinely surpass the melting point of paraffin. Maybe we need to find an histology embedding medium with a higher melting point! At the very least we need to make sure that wherever we routinely store our old tissue blocks is at least environmentally protected enough in the summer months to prevent a catastrophic "melt down." In addition, when shipping blocks for consultation or other purposes in the summer, the material needs to be shipped quickly (overnight) and preferably also insulated with a cold pack. This also holds true for unstained slides where the thin layer of paraffin on the slide will likely melt and dislodge the tissue section. Of course, stained glass slides are not a problem at the moment, and when the temperature reaches that melting point, we won't be around to worry about it anyway.
Tuesday, July 26, 2011
There is a growing trend in larger academic institutions in the U.S. toward subspecialty or modified subspecialty signout of surgical pathology specimens. This becomes a potentially viable alternative for groups having large specimen volumes (>40,000/year), but it is worthwhile to examine the forces at work and the pros and cons of this approach.
The forces championing a subspecialty approach are both internal and external. Internally, pathology faculty are keenly aware of the increasing difficulty (impossibility?) of keeping up with all areas of surgical pathology. Their diagnostic comfort zone tends to narrow with time and they'd like to narrow their practice to keep pace. As one of my colleagues once said, "Every year I know more and more about less and less. Eventually I'll know everything there is to know about just one thing, and nothing about anything else."
The external forces promoting subspecialty signout, are likely even stronger than the internal ones. They come primarily from clinicians who want their "go to" person for all of their specimens. Often this is the pathologist they interact with at their subspecialty tumor board. They're comfortable with this individual and they'd like "one stop shopping" for all their pathology specimens. They may be quite vocal in their desire that "only Dr. X" should signout their cases. They can always wish!
What are the advantages to subspecialty signout?
1. Directed expertise. There's something to be said for having the breast expert sign out all of the breast cases. They're likely to do it accurately and probably quicker than a generalist pathologist.
2. Clinician placation. Your vocal clinicians, usually surgeons, get the one-stop shopping they've been lobbying for.
3. Pathologist placation? Although the faculty may get what they think they want in terms of confining signout to their "comfort zone," they may not be happy in the long run (keep reading).
4. Training? There's a definite up side to only signing out cases with the faculty expert in a given area. Their knowledge and enthusiasm is likely to contagious. But there's a down side here as well, I think.
Against these factors must be weighed the significant disadvantages of a subspecialty approach.
1. Inefficiency. This is the biggest drawback to this approach and it occurs on multiple levels. The inefficiencies become smaller the larger the size of the practice. In smaller practices, they can be huge. Once a subspecialty approach has been adopted and faculty are only signing out cases from one or a few anatomic areas, they will rapidly lose their skills and confidence signing out anything else and will appropriately refuse to do so. Thus, there must be redundant faculty in the system for each subspecialty area to cover vacations, illnesses, etc. This can lead to a significant increase in staffing with no associated increase in revenues. On call scheduling becomes massively inefficient with multiple available individuals required to cover all of the subspecialty areas. After all, if you don't sign it out routinely any more and don't feel comfortable doing so, you'll feel even less comfortable trying to deal with a frozen section. As one of my colleagues once put it, "With subspecialty signout, you're always just one resignation away from total departmental chaos."
Because of the inefficiencies, faculty members will invariably find themselves on service more often than with generalized signout, making it almost impossible to free up substantial blocks of time for research and teaching. As there is no way to equitably divide subspecialty cases, invariably some faculty, such as those covering GI, gyn, and derm are likely to be doing substantially more service work than those covering less active services. This leads to inequities in service time and in revenue generation, which in many instances affects salaries and bonuses and creates ill will between faculty members.
In addition, the added faculty members needed often means that many individuals may not be able to cover their salaries with their clinical revenue generation. Chairs, Deans, and hospital administrators take an increasingly dim view of this. In the past, many faculty compensated by being PI's or collaborators on funded research to bolster their revenues. As we all know, in today's climate, research dollars are getting VERY HARD to come by.
The inefficiency also applies to the residents since they must either be assigned to subspecialty services themselves, and thereby miss seeing and signing out cases from other areas, or, if the residents stay on a "generalist"s system, they must hunt down and sign out with a series of faculty members every day, rather than having "one stop" signout with a generalist faculty member.
2. Training. I would argue that this is a two edged sword. The advantages are mentioned above. However, I believe that there are disadvantages as well. In subspecialty signout residents typically see how one or two experts approach a case. Subconsciously, they absorb the biases and diagnostic thresholds of these individuals with regard to "gray zone" or borderline cases. They may be surprised to find, when they leave a program that elsewhere the lines are not drawn in quite the same place. In contrast, in a generalist signout, a resident is likely to see how a dozen or more faculty pathologists approach a problematic case. In the process, they internalize the limited but real range of thresholds for problematic cases, and they are likely to leave the program with a better understanding of these gray zone areas.
3. Faculty. I mentioned above that although a department's own faculty often push for subspecialty signout, they may not, in the end be happy with the result. Old proverb: "When the gods want to punish you, they give you what you think you want." As a case in point, years ago, one of our junior faculty approached me with the request that he signout ALL of our liver biopsies. I smiled and said, "I know that you THINK you want that, but let me tell you why you really don't. First, if no one else ever signs out a liver biopsy, in a few months no one will be comfortable looking at them. Since I can't justify hiring another pathologist to just look at liver biopsies, you'll never be able to be sick or take a vacation. Moreover, you'll have to be on call every night for liver biopsy frozen sections because no one else will want to sign these out any more. .....now, do you STILL think you want to do this?"
"No." :-)
At the University of Virginia, we have been able to maintain a "focused" generalist signout with approximately a dozen faculty members covering slightly over 30,000 surgical specimens and and nearly equal number of cytology specimens per year. With the exception of neuropathology, medical renal, and dermatopathology, faculty members signout everything that comes across their scope when they are on service. That said, however, we have been careful during our hiring to make sure that we have in-house experts in all areas. Those signing out make liberal use of appropriate collegues for consultation when confronted with a problematic case.
The result is, I believe, the best of both worlds, which has freed us from the inefficiencies of a true subspecialty signout, but has provided us and our patients with expertise when and where it is needed. Faculty stay comfortable with the great majority of general surgical pathology cases, but have their areas of focus and special interest where they serve as in-house consultants. Because of the efficiency of this approach, faculty have adequate time off service and call to pursue their research.
I'm not saying that subspecialty signout isn't a viable approach, and as I indicated above, with massively large practices the efficiencies become less of a factor. I do believe, though, that the problems should be carefully considered before adopting a pure or modified subspecialty signout. It is almost impossible to revert back once this decision has been implemented for any reasonable amount of time.
Friday, July 15, 2011
In August and October of last year I wrote two blogs on my experiences with the then new Ipad. In summary, this is an excellent device geared primarily towards reading/browsing functions, and less towards data input, though it is certainly functional in that regard as well. On a recent 12-day trip away from home I made the decision to leave my trusty old Dell Latitude laptop at home and try to do everything I would need to do, including reviewing and editing my five PowerPoint presentations, keeping up with a flood of e-mails and reviewing journal articles for AJSP on my Ipad. I was a little nervous about this, but the Ipad proved to be more than up to the task. I returned home nearly completely caught up on my internet tasks. I should add that my Ipad has the built in data modem which I had not activated until this trip. On the first part of my journey the hotel WiFi was so bad that I was forced to activate the ATT 3G data modem ($25/mo for 2 GB) and it functioned perfectly. I have thus far resisted the urge to upgrade to a new Ipad 2.
As good as the Ipad his, however, it is not a true laptop, nor was it meant to be. It much closer to a large Iphone, without the phone. There are some functions that I really miss. Typing in the screen keypad is certainly do-able, but not optimal and I miss the tactile feel of real keys. More importantly, the Ipad, like the Iphone runs "Apps." Many of my favorite software programs in Windows or Mac OS do not have, at least yet, corresponding "Apps." In short, I still need a good laptop and some Windows programs for some of my favorite functions. For example, I still prefer good old Eudora for my e-mail client and HP PhotoShop for image manipulation.
So I set out to find a replacement laptop for my trusty 10-year old Dell Latitude 400 MHz machine. Being a long-time Windows user, and happy with my former Dell machine, I looked at a replacement Dell laptop. The new ones certainly blow my decade-old model out of the water. But even the 13" machine was heavy, a bit bulky, and considerably slower than I expected. One of my colleagues suggested a MacBook.
"You don't understand," I said, "I'm a Windows fanatic. I'd like to eventually learn 'Mac' but I don't want to buy a laptop that's only a Mac machine."
"Fear not," said my Mac-o-phile colleague, "A MacBook runs Windows better and faster than a Windows machine, and it also runs the Mac OS."
"How can this be?" I asked.
I did, and the rest, as they say, is history.
First, I had to decide which MacBook I wanted. I ended up getting a 13" MacBook Air because of its thinner profile and all solid state memory compared to the MacBook Pro. The 11" MackBook Air is also an excellent choice at a lower price that is close to that of a fully equipped Ipad. In terms of its construction, the MacBook Air is a thing of beauty. But there is much, much more to love. It boots to the Mac OS from its solid state memory in a matter of only a few seconds. It comes with many of the Mac programs already installed, though the Mac version of Office needs to be added. Skype runs much better on this machine in Mac OS than on my desktop Windows computer. All in all I was quite pleased with the beauty, ruggedness, small size and blinding speed of this laptop.
...but it gets even better.
I installed the Parallels Desktop software (about $90) followed by a copy of Windows 7, and I had a Windows machine that was MUCH faster than a dedicated Dell laptop. Honestly! Windows boots on this machine in seconds as well. Switching between Windows mode and Mac mode is as simple as a single click. Futhermore, in "Coherence Mode" you can run Windows programs directly and seamlessly in the Mac OS environment. Installing all this software was a snap. The entire Windows 7 OS installed in less than 15 minutes! This is much more than a Windows emulator. It is real Windows running on the MacBook processor. One of my major concerns was how peripheral hardware would function in the Parallels/Windows/Mac environment. The short answer is, "perfectly." Plug in a USB memory stick, DVD drive, or any other hardware device and Parallels asks you if you want this hardware available in Windows, Mac OS, or both. So far every piece of Windows-based software that I have tried to install on the Macbook Air has installed quickly and run perfectly and as fast or usually much faster than on a dedicated Windows machine.
I've always admired the look and quality of the MacBooks, and now I have the best of all three worlds, the quality of Apple/Mac hardware and the ability to run both Mac OS and Windows programs on the same laptop, faster than on a new dedicated Windows machine. I seriously doubt if I will ever purchase another dedicated Windows laptop, and I may well carry this philosophy over the my desktop machines when their replacement comes due.
Wednesday, July 06, 2011
In one of my earliest blogs I discussed the fallacy of confusing "cell of origin" with direction of cell differentiation. The former is essentially unknowable since it is destroyed with the next mitotic division and is also of little or no importance, except to create speculation-filled manuscript pages, whereas the latter is what we actually "measure" as pathologists.
Tissue of origin, however, is potentially knowable in most but ultimately not all cases, and is of somewhat more practical value. The "tissue of origin" question arises, of course, with regard to metastases from an unknown primary site. Its practical clinical value is governed by the degree to which the patient is a candidate for systemic therapy, and our ability to recognize primary sites for which there are specific effective treatments. Not surprisingly the powerful forces of molecular diagnostics and profit motive have been turned toward this question. There are now several FDA-approved "tissue of origin" molecular assays of varying types on the market.
With this brief background, I recommend your reading of an article in the July issue of Am. J. Surg. Pathol. entitled, "Evaluation of a Gene Expression Microarray-based Assay to Determine Tissue Type of Origin on a Diverse Set of 49 Malignancies," written by Andrew Beck and colleagues from Stanford University. The authors evaluated the "Tissue of Origin Frozen" (TOO-FRZ) assay from Pathwork Diagnostics that has been cleared by the FDA for use in identifying tumors from unknown primary sites. The authors applied this assay to a diverse group of 49 neoplasms. They divided their test tumors into several categories:
1. common morphology for a known tissue type (29 cases)
2. uncommon morphology for a known tissue type (10 cases)
3. tissue type not included in the TOO-FRX assay (3 cases)
4. malignancies of unknown primary (7 cases)
Not surprisingly, the TOO-FRZ assay was rather good with the first group, correctly identifying 26 of 29 cases with regard to site of origin. It did not correctly recognize either of two gastric cancers, and one of two pancreatic carcinomas. Also not surprisingly, things went downhill from there. Of the 10 cases with uncommon histology, only 3 were correctly identified with regard to source. Of the 7 cases from truly unknown primaries, in only two did the assay give a likely clinically useful result (a prediction of ovarian cancer in a male patient would, for example, have to be considered unlikely!) The 3 cases of tissue type not included in the development of the assay were studied to see if the typing algorithm would correctly recognize them as "none of the above." It didn't. Two of the three were incorrectly identified, and two of these were common-appearing uterine adenocarcinomas.
The authors provide a nice discussion with regard to the dropoff in performance for atypical cases. Of course, these are PRECISELY the cases for which the assay is likely to be used. Conversely, its good performance for common histologic patterns is of limited value, as these are the cases that should be identifiable on far less expensive morphologic or immunohistochemical grounds. In other words the assay is the "salt" in the old "salting the bird's tail" folklore, ie. it's superfluous.
One aspect not directly addressed by this study is the degree to which tumors that morphologically resemble those more commonly arising from other primary sites confuse the assay. For example, the lungs, ovaries, urinary bladder, sinonasal region, and other sites can give rise to adenocarcinomas that are morphologically and largely immunohistochemically indistinguishable from more common intestinal adenocarcinomas. How good are this and other assays at correctly identifying these?
It seems clear that these molecular assays are here to stay. They have been approved by the FDA and they are being aggressively marketed to variably naive clinicians and patients. They can be extremely expensive. Common sense suggests that these assays:
1. should not be used in terminally ill patients with widely disseminated carcinomas who are unlikely to tolerate or benefit from systemic treatment, regardless of tumor origin.
2. should not be a substitute for a careful clinical history and physical examination, coupled with appropriate radiographic studies.
3. should not substitute for careful morphologic study with appropriate special stains and immunnohistochemistry.
Monday, June 27, 2011
This blog entry has nothing to do with pathology or even medicine. It's just something I think about almost daily and wanted to put down in a few words while trying not to rant. ....but here's the sum of it. There's a growing epidemic of "unawareness" in the world. I blame everyone, including myself, as I think I've been guilty of all of the examples listed below and then some. But I always strive to do better. I give credit for the term "unawareness" to a long-deceased fellow pathologist and good friend, Dudley Lockhart. Dudley was one of the most observant and humorous folks I ever knew, and he made my trips to the ASCP in Chicago years ago a LOT more fun.
What is "unawareness?" It's a complete lack of appreciation for where you are in your immediate environment and how you're affecting those around you. Unawareness is closely related to but not quite the same as rudeness. The latter is typically an intentional act, whereas the former is not. For example, unawareness is someone standing next to the control panel on the elevator so that you can't select your floor without touching their derriere. Rudeness is talking loudly on your cellphone in a crowded elevator.
Here are just a few of my favorite examples of unawareness, mainly written from the point of view of the perpetrator, and encountered almost daily.
1. You wait for a family member at the bottom of a busy escalator or in a busy doorway and give them a prolonged hug/kiss/greeting, unaware that everyone behind is trying desperately to get by.
2. You walk down the wrong side of a hallway and turn corners incorrectly. All the while, you wonder why you keep running into people and why people can't seem to get out of YOUR way? Hallways are like roads, follow the same rules you would when driving! In the U.S. that means walking on the right and swinging wide on left-hand turns.
3. You and two of your equally unaware friends stretch all the way across the hall, walking slowly while holding a "riveting" conversation, unaware that the 10 people behind you can't get around you to go about their business.
4. You stand inert in the grocery checkout line while the cashier rings up all of your many items and then, at the last second, you fumble for your checkbook, making everyone behind you wait while you write a check. Isn't it easier and faster to get out the checkbook, fill in the date, payee, signature, etc... and then wait for the amount? This one is mercifully becoming much less common since few folks write or even know how to write checks any more. (It should be "cheque" anyway.)
Unawareness is basically the result of self-aborption, a common phenomenon in the "me" generation. The opposite of unawareness is, of course, awareness; awareness of where you are and how you might be affecting the people around you. Are you making things unnecessarily difficult for them or are you exerting minimal impact on those around you? These are simple interpersonal skills that every parent should teach their children. They're almost as important as how to give a proper handshake! ...but we'll save that for another day.
Friday, June 17, 2011
At a wide variety and ever increasing number of anatomic sites, surgical oncologists have been setting "guidelines" (read: mandates) with regard to the minimum number of lymph nodes that should be present in a regional node dissection. Pathologists and their advocacy organizations have to a large extent, been a part of or at least gone along with this. I freely admit to NOT being a big fan of these mandates. There are just too many variables to set these sorts of arbitrary numbers, followed by all sorts of phone calls, whining and wasted efforts when the numbers are not met in individual instances.
How many lymph nodes should be found in a nodal dissection? The ideal answer is, of course, "all of them." More realistically, the answer should be, "all of the pathologic ones." Or even more pragmatically, all that are necessary to properly stage the patient. Anyone who has been in this game for very long knows just how widely variable node counts can be in virtually identical specimens. We also know that finding nodes is an acquired skill and, at academic institutions, residents in training often need assistance from PA's and senior residents until they have acquired this skill. However, in over 35 years as an anatomic pathologist I can recall only a single instance in which an adequately trained resident or PA missed a "stage-altering" pathologic node in a nodal dissection. Yet, at our institution about once a week we are admonished by the surgeons to "go back and look" for more nodes in order to reach the mandated minimum. Such "re-looks," which typically follow preoperative node-shrinking or node-ablating radiation and chemotherapy are very time consuming and will frequently yield a few microscopic lymphoid aggregates that may be "generously" interpreted as lymph nodes or even 2-3 true mini-nodes, but these are invariably negative for malignancy.
Against this backdrop, in the June 2011 issue of Am. J. Surg. Pathol., Euscher and colleagues from the M.D. Anderson Cancer Center look at the expectations v. reality of lymph node counts for metastatic endometrial carcinomas. The findings may be immediately extrapolated to routine dissections (not sentinel lymph node studies) from other regions and carcinomas. In 258 patients they found a median of 11 pelvic lymph nodes (range: 1 to 38!) and 6 para-aortic lymph nodes (range; 1 to 25!). Subsequently embedding all the remaining adipose tissue yielded a median of 2 additional pelvic nodes and 3 para-aortic nodes. Importantly, there were no cases in which metastatic carcinoma was present exclusively in the additional lymph nodes, ie. no alterations in staging. The authors conclude that standard processing techniques suffice for the detection of positive lymph nodes and that additional more elaborate procedures are not warranted. I completely agree.
Studies of this type need to be applied to other marginally rational clinician "mandates"
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On an important and unrelated topic, Pathology Network is about to begin including clinical pathology coding in its article "channels." There will now be channels and filters for all of the clinical pathology subspecialties. This was originally necessitated with the addition of the multidisciplinary journal, Pathology, to our archive, but these new channels will be applied, where appropriate to all of the journals in our lineup.
Wednesday, June 08, 2011
I've discussed lay press articles before, particularly with regard to the New York Times piece on the missed diagnosis of breast cancer. That article was a goldmine of oversimplification and improper emphasis.
However, the June 3rd issue of Time Magazine, which is devoted to health care in general and cancer in particular contains an article by Kate Pickert entitled, "The Screening Dilemma."
This is the most succinct, best written article on the problems of cancer screening that I've encountered in decades. Virtually every aspect of screening is covered, from the viewpoints of patients, the insights of physician specialists, and the economic incentives that drive these processes. I strongly recommend that you read this and pass it on to your non-physician friends, particularly if they are "screenophiles."
Here are just a few quotes from the article to pique your interest:
"If we had a 100% sensitive test that could pick up everything a pathologist would call cancer, it's conceivable that most of us, if not all of us, would be found to have cancer."
"The problem... is that "there are really bad cancers and there are really innocuous ones that never go anywhere, and we're not good at sorting them out."
"Cancer screening is truly effective only if the growths found would eventually cause sickness and if finding those growths earlier increases the efficacy of treatment. Absent these two conditions, finding cancer via screening is what's known as "overdiagnosis," which is guaranteed to happen when screening is performed population-wide. Overdiagnosis causes harm ranging from unnecessary worry to death in rare instances."
"Here are the odds. To save the life of one woman in her 40s, 1,904 would have to undergo annual screening. Beyond inconvenience and overexposure to radiation, this excess mammography would lead to false positives; psychological stress, including depression; and unnecessary surgery. In addition, much of the abnormal cell growth detected in women in their 40s could have been detected in their 50s with no adverse effects from the delay."
"Multiple scientific trials have proved that the ubiquitous prostate-specific antigen (PSA) test saves very few lives, if any. PSA tests are notoriously unreliable, detecting potential cancers where there are none and returning normal results in some men who have malignancies. The doctor who discovered the existence of PSA,a protein that, when elevated, is sometimes an indication of cancer, has disavowed the test, calling it a 'profit-driven public-health disaster.'"
...there are many more.
I especially recommend reading the section by Dr. Jim Mold about his accidental PSA screening and getting caught in the resultant "cascade effect."
Near its end the article discusses two of the most rapidly rising cancers, at least in terms of diagnosis, thyroid carcinoma, and melanoma.
"Remarkably, many of us, possibly even most of us, will develop thyroid cancer at some point in our lives, but very few of us will die of it. In a 1985 study, researchers examined the bodies of 101 people who had died of causes other than thyroid cancer and found that a third of them contained cancerous thyroid cells. Because of the sampling method, the researchers knew that they were certainly missing some cases, meaning the percentage was even higher, and yet none of those people were killed by the disease."
Finally, theres a section on the seldom discussed economics of screening.
...but enough said, go read it!
Wednesday, June 01, 2011
It's Spring and thoughts of senior residents turn to fellowships or real-world jobs and passing their board exams. In our department, you can almost palpate the stress in the air with regard to the latter. Residents seem to disappear with books in their hands for protracted periods of time and the halls become much quieter than normal.
If you've been applying yourself during your training and have been following a methodical study regimen, and I REALLY hope that you have, then this shouldn't be an overwhelming experience. If you've been slacking off during most of your training, well.. it could be an "interesting" experience.
For pathology residents, the ASCP RISE exam, taken each year is fantastic preparation for the boards and, more importantly, should be used to point out areas of weakness requiring further effort. In addition, a number of independent and society-based courses have been developed over the years that are more or less geared to board preparation and, of course, to generate revenue on the basis of your insecurity. Hopefully, in return for your dollars, they better prepare you for your exams. I've been asked many times by residents if I think these courses are necessary or worthwhile. If you're in an average or better residency program, have been studying all along during your training, and don't feel overly stressed, then my advice would be to save your money. However, if you know you've got deficiencies and you're stressing about them, then a board preparation course might, at the very least, help to calm your nerves. The choice is up to you (and your wallet).
If you're following a self-imposed program of independent study, you'll probably learn more than in a programmed course, but it's often hard to stick with a self-study regimen given the competing factors of job, family, and other responsibilities. Just getting away for the preparation course may be beneficial. When following a self-study regimen, it's helpful to keep the big picture in mind. Ask yourself repeatedly, "Is this something I need to know, or is this a bit of minutia that I can look up when and if I ever need it." There may well be some "minutia" questions on the exam, but there will be far more of the "need to know" type.
For years I've been involved in teaching the pathology component of a national multidisciplinary course to beginning urology residents. Jay Gillenwater, the former editor of Urology, ran this course for many years and always began it with some advice to the beginning residents about how to structure their educational experience as residents and how to study for their urology boards at the end of that experience. Jay always made a number of valuable points that I think are appropriate to residents in other areas of medicine as well. Here are several of them:
1. If it's brand new information, it is unlikely to be on the boards. There's a several year lag between the time new information is presented, and it is validated, accepted, and considered appropriate for testing. Accordingly, recent editions of textbooks are more likely to contain material for board-worthy questions than the latest issues of journals (though the latter, of course, SHOULD be read for other obvious reasons).
2. As a corollary to the above, if it's controversial, it's not going to be an exam question. Test committee members have to agree on the correct answer, or the question won't make it.
3. Exams may not only contain proven, validated questions testing you, but most typically contain 20+% new questions where the question itself is being tested with regard to its difficulty and predictive value. In some instances and specialties, these new, pre-validated questions do not count against your final score, or may only partially count. The key is to not become "rattled" by more than occasional difficult or "idiosyncratic" questions. These may not count against you. The test center may (or may not) address this issue before the exam begins.
4. Don't change your first answer unless you're sure you misread the question or made an obvious mistake.
5. On some exams, wrong answers count against you but "non-answers" don't. The test center should clarify this important point. Regardless, eliminating the obvious wrong answers is the best way to approach a difficult question.
6. The questions may be difficult, but they are not meant to be purposefully tricky. Don't try to "out think" the question. If you think you know the correct answer, you probably do.
I'll add a few obvious additional points.
Get to the examination center 1-2 days early, especially if there are large time-zone shifts. This will give you time to relax, acclimatise and do some last minute reviewing.
Get PLENTY of sleep and eat properly,
Don't ruminate over questions after the exam session is over (easier said than done, I know!)
Don't be surprised if you end the ordeal feeling as though you
have obviously failed. This is a common reaction showing little or no correlation with the actual result.
Good luck!
Thursday, May 26, 2011
Most of this was written on my Ipad while being stranded in airports.....
Since the first of the year, my wife and I have made four airline trips for work and vacation. The two we traveled on together went virtually perfectly and the two we traveled on separately, including the one I'm stuck in now, were disasters for each of us. Well, OK, not a disaster in the traditional sense of an airline disaster, since there were no physical injuries, but major pains in the derriere, nonetheless.
Both involved spending restless nights on airport bench seats and major delays in getting to our destinations, which fortunately in both cases was home and not some place more time critical.
The one I'm stuck in at the moment started as a pathology committee meeting in Santa Fe, New Mexico, not the easiest place to get to, since it requires flying to Albuquerque and then an hour-long shuttle ride to Santa Fe. Getting there was uneventful. The trip home started with a return shuttle ride, right on time, that got me to the Albuquerque airport at 10:45 for a 1:15 pm flight. At about 12:45 the incoming flight landed, and the ticket agent announced that the incoming plane had a mechanical problem and could not be used for our flight to Atlanta. It would be 7:00 pm before a replacement aircraft could be flown in, thereby blowing the Atlanta connections for virtually everyone on this fully loaded Boeing 757.
A very long line immediately formed at the gate counter to get re-booked. While standing in line I decided a little proactive response might make all the difference, so I punched up the FlightTrack Pro App on my Iphone. If you travel any at all, this is an incredibly useful App. In just a couple of minutes I was able to check on all the alternate flights from Atlanta to Charlottesville and neighboring airports, select the best choice, and call a Delta customer service agent using the FlightTrack provided number. Of course the agents were all busy, but the callback service works great, and long before I was at the head of the line, I had rebooked on the best flight.
Since there was so much noise in the airport, I stayed in line to verify with a real person that I had REALLY rebooked, and to pick up my new boarding passes, meal vouchers, etc. Armed with new paperwork, I wandered off in search of food and drink and to amuse myself for the 6 hour delay, trying to find solace in the fact that I'd get to Atlanta in time to get an airline-supplied hotel room where I could get a shower, dinner and a decent rest, before finally making it home half a day later than expected. I also took some comfort in the fact that I was better off than some poor souls who had their travels so deranged that they had to stay in Albuquerque TWO full days before they could make it home.
Alas, the travel gods were not quite done with me. Right on time we boarded our replacement plane for our 7:00 pm departure, only to find that it ALSO had a mechanical problem! So after spending an hour on the plane sorting it out, off we all came to wait until 10:10 pm for our NEXT replacement aircraft. No big deal I thought, since I had plenty of time to make my connection the following morning. However, it then became clear that we wouldn't get into Atlanta until 3:30 am. Too late to mess with getting a hotel room, and I'd be consigned to airport bench napping. So, I thought I'd use my FINAL 2 hours of delay in Albuquerque getting a decent dinner and a little ethanol to help me sleep. Foiled again! The Albuquerque airport bills itself as an international terminal yet it shuts down completely at 8:30 pm. Dinner consisted of a small bag of Fritos and a cup of water..
This flight DID leave as advertised at 10:10 pm to the loud cheers of the weary and rather testy passengers. I managed to grab about an hour's fitful sleep on the airplane and two more fitful hours on a bench in the Atlanta airport, surrounded by dozens of others in the same boat. I got up just before dawn when the sounds of the workers bringing the airport to life prevented any additional rest. After splashing some cold water on my face and grabbing a cup of coffee and a donut, the caffeine, sugar and sunlight combined to make things a little more bearable. So here I sit at gate D34, killing time writing this blog on my Ipad and waiting for four more hours to pass so that I can board my plane to home. ....and hoping the travel gods are done with me, at least for now.
Postscript.
My final flight for home DID depart on time, though when I boarded the plane, a mechanic was on the phone to see if he could get a "waiver" to let the plane fly! This was the only time I actually thought I might mentally "lose it" on the entire ordeal. Fortunately, the issue was not considered a safety problem and we flew.
There is, unfortunately, nothing particularly special about this story and I'd bet that most readers could supply one as bad or much worse from recent memory. In an effort to cut costs and remain competitive, airlines are flying older and older airplanes and many are becoming maintenance hogs. The airlines would argue that they are perfectly safe, but it is difficult to argue that they are as reliable as when they were new. Approximately 20% of flights are currently delayed or canceled due to a variety of reasons, but often related to equipment. There is virtually no buffering in the system in terms of spare equipment or empty seats. When a flight is canceled and alternate flights are overbooked, days may be spent trying to get to your destination. I don't see this getting better any time soon.
On a more positive note, though, check out FlightTrack or FlightTrack Pro for your Iphone or Ipad. This is a fantastic application for finding flights, gates, departure and arrival times, terminal maps, tracking flights in the air, etc.
...and may the travel gods smile on you!
Tuesday, May 17, 2011
This morning a lead story in the news is WHY Arnold and Maria split... but you'll have to get that information elsewhere. It's true, however, that inquiring minds do want to know (everything), and this week's blog deals with information dissemination of another sort.
When Lauren Ackerman was editor of Cancer, he was known to occasionally show up unannounced at the office of someone, anywhere in the country or even the world, who had submitted and published an article in the journal. He would ask to see the microscopic slides from the cases. This must have been roughly equivalent to seeing Morley Safer and the "60 Minutes" news team at your door, and probably sent quite a few pathologists scurrying to the nearest bathroom. His reasons for doing this were multiple. Primarily, he wanted to LEARN from the cases and the best way to do that was to review the entire glass slide rather than the selected and published black & white images. Occasionally, he may well have been skeptical about the interpretation of the cases, or had other more serious concerns. He once related the story of visiting an author who had published (as I recall) three cases of a exceedingly rare entity. When confronted, it rapidly became obvious that only one case was probably real and the other two had been fabricated. This was the exception, however, and the main purpose of his announced visits was his own education.
Now imagine if you could do the same thing, effortlessly and inexpensively, or even free of charge, from your home or office! The June issue of AJSP begins with an editorial entitled, "Digital Slide Repositories for Publications: Lessons Learned From the Microarray Community," by Dr. Jason Hipp and colleagues. The concept is simple. Authors would supply glass slides from each and every case that comprised their published series. Ideally, this would include EVERYTHING, not just the H&E sections but the immunos, in-situ slides, etc. The glass slides would be scanned in their entirety (whole slide scanning) and stored on an appropriate server. After reading the article, you could go to a web site and spend hours or days reviewing the cases. In the end, if you wished, you could theoretically see everything that the authors saw to produce their histopathologic findings. Alternately, you might wish to just view a few of the H&E slides to get a much better feeling for the morphologic spectrum of the entity. The images would also be available for use by increasingly sophisticated image analysis programs and, most importantly, this system would preserve the material indefinitely.
This is far from "pie in the sky," and as the authors point out such data banks already exist for microarray data. As they also describe, there are significant but entirely manageable challenges to developing this system with whole microscopic slides, in terms of storage space, startup equipment costs, archive maintenance and preservation, privacy regulations, bandwidth to download / upload images, etc. Nonetheless, they put forward a very reasoned discussion of the enormous value of such a system and the hurdles needed to accomplish it. I firmly believe this is a concept whose time has virtually arrived, and we need to move toward this goal. Please read the editorial and think about the exciting possibilities (and the hurdles to get there).
Tuesday, May 10, 2011
One of the lead stories on the news this morning....no, NOT the one about Maria and Arnold spliting up.... was the apparent acquisition of Skype by Microsoft for a whopping $4.5 billion. My immediate reaction was, "Why would you pay that huge amount of money for something you can get for free?" Obviously, there's much more to it than that, although I noted that skeptical investors appear to have raised much the same question. Mainly, I hope this wonderful program doesn't lose its excellent qualities (including low/non-cost) under the new owners.
I had actually made a mental note to "blog" briefly about Skype based on my vacation experiences and as part of my series of comments on my Ipad. Today's headline got me thinking about this topic again. You may recall that in my first blog about the Ipad, I raised the issue of whether it was just a larger Iphone, without the phone. Over time, however, I have come to view my Ipad as a nearly indispensible tool when traveling. It allows me to do virtually everything I need when I don't want to carry my larger and heavier laptop.
At home, my wife and I have used Skype on our desktop computers to communicate with our daughters and their husbands on the "left" coast, and it gives wonderful video and audio over any reasonbly robust broadband internet connection. The software is free and so are the video/audio links, provided that you are connecting internet to internet and not direct dialing to a phone on the other end. That's a hard deal to beat! I can't help but wonder if Microsoft will let that stand. I sure hope so.
Recently, while on vacation on Bonaire in the Netherlands Antilles, we needed to call home to check on one of our dogs. The villa where we stayed had a moderately good WiFi connection, but phone contact stateside via "roaming" on my Iphone was prohibitively expensive. I decided to pursue the "direct phone connection" feature of Skype. It took about 5 minutes to download the free Skype software to my Ipad and get it installed. In order to dial directly to a phone, rather than establishing a purely internet connection, you have to pay a modest fee. I wondered initially how modest. Skype asks you to use a credit card to deposit $10 into a Skype phone account. I wondered how many seconds that would last. I shouldn't have been concerned.
A large keypad appears on your Ipad screen and with no effort whatsoever, I was able to make three fairly lengthy (5+ minute each) long distance calls stateside. The audio quality was excellent with only rare dropped words due to a large number of very well behaved Canadian college kids sharing the WiFi that I was using. Total costs for all three calls was.... $0.40. ...and the dog was fine as well!
So the reality is that the Ipad most certainly can be an "Iphone" with a good WiFi connection and Skype software. Of course, the Skype software works equally well on an Iphone when you are out of the country, have a WiFi connection and don't want to run up huge cellular roaming charges. Let's hope Microsoft doesn't mess this up, or if they do that another provider comes along with the same excellent service.
Monday, May 02, 2011
Much of what follows is derived from this Wikipedia article, and I highly recommend reading the entire Wikipedia entry on this topic as it makes for fascinating reading and historical perspective.
With the exception of an accusation of outright fraud, ie. falsified data, I cannot think of anything that would stimulate an instantaneous fear reflex in an author more rapidly than an accusation of plagiarism.
The definition of plagiarism is not straight forward but according to Wikipedia is approximately this:
Plagiarism is defined as the "wrongful appropriation," "close imitation," or "purloining and publication" of another author's "language, thoughts, ideas, or expressions," and the representation of them as one's own original work. In fact, the word plagiarim derives from the Latin word plagiarius, which means "kidnapper."
Interestingly, plagiarism is a relatively new concept in the history of literature and prior to the 18th century literature was considered, at least by many to be common property that could be borrowed or copied without attribution. Even today plagiarism is tolerated and even encouraged in certain artistic endeavors.
Although plagiarism has moral and ethical consequences, there are no legal implications. According to Wikipedia, plagiarism is not currently mentioned in ANY statute or law, either criminal or civil. It should not be confused with copyright infringement, which DOES have legal significance.
However, in the worlds of scientific research and journalism, plagiarism carries significant moral and ethical consequences. Severe sanctions are likely to be levied against those found guilty of such infractions.
In today's internet and computer intense world, plagiarism is both easier to perform and easier to detect. Software programs, loosely referred to as plagiarism detectors, are widely available. A decade ago, a physics professor here at the University of Virginia, Lou Bloomfield, created a "plagiarism detector," ran his students' semester essays from his introductory physics course through it and detected a shockingly high rate of plagiarism. The resultant stir made the press nationally and locally resulted in honor trials for 122 students. A decade later, professor Bloomfield maintains a web site devoted to plagiarism and distributes free software for its detection.
Editorial Manager, the software package used for manuscript submission and review by AJSP has recently added a "plagiarism detector" known as CrossCheck, which the editor may access to search for blocks of text copied without attribution from prior publications. As might be expected, processing a manuscript through this software does take some time.
Some ethicists have argued that in today's internet "copy and paste" world students are not properly educated regarding what constitutes plagiarism. Like pornography, it can be difficult to define. It has been suggested that more attention be paid to teaching the concept of plagiarism in secondary school education.
The concept of "self plagiarism" is an interesting one. If you re-read the definition of plagiarism above, it may be argued that self plagiarism is an oxymoron. Nonetheless the term has recognized meaning and basically refers to "duplicate publication." No theft from others is involved, but there is an element of intellectual dishonesty.
The best protection against plagiarism is the liberal and appropriate use of reference footnotes, even if those footnotes are to your own prior writings.
Wednesday, April 20, 2011
I've been traveling, back for a week and out of the country next week, so my postings may lag a bit until I return and catch up.
Television shows often live or die based on their Nielsen ratings, primarily because the networks can raise the advertising charges on higher rated shows. Because of this, T.V. producers go to great lengths to try to manipulate their ratings with hyped advertising and "cliff hanger" episodes timed for the ratings cycle.
The true equivalent of the Nielsen rating for journals, at least in terms of advertising revenue, is the circulation volume. However, in the world of scientific publications, it's the Science Citation Index (SCI) Impact Factor (IF) that gets much more attention. The IF was created by Eugene Garfield in 1960. On the surface, the IF seems like a simple thing. In a given year, the IF of a journal is the average number of citations received per paper published in that journal during the two preceding years. If a journal published 250 articles in 2006 and 250 articles in 2007, and these articles were cited a total of 2000 times in 2008, then the IF for the journal for 2008 would be 2000/(250+250) = 4.0.
Not surprisingly, IF's vary tremendously according to medical specialty. Also not surprising is the fact that editors can adopt policies which will affect the impact factor. Review articles, for example, are typically cited more frequently, so including reviews is likely to raise a journal's IF. "Self-citation" is another way to raise the IF. Articles published early in the year are available for citation for a longer time, so placing review articles in the January and February issues is particularly effective.
Interestingly, everything published in a journal is NOT a "citable item," meaning it does not go into the denominator for the IF calculation. Editorials and abstracts are NOT considered citable items so they do not figure into the denominator portion of the calculation. HOWEVER, when editorials and abstracts are cited, they are counted in the numerator of the IF calculation. Thus, a journal that publishes large numbers of abstracts once a year (you know who you are!) gets no "penalty" for publishing them and gets "credit" every time one is cited.
More recently, Thomson-Reuters, the current owner of the "impact factor" has begun publishing a 5-year as well as a 2-year impact factor. It can be argued that the 5-year IF is a better reflection of long-term as opposed to the "flash in the pan" value of a publication.
There have been many arguments raised regarding the validity and reproducibility of the IF, and these are discussed in a short Wikipedia review.
Other metrics have been proposed to better evaluate "impact." These include "immediacy index," "eigenfactor," "aggregate impact factor," "page rank" and others.
It's important to remember that IF measures how often an article is cited in subsequent pubications in a relatively short period of time. It DOES NOT measure how often an article is read or how valuable the journal readership considers the article to be.
At a Lippincott - Williams & Wilkins sponsored symposium that I attended last fall, a representative from Thomson Reuters discussed the IF and what it does and does not do. Her conclusion was that editors should publish the "best" articles that they can for their readership and let the IF fall where it may.
Friday, April 08, 2011
If you think you understand the scientific method and how to assess the validity of findings in journal articles, I'd like to call your attention to a really excellent, thought provoking article in the December 13th issue of the New Yorker. The article is still available on-line and is entitled,
The author is Jonah Lehrer. In essence this lay-press article deals in depth with the known but seldom discussed phenomenon that repeated scientific experiments often seem to give progressively "worse" (ie. less significant) results the more often they are performed. A large portion of the article revolves around researcher Jonathan Schooler who in the 1980's convincingly demonstrated that test subjects shown the image of a face, were LESS able to identify the face a second time if they were asked to describe the face in words after the first showing. This was called "verbal overshadowing" and it has important implications in eye witness accounts. If you remember my blog on the book "Blink" from a while back, this finding is not at all surprising. Schooler was meticulous in his study and in the analysis of the data and the results were quite convincing. However, every time he has subsequently repeated this experiment under exactly the same conditions, the results have been LESS SIGNIFICANT than the time before. When other labs repeated his experiment, the same thing happened; there was a distinctive downward trend towards insigificance. Schooler calls this the "decline effect."
So what's going on? As with the placebo effect discussed in my "Bad Science" blog a while back, probably much more than we fully understand. The article addresses virtually every explanation you can imagine, including the definition of significance (p<0.05), unintentional bias, regression to the mean, the tendency to report positive studies and reject negative ones, authors' tendency to present data in the best possible "light," and many others. In reality ALL of these factors, and many others are probably at work.
Importantly, the decline effect doesn't just apply to the "softer sciences" like psychology or clinical medicine. The author notes that it's been documented in physics as well. The so-called "weak coupling ratio" of decaying neutrinos has fallen by more than 10 standard deviations between 1969 and 2001. Physicists measuring the earth's gravity have found as much as a 2.5% variation from the theoretical value.
Are a lot of scientific data just background noise? Do we tend to latch onto ideas that appear to make sense and then hold on to them even after the "decline effect" says we should let go? To quote Lehrer, "The decline effect is troubling because it reminds us how difficult it is to prove anything. We like to pretend that experiments define the truth for us. But that's often not the case. Just because an idea is true doesn't mean it can be proved. And just because an idea can be proved doesn't mean it's true. When the experiment is done, we still have to choose what to believe." This may sound like scientific heresy, but the article raises some critical and only partially answered issues. I highly recommend it, but prepare to feel bewildered!
Wednesday, March 30, 2011
Languages invariably contain structures that are illogical and ideally should be altered, but almost certainly never will be. If you were designing the English language from the ground up you would never allow for so many homonyms The English language is absolutely full of them: aid/aide, ail/ale, air/heir, aisle/I'll, ate/eight, blue/blew, bare/bear, etc, etc, etc. They make it extremely difficult to learn English as a first language, let alone as a second.
Likewise, the language of pathology contains more than its fair share of fuzzy or downright inappropriate terminology which all trainees must master. "Pyogenic granuloma" is neither pyogenic nor granulomatous. In spite of the clear demonstration that these are lobular capillary hemangiomas with overlying nonspecific granulation tissue, the term continues to be used. Change does occasionally come, albeit slowly. Witness the gradual decline in the use of "malignant fibrous histiocytoma," a designation for high-grade sarcomas devoid of demonstrable mesenchymal differentiation that is widely known to be inaccurate (sorry Dr. Stout). The use of more modern techniques has wittled away many MFH's that can now be shown to display at least abortive stromal differentiation, and the remaining tumors are more appropriately designated as "undifferentiated pleomorphic sarcomas."
And then there are the eponyms of pathology. First, there's the whole apostrophe thing. I'm a firm believer that where these have historically been possessive designations, ie. Hodgkin's disease, the apostrophe should remain, but the world seems to disagree, and most of us don't seem to understand how to use the apostrophe anymore anyway. How often have you seen "it's" as the possessive form of "it," when "its" is correct and "it's" means ONLY the contraction "it is?" Dropping the apostrophe creates its own set of problems. How often have you seen "Wilm tumor?" His name was, after all, Dr. Max Wilms. I generally applaud established eponyms because they are an excellent short-hand way to convey information. In some instances, we don't even HAVE another designation. Wilms' tumors are nephroblastomas, but what else would we call Hodgkin's disease?
If you want to become an eponym, some helpful guidelines may be in order. First, you need to describe something never seen or at least never before popularized. In that regard, it may have been much better to have been born a hundred years ago when there were many more things left to be described, but fear not, there are still unknowns out there waiting for you and you have many more tools at your disposal today. Second, you need to give the "thing" a VERY LONG AND CUMBERSOME NAME. For example, Dr. Krukenberg called his tumor, "fibrosarcoma ovarii mucocellulare carcinomatodes". Note that it is NOT at all necessary to be correct in your designation. Dr. Krukenberg thought his tumor was a primary ovarian sarcoma. Wrong on both counts. He missed the gastrointestinal signet-ring adenocarcinoma primaries. The long name really seems to be the key. For example, "Small cell tumor of the thoracopulmonary region in childhood" just BEGS to be called "Askin's tumor," it's a lot shorter and easier to remember. "Bizarre parosteal osteochondromatous proliferation" was destined to become the far shorter "Nora's lesion." Likewise, "sinus histiocytosis with massive lymphadenopathy" seems like a setup for an eponym, even the somewhat long and hyphenated one of "Rosai-Dorfman disease." Conversely, verrucous carcinoma is often referred to as "Ackerman's tumor," yet this designation has never fully replaced the short and easy to remember original designation. Perhaps the ratio of the length of the original designation to the length of the author's last name gives some probability measure for the chance of an eponym succeeding as the new term. Ackerman should have called his tumor something like, "non-metastasizing locally destructive cytologically benign squamous proliferation with verrucous surface."
The next part is trickier. Someone else has to first refer to the tumor that you described by your name in a published work. I have few hints here. Luck, money, a reverent former trainee, or other considerations may be involved. There may be a substantial period of time between your description of an entity and its eponymous designation. Fritz Brenner described his tumor in 1907, but it was 1932 before Robert Meyer coined the term, "Brenner's tumor." Actually, I think he called it a "Brenner tumor" without the apostrophe; at least that's been the popular designation even before the current apostrophe witch hunt, as with Krukenberg tumor.
It seems appropriate that eponyms be granted only one per pathologist to prevent confusion. Witness the term, "Paget's disease" for example. A modifier is required to indicate whether this is "of bone," "of nipple," or "extramammary." Clearly James had too much of a good thing.
Eponyms are not awarded based on merit. Many famous pathologists richly deserving of the honor have not received it. There are no eponymous entities (that I am aware of) named for Virchow (although he does have his own journals), Stout, Scully, Dahlin, Enzinger, or Helwig, to name but a few deserving individuals who between them have described literally hundreds of new entities. In fact, their productivity probably worked against them. When you have personally described dozens of entities, which one should become "your entity?" Confusion begets indecision and the answer becomes, "none."
Although eponyms might be considered to grant their designee some measure of immortality, they may, in fact, have a finite lifespan if our understanding of the original entity changes measureably. Drs. Krukenberg, Hodgkin, and Brenner seem destined for immortality, but Drs. Ewing and Askin have seen their tumors absorbed under the PNET rubric. C'est La Vie.
Wednesday, March 23, 2011
All of us during our training heard phrases like, "You won't see it if you don't look for it." Hopefully, we all internalized that bit of truth. As an excellent example of this phenomenon of selective attention, please view the following video linked below. (Apologies if you've already seen it!)
Pay careful attention to the number of times the team dressed in white passes the basketball, and count the number of "white team" passes. Concentrate as if your life, or more appropriately a patient's life depended on you getting the correct answer. Don't read the rest of the blog until you've viewed the video.
(scroll down for more!)
The correct answer is 15 passes!
The first time I saw this, I got the right answer but I did not see the gorilla at all. I was vaguely aware of a form moving through the field, but it wasn't dressed in white and passing a ball, so I filtered it virtually completely out. If you think this has tremendous applicability to surgical pathology, you're absolutely right. Have you ever missed, or almost missed a lymph node totally replaced by small cell lymphoma or chronic lymphocytic leukemia while looking intently for the metastatic carcinoma? How about missing a small focus of squamous dysplasia in a hemorrhoid specimen? I'm certain that you can think of many other potential pitfalls in this regard.
Because of the above, it's always good to have a mental checklist for virtually every type of specimen. Lymph node for metastases - don't forget to check the lymphoid component. Hemorrhoidectomy - don't forget to check for dysplasia. There are many other examples and you're invited to submit your favorites in the comments section.
Wednesday, March 16, 2011
The 100th annual meeting of the USCAP was held at the end of February and the beginning of this month in San Antonio, Texas. Mercifully, the snow and bitter cold (for San Antonio) from just a few weeks earlier were gone and the weather was quite conducive to utilizing the River Walk. Given the time of year when the meeting is held, the USCAP is often plagued by bad weather hampering travel to or from the meeting, and this is especially problematic when the meeting is in February or early March. We escaped this year.
This was the second largest meeting in the history of the organization, with over 4200 attendees. Pathologists from all 50 states were present. In addition, almost 900 of the registrants were international visitors from 61 countries other than the United States and Canada (21% of the total registrants).
This was also Fred Silva's last meeting as executive vice president and the academy gave him a richly deserved royal send off, complete with an official portrait by Chris French. Kudos to Fred for an outstanding job! He's being replaced by Dr. Bruce Smoller, former Chair of Pathology at the University of Arkansas.
It has never been possible to experience more than a small fraction of what's going on at the USCAP and as the meeting grows this becomes ever more true. In the old days, proferred papers were presented in a few rooms next to each other and it was possible to jump from room to room between presentations; and many listeners did just that. Now the rooms are larger, more numerous and more widely separated and the listeners camp out in one session with little turnover between speakers. I DO wish that the USCAP would book LARGER ROOMS for the platform presentations. Almost ever session I attended was standing room only and the air conditioning wasn't remotely up the the task of cooling with so many bodies. It would also help if the seating had more aisles, as many empty seats in the middle of very long rows cannot be easily and unobtrusively accessed during a presentation. But this is a minor (and recurring) complaint in an otherwise outstanding meeting!
There's no way I can cover even a tiny fraction of what was presented there, but I would refer you to the USCAP web site where a plethora of meeting materials are available for the taking. Instead I'll touch on a just a very few points or trends.
1. The future of pathology is in good hands. I mentioned this a couple of blogs ago with regard to my course in Hawaii, but it was even more evident at this meeting that the next generation of academic pathologists is more than up to the task of carrying our profession forward.
2. Molecular pathology has come of age. When molecular pathology first sprang into being some of its overly zealous proponents were quite vocal that they were about to replace H&E morphology. Similar proclamations were, of course, also made for electron microscopy and immunohistochemistry during their infancy. Such claims have now completely disappeared. Instead, there is now the widespread recognition that molecular pathology has a vital, undisputed role as an extremely powerful tool in our diagnostic armamentarium, but it does not replace older techniques. Along these lines, I arrived in town on Sunday afternoon and sat in for about half of the special course on molecular pathology organized by Dr. Jennifer Hunt. This was a truly outstanding event that EVERY pathologist should attend. When properly explained these initially arcane-sounding techniques are both easy to understand and marvelous to contemplate. I can now (FINALLY) look at a Sanger sequencing plot without curling up into the fetal position!
3. An interesting trend. A few months ago I began noticing an interesting phenomenon in a few of the manuscripts submitted to AJSP and this continued at the meeting. Tumors are occasionally being categorized according to lineage (direction of differentiation) based on supposedly specific immunohistochemical stains, when the H&E and/or clinical features provide limited or even no additional support for that interpretation. A couple of examples follow. An entity called poorly differentiated chordoma has been described that consists of a pleomorphic, mitotically active epithelioid cells with little or no light microscopic resemblance to classical chordoma but expressing the apparently notochord- and chordoma-specific marker, brachyury. These tumors also show loss of INI1 as seen in rhabdoid tumors and epithelioid sarcomas. The tumors DO occur in the same anatomic areas as chordomas, but are they chordomas with INI1 loss or rhabdoid tumors expressing brachyury?
As an even more contentious example, we now have the entity of "epithelioid sarcoma-like hemangioendothelioma" (aka "pseudomyogenic hemangioendothelioma") with the endothelial differentiation based solely on CD31 and FLI-1 positivity. The tumors exhibit no clinical or light microscopic features of endothelial cells, and in fact much more closely resemble other stromal elements. You can no doubt think of other examples such as "myoepithelioma of bone." Are we expanding the spectrum of previous neoplastic categories, or are we being led astray by over reliance on a technique that is never 100% specific? Time will tell. These studies and others were done by well respected colleagues and friends. I wouldn't bet against them, but I am a little skeptical.
...next time, an optical illusion with diagnostic consequences!
Friday, March 04, 2011
In my last blog, I mentioned our role to combat patient and naive clinician exploitation by molecular profiling labs with tools of dubious value. This is not an easy job. Here's one of my recent failures in this regard.
Like most consultants with an interest in head and neck, I get a lot of thyroids for review and a month or so ago I had one that was a straightforward follicular variant of papillary carcinoma. A week or so after signing it out I got a call from the patient's clinician in a nearby town. So far so good. The clinician wanted to know if we had assayed the tumor for BRAF mutations. When I said we hadn't the trouble started.
I was well aware of increased interest in BRAF because of its new role in promising targeted therapy of malignant melanomas with this mutation, and we are part of the evaluation of this at UVa, so the assay gets done on most of our melanomas. I was also aware of a few papers showing some decreased survival for papillary thyroid carcinomas with BRAF mutations, but the differences were, at least in my view, minor in a tumor with an overall excellent prognosis, and it was unclear if they held up in rigorous multivariant analysis when controlled for stage and some known more aggressive subtypes. Moreover, there is already a superb targeted therapy for thyroid carcinoma..... radioactive iodine.
The conversation went just about like this (honest!):
C = clinician
M = me
C: Did you assay Ms. X's thyroid carcinoma for BRAF?
M: No, we don't do that.
C: Why not? I want it done in this case. Can you do it?
M: Your pathologist has the block. If you really want it done, talk to him.
C: Why can't you do it?
M: Because it's expensive and of no therapeutic value.
C: That's not true, it's a great prognostic marker.
M: Really? That's not my read on the literature. It seems to be at least in part a surrogate marker of high stage or poorer prognosis subtypes like tall cell. Anyway, even if it did have limited prognostic value for these usually cured tumors how would it affect your therapy? There's already GREAT therapy; surgery and if needed radioactive iodine, the mother of all targeted therapies.
C: I can't believe you don't do this. They do it on all their thyroids at Elsewhere Memorial. (They DON'T, I checked.). You guys call yourselves an academic institution and you're SO behind the times on this.
M: Tell me how you would use this information. This was a small encapsulated tumor with an excellent prognosis, regardless.
C: I can't believe you don't do this! I'm going to send you some papers so you can come into the 21st century.
M: You haven't answered my question. Every test should have a clinical branch point or else it's of no value.
C: I'll send you the papers, then you'll see.
-Hang-up-
I never got the papers. I must admit this call left me feeling a little "inadequate" and sent me running to do a quick literature search and make a call to a friend at Elsewhere Memorial to see if the world had unknowingly passed me by on this. But it hadn't. Mainly, I was depressed at my inability to convince a private practice clinician that just because a test is available doesn't mean it's needed or indicated. At best this is probably a repetitive process, easier to do with clinicians you see every day in your own institution.
I was again reminded of Ben Goldacre's admonition in Bad Science that you can't reason someone out of a position they didn't use reason to get into. Unfortunately, we'll have to deal with issues like this more and more. If these excesses come under Medicare scrutiny the result is likely to be across the board reimbursement cuts including expensive items that ARE of clinical value.
Thursday, February 24, 2011
For the last week I've been attending and participating in a surgical pathology course on the Big Island of Hawaii. From here I'll travel to San Antonio for the 100th USCAP meeting. This is my fourth trip to Hawaii in the last decade to take part in these courses, which are organized by Scientific Symposiums under the direction of Dr. Jim Bennington, along with Carol and Larry Haag. Every time has been an excellent experience for me as a speaker and listener, and the attendees seem to enjoy it as well, as many have been here a dozen or more times.
Conflict of interest (COI) disclosure: I was compensated for my travel and expenses plus an honorarium each time that I participated. I make no claim of being completely objective, particularly since the beautiful weather here makes it virtually impossible to fully separate the quality of the venue from the quality of the presentations. There are multiple other privately and institutionally run pathology meetings of this type with similar high quality presentations, though they can't (in my biased opinion) match the location, and hence the very high repeat attendance here. The course is fully ACGME accredited for 25 hours and also offers an on-line post-meeting test for SAM credit.
So take this as an admittedly biased "plug" for this meeting. If Hawaii is a little too far or expensive for you, Scientific Symposiums runs quality-identical meetings on the east coast in Hilton Head, South Carolina.
(end of my COI "plug")
Sitting in this meeting after giving my own talks I kept reflecting on a few points.
Pathology is evolving at a rapid rate. Long gone are the days when residents could leave their training and remain "functional" as diagnostic pathologists with little or no continuing education for the rest of their careers, though sadly some still seem to try. More than half and probably close to 90% of what I use in day-to-day diagnosis has been learned after my fellowship.
The integration of clinical information, H&E morphology, immunohistochemistry, and molecular diagnostics has made our specialty so much more than it was a few decades ago when diagnoses were made by assertion and he/she with the most gray hair carried the day. .....and just when I was starting to get some gray hair "cred". Having begun my career in the era of electron microscopy and seen the subsequent development of immunohistochemistry, in-situ hybridization and a host of other molecular techniques, it is clear that each addition, though often touted by its zealots as spelling the end of H&E morphology has instead assumed its rightful place as a valuable adjunct to the H&E slide. I can't imagine signing out surgical pathology consults for long without these additional tools. Far from denigrating the H&E slide, these techniques have provided validation for many careful morphologic observations of our predecessors and have shown us where they occasionally went astray. The trick of course is to know when to use these ancillary techniques and when they are a waste of the shrinking healthcare dollar.
We have a critical role in regard to the above, because private companies with primarily profit motives increasing "hawk" molecular tests of dubious value directly to our naive clinician colleagues and even their patients. If there's a molecular test that has critical clinical implications, like FISH assays for Her2 in breast carcinoma then we must champion them, but when a company pushes a $5000 gene profiling test with little or no proven clinical utility, we must be the ones to show that the emperor has no clothes.
"Good ole boyism" is long gone. This seems obvious today, but when I began my career, surgical pathology, particularly academic surgical pathology, was an almost exclusively male activity, with only a few notable exceptions. Those days are also, mercifully, long gone. Of the five speakers at my course in Hawaii, three (the youngest three) were women. All three are already well-established academicians and their talks were some of the best at the meeting. Hardly surprising, I suppose, but worth noting. Moreover, I am in awe of their ability to juggle their family lives with their professional lives and still achieve academic success. There is no doubt that one of the attractions of pathology for both men and women is the ability to be successful while still maintaining some semblance of an outside life. Obviously, to base a career solely on this feature would be a big mistake, but it gives those who genuinely enjoy pathology another reason for this career choice. It was a factor in my own decision years ago. Today's medical graduates think more carefully than ever about lifestyle issues. No wonder surgery residency applications are way down! If lifestyle decisions help us attract the best and the brightest to pathology, then we benefit from this shift.
Pathology is in good hands. Sitting in my course this week and listening to three superb "youngsters" make their presentations and thinking about many others just like them that I'll see next week at the USCAP, it solidified my belief that the next generation is more than up to the task of taking up the mantle of academic pathology and greatly extending its boundaries. These rising stars are well-versed in morphology as the cornerstone of diagnostics, but they also know its limitations and when the "new" can improve on the "old." You'll forgive those of us with some mileage and gray hair if we're not QUITE ready to exit the scene, but it's comforting to know that when we do we'll leave things in good hands.
Monday, February 14, 2011
A large part of the upper-level teaching of pathology at academic institutions is based on consultation cases sent in from outside pathologists. At the University of Virginia we receive about 3,000 consult cases a year and these are invaluable in the training of our fellows and senior residents.
My colleagues and I would like to sincerely thank all of you who send us consults. They are invaluable teaching aids.
With the above being said, and sincerely meant, I would like to point out a few ways in which the consult experience can be optimized for all involved. Most of these points are simple or even simplistic, but this list may serve as a guideline, particularly for newly graduated pathologists who find themselves in need of aid.
1. Clinical history. You probably didn't get much (if any) with the specimen request form, but if it's a problematic case, a quick call to the clinician may be enlightening. Please pass this information on with the consult slides. If the case is a bone lesion, a copy of the radiographs should be included or, at the very least, a copy of the radiologist's report.
2. What do you think? It's very helpful to know what the contributor was thinking about the case. This is particularly important for tailoring comments to you in the note.
3. Pick and choose. Although it's quicker to get recuts on an entire case, have your secretary box it all up and send it off, it's BETTER if you choose a few key slides from the case and do not overload the consultant unnecessarily. You should dot areas of interest and these can be addressed in the consultant's note.
4. Include unstained slides or paraffin block. Although this is not always necessary, in today's world most consultation cases need additional studies. This is particularly true for "undifferentiated" or unusual malignancies, possible lymphoproliferative lesions, possible infections, etc. If you don't want to send a representative paraffin block, then include a dozen unstained slides on coated glass, suitable for immunohistochemical or in-situ hybridization studies. Having to request these materials just delays the ultimate diagnosis. Do not send wet tissue unless you have made specific advance arrangements to do so.
5. Allow retention of slides. Consultation material is an invaluable resource for academic research. Please allow the consultants to retain at least some H&E-stained and unstained slides. If you require the return of all H&E-stained slides prepared at your institution, then please include unstained slides or a paraffin block so that additional slides can be prepared and retained by the consultant. Paraffin blocks will be returned ASAP unless there is specific agreement to allow retention of the block.
6. Include appropriate contact information. Most consultants call and/or fax pathology reports to the contributors. Your full name, address, fax number, and phone number should be included in the report. Likewise, include the patient's full name and their insurance information for billing purposes (unless the consultant only bills the contributor).
7. Properly pack and ship the case. Don't put slides in plastic slide holders until the Permount has adequately dried. I've had to use a bandsaw, on occasion to extract slides securely glued with Permount into slide holders. Tape the slide holders shut securely, pad the package and ship via Fed. Express or other fast carrier. All of us looking at these cases have received packages in which the slide carriers opened in shipping, the slides slipped out and all promptly shattered
8. Feel free to call. All consultants that I know are happy to discuss a case with the contributing pathologist, or if needed the treating physician. On our service, we typically have the fellow call the contributor after we've reviewed the case to discuss the findings (this is a great way for them to find out about jobs, and for you to find candidates!). However, if you need more information, you should contact your consultant directly. In contrast, most consultants do not wish to discuss cases with patients. It is impossible in a phone call to determine that the individual has been properly identified as the patient and HIPAA regulations could easily be violated here. It is also quite possible that since the consultant is not familiar with all aspects of the case, he or she may well make unintentionally inaccurate statements, particularly with regard to prognosis and therapy. These are issues best handled by the treating physician.
9. A consultant is not the primary pathologist. A consultant renders an opinion on a limited amount of material out of context from the treating institution. Consultants are human and make mistakes. If the consultant's opinion seems "off base," then by all means seek additional aid. Ultimately, the final decision falls to you, the primary (ie. "treating") pathologist, though seeking consultation certainly shows due diligence and even if the consultant (and you) are ultimately wrong, the fact that you sought expert aid goes a LONG WAY to support you if the lawyers come calling.
I have back-to-back meetings beginning at the end of this week, with the second being the USCAP meeting in San Antonio. My next blog will be delayed because of this, but I'll report on what new trends were spotted at USCAP when I return. I hope to see you there!
Thursday, February 03, 2011
For now, this is the last in my immediate series of tips for authors, though I suspect there will be more in the future.
Many pathology journals have eliminated case reports from their publication repertoire. I understand their reasoning but I don't completely agree with it. Case reports often appear at editorial offices in large numbers tying up staff and reviewer time. As a group they are not likely to be highly cited, lowering the journal's impact factor (more about impact factor in an upcoming blog!). Nonetheless, AJSP continues to publish occasional case reports (0-2/month), although we accept fewer than 5% of submissions. As editor of AJSP, I have been reluctant to completely eliminate case reports, because they can occasionally be valuable or even, please pardon the over used phrase, "paradigm shifting." They also provide the initial foray into publication for many residents, fellows, and even junior faculty members. There are journals in our specialty devoted entirely or almost entirely to publishing case reports, and if this function serves to promote interest in academic pathology among our trainees, then I certainly applaud it.
To return to the title of this blog, "what constitutes a good case report?" Well, for starters, let's deal with what doesn't. Rarity per se is just not sufficient. The first example of tumor X occurring in a hithertofore undescribed location is unlikely to teach us much if anything about tumor X, except perhaps that the scope of its distribution is a bit larger than previously described. This isn't surprising and seldom very problematic. After all, the authors figured it out, and you probably could have as well. Remember the "Man in Istanbul" anecdote in my "Ackermanisms" blog? Likewise, a "collision tumor" formed by the rare intersection of tumor X and tumor Y is nothing more than a medical curiosity, telling us virtually nothing intrinsic about either tumor X or Y. Eventually, given time and a large enough population, almost every tumor will collide with every other tumor. OK, it's HIGHLY unlikely a prostate carcinoma will collide with an endometrial carcinoma, but you get the point.
Molecular studies based on single case reports are virtually always problematic, because without a series, each showing the same anomaly, it's impossible to tell if a genetic defect is random or potentially defining of the lesion.
In order to be publishable (at least in AJSP), a case report should provide information that extends beyond the case itself. Ideally, it should alter our thinking about an entity. As two examples, I'll use a couple of case reports that I co-authored quite a while ago. I use these as examples simply because I'm very familiar with them. Many, many better case reports exist.
In the mid-1980's immunohistochemistry was really coming to the forefront in pathology. Leukocyte common antigen (LCA) had just become available commercially. Simultaneous with the acquisition of the antibody in our department, we encountered a case of so-called "malignant angioendotheliomatosis." The intravascular cells stained strongly for LCA and we (Ute Wrotnowski, Philip Cooper, and I) went on to report this case and propose that malignant angioendotheliomatosis was actually an "angiotropic" or intravascular lymphoma, rather than an endothelial cell neoplasm. This and other subsequent larger studies led to a total rethinking about this lesion.
Similarly, I was involved in a case report describing an epithelioid ("histiocytoid") hemangioma of the testis. As such it sounds like nothing more than a funny lesion in a funny place, not enough justification for publication. However, we went on to review the literature on adenomatoid tumors of the testis and to suggest that some reported vascular adenomatoid tumors more likely represented epithelioid hemangiomas, rather than mesothelial lesions. Subsequent studies showed this to be true and that other epithelioid vascular tumors, such as epithelioid hemangioendothelioma could mimic mesothelial proliferations (mesothelioma in this instance).
So a good case report makes an observation and then uses this observation to improve or alter our understanding of an entire entity. It's not just a "funny lesion in a funny place."
Wednesday, January 26, 2011
As promised, a few more tips, this time dealing with illustrations.
At the risk of stating the extremely obvious, pathology is an inherently visual specialty. I often have to remind the journal production staff of this as they try to shrink critical figures to fit into spaces that are much too small. The key to convincing reviewers and readers that your entity has been properly interpreted often lies entirely with the figures.
In the "not so good old days" when you wanted to illustrate a manuscript, you took your handful of glass microscopic slides to the hospital's medical illustration department. There, a photographic expert worked with you to produce nearly perfect images, typically on an extremely nice, state of the art photomicroscope. You picked the field and the magnification and the photo assistant often did everything else including checking the focus and setting the Köhler illumination and light intensity. Large 4" x 5" negatives were often used, giving superb resolution and the photo assistant carefully printed your picture, manipulating the exposure time, contrast, and dodging/burning the print to produce even lighting. The result was typically a perfect or near perfect black and white image.
Today, your medical illustration department has probably been phased out, a victim of the advent of color digital photography, PhotoShop, and PowerPoint. The digital photographic equipment that exists today is of unparalleled quality and comes at increasingly lower prices. This, coupled with the wide availability of easy to use image software, means that photos submitted for publication today should be essentially flawless. Yet, sadly, they are often worse than those submitted in the pre-digital era. In large part, I believe this is due to the fact that you no longer have photographic experts to help you. Now YOU must be the expert.
Most authors do well with focus, but they often fall woefully short with regard to brightness, color balance, contrast and uniform lighting. Most of these problems can avoided up front by properly adjusting the microscope and setting the color balance before taking the photomicrographs. Less than perfect figures can be adjusted with image software such as PhotoShop. The goals for the end result are simple.
1. The background should be white or very light gray, not green, blue or yellow.
2. The image should have sufficient contrast and not appear washed out.
3. The image should have a uniform brightness across the field without dark corners.
Adjusting brightness and contrast is typically easy. Adjusting color balance takes a little more practice. Uneven lighting (usually dark corners) can be corrected by "dodging" the corners. Areas that are too light can be "burned." These are techniques well known to pre-digital film-based amateur photographers but they are easily done by virtually anyone with current software. LEARN THEM!
Don't be afraid to try these techniques. Often when I ask authors to improve their illustrations the revised photos are a step in the right direction but go only about 10% of the way toward what is needed. For each change that you make to a figure, it is best to purposefully go a little too far in the direction needed and then "back up" to what appears best, rather than making small incremental changes. It also helps to walk away from the figure for a while and then come back to it, as you eye tends to compensate for errors over longer periods of time.
It is critical to emphasize, of course, that the purpose of editing a photo is to make it a more faithful rendition of what is seen through the microscope. These techniques must NOT be used to create a false reality. For example, contrast, brightness and color balance should not be manipulated to make weak immunohistochemical staining look stronger than it really is.
Authors need to carefully chose the magnifications that they use. Low-power images are important to show the overall context of the lesion. High-power images are needed to show the cellular makeup of the lesion in more detail. The authors should repeatedly ask themselves if they have documented the lesion in sufficient detail to allow the reader to recognize it when encountering it in their own practice. As mentioned above, poorly illustrated manuscripts cause reviewers (and readers) to question the correctness of the diagnosis.
Finally, a word about color submission format. Most of us manipulate color images in RGB (red-green-blue) format. This is fine for PowerPoint or any other electronic usage. However, at some point when an image is going to be printed on paper it must be converted to CMYK (cyan-magenta-yellow-black) format. This format corresponds to the available inks used in printing. Typically converting an RGB image to CMYK results in only minimal alteration in color balance, but occasionally the changes can be more dramatic. For this reason, it is always BEST to submit an image for printing as CMYK, although most of the time the conversion is not noticeable.
Tuesday, January 18, 2011
I promise that I'll get back to my tips for authors shortly, but this story caught my attention recently and deserves comment.
In 1998, Dr. Andrew Wakefield and colleagues published an article in the Lancet purporting to show an association between the development of autism and the MMR (measles, mumps, rubella) vaccine. Although this article was later renounced by 10 of its 13 authors and subsequently retracted by the Lancet, the topic caught on in the lay press and spooked a lot of well-meaning but scientifically illiterate parents. In addition, equally ill-informed but well-meaning celebrities like Robert F. Kennedy Jr. and Jenny McCarty have fueled these fears. Vaccination rates plummeted and frivilous lawsuit rates skyrocketed. Governments had to indemnify vaccine makers to prevent ALL vaccine production from coming to a screeching halt. As herd immunity dropped in susceptible populations, outbreaks of measles, mumps and rubella appeared across the world. Thousands of children and adults needlessly became ill and some needlessly died.
Actions have consequences.
Although the medical establishment might be accused of not policing itself as well has it should have, one man, a journalist, Brian Deer has been investigating this case for years. In a recent issue of the British Medical Journal (BMJ), Deer published the results of his re-review of the medical records and interviews with the parents of the 12 children comprising the Wakefield study. These children were said to have been "normal" before and autistic after receiving the MMR vaccine. Misrepresentations were found in all cases and, in particular, 5 of the children said to be "normal" initially were actually known to have significant developmental anomalies before being vaccinated.
In an editorial accompanying Deer's article in the BMJ, editor Fiona Godlee called the initial study an "elaborate fraud," knowingly perpetrated by the author, and urged editors of other journals to review all prior publications by Wakefield to see if they should also be retracted. Wakefield was stripped of his British medical license last May.
Of course, following the initial Wakefield study, there were MANY subsequent studies, none of which showed ANY association between autism and vaccination. And unlike the initial Wakefield study involving only 12 children, these subsequent studies involved MILLIONS of children (2 million in a study from Finland and 3 million in study from Boston University).
One might assume that this thorough debunking of the initial TINY (and now known to be fraudulent) outlier study might quickly put an end to all of this, but then again it probably won't. The press is certainly to blame in large part for this continuing silliness. They invariably present both sides of an argument as if they deserve equal weight. Thus, Dr. Wakefield is given equal time to spout off on this topic, as are other completely science illiterate "experts." As Bill Mahrer once said, when the argument is about a scientific issue, non-scientists don't get to have a voice in the discussion. And all issues do not have two equal sides. Yet, I fully expect to one day see a program on CNN or another major network called, "The Earth, Flat or Round? You Decide."
Medical researchers could, I think, help bring some rationality to this by addressing two issues in the lay press that crop up again and again in the comments of those who continue to believe this association.
1. Why is autism seemingly increasing in frequency? This seems to me to be almost certainly due to increased awareness. The term was virtually non-existent when I was a child. I first encountered the word as a junior in college. In the past, children with varying degrees of autism were undoubted labelled using terms ranging from introverted or shy, to mentally handicapped (the term at that time was "retarded"). The same argument can be made with regard to attention deficit disorder (ADD). It has always been around, we just didn't have a good name for it before. We called these kids, often boys, "daydreamers" when I was in elementary school.
2. Why are there anecdotal stories of apparently normal children becoming autistic after vaccination? Are vaccinations routinely given at about the same developmental time when the symptoms of autism become most obvious? Does the mild fever often associated with vaccinations exacerbate the symptoms that were there anyway? By statistical chance alone, how many cases of autism would be expected to develop around the time of childhood vaccinations in the U.S. population?
A recent poll on the MSNBC website, "TodayMoms" indicated that over 30% of parents currently believe in an association between autism and vaccinations. We can only hope that number will start to fall, but to paraphrase a quote from Ben Goldacre's book, "Bad Science," you can't reason someone out of an opinion they didn't use reason to form.
Wednesday, January 12, 2011
I'll get back to my comments for authors shortly, including some comments on illustrations and what constitutes (in my opinion at least) a publishable case report. However, right now I want to update you on the addition of a new journal to the Lippincott - Williams & Wilkins (LWW) publishing lineup. LWW has become the publisher for Pathology, the official journal of the Royal College of Pathologists of Australasia.
This means that Pathology will be (in fact it already is) a component of Pathology Network and will be available for institutional on-line access exclusively through the OvidSP system. A brief press release with further details regarding this addition can be found here.
I've been a long-time fan of this journal and I'm delighted that it is now included in Pathology Network. Because Pathology publishes very practical articles in both anatomic and clinical pathology, it will be a valuable addition to our lineup.
Monday, January 03, 2011
Several of you have asked that I donn my journal editor's hat and use this blog to provide some tips for beginning authors. Since this is an important topic and I'm always looking for new blog ideas, I'm happy to do so. This will require several "postings," so if this isn't a topic of interest, bear with me.
For now, I'll assume that you have a worthwhile project, that you have put forward a question or hypothesis and devised a study to answer it. The data have been collected and analyzed and it's time to put pen to paper. In a later blog we'll try to consider what constitutes "worthwhile."
1. Pick your preferred journal BEFORE you start writing. When considering where to send you work, think about the findings of the study and for whom these results are likely to be most valuable. Since such decisions are rarely "black and white," picking the journal ahead of time allows you to adjust your focus. It should be obvious, but in order to do this, you must know something about the journal to which you wish to submit. You should have read the journal and gotten a good feel for the quality and content of the journal and an understanding of its readership. I'm always amazed when I get letters of inquiry asking, "Does your journal publish X". I'm invariably tempted to reply, "Have you ever LOOKED at the journal?" ...but discretion gets the better of me.
2. Know the relevant literature. This is critically important. If you think you're describing an new entity, how can you be sure? Since few things are really new, it is likely that your entity has been described before under different terminology. Based on your understanding of the pathology, you should be able to make educated guesses about what your entity might have been called in the past, review the studies of these entities and see if you can find examples of your cases there. As a simple example, if you're reporting the first series of solitary fibrous tumors of the head and neck, you might readily suppose that prior to the popularization of this entity, identical cases were most likely interpreted as "hemangiopericytomas." Does review of old series, esp. figures and microscopic descriptions, support this? If you're reporting on a well-established entity, how do your findings fit with those of prior studies?
3. Point out the relative weaknesses in your study and address them forthrightly. Pointing out the weaknesses in your own work may seem ill advised, but quite to the contrary it will endear you to the reviewers, editor, and readership. The reviewers will invariably spot these anyway. Ignoring them or trying to "sweep them under the carpet" won't help, but the reviewer will gain respect for you if you forthrightly point them out and deal with them.
4. Put youself in the reviewers' place, imagine their questions and address them. This point is related to but slightly different from #3. When writing your text, ask yourself what questions or problems the reviewer is likely to raise and address them. For example, the May 2010 issue of AJSP contains an article on mammary analogue secretory carcinomas of salivary gland. On first viewing, any reader (or reviewer) glancing at the figures is likely to immediately ask, "Why aren't these just acinic cell carcinomas?" The authors anticipate this issue and quite convincingly deal with it.
5. Don't over rate or over interpret your findings. Read my blog from November 16th entitled, "Less is more." Be careful to distinguish what your data show from what they MIGHT mean. If you're studying a protein's expression by immunohistochemistry, you're NOT studying its precursor RNA or DNA.
6. The Abstract is the first and in some instances only encounter a reader may have with your study. It is the only form of your work that is readily accessable in many on-line retrieval systems. Take extra time to make it readable, yet as full of data as possible. Phrases such as, "findings will be discussed" are of no value. Keep accepted abbreviations to a minimum in the Abstract and don't introduce any new ones here.
7. Severely limit new abbreviations. PLEASE, take pity on the readers (and reviewers). Every abbreviation, but particularly the new ones coined just for your study, requires a moment of mental translation each time they are encountered, and this greatly slows the flow of your manuscript and makes it difficult, or in some cases almost impossible to read and interpret. As an editor, I would much rather take the extra space to publish the spelled out term.
8. Follow the proper journal format. (see #1 above). Be familiar with the format of articles in the journal to which you're sending your manuscript. How is the abstract structured? Are there key words? What is the reference format? Are they in alphabetical order or order of citation? When articles don't match a journal's format, reviewers and editors often assume (usually correctly) that the manuscript has been rejected by another journal and quickly resubmitted without re-formatting.
9. Submit a grammatically and stylistically perfect text. Do NOT depend on the reviewers or copy editors to point out and correct these often minor but not insignificant issues. If the text contains multiple misspellings, subject-verb disagreements, etc. the reviewer is likely to wonder if the authors were as sloppy with their study as they are in reporting its findings.
10. If you are submitting to a journal published in English and it is not your native tongue, seek help. Don't depend on the reviewers to understand what you meant or on the publisher's copy editors to correct your misusages. Seek help from someone who doesn't just speak English as their native tongue, but someone who is familiar with medical and particularly pathology jargon.
It's important to remember that a well-written, nicely illustrated study is FAR more likely to be accepted than a poorly written and poorly illustrated one, even if the topic is not as appealing. Don't expect the topic to sell itself; that's your job as author.
Friday, December 17, 2010
Unless you've only been practicing for a few months, are in a solo practice, or you are truly faultless (and if you are we'd ALL like to meet you!) you've experienced the "joy" of having a colleague come into your office with a slide in his/her hand, and ask if you'd take another look at a case that you called "X". What happens after this is highly pathologist specific, but it's critical for patient care that we arrive at the proper end result. It's important to keep in mind that the quicker an error is caught the better so this is a good thing! At our institution virtually every malignant diagnosis or case where there is clinical suspicion of malignancy gets reviewed at an organ-specific tumor board, usually by the in-house specialist in that area of pathology, so every malignancy gets at least two "looks," and often more since fellows are in the loop as well, before any definitive treatment is given.
The first issue, of course, is whether you're really wrong. Needless to say, egos can be problematic at this juncture. Basically, there are two kinds of diagnostic errors, either you didn't see a key feature or you saw it, but your interpretation is different from that of your colleague. If it's the former, ie. you missed the small focus of high-grade dysplasia in the cervical cone specimen, it's usually pretty obvious that you've made a mistake. In my case there's usually a brief moment of cursing and sulking involved, followed by promptly issuing an amended report, and calling the clinician if the change is clinically significant. Things become more problematic when there's a genuine difference of opinion with regard to interpretation. For example, you think the bladder biopsy shows carcinoma in-situ and your colleague thinks it's reactive atypia. These cases need to be double-scoped and reviewed carefully. Here's where ego v. insecurity need to be brought under control. If you really think you're right, don't automatically "fold" and explain why to your colleague. But if you see that you may have over called the case, don't let your ego stand in the way of correcting things. If it's really problematic, sleep on it and look at it again in the morning. It's amazing how much different (and clearer) things look the next day. However, before reaching this point, contact the clinician and let them know that some questions have been raised about the diagnosis and more study is required. You don't want any major intervention until this is worked through.
Just as the man with two watches never knows what time it really is, the pathologist with two diagnoses is never certain either. In such cases, it is always helpful to seek additional opinions. If the consensus is against you, admit it, change the report and move on. If there's still uncertainty, craft an amended report that expresses this uncertainty and, if possible, directs the clinicians down a course likely to sort things out and do the least patient harm along the way.
We are not expected to be perfect, and as one of my more enlightened surgical colleagues used to say, "Pathology is too difficult for human beings." We are however, required to be scrupulously honest and professional. Document the amended diagnosis and explain why the case was difficult in a forthright note in the amended report. Under NO CIRCUMSTANCES should the medical record be altered in any fashion to cover up the original interpretation. Doing so converts a legitimate change in diagnosis likely to be well within the standard of care into a potential criminal fraud case. In all likelihood your malpractice insurance won't cover you. Nothing excites a plaintiff's attorney more than spotting something like this. They'll jump at every one of these cases and win them all.
There's a variation on this theme that's equally (or more) important. You've made a diagnosis, and the clinician calls you up surprised at what you've said. For example, you diagnosed a low-grade adenocarcinoma of the breast, and the mammographer has been following the lesion and it has remained radiographically unchanged for 5 years. Maybe the mammographer did two biopsies that day, one was called malignant and one was benign, and the results are exactly the opposite of what was expected, raising the specter of a specimen labelling problem. The EXACTLY WRONG thing to do in this circumstance is to flippantly say you're sure you're right and go back to whatever you were doing. I've seen several lawsuits that could have been easily avoided by NOT taking this approach. A BIG warning light has gone off (clinician diagnostic dissonance) and you've ignored it. Good luck! You'll need it.
My approach whenever this happens is to tell the clinician to hold up on treating the patient (or informing them of the diagnosis), and I'll review things and get back to them ASAP. We're usually correct, but don't take the chance. Also, if any concerns remain, consider the option of placing an addendum note on the pathology report that you have re-reviewed it because of clinician concern and confirmed the diagnosis.
Thursday, December 09, 2010
Our laboratories at U.Va. were up for their bi-annual CAP inspection and the team showed up this Monday. Although the exact time of arrival is not fully known until they show up on your doorstep, we knew it was getting close, as we had been told they'd be here before the end of the year.
Although some may view these inspections with a sense of dread, and I admit that I did as well when I first took over as a director in our department, I've come to find them enlightening and actually enjoyable experiences. In fact, I've come to believe that of all the CAP's miriad activities, many of which I find to be of dubious value as my previous blogs will attest, I think the inspection program is their most valuable asset.
I also admit that my now enjoyment of these reviews is due in large part to the fact that we are blessed at U.Va. with excellent hospital staff and a faculty QA officer who make this process almost transparent for the rest of us. Once again the process was completely benign and our multi-site AP and CP labs received only a handful of easily correctable Phase 2 violations and no Phase 1 problems. As the chief of the inspection team joked at the closing session, we have to find some Phase 2's or the CAP won't reimburse our airfares! Virtually all of the Phase 2's were corrected on site before the inspectors left.
So why have I come to really value and even enjoy these inspections?
Although some of the checklist items certainly could be considered "picky," most are valid and following them results in improved patient care, which is after all why we're clinicians.
These reviews are, or are meant to be, non-confrontational and supportive rather than combative. The inspectors are our colleagues and we all have the same goals.
The inspection team almost invariably asks if there are issues with the local hospital administration for which they can be supportive. This has been very valuable to us in the past when we needed more space for laboratory functions. Our administrations, present at the closing session, were told in forceful terms in those instances that our space WAS inadequate, echoing our concerns and aiding in our obtaining additional space.
A positive CAP inspection puts pathology laboratories on a sound footing during JCAHO hospital reviews. In the past JCAHO reviewers virtually never even visited pathology laboratories when they had a CAP accreditation. They do now occasionally make directed reviews, often of the blood bank or other high profile areas, but for the most part we are out of their "crosshairs" thanks to a solid CAP assessment; and if they do visit, following CAP guidelines puts us in an excellent position. This is comforting because, unlike the CAP reviews, those guys DO make me a little nervous!
Finally, the inspection process is an excellent learning experience, both for the inspectees and, especially, for the inspectors. Many of my colleagues at U.Va. have participated in and headed inspection teams at other hospitals and invariably they have returned with new ideas, protocols, checklists, etc. that they found helpful for us during their inspection. This sort of "cross pollination" may well be the best feature of the inspection process.
Wednesday, December 01, 2010
Last week I recommended a book for your holiday reading pleasure. This week, I'd like to recommend one that you should consider giving to your intellectually curious but non-medical friends, family members, etc. who like to read. These are the folks who, when they find out you're a pathologist at some point invariably ask, "What exactly IS cancer, anyway?" And while you're buying copies for your friends, keep one for yourself, it's an excellent read. But first (again), a brief digression.
When I was in medical school, like all of us, I went through the process of deciding what area of medicine was going to be right for me. Although I was fascinated by cancer from the very beginning, one very early elimination was medical oncology. Working surrounded by such pain and suffering and able to do so little for so few seemed, to me at least, to be a recipe for frustration and depression. I remember coming home from a tough week on the cancer wards, looking forward to a night out at the movies with my wife and friends.
"What's the movie?" I asked.
"Terms of Endearment," my wife said.
"Fine," I said, knowing nothing about the plot, "as long as no one dies of leukemia. I've seen way too much of that already this week."
The look on my wife's face said it all. "We need to pick another movie," she said.
I certainly admire and applaud those who have the proper makeup for this important work. I don't.
Reviews of this book have been glowing to say the least. Check out some of the reviews on the Amazon web site. Below are some excerpts from one by Kenneth E. MacWilliams:
"The book itself is a tour de force. It is the first book of such extraordinary scope regarding cancer. Its architectural structure brings to mind Melville's Moby Dick and how effectively and artfully Melville braided together the three strands of his great classic: a grand adventure story, the technology of whaling, and a treatise of humanity and philosophy. Equally effectively does Mukherjee weave together all the various facets of this iconic disease throughout history, from describing cancer from the patient's perspective, to viewing the never ending battles of physicians and medical researchers with cancer over the centuries, to examining the mysteries of the cellular nature of cancer itself and what really goes on in there, to the pro and con impact of this never ending plague on the spirit of the individual human and on our race as a whole, to peering into a crystal ball for a glance of cancer's and our future together. While doing all of this the alchemy of Mukherjee's writing continually turns science into poetry and poetry into science."
"Simply put, it is so good, and so incandescently clear and lucid, and so powerful, and so engrossing, and so easily consumed that you will not lay it down without someone or circumstances forcing you to."
"Had I read this book in my teens I would have found my life's career. I can only imagine that while you are reading this book, somewhere there will be some very young teenage girl or boy who will also be reading it at the same time you are, and who will become totally hooked by this book just as you will be, and who will go on to make a career in cancer research, a career that might provide the breakthrough that humanity has been searching and hoping for all of these many centuries. Thus, although you will never know it, you will have "been there" at the initial motivation of that person and thus indirectly present at the earliest genesis of the eventual great idea."
"This book has THAT potential. It is THAT good."
Tuesday, November 23, 2010
The end of the year holiday season is approaching and regardless of your religious affiliation (or lack thereof), you're probably going to have a little time on your hands for reading. Maybe relatives already are nagging you about what they can give you. Here I'll make a suggestion that won't break the bank and I can virtually guarantee you'll enjoy. ...but first I'll digress a bit, so stick with me.
Before medical research developed the tools to work more easily with dead/fixed human tissues, cell lines were a (THE?) major research tool of human biology, and they are still used for a wide variety of purposes. Anyone remotely familiar with tissue culture has heard of HeLa cells. I was first introduced to them in college in the 1970's. Although "immortalizing" cells to grow in culture is notoriously difficult and many cell lines have extremely complex growth requirements, HeLa cells are well known for their robustness. In fact, they are so easily grown that they often must be highly isolated from any other cell lines, or they will contaminate and "take over" other cell cultures. Stories relating to this are legendary in the cell culture lore. One told to me related to a cell line of a supposedly rare tumor sent to a US researcher from a lab in central Russia... you guessed it. They were HeLa cells. Others have noted that HeLa cells can be cultured from the countertop surfaces of labs that have been exposed to them. Amazing. HeLa cells have been into space. They have played pivotal roles in vaccine development and production, they have helped unlock the human genome and much, much more.
Most of us know that HeLa cells were derived from a squamous cell carcinoma of the cervix and many of us know that "HeLa" was derived from the patient's name. I was once told, erroneously, that the patient's name was Helen Lane. Of course, it was actually Henrietta Lacks, and she was an African American woman living in Baltimore who was treated at Johns Hopkins Hospital. The rest as the say, is history. But the history has never been properly chronicled until now.
In her first effort as a writer, Rebecca Skloot spent 10 years researching this story and has created an amazing book entitled "The Immortal Life of Henrietta Lacks." The book follows the discovery of all the fascinating details of Henrietta's life and cells, in part through the eyes of her younger daughter Deborah.
Jad Abumrad, host of the public radio show, "Radiolab" wrote an excellent review on the Amazon web site. The following are some excerpts from his review which may be read it its entirety here.
"Honestly, I can't imagine a better tale."
"A detective story that's at once mythically large and painfully intimate."
"But what's truly remarkable about Rebecca Skloot's book is that we also get the rest of the story, the part that could have easily remained hidden had she not spent ten years unearthing it: Who was Henrietta Lacks? How did she live? How she did die? Did her family know that she'd become, in some sense, immortal, and how did that affect them? These are crucial questions, because science should never forget the people who gave it life. And so, what unfolds is not only a reporting tour de force but also a very entertaining account of Henrietta, her ancestors, her cells and the scientists who grew them."
"Rebecca Skloot tells the story with great sensitivity, urgency and, in the end, damn fine writing. I highly recommend this book." --Jad Abumrad
.... and so do I
Tuesday, November 16, 2010
Authors often have a tendency to overstate the value of their findings and to produce articles which are far too long. Editor's have a natural tendency to accept shorter, well-written articles over longer, poorly written ones, and authors should keep this in mind. As a corollary, abbreviations should not be used as a substitute for tightly written prose. In fact, abbreviations should be used as little as possible. Authors need to have sympathy for their readers!
For the best example that I can imagine of "less is more" in the medical literature, I would refer you to the April 25, 1953 issue of Nature and a 1 page letter to the editor beginning on page 737. As you may have guessed, this letter describes in simple, understated terms, perhaps the most important biologic discovery of the 20th century. The first paragraph consists of a short two sentences:
"We wish to suggest a structure for the salt of deoxyribose nucleic acid (DNA). This structure has novel features which are of considerable biological interest."
What do the authors say about the significance of their discovery?
"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."
Now THAT'S understated (some have even called it "coy"). But the Nobel Prize committee still got the message.
Nature has an excellent web site honoring their most famous letter. I particularly recommend the article about Rosalind Franklin, who most certainly should have shared in the prize, though interestingly she remained close friends with Watson and Crick until her untimely death from ovarian cancer.
Wednesday, November 03, 2010
A recent article published in the October issue of "Nature Reviews Cancer" has been picked up at multiple lay press sites and on the news services. You may have already seen it, as well. In brief, two anthropologists failed to find any evidence of cancer in a review of a large series of mummies and on this basis they concluded that cancer was virtually entirely a man-made disease. This is an interesting but highly flawed premise from several perspectives, as has been pointed out by others in the lay press articles. One wonders about the medical background of the authors.
Quite a few obvious problems rapidly come to mind. First, cancer as a substantial cause of mortality is almost entirely a disease of older age. During the era in which the mummies studied lived, lifespan was extremely short. To live into your early 40's was quite an accomplishment. Our ancestors simply didn't live long enough for cancers to develop in any significant numbers.
Then there's the issue of detection. Many ( most? all?) mummies had their internal organs removed and preserved poorly or not at all. One can imagine that tumors of organs or soft tissues, not causing obvious bone destruction could be difficult or impossible to detect in many mummified specimens.
We know, increasingly, that many relatively common adult tumors such as colon, breast, ovarian, and pancreatic cancers, among others, have a substantial genetic component that almost certainly has existed for many thousands of years. From an evolutionary perspective, genetic defects, in this case oncogenes, that don't express themselves until much later in life when our offspring (ie. our DNA) have passed into independence have little or no evolutionary pressure against them. These genes lay dormant until lifespan increased enough for them to be expressed in significant numbers.
Finally, it is well known that there are many naturally occurring causes of cancer that existed long before the mummies in this study walked the earth. Viruses have been around a LONG time and an increasing number of them are well established causes of human cancers. Just to name a few: HPV, EBV, HHV8, and Hepatitis-B. Sunlight, asbestos, and many other naturally occurring agents are known to be carcinogens.
Even with the above serious issues, however, the study does raise some interesting points worth remembering. Most common and often fatal cancers DO have a significant man-made component. Before the advent of automated cigarette manufacturing, lung carcinomas were so rare as to be medical curiosities. Asbestos, though a natural mineral, did not become a significant cause of malignancies until the industrial age mandated its mining and manipulation into a wide variety of insulating products. Leukemias and thyroid carcinomas have been convincingly linked to radiation exposure from nuclear testing. Adjuvant hormone therapy (estrogens) has been strongly linked to uterine and breast carcinomas And the list goes on. In many of these cases there is probably an associated genetic predilection that on its own was not sufficient to cause malignancies to develop, but the environment was the critical factor.
If all this seems straightforward, it is. And these are the kinds of facts that anyone walking and breathing should probably know.... But if you want to get really depressed, read some of the blog comments on a couple of the lay press web sites regarding this article:
...unfortunately ignorance about basic medicine abounds. One writer in "The Week" expressed concerns about the article, " Because it could lead people to worry more about "carcinogens in the air or chemicals in their food" than the lifestyle choices that actually can improve your health, says the Telegraph's Tom Chivers. "Smoking, obesity, alcohol, [and] exposure to the sun" are demonstrably bad for your health, and can lead to cancer. "We shouldn't let a few ancient Egyptian corpses" distract us from that."
Agreed!
Monday, October 25, 2010
In the interim since my initial comments on the Ipad, I've continued to find new uses, and the product has continued to mature, which is to say that its applications (Apps) have continued to mature and multiply!
It is important to keep in mind that the primary function of the Ipad is the viewing and manipulation of data. Inputting large amounts of data (text, etc) is not quite as easy as at a conventional desktop or laptop keyboard. Still, the Ipad keyboard in "landscape" mode is almost standard size and can be typed on relatively easily. Not having the tactile feel of the keys is the major limiting factor, at least for me. Fear not, however. If you want to write the great American novel, there are separate full-sized keyboards with BlueTooth linking to your Ipad.
One of my key requirement has been the ability to manipulate PowerPoint presentations with the Ipad. The updated Keynote software now allows not only the viewing of PowerPoint presentations, but also allows them to be edited and saved in PowerPoint format. I'm still not fully functional with this new upgrade, but it appears to do everything that I require.
There are now VGA adapter cords that allow PowerPoint presentations to be displayed on an LCD projector from an Ipad. I've seen these in action and they are quite impressive. This means that even if where you're going to talk doesn't have a laptop or PC, you can give the presentation entirely from your Ipad if you have a VGA cable and access to an LCD projector.
My two major dislikes with the Ipad remain the lack of a USB port to allow for easy data transfer with a flashdrive, and the lack of an "Explorer" equivalent to allow easy viewing of files and directory structure. The second I can live without. The first needs to be fixed ASAP in the next version. I know the reasoning for not including a USB port. Data can be stored online at "MobileMe" or similar sites, downloaded to the Ipad, manipulated, and uploaded back to the web storage site. This works fine if you've got a FAST internet connection but these don't always exist and even the fastest internet connection can't come close to a USB 2.0 port for data exchange and PowerPoint presentations that pathologists make have lots of images and are huge files!. It would be SO MUCH BETTER if you could edit your PowerPoint presentations on your Ipad, then quickly download them to a flashdrive for presentation on someone else's hardware at a meeting.
Still, it is clear that the Ipad and its competitors are not only here to stay, they are experiencing exponential user growth. Several other manufacturers are about to release Ipad equivalent computing tablets. Apple sold 3 million of these devices in the first month and projects 20 million units sold in the first year. In a recent survey 20% of physicians indicated that they owned an Ipad or planned to buy one within the next year. These devices will ultimately replace many desktop and laptop computers.
I've spent the last two days with journal editors from around the world at a meeting in Chicago sponsored by Lippincott - Williams & Wilkins. The main purpose of this meeting was to explore the future of medical publishing, and one of the crystal clear conclusions is that electronic computing tablets and other even more mobile devices like smartphones are the wave of the future. You can expect more and more Apps designed to bring medical literature to your Smartphone or Ipad as simply and seamlessly as possible. The first "wave" of electronic media access was predominantly based on the CDrom, the second wave is the internet via Internet Explorer, Safari, or similar web browsers, the third wave, which is already well underway, will be tailor-made Apps that allow the user of a PC, tablet computer, or smartphone to quickly and easily download information. Although these Apps use the internet, they free the user from the often tedious keystrokes necessary to get the browser interface to do what you want.
Sent from my iPad! :-)
Thursday, October 14, 2010
It could be argued that surgical pathologists have two primary and related roles, first to provide a diagnosis and, second, when appropriate as with malignancies, to supplement that diagnosis with therapeutically useful prognostic information. The two are closely related since a diagnosis, in and of itself, often conveys considerable prognostic information. No one would consider making a diagnosis of cutaneous malignant melanoma without providing information regarding depth, growth phase, and signs of regression. To this list we now increasingly requested to provide information regarding BRAF mutation status as this appears to impact the value of a new treatment modality. It is clear that just as with Her2/neu status for breast cancer, an increasing number of clinically (therapeutically) relevant markers is likely to become available and ultimately gain "standard of care" status. This is a good thing and pathologists should embrace their expanding role in studying molecular and protein markers of demonstrated therapeutic value.
Unfortunately, for every molecular or protein prognostic study that ultimately gives rise to a new treatment, there are thousands (probably tens of thousands!) that do not. Indeed, if we are to judge by the submissions sent to Am. J. Surg. Pathol., prognostic studies greatly outnumber diagnostic studies, and yet the vast majority of these are destined to have very limited or no clinical relevance. A few undoubtedly will and the editorial boards and editors around the world try to decide which are which. But most prognostic marker studies, even those published in prestigious journals, are destined to fade into obscurity. Why are there so many of them? Is diagnosis so easy that diagnostic studies are no longer "cutting edge" and no one is interested in pursuing them? I seriously doubt it. The reason, I suspect, is that prognostic studies are incredibly easy to do. If one has a well-characterized patient population "immortalized" in a tissue microarray, then it can be subjected to an almost limitless number of protein prognostic studies using immunohistochemistry. A similar approach can be applied to molecular/gene studies.
Cells are filled with hundreds of proteins, derived from their corresponding genes. After neoplastic transformation there are only three options for each of these, they are either under expressed, over expressed, or expressed at the same level as in their non-neoplastic counterpart cells. Each of these proteins/genes is being subjected to study for prognostic significance in multiple tumor systems and the results dutifully submitted for publication. The result is a very low signal-to-noise ratio in the current medical literature. If the marker is over expressed, it is often touted as a potential therapeutic target, even though in almost all instances the over expression is much more likely to be an epiphenomenon, far down stream from a more critical genetic derangement. In addition, the marker studied may be so commonly expressed in normal cells throughout the body that any targeted therapy is likely to have serious or fatal side effects. These thoughts seldom seem to enter the authors' minds, however, as such studies almost invariably end with statements that alterations in the expression of this protein/gene are undoubtedly pivotal in the development of neoplasm X and targeted therapy directed against the protein in question will undoubtedly be of therapeutic value in the treatment of neoplasm X. Every author wants to score a "Gleevec cures GIST," home run but such results are rare.
There are often many more problems with such prognostic studies. The protein-based studies often depend on quantitative immunhistochemical evaluations, an extremely difficult endeavor filled with many pitfalls relating to tissue fixation, processing, etc. Reproducing such studies is notoriously difficult, as witnessed by the well-known problems with Her2 immunohistochemical assays. In many instances the prognostic effect shown is very slight and of no clinical significance on a case by case basis. When prognostic effect is shown, is it simply a surrogate marker for a more traditional prognostic factor such as tumor grade or stage? Multivariate analysis must be a part of any such evaluation, but the trick here is to be certain that ALL other known prognostic factors are considered along with the marker under evaluation. Most studies lack sufficient numbers to produce these large multivariate analyses and instead a few but by no means all other prognostic factors are considered in the analysis.
None of this is meant to imply that protein/gene prognostic studies are a bad thing, per se, but rather that the data derived from most of them is likely to have little or no value in routine clinical practice and therefore is unlikely to be of interest to the average surgical pathologist, almost all of whom would rather read about how to diagnose a problematic variant of neoplasm X.
Wednesday, October 06, 2010
Pathologists have been accused of having a food fixation when it comes to many of our descriptive terms such as "nutmeg liver," "strawberry gallbladder," "bread and butter pericarditis," "oat cell carcinoma," "coffee bean nuclei," etc. Nonetheless, these descriptive terms do an excellent job of conveying their intended meaning and they've hung around for a long time.
However, some of our nomenclature over the years has been decidedly wrong headed, and although many of these bad terms have fallen by the wayside, many are still around. As examples of bad diagnostic terminology that has almost completely disappeared, I would offer the following examples:
1. Benign fibrous mesothelioma. They're fibrous, usually but not always benign, but they have nothing to do with mesothelium. It's better to call them solitary fibrous tumors.
2. Intravascular bronchioloalveolar tumor (IVBAT) and sclerosing epithelioid cholangiocarcoma. Wrong on both counts. These are both now known to be epithelioid hemangioendotheliomas.
3. Malignant angioendotheliomatosis. Contrary to initial belief these are not tumors of endothelial cells, they're intravascular lymphomas.
4. Leiomyoblastoma. We now know that these gastric tumors are better interpreted as GIST's.
5. Minute pulmonary chemodectomas. These aren't paragangliomas, they're meningothelial-like nodules.
There are other terms that we all know are bad and are decreasing in usage, but they still manage to hang on by the weight of their accumulated literature and the information they convey to clinicians. I few more examples from this group:
1. Malignant fibrous histiocytoma. We got the malignant part right, but they're seldom very fibrous and have nothing to do with histiocytes, though they may occasionally stain for CD68. This is the default pattern for high-grade sarcoma. The much better term of "undifferentiated pleomorphic sarcoma" should replace MFH ASAP.
2. Lymphoepithelioma. When this term was developed both the epithelial and lymphoid components were thought to be malignant. Undifferentiated carcinoma, lymphoepithelioma type, is a better term.
3. Hemangiopericytoma. Sorry Dr. Stout, but most things called this are solitary fibrous tumors or perhaps malignant tumors (ie. synovial sarcoma, mesenchymal chondrosarcoma, etc.) with a non-specific pericytic pattern. Tumors with true pericytic differentiation, encountered mainly in the head and neck, should be termed "glomangiopericytomas."
And finally, there are those truly awful designations that still keep popping up in pathology reports and the literature, and show no signs of dying out. A few examples from this group include:
1. Pyogenic granuloma. Wrong on both counts. These are not pyogenic and not granulomatous. This term gets used for two unrelated lesions, granulation tissue, and lobular capillary hemangioma.
2. Synovial sarcoma. This one isn't going anywhere, but we all know the tumor has absolutely NOTHING to do with synovium, though vanishingly rare intra-articular examples have been reported.
3. Nodular fasciitis and other forms of fasciitis. Not a terribly bad term but in spite of the "itis" designation, this is not an infectious or a primarily inflammatory process, at least in the conventional sense.
4. Carcinoma in-situ. Is it really carcinoma if it's still in-situ and incapable of spreading? ..nuff said. This one has gotten us into lots of trouble and continues to do so. See our earlier breast cancer discussions.
These lists are but the mearest appetizers of the bad terminology that has gone, is fading, and is still in constant use in our world. I invite and encourage you to submit your own "favorite" bad pathology term in the comments section below, with a brief description of why it's a bad one. Since the comments are moderated it may take up to a day to see your posting appear on the blog and some minor editing may be done before acceptance.
Wednesday, September 29, 2010
It's always exciting when our understanding regarding some aspect of medicine or pathology undergoes a radical change. When I was an undergraduate science student, I don't think my professors, who were otherwise excellent, did as good a job as they could have at listing the questions that remained to be answered or areas in which our thinking might radically change in science. So it is with pathology. Our trainees are apt to think that all of the "good stuff" has already been discovered and cataloged. This is far from the case. The reality is that we don't know what we don't know and, in addition, we don't know what we know incorrectly.
For generations gastric ulcers were absolutely "known" to be due to excess gastric acid secretion and a variety of surgical procedures were developed to decrease acid secretion and increase gastric emptying. These procedures were variably successful. Then two Australians, Robin Warren, a pathologist, and Barry Marshall, a young gastroenterologist, turned the medical world upside down by convincing even the skeptics (and there were many) that gastric ulcers were an infectious disease. They were justly awarded a Nobel prize for this work, one of the very few involving a pathologist. Today we all observe Helicobactor pylorii organisms in gastric biopsies. They were always there, waiting for their significance to be discovered, and greatly rewarding those who made the mental leap.
Most of the time, unfortunately, changes in treatment are slow in coming after radical changes in understanding. For generations surgeons "knew" that cancer spread by tiny fingers of tumor growing out from the main tumor mass (cancer -> the crab), and the way to cure the disease was with locally radical surgery. Breast cancer, regardless of tumor size, was treated by the Halsted radical mastectomy with removal of chest wall musculature, soft tissue sarcomas, even small ones, were treated by amputations, etc. With time it became clear that cancers could spread by direct extension but the development of embolic lymphovascular metastases was typically the life threatening factor and these metastases often occurred before the primary tumor was even detected. Local cancer resections became more limited and tailored to individual tumor locations and size. Yet, it took decades for this change to come about and even now it is not complete. Witness the huge local resections still typically done for cutaneous malignant melanomas, yet, with the exception of a few variants such as desmoplastic melanoma, local control never has been the issue with this disease.
For years, we pathologists all "knew" that pseudomyxoma peritoneii (aka "jelly belly") developed from low-grade ovarian mucinous neoplasms. Only in the last decade or so has it become clear that the vast majority of low-grade mucinous tumors involving the ovary and the peritoneum arise from the appendix (who would have guessed!). Yet we still receive ovarian resection specimens for mucinous neoplasms where the surgeon has not removed the appendix.
Within the past several years pathologists have been overturning another "truth" of ovarian pathology, that serous ovarian carcinomas arise from ovarian surface inclusions. It is becoming increasingly clear that most (?almost all) high-grade ovarian and peritoneal serous carcinomas in fact arise from the fallopian tube, particularly the fimbrae of the tube. In the current Featured Articles section of Pathology Network is an article from AJSP posing the question, "Are all pelvic (nonuterine) serous carcinomas of tubal origin?" The data are becoming overwhelming. One wonders how long it will be, though, before gynecologic surgeons leave the ovaries in place and remove only the fallopian tubes prophylactically when doing hysterectomies for non-ovarian pathology in pre-menopausal women.
....and from where will the next big shift in thinking come?
Wednesday, September 22, 2010
The recent New York Times article regarding an error in breast cancer diagnosis, commented upon in several of my earlier blogs, continues to draw attention to the poorly understood fields of pathology and cancer biology. Quite a few of you have commented to me privately about the issues involved and you also should feel free to post comments here.
Dr. Diane Schecter, a pathologist in White Plains, NY, has tried to formally respond to the New York Times article in several venues, as of yet without success. This is unfortunate as a number of the issues in the article clearly need clarification or refutation. She has written an Op Ed piece which I sincerely hope finds publication in the NYT, but even if it doesn't she has allowed me to share it here. It is an excellent summary of who we are, what we try to do and the problems created by bad nomenclature leading to bad medicine.
***************
Although this op-ed is obviously in response to your front page piece "Prone to Error: Earliest Steps to Find Cancer" by Stephanie Saul, it provides information and and opinions that deserve to be heard. I am a surgical pathologist with 25 years experience. I attended Cornell University Medical College followed by seven years of residency in surgical pathology. Women need to know this.
To the Op-Ed Editor:
Although I do not believe the op-ed page of the New York Times is the most appropriate forum for a discussion of the complex issue of pre-cancerous breast lesions, recent negative press directed at general surgical pathologists compels me to make my voice heard. And the lack of an adequate response from leading pathology organizations has added to my determination to clarify several issues for the public.
First, some basic facts: Pathologists are physicians who render diagnoses based on microscopic examination of cells and tissues. It is the pathologist, not a surgeon or oncologist, who performs this vital task. A pathlogist attends medical school, followed by at least four years of residency. For most cancers, a patient's diagnosis is based largely on the pathologist's findings.
With the advent of mammography, pre-cancerous lesions of the breast became an increasingly important category of breast pathology. Ductal lesions can roughly be categorized along a continuum from duct hyperplasia (benign) through atypical duct hyperplasia (ADH - a borderline lesion) to ductal carcinoma in situ ( DCIS, a cancer confined to the breast ducts, meaning it is not invasive.) Seems straightforward right? In practice it is not. That is the truth, although it is uncomfortable for both patients and surgeons to accept. Yes, many cases are straightforward, but many are not. In this, the work of the pathologist does not differ from that of colleagues in clincal medicine. A pathologist's diagnosis is based on knowledge and experience applied to a specific patient.
Numerous studies have shown that even the most experienced pathology experts disagree on the diagnosis of pre-cancerous breast lesions in a significant proportion of cases. Yet, the medical community continues to treat these lesions as totally distinct entities with radically different therapies. Too little attention has been paid to the controversy over how some of these borderline breast lesions should be treated and the suggestion by some that they are over treated. Currently, ADH and low-grade DCIS are treated in radically different ways. Clinical medicine needs to accept the reality of grey-zone (borderline) diagnoses and modify therapy accordingly. This is an aspect of breast cancer care that the public needs to know about and which, ultimately, is much more important than any erroneous perception of pathologist "error."
Meanwhile, surgeons need to explain to patients the continuum concept and emphasize that pre-cancerous lesions are just that: they are not invasive cancer. There is a pervasive hysteria and panic in this country about breast cancer that is fueled in part by advocacy groups. This hysteria has found its way to patients with pre-cancerous lesions as well. This hysteria is harmful to patients. Surgeons need to send their cases to pathologists they trust, based on experience, and they need to communicate that trust to their patients. Patients should be encouraged to speak to their pathologists if there are questions not answered by their surgeons. Pathologists need to be more visable and accessible.
It is not my intention to deny that occasionally pathology mistakes are made. But the insinuation that pathologists regularly misdiagnose pre-cancerous breast lesions is unfounded. There are scattered studies, some by individual pathologists, indicating "misdiagnoses" and others indicating differences of opinion. Other studies indicate a high level of agreement when breast cases are reviewed. Heresay, "personal communications" and "estimates" of error rates are not the way medicine is evaluated.
Pathologists are not known to be an outspoken group. In fact, they are so quiet most patients do not even know they exist. But everyone has their limit. And this was mine.
Diane J. Schecter, M.D.
Staff Pathologist
White Plains Hospital Medical Center
White Plains, New York
Thursday, September 16, 2010
A residency in any specialty is an apprenticeship, also known as on the job training. This form of learning began in the middle ages. It worked well then and it works well today, but it requires discipline and determination on the part of the resident to maximally benefit from this system. When I was a resident, formal hour-long didactic lectures were almost non-existent, and confined to talks given by occasional visiting professors. Most quasi-formal teaching was based on unknown slide conferences. Multi-headed scopes were new to the scene and many attendings did not have them. It's hard to imagine how learning could take place in that environment and yet it did. Often the attending would move aside to let you see some feature, or mark an interesting area of a slide for you to study on your own. In this environment it was painfully obvious that you were almost entirely responsible for your own education and you had to develop your own formalized self-study program if you were to have a hope of succeeding. My colleagues and I read textbooks and the latest pathology journals cover to cover, in addition to doing directed reading about our interesting cases.
The situation today is different. Although the general format of a residency is the same, there are now many more formal didactic lectures and mini-lectures, in addition to the more traditional unknow slide conferences. Every attending has a double-headed microscope and, as much as the time pressure and case volume will allow, one on one teaching is rendered during signout. In short, the resident today is exposed, passively, to much more information than 30 years ago, and of course there is MUCH MORE to learn. All in all these are very good changes, and I would certainly not advocate a return to the not so good old days. In this new environment, however, it is tempting to think that simply going through the daily motions of a residency will lead to the osmotic absorption of sufficient knowledge. If "sufficient" is defined as "enough to pass the boards," this approach often, but not invariably, works, but if "sufficient" is more appropriately defined as everything you need to know to be a well-trained entry level pathologist ready to embark on a life-long career of continued self-directed educational growth, the answer is emphatically NO. Study habits, good or bad, internalized during this critical time in training are likely to carry through for the rest of your career.
So what words of advice do my colleagues and I try to impart to our new first year residents in anatomic pathology? First, a residency passes by extremely quickly, so hit the ground running. You can't recognize abnormal if you don't know normal histology and since medical schools today greatly downplay (or eliminate) learning histology, most residents are totally unprepared in this regard. Although I'm obviously biased, Histology for Pathologists is a "must read" for new residents and it should be read in its entirety. There isn't an alternative currently available to this text. Second, all residents need to buy and systematically read a textbook of surgical pathology. Although again I'm obviously biased toward Diagnostic Surgical Pathology, there are several good choices here, so pick one and have at it, reading at least a couple of chapters a week. These texts should also be consulted for directed readings during review of cases prior to signout. Learning and retention are maximized when you have a concrete case in hand to go with the textbook descriptions. Perhaps most importantly, residents need to develop the habit of keeping up with the current pathology literature. Whether they elect to subscribe to journals and get paper copies, my personal preference due to my age, or to review journals on-line with their own subscriptions or through hospital-based subscriptions such as Ovid, they should at least read the Abstracts of the monthly articles in the diagnostically based pathology journals (guess my bias here!). The Pathology Network on-line service, of which this blog is a component, is an excellent source of up-to-date on-line pathology information, including excellent review articles. It is particularly valuable for those without adequate time to review library sources or those in private practice without library-based on-line subscriptions.
Come earlier and stay later. Although the ACGME puts strict guidelines on the amount of time that residents can spend "on service," this does not apply to time spent in self-study. Virtually all pathology departments today have computerized systems allowing easy retrieval of slides for review by diagnosis. Make good use of this resource. After you've signed out a case of a testicular seminoma, for example, retrieve some other testicular or ovarian germ cell tumors to review for comparison. A single glass slide is packed with thousands of times more visual information than a single photograph in a textbook.
Anatomic pathology residents today need to know several orders of magnitude more than their generational predecessors. When confronted with this vast volume of material it is easy to be confused, disheartened, and perhaps give up on a systematic approach to self-study. Please don't! Many residency programs provide study guides, learning objectives, and study slide sets to help guide you along the path. If your program doesn't have such formal aids, seek guidance from your program director or appropriate faculty. They are there to help but in the end, you must shoulder the responsibility for your own education. It's part of what defines a professional.
Wednesday, September 08, 2010
I suspect that we would all agree that most of the world is woefully lacking in an understanding of basic scientific facts. Feel free to blame the educational systems, parents, teachers, the students themselves, etc. It could be argued that if you're not headed for a scientific career you don't need to know Newton's laws of motion or whether amino acids are right- or left-handed. However, regardless of what you end up doing with your life, everyone should have a basic understanding of how science works. By that I mean how scientists make observations, develop an hypothesis, devise logical experiments to test that hypothesis, and accept, modify, or reject their initial theory on the basis of the results. An understanding of the scientific method and the logic behind it would stand everyone in good stead as they are barraged daily with all sorts of hyped and overtly false claims from the "snake oil" sellers in the world around us.
In short, we are surrounded by bad science or non-science masquerading as science and when the world believes this foolishness bad things can happen. And because the media is full of folks who have ABSOLUTELY no understanding of science, pseudoscience and real science are often equated. So we are told that the mercury based preservative in vaccines causes autism and millions of children go unvaccinated, unnecessarily catching and spreading measles, mumps, whooping cough, etc. and occasionally dying totally unnecessarily. Famous misinformed people such as Robert F. Kennedy Jr, hop on the bandwagon and then the lawyers become involved, suing the vaccine manufacturers, delaying and increasing the cost of vaccine production and everyone suffers as a result. And all of this hysteria might have been avoidable if only logical, sane, scientifically grounded folks had taken a look at the (non)data on which these claims were based. But then again it might not (see my last paragraph below). There are, of course, many many more examples of bad or non-science being passed off as sound results. The homeopathic medicine culture and the cosmetics industry are particularly fertile grounds in this regard.
If any of the above is of even slight interest, then I strongly recommend the paperback book, "Bad Science" by Ben Goldacre (HarperCollinsPublishers, 2008). Mr. Goldacre is a British MD who writes a column in the Guardian newspaper by the same title as his book. This is an outstanding discussion of quackery that masquerades as science in the world today. A few chapter titles, with brief comments from me may entice you a bit more:
"Homeopathy"
The dilutional factor is so great that if one molecule of the original substance remains, the total volume would be greater than the volume of the known universe. Homeopathy is a huge tribute to the placebo effect.
"The Placebo Effect"
We all know something about this, but NOBODY fully understands it. Dr. Goldacre gives an incredibly lucid description including some truly mystifying psychological and physiological aspects of this effect.
"Is Mainstream Medicine Evil?"
Evidence-based medicine has done nearly miraculous things to improve and prolong life but the alternative medicine cult needs a scapegoat and we're it.
"Why Clever People Sometimes say Stupid Things"
"The real purpose of the scientific method is to make sure that nature hasn't mislead you into thinking you know something that you actually don't know." To phrase it more simply, the human mind sees patterns in chaos where patterns don't really exist.
"Health Scares" and "The Media's MMR Hoax"
MRSA, vaccines, preservatives, truly bad data, hype, etc... It's all laid out for the reader in fascinating detail.
In summary, this book is about thinking logically, skeptically, and applying the scientific method, but don't be surprised if you can't alter a "non-believer's" opinion with the facts. To quote the author, "You cannot reason people out of positions they didn't reason themselves into."
Tuesday, August 31, 2010
The short answer to the question posed in the title is yes, but probably much more rarely than most physicians think. Most general practicioners ask about a family history of prostate cancer and use that information as an important factor to help decide whether a patient should or should not have a serum PSA level drawn, which may, of course, lead to subsequent biopsies. Their reasoning is based on a number of studies showing an apparently rather strong genetic association for prostate cancer, particularly between male siblings (approximately 3-fold increased risk).
An article published in the August 19th issue of the JNCI entitled, "Effects of Prostate-Specific Antigen Testing on Familial Prostate Cancer Risk Estimates" calls this association into question and indicates that much of the presumed increased risk may simply be due to patient (and physician) concerns leading to increased PSA testing in brothers of patients diagnosed with prostate cancer. This, in turn, leads to increased biopsy diagnosis of small T1c tumors that are VERY prevalent in older males and would otherwise go undetected. Many (most) of these tumors were likely to be clinically insignificant as well. This article is discussed in some detail in a recent Medscape review. You may need to create a free account to see this or try doing a Google search for "familial prostate cancer" and you may be able to get to it without a log-in. This is a sobering example of the inherent problems with case-control studies and the need to control for every possible variable. In this instance, failure to control for rate of PSA screening led to grossly inflated risk estimates. In short, sometimes we get it wrong in spite of the best intentions. In a future blog, I'm going to discuss a fascinating book entitled, "Bad Science" by British physician Ben Goldacre that deals with unintentional and intentionally bad science in today's world. If you're interested, it's a great read... but more on that later.
Tuesday, August 24, 2010
First, a confession. I'm not a Mac-o-phile. I use a PC at home and in my office, and I've written a fair number of software programs for the PC Windows environment. Nonetheless, I much admire Steve Jobs' style and the cult-like following his products have engendered. I have an Iphone 4, and I consider it one of the finest bits of technology that I've ever seen. The fuss about the antenna on the Iphone 4 is grossly over-hyped. The number of applications (Apps) is mind boggling and continues to grow daily. If you can tolerate the small screen and keyboard necessary to make this a pocket item, there's almost nothing you cannot do with it. For example, by installing the University's VPN client, I can signout my surgical pathology reports over my Iphone. I won't deal with the merits and failures of ATT's cellphone system, but rumor has it that Verizon will also get the Iphone after the first of the year.
Against this background, I thought that I'd give the Ipad a try. Overall the experience has been a positive one and it continues to impress me daily as new Apps appear, but it doesn't have the "gee whiz" factor of the Iphone. If you're thinking about getting an Ipad, keep in mind that this is NOT a laptop computer. You can get a quite nice, though probably slightly larger laptop for what you'll pay for an Ipad. If you want/need a laptop, get one instead.
My goal was to get enough functionality on the Ipad that I did not have to take my trusty (and now rather ancient) laptop with me on my travels. That meant, first, the ability to check my e-mails and respond as needed. The Ipad handles this extremely well. The much larger keyboard than the Iphone's makes typing almost as easy as on a standard keyboard and e-mail responses, even lengthy ones, are easily handled. Second, I needed internet access to handle my editorial duties for AJSP and Path Network. The Safari web browser on the Ipad is extremely fast. Unfortunately, though, the Ipad and Iphone do not support "Flash" plug-ins, and Editorial Manager uses a Flash plug-in to "assemble" a manuscript from the cover letter, text, figures, and tables. This is at most an inconvenience as each of the components can be downloaded separately for viewing. Alternately, using a "thin client" and a VPN connection, I can connect to a Windows server here at U.Va. and create a "virtual PC" window on the Ipad. This is only a little slower than a direct connection. At the moment, methods of moving around in the virtual PC window are not as easy as I would like, but these Apps are improving daily. Using the thin client connection I can, as with the Iphone, signout my pathology reports with the Ipad and doing so is much easier on the larger screen.
Another major requirement was the ability to view and ideally edit my PowerPoint presentations on the Ipad. Currently, there is no true PowerPoint App for the Ipad/Iphone. There are, however, excellent PowerPoint viewers which allow one to review PowerPoint presentations (the images look fantastic on the Ipad screen), but they cannot be edited and exported as a PowerPoint presentation. Not ideal, but not a major problem and with luck a full function PowerPoint App will eventually appear. Though I have not done it yet, I'm told that there is also the ability to connect the Ipad output to a video projector, and run your PowerPoint talks directly from the Ipad. This requires a separte interface cord.
So with just a little bit of effort, I got the Ipad up to speed for my major out of town requirements and it is considerably smaller and has a much higher resolution screen than my trusty old laptop. Of course, the Ipad excels at tasks like displaying YouTube or Netflix videos and it is very simple to download one of these and view it in lieu of the inflight movie when you're travelling. All the music functionality of the Iphone is also present on the Ipad and it's simple to synchronize between the two.
Here are a few of the downsides that I don't see and would like to.
1. Data/file transfer. The Ipad could REALLY use a USB port or a card port such that files could easily be transferred to/from the Ipad with a USB thumbdrive or data card. Instead, files need to be loaded to a server site like "MobileMe" and then downloaded from there with appropriate software onto the Ipad.
2. No directory structure. The Ipad doesn't have a classic directory system and there's no equivalent to Windows Explorer to see what files are present. I really miss this feature. It would be fantastic to be able to scroll through the directory, click on a file, and have the appropriate software open it. In fairness, there are ways around this that generally involve starting a software App first, then having it list the available files to be opened.
3. No case. I hate to be a whiner, but for what an Ipad costs, Apple should throw in a case! This thing really has to have one for protection of the screen.
The Ipad can be thought of as a large Iphone, minus the phone, or as a hybrid between a laptop and an Iphone. Like all hybrids, its somewhat nebulous existence between two worlds makes its longevity questionable. As Iphones get faster and faster processors, might the Ipad simply be replaced with an "Iscreen" and keyboard that your Iphone connects to, giving you all of the functionality of the Ipad, without the added cost of a separate processor, memory, etc? Makes sense to me!
Tuesday, August 17, 2010
I've asked Dr. Raymond Sobel, Professor of Pathology at Stanford University and editor-in-chief of the journal containing the article to post a guest blog on this topic. Thanks for doing this, Ray!
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Motor neuron disease (ALS, Lou Gehrig’s disease) is a fatal progressive degeneration of motor neurons in brain and spinal cord. Some 90-95% of ALS cases are sporadic; some familial forms are associated with a variety of gene mutations.
Although the etiology of sporadic ALS is unknown, it has long been suspected to involve interactions between genetic and environmental risk factors. CNS trauma has been one of the strongest and most consistent contenders for initiating the molecular cascades that result in ALS.
Previous studies, particularly on Gulf War and other military combat veterans, Italian professional soccer players and US professional football players, suggest an association between head injury and ALS.
Repetitive head injury is associated with the development of chronic traumatic encephalopathy (CTE), a progressive tauopathy clinically associated with behavioral and personality changes, parkinsonism, and dementia and characterized by neurofibrillary tangles throughout the brain in the relative absence of β-amyloid deposits.
Last year, Ann McKee and her colleagues at the Center for the Study of Traumatic Encephalopathy at the Bedford VA and Boston University School of Medicine reported their findings of tau and TDP-43 in the brains of professional athletes who had had repeated concussions and had developed CTE. This is essentially a newly characterized disease.
In a paper published on-line on August 17 in the Journal of Neuropathology and Experimental Neurology, McKee et al report their study of 12 cases of CTE in which they found widespread TDP-43 proteinopathy in the brain. In addition, 3 of the athletes with CTE had also developed progressive motor neuron disease prior to death. In those cases, there were abundant TDP-43+ inclusions and neurites in the spinal cord, tau neurofibrillary changes, motor neuron loss, and corticospinal tract degeneration, i.e. the major pathological features of ALS.
This is the first pathological evidence that the repetitive head trauma experienced in collision sports might be associated with the development of a motor neuron disease in some individuals.
The study is important because it could partly explain the association of ALS with head injury and because it provides a clue to the pathogenesis of some cases of ALS.
It has attracted considerable media interest, particularly in the US and Europe, because of the implications for professional and non-professional collision sports and military combat. People who experience repetitive, seemingly mild, head injury or concussion might be at risk for developing a brain disease later in life.
The study demonstrates how autopsy examination can elucidate the pathogenesis of major neurological diseases such as ALS, Alzheimer and Parkinson diseases. We can only advance research in these diseases by learning from this type of study. Further work is necessary for confirmation and for investigating mechanisms that may lead to the development of therapies and prevention of ALS.
The full-text of the article is available on the Journal of Neuropathology and Experimental Neurology website at www.jneuropath.com
Raymond A. Sobel, MD
Professor of Pathology
Stanford University School of Medicine
Friday, August 06, 2010
There are an infinite number of ways to divide any population into two or more groups. Some may be modestly useful, most are not, and all are subject to often large exceptions. Nonetheless, one perhaps thought- provoking way to think about surgical pathologists is to consider whether they (or you) are primarily "morphocentric" or "clinicocentric."
First there are those for whom the recognition of a subtle microscopic pattern brings great gratification and, in and of itself, provides the major source of enjoyment from being a pathologist. These are the "morphocentric" pathologists. Experts with this tendancy are often "splitters" and have defined many of the entities that we recognize today. We owe them a great deal. They are often but not invariably found in academic institutions. In its heyday, the AFIP was a bastion for morphocentric pathologists, and a huge number of entities was "born" in that windowless building (bunker). Morphocentrists are not unaware of the clinical consequences of their pathologic discoveries, but the consequences may not always be fully considered or emphasized. Any consultant is removed to a degree from the patients supplying the diagnostic tissue, and the AFIP was a purely consultative service often far removed from the clinical results of its diagnoses. It has been argued that because of this and the fact that many cases seen at the AFIP were recurrent or otherwise problematic, there was a tendency to over emphasize aberrantly aggressive behavior leading to over labelling some entities as malignant. An example would be "well-differentiated liposarcoma of the extremities," a lesion now generally diagnosed as "atypical lipomatous tumor," and of course there are others. I don't mean to pick on the AFIP. Their contributions to pathology are beyond measure, but they are the best and largest example I can think of, of a collection of pure, or nearly pure morphocentric pathologists.
Historically many surgical pathologists began their careers as surgeons, internists, gynecologists or other clinicians who became enamored with pathology and switched careers but maintained their strong clinical ties. I'll call these "clinicocentric" pathologists. This was the norm in the infancy of surgical pathology, and the giants such as Stout, MacCarthy, Ackerman, and others who followed this path retained a strong clinical orientation. They were experts at morphology but their primary concern was always how the disease would behave and what would be the best course of treatment for the patient. They were attracted to surgical pathology because it is the pathology of the living and they enjoyed influencing patient care. They often had discussions at the microscope with the patient's surgeon. Mapping a course of action was more important than the words placed on the pathology report. Since few pathologists today begin their careers as clinicians, trainees with a built in clinical bias may be fewer in number, but this approach can still be taught and is taught in many programs today. If you enjoy discussing cases with your clinical colleagues, presenting cases at working tumor boards, etc., you may be a clinicocentric pathologist.
Whether you are morphocentric or clincocentric may affect the terminology you adopt to describe a new entity. "Carcinoma in-situ" is a distinctly morphocentric term because it acknowledges the morphologic identicality with invasive carcinoma, though ironically it was first used by Broders at the Mayo Clinic, a distinctly "clinicocentric" institution. Subsequently, howvever, other clinically oriented pathologists argued that this term was fraught with the potential for misunderstanding and carried the emotionally powerful designation of "carcinoma" for a non-metastasizing lesion. From this concern came the growing list of intraepithelial neoplasias, initially championed for the cervix by Ralph Richart, a gyncologist/gynecologic pathologist with a distinctly clinical "bent."
At the extreme, your "centricity" may color your diagnoses. In the early days of my training, my clinicocentric mentors would often discuss cases with the submitting clinicians while I was in attendance as the resident or fellow. If the case were borderline morphologically, a decision was often made based on which diagnosis was likely to do the patient the least harm. A true morphocentrist might never consider this approach. Thus, if the surgeon knew that the patient was an overt cancerphobic likely to demand overly aggressive therapy, a small focus of atypical glands/ducts in the prostate or breast was likely to be called "atypical" but not clearly malignant/in-situ, whereas such a "shading" of the diagnosis would not be required if the biopsy came from an 85-year-old patient not to be treated further, regardless of the terminology applied to the lesion. The same technique might also be applied when the surgeon was known to be overly aggressive! Today, this approach leaves you liable to being labeled by the "experts" as incompetant and and may leave you liable for much more when the lawyers come calling. Yet, which approach is ultimately better for the patient?
Wednesday, July 28, 2010
In the interim since last week's blog regarding the DCIS controversy in the New York Times, there has been a flury of activity in the pathology community on this topic, both with regard to the article's content and in particular to the CAP's unilateral decision to institute a certification program against the wishes of the American Board of Pathology (ABP) and virtually every other pathology society or organization in the United States. It should be emphasized that the ABP is the only officially recognized certifying agency for our specialty in this country. There's a reason why every medical specialty charters and recognizes one official certifying agency; it assures uniform quality and avoids the chaos of multiple, often competing "boutique" certifications. If an organization not chartered to provide recognized certifications develops a "voluntary certification program" likely to dramatically increase their revenues, is this a conflict of interest? Is the primary motivation educational, to improve patient care, or to enhance monetary gain? Likewise, if pathologists developing the certification program stand to materially increase their own consultation practices because of their leadership in the program and because only a relatively small number of pathologists is likely to meet their case load requirements, is this a conflict of interest? I encourage you to read this statement signed by officials of the USCAP, ASCP, ADASP, APC, and ASIP.
On my local level, the "patient requests second opinion" breast consults have increased in the last week and at least one of my departmental colleagues has received a call from a patient regarding her diagnosis of high-grade DCIS, to inquire if she were board certified and saw over 250 breast cases per year! ...gee, I wonder where the patient got that number from? To help deal with this situation we are in the process of developing an informational summary for patients detailing how our diagnostic breast service functions. In particular every breast biopsy with any atypical or malignant findings is always reviewed by at least two separate attendings (the primary pathologist and the attending reviewing cases for the breast tumor board), a resident and a board certified fellow in our gynecologic/breast fellowship. Borderline or otherwise problematic cases are frequently reviewed by several additional attendings to reach a consensus diagnosis.
In the July 21st issue of Newsweek a follow-up article approaches this topic in a somewhat more balanced fashion, though it also touts the CAP's certification program and emphasizes the need for more pathologists to be trained as breast cancer specialists. I would not argue with a request for more and better training and funding fellowships through philanthropies would always be appreciated. That's precisely how our gynecologic/breast fellowship exists at U.Va. However, neither article really gets to the fundamental issue of "gray zone" pathology and diagnoses of assertion without meaningful biologic behavioral differences to support the assertion. As one of my colleagues stated, "experts disagree but non-experts make errors."
Although I haven't seen the case described in the original New York Times article, the text certainly suggests that this was NOT a gray-zone case and represented a below standard-of-care error that was not likely to be made by any competent, ABP certified and reasonably experienced surgical pathologist. In that regard, I suspect that there's nothing particularly special about the fact that this was a breast case, and the hospital employing this pathologist might do well to have random cases from other organ systems in their files reviewed. The case also highlights the significant problem of solo practice. It's hard to imagine not being able to walk down the hall and share a problematic case with several colleagues. Even the best of us needs our colleague's expertise and continues to learn from them.
Wednesday, July 21, 2010
The July 19th issue of the New York Times contains an article that should be must reading for surgical pathologists. It deals with a woman who was originally diagnosed as having low-grade (solid, cribriform) DCIS of the breast and underwent a quadrantectomy and radiation therapy. Subsequent review changed the diagnosis to something less, presumably usual-type ductal hyperplasia.
The article deals in large part with the difficulties in diagnosing these low-grade in-situ lesions but suggests, or at least implies that the problem is largely one of expertise. Enter the College of American Pathologists with its highly controversial proposal for "voluntary" certification in breast pathology, and enter the federal government with a funded study on diagnosis of breast lesions, suggesting a 17% error rate for DCIS.
Few would deny that there are occasional inept pathologists out there and the pathologist in this case was not board certified at the time of this (mis)diagnosis, but the available data suggest that "experts" in breast pathology disagree with regard to these borderline in-situ lesions at almost the same rate as qualified community pathologists. It is true that education, well-articulated criteria and experience will help lower the error rate, but they will certainly not eliminate it. Indeed, defining "error" in these gray-zone cases may be difficult or impossible. I believe that the CAP's "voluntary certification" program is misdirected and will not solve the problem. Moreover, with help from lawyers and insurance companies it is likely to start us down the wrong road to multi-organ certification mandates.
To paraphrase my friend and colleague, Dr. Mark Stoler, the current president of the ASCP, although subspecialty education and more importantly second opinions can help minimize these diagnostic variations, education or certification will not eliminate them from the subspecialty of breast pathology or any other subspecialty. Rather, clinical medicine must understand and acknowledge the issues and realities of some borderline (subjective) pathologic diagnoses and modify their approaches to patient therapy that have diagnoses in these gray-zones. There is no biologic reason to believe that ADH and DCIS are distinctly different entities and, to put it plainly, the idea that clinicians should radically treat low-grade DCIS as opposed to ADH is just as much or more a part of the problem raised by the NY Times article than any perception of pathologist error.
We are of course at least partly responsible for this situation because we have given these two very closely related lesions, ADH and DCIS, such radically different names. Patients and reporters are often ill-equipped to distinguish carcinoma in-situ from any form of invasive carcinoma. The power of that word should never be under estimated, and we should have devised a more judicious term for these non-invasive, non-life-threatening but pre-cancerous lesions.
Wednesday, July 14, 2010
I'm more than a little reluctant to share this tale because it doesn't present my native intelligence in a very good light, but perhaps sharing this cautionary story will prevent other near or real disasters.
For about five years I have kept all of my pathology-related work on a single external 250 GB USB hard drive..... You can guess what's coming. A few weeks ago I noticed that it was taking longer than normal to access files on the drive... Sign #1 which I ignored. About a week after that I noticed that the drive was occasionally making a "clunking" sound when it powered down... .Sign #2 which I also ignored. Then, you guessed it, one Monday morning I powered it up and it wouldn't function at all. This drive contained every PowerPoint talk I've ever given, every digital photo I've ever taken, all the textbooks I've written and edited, including all the photos, and, importantly, everything relating to the upcoming 4th series AFIP fascicle on the Upper Aerodigestive Tract which is nearing completion. I had backups for some but probably less than 30% of this material and, in particular, I had no backup for the new ENT fascicle and several new talks that I had developed over the Spring. I worked in the construction industry to help put myself through college, and I acquired a robust vocabulary of curse words which I unleased explosively at the time, almost entirely directed at my stupidity rather than the hard drive's failure. I then began to feel really sick to my stomach.
It took several days to find out if I was to be saved, but fortunately, in this instance luck won out over stupid, and I was able to have all of my data retrieved thanks to a wonderful company in town that specializes in hard drive recovery at a VERY modest price. I would gladly have paid, much, MUCH more!
The moral of this story is simple. A hard drive is a mechanical device. It's not a question of IF it will fail, it's simply a matter of WHEN it will fail. If you don't have up-to-date backups, you'll be in trouble when this inevitably happens to you and luck may not win this time. Often the drive will give you warning signs before it fails completely. DON'T IGNORE THEM!
I replaced the defective hard drive with a RAID hard drive system running two 1 TB hard drives in parallel. In theory if one fails the data is safe on the other and the failed drive can be replaced. That's a first step to data safety, but it's really not sufficient. Off-site backup is really mandatory if you care about your data. If you're compulsive you can do this by methodically copying new files onto a USB "thumb drive," carrying them home and downloading them to a backup hard drive outside of your office. Sooner or later, though, you'll forget to do this, or worse, you'll get confused and replace the new data with an old file. A much better solution is an on-line, off-site automated backup system. These are relatively inexpensive and virtually guarantee data survival.
If a hard drive failure happens to you I hope you're better prepared than I was and, if you aren't, good luck! By all means, however, if you don't have backups search for a data recovery company. They have very sophisticated tools and may well be able to retrieve everything from your damaged hard drive, or at least much of the material. These are the same tools used to extract data from flight recorders after airplane crashes. If necessary, these folks will go as far as disassembling your hard drive in a clean room and installing the media in a new drive system. But expect to pay.
...and then there are viruses to worry about!
Tuesday, July 06, 2010
Pathology has a rich history invested by many famous characters, some still living and many, unfortunately, no longer with us. In the latter group are the likes of Stout, Ackerman, Lattes, Dahlin, Soule, Enzinger, Spjut, Bauer, Helwig, Castleman, and many, many others who were founders of our field and, in addition to being outstanding and highly productive pathologists were often extremely interesting and engaging individuals.
Quite a few years ago the A.P. Stout Society meeting included a presentation about Dr. Stout by several of his then aging trainees. Many of us in the audience hoped to hear about Dr. Stout, the person. What was he like? What were his outside interests? Did he have a sense of humor? What were his favorite sayings? What was it like to sign out with him? We were eager to hear from those who actually knew and worked with the legend and could "flesh out" his persona. What followed, however, was a detailed but impersonal recitation of the accomplishments of Dr. Stout the pathologist. This was information that could have been gleaned from a literature search by anyone without much difficulty. Most disappointing, and the opportunity is now lost forever.
I was fortunate in my early training to meet or at least hear many of the legends of pathology while they were still among us. I was especially fortunate to be able to spend a considerable amount of time with Dr. Lauren Ackerman during his multiple trips to Charlottesville to visit his former trainees, Drs. Tom Tillack, Robert Fechner, and Phil Feldman.
That Dr. Ackerman was one of the early greats of surgical pathology is undeniable, but I will not dwell on his many professional accomplishments in this area, except to say that I believe his greatest gift was not his amazing skill as a surgical pathologist and author, but his ability to recognize budding talent wherever he encountered it, attract it to St. Louis, nurture it and send it out upon the academic pathology world. This first generation of trainees includes such notables as Spjut, Rosai, Kempson, Dorfman, Fechner, Dehner, Bauer, McGavran, Saltzstein, Grisham, Askin, and multiple others who went on to become directors of surgical pathology and carry on the legacy. I know of no other pathologist of his or any other generation who had nearly so large an effect on the future of our field.
What follows are some comments about what Dr. Ackerman the person was like, as well as some anecdotes and "Ackermanisms," many of which will be well known to those who knew him far better than I did.
He loved wines (especially French Bordeaux), golf, fishing, travel, reading, and opera.
He didn't care about his honoraria for speaking, but he did require an excellent meal and the ability to select the wines with dinner. He was also known to occasionally select the other diners' entrees.
He had a fantastic memory, even in his 80's. I once saw him at a meeting after not seeing him for two years. He immediately remembered the conversation we had been having two years earlier. I had completely forgotten.
When he traveled he liked to carry a paperback to read, ripping out the chapters as he was done with them, and throwing them away until in the end there was nothing left.
He could be extremely charming but he did not suffer fools or those who he considered "false" or wasters of his time. Once, when an extremely well-known pathologist began fawning over him while he was chatting with another colleague and me, Dr. Ackerman turned abruptly while muttering that he needed to freshen his wine (the glass was quite full). He returned quickly when the "fawner" had departed, announcing that, "I detest that man, he exudes crap."
He had strong opinions about other pathologists and he was not opposed to expressing them. Some such as Dave Dahlin and Howard Dorfman, commanded his great respect. Those he did not respect often felt the sting of his often caustic wit.
His trainees revered him and, even when famous in their own right, virtually never referred to him by anything other than "Dr. Ackerman," at least in public. The approach of a visit from him was usually a cause for a panic-like response from his trainees to make certain that everything was in order and no residents said anything stupid or embarassing when he called on them to diagnose the cases he had sent ahead of his visit. The cases invariably consisted of a potpourri of amazing tumors, some from animals, and all extremely interesting.
He loved to look at cases. On a typical visit he would ask to spend an hour or so a day with several of us looking at slides we had collected to show him. When he liked a case, the slide would be placed on the left side of the scope. At the end of the session, the chosen slides would be ceremonially collected and placed in his shirt pocket. I once showed him a case that I thought was a parathyroid carcinoma. He looked carefully at the slide, shook his head and said, "I know why you say that because it's got the features that Castleman and Roth discuss in their fascicle, but I can tell you that nothing will ever happen to this patient." He was, of course, correct.
He had an excellent sense of humor and was not above telling slightly off color jokes, often with a golfing-related theme.
At a restaurant when he had for the third time asked for a specific bottle of wine, only to be told that the cellar was out of that selection, he announced to the wine steward, "This is the list of wines that you wish you had. Could you please bring me the list of wines that you actually have?"
He once visited our house and thoroughly charmed my wife and two young daughters (one of whom is now a resident in pathology). The daughters talked for many years afterward about "Dr. Lauren." They managed to get away with using his first name. On that visit, I served him the only wine we happened to have at the time, an acceptable but certainly not outstanding California chardonnay. With some trepidation, I asked him if the wine was OK. He sipped it, paused, smiled, and said politely, "It's wine."
He once received a consult which he diagnosed as "Spitz nevus." A few years later the contributing pathologist sent him a large lymph node metastasis with a note saying, "What do you think of your diagnosis now?" Ackerman simply penned across the contributor's letter, "Obviously, the same damned thing you do!" ...and immediately sent it back.
He had a deep and genuine concern for his trainees, and wanted them to be successful and happy in their personal lives. He stayed in close contact with many of them throughout his life. When one trainee contracted T.B. and had to spend time in a nearby sanitarium, Ackerman visited him on the weekends. Interestingly, Ackerman had also developed T.B. during a medicine residency, began looking at slides in the sanitarium and launched his career in pathology.
He embraced new technology readily, being an early proponent of electron microscopy and immunohistochemistry, but always placing them in proper perspective with the H&E-stained slide. He would no doubt also have embraced molecular diagnostics as well.
He was a big proponent of the afternoon nap, often dozing on the couch in his office, then waking and off the top of his head, dictating a chapter for his surgical pathology textbook.
One of his favorite anecdotes was "the man in Istanbul," which was meant to convey that you should be able to recognize a tumor in an odd location, just as you should recognize your next-door neighbor, even if you unexpectedly encountered him on the street in Istanbul.
Another of his favorites, meant to convey the value of clinical information, was known as "Napolean's bust." As I recall the story, he once encountered a rectal biopsy showing florid keratinizing squamous metaplasia and raising concern about carcinoma. Ackerman tracked the patient down to the psychiatric ward and determined that the patient was schizophrenic and his prized possession was a bronze bust of Napoleon which, for safe keeping, he stored in his rectum. The resulting effect of this longstanding action was the diffuse keratinizing squamous metaplasia seen on the biopsy.
Dr. Ackerman's powers of observation were extraordinary. At a departmental dinner party he sat next to my wife. We had two daughters at the time. He asked my wife if we were done having children and she said yes. He paused, looked at her for a second and said, "I think that you will have one more." Unknown to us she was, in fact, carrying an ectopic pregnancy that ruptured a week later.
Dr. Ackerman died in StonyBrook, Long Island, NY on July 1993 at the age of 88 years of a high-grade cecal adenocarcinoma that spread throughout the abdomen. I'm told that the tumor had neuroendocrine features, but I never saw it. It was discovered during the repair of an abdominal aortic aneurysm.
Further details about Drs. Ackerman, Stout and other notables of our field can be found in the excellent book, "Guiding the Surgeon's Hand. The History of American Surgical Pathology," edited by Juan Rosai.
Wednesday, June 23, 2010
I don't want this blog to turn into a series of negative rants, such that I come across as a grumpy old(er) man, but I will discuss one topic about which I and many of my colleagues feel strongly.
Having worked their way up from kindergarten, through grade school, and undergraduate programs, the expert educators (ie. Ed.D.s) of the world have now turned their sights on "improving" how medical schools teach medicine. Unfortunately, they seem to have convinced the deans and accrediting agencies of their expertise in this regard without any (as far as I can tell) outcomes analysis.
Like most of you, my first 24 months of medical school was the traditional specialty-directed approach with first year consisting of normal biochemistry, anatomy, histology, physiology, etc. The second year was devoted to disease, again in a specialty-directed format with courses in pathology, pharmacology, hematology, mechanisms of disease (internal medicine), etc. The backbone of each course was a series of 1-hour lectures, often followed by labs or tutorials in smaller groups. There was a huge amount of material that had to be mastered and in many instances just simply memorized. The lecture format is a tremendously efficient albeit passive way of imparting a large amount of information in a limited time and giving appropriate weight and context to the facts presented. Not long after I graduated, many medical schools switched to a more disease-oriented approach in which, for example, the normal anatomy, histology, and physiology of the liver, the pathology of its diseases, and the clinical features and treatment of those diseases were presented more or less together. This approach had much to recommend it and was still basically centered around the lecture format.
Now, however, the experts have decided that lecture-based learning is just too passive and medicine should be learned through directed discovery in which a small group of students, with a prior reading assignment and limited guidance from a faculty leader discuss topics together and discover the principles of medicine on their own. This would be an interesting and maybe even a beneficial approach IF medical school were a 5- or 6-year program. But this new approach is now frequently being combined with a reduction from 24 to 18 or fewer months of training in the fundamentals of medicine before ward rotations begin. This approach may be active but I believe that it is FAR, FAR too inefficient and unorganized to allow for meaningful training, especially when combined with an abbreviated schedule.
Although the lecture-based system for the first half of medical school training has worked well for generations, the accrediting agencies, as well as many medical school deans and their underlings, appear to have accepted the need for change and are mandating an "active self-discovery" approach to medical education with no evidence that this system will actually be an improvement. It won't be. The emperor has no clothes. And what wakes me up at night is the sobering fact that these haphazardly educated students, likely to know some things well and many things not at all, will be taking care of me in my old age..... and you too!
I promise my next blog will be positive, light-hearted, and maybe even humorous.
Monday, June 14, 2010
From time to time, I'll use of this forum to express my concerns with regard to some common and recurring mistakes, problems, or areas of at least fuzzy logic in pathology publications. A short, but by no means complete list might include such topics as, over-reaching interpretation of results, confusing association with causation, excessive abbreviations, and the apparently increasing difficulty in producing readable grammatically error-free manuscripts. I'll start with the flawed concept of determining cell of origin. This discussion will borrow heavily from an editorial that I published in Modern Pathology about 1995. In the intervening 15 years many have gotten the point, but some remain to be enlightened.
Pick up any journal dealing with human neoplasia, and you will often find comments that this or that cellular phenotypic feature provides insight into the cell of origin, ie. histogenesis, of a neoplasm. When the putative cell of origin is not a known constituent of the organ or tissue in question, the resultant intellectual machinations evoked to explain this deviant cell line can dwarf all other aspects of the publication.
The early version of the APUD cell theory was a prime offender in this regard. The concept that normal neuroendocrine cells must arise from neural crest precursors is simply not in keeping with more recent and more detailed observations. And if normal cells are not so constrained, than neoplastic ones certainly are not. Neoplastic cells have, unless lost through genetic aberration, a full complement of genetic information and part of their nature is the inappropriate derepression and expression of such information. The latter expression can be observed directly and tells us a great deal about what the cell is doing, but inferences about where the cell came from are just that...inferences. Witness in this regard the body of literature regarding aberrent expression of intermediate filaments in a wide variety of neoplasms. Several increasingly contentious examples of "histogenetic-morphogenetic" dissonance will further illustrate this point. Embryonal rhabdomyosarcomas unequivocally express skeletal muscle differentiation. Does this mean that they derive from pre-existent skeletal muscle. We would all, I hope, agree that this is highly unlikely, at least in adults where normal skeletal muscle is a fixed, post-mitotic cell population. In addition, rhabdomyosarcomas, clearly arise in tissue devoid of skeletal muscle. Indeed, a whole host of soft tissue sarcomas including chondrosarcomas, osteosarcomas and others, arise in sites where similar normal constituents do not exist.
Small cell (neuroendocrine) carcinomas seem to occur virtually everywhere and were once considered to derive solely from neuroendocrine precursor cells as per the APUD cell theory. This led to considerable conceptual distress among authors whenever such tumors were documented in tissues, like the uterine cervix, not demonstrated to contain normal neuroendocrine precursor cells. The clear-cut demonstration in the last several decades of divergent differentiation in such tumors, with mixtures of squamous, glandular, and neuroendocrine features, often in the same cell, has led to the general agreement that such tumors do not need to derive from a neuroendocrine precursor. Freed from this conceptual constraint, we can now ask more important and potentially answerable questions such as, "Why do so many highly malignant, rapidly growing, small cell neoplasms express neuroendocrine features?" Are they in some manner recapitulating the prominent neural and neuroendocrine differentiation seen early in embryonic development? (ie. does "oncology" recapitulate ontogeny?). Said differently, are the genes derepressed to produce the rapid growth and cytoplasm-poor features of these cells linked to genes of neuroendocrine differentiation because this pattern has ontogenic significance?
Finally, even the medullary carcinoma of the thyroid gland, once believed to be solely the offspring of the parafollicular or C-cell, has come into question, though many current discussions continue to indicate that this is a tumor derived from C-cells. The recognition of tumors with both follicular and parafollicular features has suggested that medullary carcinomas may not invariably derive from C-cells. Indeed, the reputed origin of the C-cell, itself, from the neural crest has been brought into serious question. A wag in the pre-genetic era once said that cell of origin, like paternity, was a matter of faith. With the advent of genetic testing, paternity is now a matter of fact. Cell of origin, however, remains elusive and of questionable value. We are observing cells at a single point in time, and the observations we are making directly relate only to the differentiation of those particular cells. The features of their neoplastically transformed "parent" cannot be observed since this cell was destroyed with the first mitotic division. We can make only one unequivocally correct statement regarding the cell of origin of any neoplasm, we just need to go back far enough in time. Every neoplasm definitely derived from its host zygote!
Monday, June 07, 2010
A couple of years ago one of our eager beaver young hospital attorneys representing our self-insured malpractice plan contacted our pathology department business manager to see if any pathologists were, "practicing pathology outside of the state." Since, as in many academic institutions, we get thousands of consults a year from across the country as well as internationally, the immediate (and perhaps naive) answer was "yes." ...and the immediate response from the eager beaver attorney was, "That's illegal and has to cease, until licenses are obtained in all states from which consults are submitted." Needless to say, the prospect of obtaining and maintaining licensure in 50 states was cost and time prohibitive. But our consults are the backbone of our fellowship training and form the basis for many clinicopathologic studies derived from this material. This untenable situation led several of us on a nearly 2-year trip down the telemedicine "rabbit-hole" from which we have finally emerged with a lawyer-acceptable compromise at our institution to a truly baffling patchwork set of state statutes.
I'd like to share some of our findings regarding this potentially problematic issue which many (most?) academic departments seem to have chosen (perhaps correctly!) to ignore. Although their verbiage often speaks of protecting the patient, telemedicine laws were devised PRIMARILY to protect physicians, mainly pathologists and radiologists, from loss of business and revenue due to the shipping or electronic transfer of specimens or radiographic images across state (or national) borders for PRIMARY DIAGNOSIS. In support of that fact, as a general rule, smaller more rural states typically have stronger telemedicine laws as their smaller medical practices were perceived by their physicians to be more vulnerable to out of state diagnosis, leading to pressure on legislators to write tougher laws. Larger states such as New York and California, in contrast, tend to have more limited laws in this regard. Two facts, and perhaps only two, become clear in reviewing the patchwork of 50 state telemedicine laws. 1. When it comes to pathology specimens and radiographs, the practice of medicine is said to take place at the point where the patient is located, NOT at the point where the primary diagnosis was rendered. 2. If you are obtaining specimens from another state for primary diagnosis, you NEED to be licensed in that state.
With regard to interstate physician-directed pathology consultations, our main area of concern, things are MUCH, MUCH more cloudy. Speaking with representatives of state medical boards (usually lawyers) does VERY LITTLE to enlighten things. In short, they don't know or are afraid to offer an opinion. One fundamental issue, getting back to our business manager's comment, is whether a physician-directed consult constitutes the practice of medicine. The main argument in favor of this is that the consultant bills (usually the patient) for this service, constituting a contractual arrangement. Yet, others argue that this does not equate with the practice of medicine because, 1. The consultant has no direct contact with the patient, 2. The consultant provides an opinion based on limited information, 3. Most importantly, the consultant's opinion does not constitute the final diagnosis of the case. The primary pathologist has the responsibility to synthesize one or more consultants' opinions and provide the final diagnosis. Discussions with state board representatives on this point yield opinions that consultations ARE the practice of medicine, they ARE NOT the practice of medicine, or "it's unclear." I would point out that virtually all lawyers would agree that a pathology consultation request from a lawyer regarding the diagnosis in a potential medicolegal case does NOT constitute the practice of medicine.
Discussions of this topic with state medical societies, particularly officers in state pathology societies, many of whom were consulted regarding their state's telemedicine laws, yields a firm consensus that these laws were NEVER meant to limit a physician's ability to seek expert consultation across state lines, when needed. Indeed, to do so would adversely affect patient care, and patient care is the issue which virtually all telemedicine laws state that they seek to optimize. Most (but not all) states provide at least a vague exemption for physician-directed consultations provided that they are "infrequent" and on a "case by case basis." Some, such as West Virginia set a specific limit for consultations (12 per year), after which the consultant must be licensed in the state. It seems clear that the purpose of this verbiage is to prevent "back door" primary diagnosis. In other words, to prevent a pathologist or radiologist from sending virtually all of their cases out for primary diagnosis under the guise of obtaining a "consultation." Along these lines, some states make it clear that no contractual arrangement should exist between the consultant and the primary physician.
What do our national pathology societies say about this issue? Unfortunately, not very much. To my knowledge, only the College of American Pathologists has specific guidelines with regard to interstate consultations, and these guidelines indicate that medical licensure in the referring state is not required. Of course, as any lawyer will tell you, guidelines don't mean much when they conflict with state statutes.
Where does this leave the consultant? It seems clear that examining consultations from out of state, without a license in the referring state, does NOT violate the spirit of any telemedicine law, provided that the consultations are "infrequent" and on a case by case basis, without a contractual arrangement with the contributing pathologist, ie. all of their consults go directly to you or your institution. Nonetheless, some states do not provide for this specific exemption and examining consults from these states could leave the consultant open for legal action, though the chances of someone bringing such action when only optimal patient care was being sought, seem to be virtually zero. Nonetheless, you may want to take a look at some of these laws. The issue of medicolegal liability for rendering a consultation is a separate and only partially related issue that I will not address here, except to say that I am unaware of a successful lawsuit against a pathology consultant, though certainly anyone can be sued at anytime for any thing, and there may be a few such cases out there. The difficulties in successfully suing a consultant are many, but perhaps not insurmountable.
It is clear that the use of telemedicine is only going to increase with time and there is a growing need for a uniform national code with regard to its practice. This issue also brings into focus the arguments in favor of a national medical license. A movement in this regard has already begun and is likely to gain momentum with time.
Wednesday, May 26, 2010
Ask any practicing pathologist or upper level resident to describe their diagnostic criteria for any lesion and you'll get a verbal laundry list of features, just as one would find in any textbook description. What is an adenocarcinoma? It's a malignant tumor usually composed at least in part of glands, which are in turn circular arrays of polarized cells (more basal nuclei) around a central lumen. Ask about a squamous cell carcinoma and words like keratin, eosinophilic, pavement stone, pearls, cell attachments, dyskeratotic, and hyperchromatic will spout forth. And yet, this is most certainly NOT how we function when we're actually MAKING diagnoses. The reality is that the diagnostic process in surgical pathology is an inherently non-verbal, right brain, pattern recognition process that takes place extremely rapidly without our being fully aware of what's going on. We look at a slide and almost instantly the right side of our brain tells us that this is a squamous cell carcinoma. After that, at a much more leisurely pace our left brain confirms the diagnosis by ticking through at least a partial list of features that should be present: yes, the nuclei are pleomorphic and mitotically active; yes, there are keratin pearls; yes, there is an infiltrating growth pattern.
The initial diagnosis is reached blindingly fast and non-verbally by our right brain, but NEEDS to be confirmed by our rational left-brain side. Those who lack the right brain skills of pattern recognition are often said to lack the "eye" needed for surgical pathology. When given a slide they mentally wander aimlessly through lists of diagnostic criteria until, if they're lucky, they hit upon the proper answer, but they are seldom sure of themselves. Those who have excellent right brain diagnostic skills, ie. the "eye," but fail to subject their snap diagnosis to left-brain review are quite often correct, but set themselves up for the occasional VERY bad mistake.
The ability of the brain to make nearly instantaneous decisions based on visual, non-verbal cues is undoubtedly of great evolutionary value. Is the person running rapidly toward me angry, happy, friend, foe, dangerous, etc? An instantaneous reaction is required and there's not time for the left brain to search the laundry lists of facial features. Although we don't really understand what's going on in our right-brains and cannot verbalize what are at their core non-verbal phenonmena, a tremendous amount of our brain power is devoted to such "cue reading." It is the core of social interaction, as well as, among many other things, microscopic diagnosis.
Kim Peek, the "megasavant" who was the basis for Dustin Hoffman's character in Rain Man, had a number of severe CNS structural abnormalities including agenesis of the corpus callosum. The result was an individual with, in essence, a brain with two left sides. He had an unfathomable memory for anything he had ever read, seen or heard, but he could not read facial cues or react appropriately in simple social situations. He could have undoubtedly given the definitions, word for word, for any tumor from any text he had ever read, but he would have been helpless looking through a microscope.
If you're interested in how the right brain functions, and as a pathologist you probably should be, I strongly recommend the book, "Blink, The Power of Thinking without Thinking," by Malcolm Gladwell. Mr. Gladwell is also the author of "Tipping Point." "Blink" is a short and fascinating tour through the non-verbal world of the right brain. You'll learn when to trust it and when to question its decisions, good skills for a pathologist!
Monday, May 10, 2010
When I was a resident in pathology, mammography was just coming into existence. All that we knew about lobular carcinoma in-situ (LCIS) of the breast was based on studies including several large ones from Memorial Sloan-Kettering and Columbia University in New York, in which the LCIS was almost always of sufficient size to produce a mass lesion. Based on these studies we learned that about 33% of patients with LCIS would ultimately develop invasive carcinoma, but the invasive tumors were as likely as not to be contralateral. Armed with these data and perhaps with some encouragement from overly zealous but well-meaning surgeons, many women with LCIS underwent bilateral mastectomies. When mammography led to the detection of much smaller, non-palpable foci of LCIS the biologic behavior of the larger LCIS foci was (wrongly) extrapolated to these much smaller lesions and many women continued to receive aggressive surgery. With time, we have recognized this error.
It seems to me that we are in a very similar situation today with regard to prostatic adenocarcinoma. With the advent of racemase and basal cell markers we now confidently diagnose extremely small foci (3-5 glands) of well-differentiated prostatic adenocarcinoma that prior to the advent of these immunohistochemical aids would NEVER have been interpreted as full-fledged malignancies. Certainly we cannot extrapolate the biologic behavior of such minute foci based on data from the pre-immunohistochemistry era. If we attempt to influence therapy by downgrading such minute foci as "atypical," experts in the field will rapidly overturn our diagnoses and cast aspersions on our acumen. Do urologists understand that we have substantially extended our diagnostic criteria for minimal prostatic carcinoma in the last decades? Most probably do, at least to some extent. Do patients? Probably not. The word carcinoma has such powerful connotations that many patients hear nothing else when given that diagnosis. Coupling a cancer phobic patient with an eager surgeon then leads to prostatectomy, radiation therapy, or both, often with attendant morbidity.
Urologists will point to national cancer statistics showing a great increase in prostatic adenocarcinomas with no increase in overall mortality from the disease over the last decade as evidence that they are doing a great job treating this disease. Pathologists know better. The prevalence of occult low-grade prostatic adenocarcinoma is extremely high. In fact, at least one study has suggested that the probability of finding a focus of carcinoma in a thoroughly sampled prostate at autopsy is about the same as the patient's age. They may also argue that small foci of carcinoma in a biopsy may be the edge of a much larger neoplasm. This may certainly be the case in some instances. It is unlikely, however, that watchful waiting, monitoring changes in serum PSA and rebiopsy will adversely affect the ultimate outcome. Urologists will counter that such an approach may leave them liable for lawsuit if a subsequent clinically significant carcinoma is detected.
Needless to say, this is a complicated issue involving well meaning individuals. Many other factors including family history, PSA trajectory, patient reliability for follow-up, patient wishes, etc. come into the decision making process with regard to therapy. It seems clear, however, that currently far too many patients are undergoing aggressive prostatic therapy for incidentally (non-palpable) detected small carcinomas, when only a small minority are likely to have clinically significant tumors removed.
Monday, April 26, 2010
If you think you can always scan prostatic biopsies and prostatectomies at 4x and rapidly identify all foci of carcinoma based on the low-power glandular architecture, think again. In this article by Dr. Peter Humphrey and colleagues from Barnes Hospital, the authors describe a microcystic pattern of prostatic adenocarcinoma with a treacherously benign low-power appearance mimicking hyperplasia or atrophy. Only by going to higher magnification can one see the nuclear features of malignancy in these glands and subsequent immunohistochemical stains will confirm malignancy with AMACR expression and absence of basal cell markers. Reading this article will undoubtedly cause you to ask yourself, "How many of these have I missed?"
Although we often use vascular invasion as strong support for a diagnosis of malignancy, the association is certainly not absolute. In the uterus, the process of curettage may iatrogenicaly create vascular "invasion" and menstrual endometrium may spontaneously gain access to vascular spaces during the process of shedding and be transported to adjacent structures such as the cervix. Vascular involvement is the sine qua non of so-called intravascular leiomyomatosis, a benign but often microscopically alarming process. In this article, the authors document that vascular invasion was present in 12.4% of a large series of patients with adenomyosis, and often involved multiple vessels. When the intravascular component consists of endometrial stromal tissue only, it may be confused with low-grade endometrial stromal sarcoma, a tumor known for its often extensive vascular (usually lymphatic) involvement. The authors provide some guidelines for making this distinction, which in some instances may be difficult.
Thursday, April 08, 2010
The 99th meeting of the United States and Canadian Academy of Pathology (USCAP) has come and gone. This is a meeting FOR practicing anatomic pathologists, run BY practicing anatomic pathologists and is really a "must attend" for both academics and private practicioners.
I attended my first USCAP meeting in 1978 and with one exception when I was sidelined with some foot surgery, I've been to every one since. This is THE forum for cutting edge diagnostically relevant anatomic pathology. The integration of the companion societies into the USCAP format has been a tremendous educational plus for attendees and their Sunday sessions often contain many of the meeting highlights.
I continue to marvel at how much information can be crammed into a 10-minute platform presentation. These have always been my favorite part of the meeting. When the USCAP was much smaller it was possible to jump from session to session fairly easily to "cherry pick" your favorite talks. This was common practice and people jumped from room to room with noisy regularity. Now that there are more platform sessions covering much more space, this is almost impossible and most of us camp out in one platform session for the duration. There is no doubt in my mind that this is by far the best way to pick up new information at the meeting.
Poster sessions continue to grow and provide many trainees with their first exposure to this meeting. Many could not attend without an accepted presentation. Actually learning from the posters, however, requires considerable pre-meeting preparation. One needs to carefully study the abstracts and identify a handful of posters in each session that can be studied in detail. Without such a game plan, wandering through the packed isles of posters is unlikely to yield a great deal of new information, though it is a great way to see old friends.
For academics, the USCAP is a source of renewal. Sitting in on platform presentations almost invariably leads to ideas for spin-off projects. It is a chance to socialize with colleagues, many of whom we see ONLY at this meeting, and to plan interdepartmental collaborative projects for the future.
Although many private practicioners attend and enjoy the platform and poster sessions, and I would encourage all of you to do so, some elect to come only for the second half of the week dominated by the long and short courses. The makeup of the attendees clearly changes on Tuesday afternoon, with many academics departing and private practioners arriving. Since I began coming to this meeting over 30 years ago, this has been the case, and it is a testament to the foresightedness of the early planners that this "something for everyone" approach was adopted for this meeting long ago.
Is the meeting perfect? No, but then nothing is. The venue is often too small, the poster sessions are crowded, and the Academy invariably fails to reserve nearly enough hotel rooms for attendees (so book EARLY!), but these are minor points. I also believe that the evening sessions should begin and end much earlier to allow one to attend and still have an excellent dinner with colleagues afterwards. But then we vote with our feet and these sessions are well attended in their current format, though I usually succumb to the urge for a good meal and drink.
Committee members, speakers and officers of the USCAP come and go with regularity and the continuity of the academy resides at the Augusta office. In that regard, the executive vice president is the cornerstone of the USCAP. For over a decade Fred Silva has filled this role with unbelievable skill. The inovations that he has brought to the USCAP are far too many to list. Fred has announced his impending retirement and a committee has been charged with finding his replacement... successor really, as Fred cannot be replaced!
See you next year, the 100th meeting of the USCAP, in San Antonio. I suspect something special will be in store to celebrate this anniversary.
Friday, March 19, 2010
Welcome to the P ⁿ inaugural blog on Pathology Network! My goal here is to present some opinions, raise some questions, highlight some controversies, and hope to stimulate some instructive discussion. As someone trained in the 70's in medicine and surgical pathology I've witnessed an explosive increase in our knowledge base with no end in sight. Like all of you my age, my formative medical and pathological knowledge was gained by reading PRINTED textbooks and journals. My college computing course consisted of childishly simplistic programs written in Fortran, typed onto punch cards
and run on a gigantic IBM mainframe computer.
 You turned in your stack of cards and came back a few hours later to get your printout. God help you if you jammed the mainframe in a "do loop" with a carriage feed each time around. The computing staff would have some choice words for you when you came to pick up your printout. None of us could have remotely guessed where we'd be 30 years later. When journals first became available in electronic as well as printed format, those of us who trained in the 70's and before viewed the electronic version with considerable skepticism or ignored it altogether, but most of us have come around with time and our trainees never had this problem to begin with. The reality is that for many journals, including those of LWW, the electronic version of the journal is now the "version of record", it is the print version that is secondary. Even my wife with a Masters in English, a steadfast love of printer's ink and a personal book collection that would rival a moderate-sized public library has shown interest in getting a Kindle. Brave new world.
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About the Author
 Stacey E. Mills, MD
Stacey E. Mills, MD, a graduate of University of Virginia (UVA) and the UVA Medical Center, has authored nearly 230 articles, 20+ books, atlases and monographs—including the renowned Sternberg's Diagnostic Surgical Pathology. He has been a practicing Professor and Staff Pathologist at UVA for 30+ years and is Director of Surgical Pathology and Cytopathology. His clinical specialty is general surgical pathology with emphasis on neoplasms and neoplasm-like lesions. Dr. Mills is also Editor-in-Chief of The American Journal of Surgical Pathology.
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