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Pⁿ Blog
The Pⁿ Blog is a forum for opinions, questions, controversies, and instructive discussions across the field of pathology and its relevant subspecialties.
Friday, March 04, 2011
I can't believe you don't do this!
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.
4/13/2011
Prof. PETER P. MOLNAR MD said:
I was somewhat relieved reading Stacey's last story - it does happen here in Hungary as well. I have two additional comments to make. 1. We also have to be prepared to face questions and demands from patients, or their relatives who get motivated by some private physician or get the wrong message from some inadequate cyberspace source. It can get really uncomfortable. 2. The other side of the coin is when the clinician "does not believe" that a molecular test has either diagnostic and/or prognostic/predictive value and thus decides against the test. I have had that experience in my Medical Center when the neurosurgeons doubted the value of 1p19q chromosomal analysis in certain gliomas (the system is set up in such a way that they have to cover the expenses). That time has passed but we are still far from being able to do MGMT methylation analysis or a proper IDH1 immunohistochemistry. These experiences can be equally frustrating and result in sleepless nights vis-á-vis the Hippocratic
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.