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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.
Wednesday, September 29, 2010
Paradigm shifts in medical thinking.
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?
10/4/2010
said:
There are many references, easily found on Google or PubMed. Here are a couple: Young RH, Gilks CB, Scully RE. Mucinous tumors of the appendix associated with mucinous tumors of the ovary and pseudomyxoma peritonei. A clinicopathological analysis of 22 cases supporting an origin in the appendix. Am J Surg Pathol. 1991;15:415–429. Seidman JD, Elsayed AM, Sobin LH, Tavassoli FA. Association of mucinous tumors of the ovary and appendix. A clinicopathologic study of 25 cases. Am J Surg Pathol. 1993;17:22–34.
10/1/2010
Dr. dilip ram said:
Dear Dr. Mills, I would be grateful if you can share with us the link(s) for the review article(s) clarifying the fact that the vast majority of low-grade mucinous tumors involving the ovary and the peritoneum are now believed to have arisen from the appendix. regards, Dilip Ramrakhiani,MD Assistant Professor & Staff Pathologist Department of Pathology SMS Medical College & Attached Group of Hospitals Jaipur Rajasthan India
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.