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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.
Monday, February 10, 2014
Rethinking Mammary Atypical Hyperplasia

Pathologists and clinicians have been taught for decades that atypical lobular hyperplasia (ALH) and atypical ductal hyperplasia (ADH) of the breast are fundamentally different lesions.  ALH has been viewed as a marker for subsequent carcinoma of lesser predictive power than lobular carcinoma in situ (LCIS), and associated with increased risk of carcinoma in either breast (although Page and colleagues did show that 2/3rds of subsequent carcinomas occur in the ipsilateral breast). 

ADH has been viewed traditionally as a precursor lesion with more power than ALH to predict subsequent carcinoma, predominantly in the same breast.  Surgeons will often do reexcisions when ADH is present at the margin but almost all will ignore margins positive for ALH (or even LCIS). 

A recent article published in Cancer Prevention Research based on a large study from the Mayo Clinic calls these assumptions into question.  I recommend reading it and passing it on to your colleagues, both in pathology and the clinical specialties involved in breast disease management.  There are a LOT more data in the text than are briefly discussed here.
The study involved almost 700 women with atypical hyperplasias, 330 with ADH, 327 with ALH, and 32 with both.  This is by far the largest follow-up study in the literature on atypical hyperplasias of both types. To cut to the chase, the conclusion can be summarized in the following quote from the manuscript, "Our observations do not support present assumptions that ADH and ALH have substantively different behaviors.  More DCIS may occur in women with ADH than ALH (25% vs. 13%, p=0.07), but numbers are small and this was not statistically significant." 
Both ALH and ADH have features suggestive of precursor lesions and risk indicators.  When carcinoma arises (either in-situ or invasive) both are predominantly associated with ductal as opposed to lobular carcinomas (ALH -> 77% ductal, 17% lobular; ADH -> 78% ductal, 8% lobular).  Two-thirds of subsequent carcinomas arose in the ipsilateral breast in both ALH and ADH patients.  Both ALH and ADH showed a tendency for contralateral carcinomas to develop later in life. 
This is an valuable study that is packed with information, presented in a well-written format.  Table 2 is especially data dense. 
The authors conclude with the following:
"In summary, these findings underscore the importance of both ADH and ALH as premalignant lesions arising in an
altered tissue bed. The affected breast is at especially high risk for breast cancer in the first 5 years after diagnosis of breast cancer, with risk remaining elevated in both breasts long term. Both ADH and ALH portend risk for DCIS and invasive breast cancers, predominantly ductal, with two thirds moderate or high grade. These longitudinal data can help to inform clinical management strategies."
Although I think this is a very good study, I do have concerns that clinicians will interpret it to mean that ALH should treated more aggressively.   I would argue that it rather suggests that ADH be treated more like ALH.  The other problem(s), of course, are the distinctions between ALH & LCIS, and ADH & DCIS.  A topic we've dealt with before. 
Dr. Dilip Ramrakhiani MD said:
Well Stacey, I had a suggestion. Why not have an app of pathology network in which your pearls of wisdom and the points of best practice you highlight can be read on the go. Also your podcasts on topics in general surgical pathology would be welcome as they can be heard while on treadmill at the gym or while driving to and from work. All my clinical colleagues listen / watch the latest developments in their field on the go through podcasts on their iphone/ ipad do you know any such podcasts for surgical pathologists if not why don't you guys start one? [Dr. Mills replies: Certainly worth considering and I'll discuss it with the publisher. I just need more hours in the day! At the moment, the 6th edition of Diagnostic Surgical Pathology is occupying a LOT of my time! Thanks for your comments!]
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.