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Image of the Week
Edited and moderated by Stacey Mills, MD, Pathology Network's Image of the Week Blog is a forum for the discussion of interesting and often diagnostically challenging pathology images.
Friday, September 13, 2013
A 34-year-old woman with a uterine mass.
A 34-year-old woman presented with a uterine mass and associated bleeding.  Following examination and laboratory testing, a D&C was performed and yielded the tissue seen here. 
What is your diagnosis?
This is an obvious trophoblastic proliferation with well-formed villi and prominent trophoblasts.  A p57 immunohistochemical stain was performed and yielded the results shown below.
Note that virtually all of the decidual cells and some of the syncytiotrophoblasts show strong nuclear staining for p57.  However, the cytotrophoblasts and villous stromal cells are entirely negative for p57.  These findings support the diagnosis of a true (hydatidiform) mole.  Because true moles are typically XX with both sets of chromosomes paternally derived (true moles are "daddy's little girls"), p57 lacks the maternal imprinting needed for positivity in the completely paternally derived fetal villi and cytotrophoblasts.  The maternally derived decidual cells provide a good internal control.  Why some of the fetal, paternally derived syncytiotrophoblasts typically show some staining is unclear (at least to me), but this is a common finding that should not cause diagnostic confusion.
Although this is a rather straightforward example of a true molar pregnancy with obvious trophoblastic proliferation, the distinction of true mole, so-called partial mole (I REALLY DISLIKE that term!), and hydropic change in an early aborted pregnancy can be extremely difficult, with an associated very high interobserver variability based on H&E images alone.  p57 negativity as seen in this case is an excellent marker for true mole and we typically use the Her2 in-situ hybridization assay as an easy way to identify the triploidy of so-called partial mole (hydropia of triploid pregnancy).
It is undisputed that true mole carries a significant increased risk for subsequent persistent trophoblastic disease and should be appropriately recognized so that patients can have necessary follow-up.  I remain skeptical that so-called partial mole carries a risk of subsequent trophoblastic disease any higher than that seen following normal pregnancy which, while quite low, is not zero.  I suspect that many examples of so-called partial mole giving rise to persistent trophoblastic disease represent misdiagnosed true moles and such cases should bs subjected to retrospective study. 
I love the comment.."Daddy's little girls".......tells a lot about the pathogenesis and why negative......thanks for the lovely terminology......Dr. Mills...
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.