Lotfalla, Mira

Abstract Introduction/Objective Microglandular adenosis (MGA) of the breast is an uncommon lesion characterized by a benign course. However atypical MGA (AMGA) and MGA-associated carcinoma have been described, suggesting that MGA may represent a non-obligate precursor of carcinoma. We report five cases of MGA-associated breast carcinoma and describe the key pathological features of this entity. Methods/Case Report Five cases of MGA-associated breast carcinoma were identified. Clinical data, histologic and immunohistochemical characteristics were reviewed and analyzed. Results All cases involved women with ages ranging 48 to 75 with a median of 70. Four of five cases demonstrated invasive carcinoma, while one case showed ductal carcinoma in-situ (DCIS). Invasive carcinomas encompassed various histologic types: metaplastic carcinoma with chondromyxoid matrix production (2 cases), invasive carcinoma with secretory features (1 case), and invasive carcinoma of no special type (ductal) (1 case). A morphologic transition from MGA to AMGA to carcinoma was observed in all cases. S100 was consistently positive in all cases. Myoepithelial markers demonstrated the absence of myoepithelial cells in the invasive carcinoma as well as MGA / AMGA component. Conclusion This series highlights the histologic spectrum and key diagnostic features of MGA-associated carcinoma. Awareness of this entity is crucial for appropriate diagnosis and clinical management.

Abstract Objectives Mucinous cystic neoplasm of the liver is characterized by neoplastic mucinous and/or biliary epithelium surrounded by ovarian-type stroma. Immunohistochemical studies have shown that the ovarian-type stroma expresses estrogen receptor, suggesting potential hormonal responsiveness. The molecular biology of mucinous cystic neoplasm of the liver remains poorly studied. Methods Transcriptome sequencing and immunohistochemistry were performed on a series of mucinous cystic neoplasms. Results Mucinous cystic neoplasm of the liver exhibited significantly increased RNA expression of ovarian stromal markers WT1, PR, and ER2 and sex cord stromal markers SF-1, inhibin-α, and calretinin compared with nonneoplastic liver. Immunohistochemistry confirmed the RNA-level data. Evidence for sex hormone biosynthesis was identified by significant overexpression of multiple estrogen biosynthetic enzymes. Expression of 17β-hydroxysteroid dehydrogenase 1 was confirmed immunohistochemically. Pathway analysis also identified significant upregulation of the hedgehog and Wnt pathways and significant downregulation of T-helper 1 and T-helper 2 pathways. Conclusions Mucinous cystic neoplasm of the liver recapitulates ovarian stroma at the morphologic, DNA, RNA, and protein levels. These data support the concept that this tumor likely arises from ectopic primitive gonadal tissue and/or stromal cells with capacity to transdifferentiate to ovarian cortical cells.

Epithelioid hemangioendothelioma (EHE) is an uncommon low-grade malignant vascular tumor that may arise in soft tissue/bone or visceral sites such as the liver and lung. As this tumor exhibits epithelioid morphology, it frequently causes diagnostic confusion with other epithelioid vascular neoplasms as well as carcinoma. While 90% of classic EHE are driven by aWWTR1-CAMTA1fusion gene, a histologically distinctive subset of EHE has been recently shown to harbor a different fusion gene,YAP1-TFE3. This variant is likely underrecognized given its rarity and only recent description. Notably, EHE frequently involves the liver but only one case of hepaticYAP1-TFE3rearranged EHE has been reported to date. We present the second case ofYAP1-TFE3rearranged EHE affecting a 65-year-old woman and presenting as multiple liver masses, with characterization of the fusion gene at the transcriptomic and genomic levels. There are several educational points noted from this case.YAP1-TFE3rearranged EHE shows distinctly vasoformative foci, unlike classic EHE and mimicking angiosarcoma or epithelioid hemangioma. The tumors cells show a histiocytoid appearance with voluminous cytoplasm, similar to otherTFE3-rearranged tumors. Finally, in the liver, this tumor may in part mimic focal nodular hyperplasia of the liver which is an underrecognized diagnostic pitfall. This report highlights the key diagnostic and genetic features of this newly recognized variant of hepatic EHE to aid pathologists in appropriately classifying these tumors.