The Histologic Features of Endometrial Stromal Sarcomas Characterized by YWHAE Rearrangement – Distinction from Usual Low-Grade Endometrial Stromal Sarcoma with JAZF1 Rearrangement.
Cheng-Han Lee, Adrian Marino-Enriquez, Matt van de Rijn, C Blake Gilks, Maria Debiec-Rychter, Paola Dal Cin, Jonathan A Fletcher, Marisa R Nucci. Brigham and Women's Hospital, Boston; Stanford University Medical Center; Vancouver General Hospital, BC, Canada; Catholic University of Leuven, Belgium
Background: Endometrial stromal sarcoma (ESS) is a genetically heterogeneous group of uterine sarcomas; about half harbor JAZF1 rearrangement while the genetics of the remaining half is undefined. We recently identified a novel translocation-induced genetic rearrangement involving YWHAE as the pathognemonic abnormality in a subset of ESS and we describe here the histologic features of this genetic subtype of ESS.
Design: A total of 11 ESS with YWHAE rearrangement was identified through multi-institutional review of cytogenetics data and FISH screening. The histology and the immunophenotype (ER, PR and CD10) was examined in 8 primary tumors and 3 metastatic tumors, in comparison to 20 JAZF1-rearranged ESS.
Results: All YWHAE-rearranged primary ESS had epithelioid areas in which the tumor cells were arranged in a nested pattern with fine stromal capillary network. The cellularity ranged from highly cellular with a small round blue cell appearance to moderately cellular with tumor cells possessing a moderate amount of eosinophillic cytoplasm. In contrast to ESS with JAZF1 rearrangement which usually display small nuclei with < 5MF/10HPF, the YWHAE-rearranged epithelioid cells had larger nuclei with more irregular contour, and all cases showed more than 10 MF/10HPF in addition to tumor necrosis. 5 of the 8 YWHAE-rearranged primary ESS contained an admixed cytologically-bland mitotically-inactive spindle cell component in a fibrous/fibromyxoid background. In 3 YWHAE-rearranged ESS, only the metastatic tumors were examined: these included two lung metastases with mitotically active epithelioid areas (one with admixed spindle cell component), and one vaginal metastasis where the tumor showed only a low-grade appearance. Immunohistochemically, the spindle cell component (in both primary and metastatic tumors) consistently exhibited ER and PR immunoreactivity with variable CD10 positivity while the epithelioid cell component lacked ER, PR and CD10 immunoreactivity. Staging information was available for 6 primary tumors, of which five were associated with advanced-stage disease (FIGO stage 3) at presentation.
Conclusions: We describe a new molecularly-defined subset of ESS, containing YWHAE oncogenic rearrangement, and exhibiting higher-grade histologic features than those in classic ESS with JAZF1-rearrangement.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 8:15 AM
Platform Session: Section D, Tuesday Morning