High-grade transformation of low-grade endometrial stromal sarcomas lacking YWHAE and BCOR genetic abnormalities

Youran Zou, Gulisa Turashvili, Robert A. Soslow, Kay J. Park, Sabrina Croce, W. Glenn McCluggage, Colin J.R. Stewart, Yoshinao Oda, Esther Oliva, Robert H. Young, Arnaud Da Cruz Paula, Kimberly Dessources, Charles W. Ashley, Martee L. Hensley, Stephen Yip, Britta Weigelt, Ryma Benayed, Cristina R. Antonescu, Cheng Han Lee, Sarah Chiang

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Abstract

High-grade histologic transformation of low-grade endometrial stromal sarcoma (LGESS) is rare. Here, we describe the clinicopathologic features and gene fusion status of 12 cases (11 primary uterine corpus and 1 primary vaginal), 11 diagnosed prospectively from 2016, and 1 retrospectively collected. Targeted RNA sequencing and/or fluorescence in situ hybridization was employed in all cases. High-grade transformation was seen at the time of initial diagnosis in eight patients and at the time of recurrence in four patients, 4–11 years after initial diagnosis of LGESS. High-grade morphology consisted of generally uniform population of round to epithelioid cells with enlarged nuclei one to two times larger than a lymphocyte, visible nucleoli, and increased mitotic index (range, 6–30; median, 16 per 10 high-power fields); there was often an associated sclerotic and/or myxoid stroma. Estrogen receptor, progesterone receptor, and CD10 expression was absent or significantly decreased (compared with the low-grade component) in the high-grade foci of five tumors. One tumor demonstrated positive (diffuse and strong) cyclin D1 and BCOR staining. p53 staining was wild type in both components of all eight tumors tested. JAZF1-SUZ12 (n = 6), JAZF1-PHF1 (n = 3), EPC1-PHF1, (n = 1), or BRD8-PHF1 (n = 1) fusions were detected in 11 tumors; no fusions were found in one by targeted RNA sequencing. Patients presented with FIGO stages I (n = 4), II (n = 4), III (n = 1), and IV disease (n = 2). Median overall survival calculated from the time of histologic transformation was 22 months (range, 8 months to 8 years) with five patients who died of disease 8–18 months after transformation. High-grade transformation may occur in LGESS with JAZF1 and PHF1 rearrangements at the time of or years after initial diagnosis. Such high-grade transformation is characterized by nuclear enlargement, prominent nucleoli, and increased mitotic index compared with typical LGESS. Histologic high-grade transformation may herald aggressive behavior.

Original languageEnglish
JournalModern Pathology
DOIs
Publication statusAccepted/In press - Jan 1 2020

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All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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Zou, Y., Turashvili, G., Soslow, R. A., Park, K. J., Croce, S., McCluggage, W. G., ... Chiang, S. (Accepted/In press). High-grade transformation of low-grade endometrial stromal sarcomas lacking YWHAE and BCOR genetic abnormalities. Modern Pathology. https://doi.org/10.1038/s41379-020-0535-y