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

   

Authors:	Zou, Y.; Turashvili, G.; Soslow, R. A.; Park, K. J.; Croce, S.; McCluggage, W. G.; Stewart, C. J. R.; Oda, Y.; Oliva, E.; Young, R. H.; Da Cruz Paula, A.; Dessources, K.; Ashley, C. W.; Hensley, M. L.; Yip, S.; Weigelt, B.; Benayed, R.; Antonescu, C. R.; Lee, C. H.; Chiang, S.
Article Title:	High-grade transformation of low-grade endometrial stromal sarcomas lacking YWHAE and BCOR genetic abnormalities
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. © 2020, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
Keywords:	adult; cancer survival; clinical article; controlled study; human tissue; aged; middle aged; cancer surgery; primary tumor; unclassified drug; oncoprotein; human cell; overall survival; clinical feature; cancer recurrence; comparative study; gene targeting; metastasis; gene expression; vagina; cell population; retrospective study; wild type; protein p53; carcinogenesis; fluorescence in situ hybridization; gene rearrangement; staining; gene fusion; recurrent disease; mitosis rate; cell nucleus; estrogen receptor; progesterone receptor; cyclin d1; malignant transformation; epithelioid cell; lymphocyte; gynecologic surgery; uterus; sclerosis; endometrial stromal tumor; fusion protein; molecular pathology; mitosis index; endometrium sarcoma; cd103 antigen; international federation of gynecology and obstetrics; human; female; priority journal; article; rna sequencing; median survival time; bcor protein; brd8 phf1 fusion protein; epc1 phf1 fusion protein; jazf1 phf1 fusion protein; jazf1 suz12 fusion protein; ywhae protein
Journal Title:	Modern Pathology
Volume:	33
Issue:	9
ISSN:	0893-3952
Publisher:	Nature Research
Date Published:	2020-09-01
Start Page:	1861
End Page:	1870
Language:	English
DOI:	10.1038/s41379-020-0535-y
PUBMED:	32317704
PROVIDER:	scopus
PMCID:	PMC8288077
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083729919&doi=10.1038%2fs41379-020-0535-y&partnerID=40&md5=caccdda9eea0baed3bdd62ca1f6b7c1b
Notes:	Article -- Export Date: 1 October 2020 -- Source: Scopus

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