TY - JOUR
T1 - Undifferentiated uterine sarcomas represent underrecognized high-grade endometrial stromal sarcomas
AU - Cotzia, Paolo
AU - Benayed, Ryma
AU - Mullaney, Kerry
AU - Oliva, Esther
AU - Felix, Ana
AU - Ferreira, Joana
AU - Soslow, Robert A.
AU - Antonescu, Cristina R.
AU - Ladanyi, Marc
AU - Chiang, Sarah
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Undifferentiated uterine sarcoma is a diagnosis of exclusion with limited molecular genetic data available. Recent recognition of high-grade endometrial stromal sarcomas with diverse genotypes suggests that some tumors classified as undifferentiated uterine sarcomas may represent misdiagnosed high-grade endometrial stromal sarcomas. Archival material from 10 tumors diagnosed as undifferentiated uterine sarcomas in 2009 to 2017 were collected. BCOR immunohistochemistry and fluorescence in situ hybridization (FISH) using break-apart probes flanking BCOR, ZC3H7B, CCNB3, YWHAE, NUTM2, JAZF1, and BCORL1 were performed. Tumors lacking or harboring gene rearrangement with no known fusion partner by FISH were subjected to targeted RNA sequencing. Morphology was correlated with FISH and sequencing results. BCOR expression was moderate to strong in .50% of cells in 8 tumors, while weak in 5% cells and negative in 2. FISH detected mutually exclusive ZC3H7B-BCOR and YWHAE-NUTM2 fusions in 3 uniform undifferentiated uterine sarcomas; 2 pleomorphic tumors harbored YWHAE rearrangement with no known partner. Targeted RNA sequencing of 5 FISH-negative uniform undifferentiated uterine sarcomas detected BRD8-PHF1 and YWHAE-NUTM2B fusions and BCOR internal tandem duplication in 4 of them. Tumors with YWHAE-NUTM2 fusions and BCOR genetic abnormalities showed morphology characteristic of high-grade endometrial stromal sarcomas. No fusions were detected by sequencing in the tumor with YWHAE rearrangement only by FISH. Most tumors classified as undifferentiated uterine sarcomas represent misdiagnosed high-grade endometrial stromal sarcomas. BCOR expression in .50% of cells may help triage tumors for molecular confirmation of highgrade endometrial stromal sarcoma-related genetic abnormalities. Novel YWHAE rearrangements may define a subset of true undifferentiated pleomorphic sarcomas.
AB - Undifferentiated uterine sarcoma is a diagnosis of exclusion with limited molecular genetic data available. Recent recognition of high-grade endometrial stromal sarcomas with diverse genotypes suggests that some tumors classified as undifferentiated uterine sarcomas may represent misdiagnosed high-grade endometrial stromal sarcomas. Archival material from 10 tumors diagnosed as undifferentiated uterine sarcomas in 2009 to 2017 were collected. BCOR immunohistochemistry and fluorescence in situ hybridization (FISH) using break-apart probes flanking BCOR, ZC3H7B, CCNB3, YWHAE, NUTM2, JAZF1, and BCORL1 were performed. Tumors lacking or harboring gene rearrangement with no known fusion partner by FISH were subjected to targeted RNA sequencing. Morphology was correlated with FISH and sequencing results. BCOR expression was moderate to strong in .50% of cells in 8 tumors, while weak in 5% cells and negative in 2. FISH detected mutually exclusive ZC3H7B-BCOR and YWHAE-NUTM2 fusions in 3 uniform undifferentiated uterine sarcomas; 2 pleomorphic tumors harbored YWHAE rearrangement with no known partner. Targeted RNA sequencing of 5 FISH-negative uniform undifferentiated uterine sarcomas detected BRD8-PHF1 and YWHAE-NUTM2B fusions and BCOR internal tandem duplication in 4 of them. Tumors with YWHAE-NUTM2 fusions and BCOR genetic abnormalities showed morphology characteristic of high-grade endometrial stromal sarcomas. No fusions were detected by sequencing in the tumor with YWHAE rearrangement only by FISH. Most tumors classified as undifferentiated uterine sarcomas represent misdiagnosed high-grade endometrial stromal sarcomas. BCOR expression in .50% of cells may help triage tumors for molecular confirmation of highgrade endometrial stromal sarcoma-related genetic abnormalities. Novel YWHAE rearrangements may define a subset of true undifferentiated pleomorphic sarcomas.
KW - BCOR
KW - endometrial stromal sarcoma
KW - PHF1
KW - undifferentiated endometrial sarcoma
KW - undifferentiated uterine sarcoma
KW - YWHAE
UR - http://www.scopus.com/inward/record.url?scp=85061936146&partnerID=8YFLogxK
U2 - 10.1097/PAS.0000000000001215
DO - 10.1097/PAS.0000000000001215
M3 - Article
C2 - 30789359
AN - SCOPUS:85061936146
SN - 0147-5185
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
ER -