ZC3H7B-BCOR high-grade endometrial stromal sarcomas: A report of 17 cases of a newly defined entity Journal Article

Authors: Lewis, N.; Soslow, R. A.; Delair, D. F.; Park, K. J.; Murali, R.; Hollmann, T. J.; Davidson, B.; Micci, F.; Panagopoulos, I.; Hoang, L. N.; Arias-Stella, J. A. 3rd; Oliva, E.; Young, R. H.; Hensley, M. L.; Leitao, M. M. Jr; Hameed, M.; Benayed, R.; Ladanyi, M.; Frosina, D.; Jungbluth, A. A.; Antonescu, C. R.; Chiang, S.
Article Title: ZC3H7B-BCOR high-grade endometrial stromal sarcomas: A report of 17 cases of a newly defined entity
Abstract: High-grade endometrial stromal sarcoma likely encompasses underrecognized tumors harboring genetic abnormalities besides YWHAE-NUTM2 fusion. Triggered by three initial endometrial stromal sarcomas with ZC3H7B-BCOR fusion characterized by high-grade morphology and aggressive clinical behavior, we herein investigate the clinicopathologic features of this genetic subset by expanding the analysis to 17 such tumors. All of them occurred in adult women with a median age of 54 (range, 28-71) years. They were predominantly based in the endomyometrium and demonstrated tongue-like and/or pushing myometrial invasion. Most were uniformly cellular and displayed haphazard fascicles of spindle cells with mild to moderate nuclear atypia. Myxoid matrix was seen in 14 of 17 (82%) tumors, and collagen plaques were seen in 8 (47%). The mitotic index was >= 10 mitotic figures/10 high-power fields (HPFs) in 14 of 17 (82%) tumors with a median of 14.5 mitotic figures/10 HPFs. No foci of conventional or variant low-grade endometrial stromal sarcoma were seen. All tumors expressed CD10 with only limited or absent desmin, SMA and/or h-caldesmon staining. ER and PR expression in >5% of cells was seen in 4 of 12 (33%) tumors. Diffuse cyclin D1 and BCOR immunoreactivity was present in 7 of 8 (88%) and 7 of 14 (50%) tumors, respectively. Fluorescence in situ hybridization or targeted RNA sequencing confirmed ZC3H7B-BCOR fusion in all tumors, including four and two previously diagnosed as myxoid leiomyosarcoma and undifferentiated uterine sarcoma, respectively. Limited clinical data suggest that patients present at higher stage and have worse prognosis compared with published outcomes in low-grade endometrial stromal sarcoma. Tumors with ZC3H7B-BCOR fusion constitute a distinct group of endometrial stromal sarcomas with high-grade morphology that should be distinguished from other uterine mesenchymal neoplasms that may demonstrate myxoid morphology.
Keywords: acute myeloid-leukemia; rearrangement; somatic mutations; internal tandem duplication; inflammatory; myofibroblastic tumor; bcor; clear-cell-sarcoma; round-cell; mesenchymal neoplasms; ywhae-fam22; myxoid-leiomyosarcoma
Journal Title: Modern Pathology
Volume: 31
Issue: 4
ISSN: 0893-3952
Publisher: Nature Publishing Group  
Date Published: 2018-04-01
Start Page: 674
End Page: 684
Language: English
ACCESSION: WOS:000430404600014
DOI: 10.1038/modpathol.2017.162
PUBMED: 29192652
Notes: Article -- Source: Wos
Altmetric Score
MSK Authors
  1. Meera Hameed
    138 Hameed
  2. Mario Leitao
    307 Leitao
  3. Cristina R Antonescu
    609 Antonescu
  4. Marc Ladanyi
    870 Ladanyi
  5. Kay Jung Park
    182 Park
  6. Martee L Hensley
    220 Hensley
  7. Robert Soslow
    643 Soslow
  8. Rajmohan Murali
    156 Murali
  9. Achim Jungbluth
    340 Jungbluth
  10. Denise Frosina
    84 Frosina
  11. Deborah F DeLair
    86 DeLair
  12. Rym Benayed
    72 Benayed
  13. Sarah   Chiang
    42 Chiang
  14. Natasha Elizabeth Lewis
    9 Lewis