title: The clinicopathologic features of YWHAE-FAM22 endometrial stromal sarcomas: a histologically high-grade and clinically aggressive tumor.
abstract: Endometrial stromal sarcoma (ESS) is a genetically heterogenous group of uterine sarcomas, of which almost half are associated with JAZF1 rearrangement. We recently identified a novel genetic fusion between YWHAE and FAM22A/B in ESS harboring t(10;17)(q22;p13) and herein describe the clinicopathologic features of 13 YWHAE-FAM22 ESS cases (11 primary and 3 metastatic) and compare them with 20 ESS cases with JAZF1 rearrangement. Ten of 11 primary uterine tumors contained morphologically high-grade areas composed of round cells arranged in nests with a delicate stromal capillary network. The tumor cells showed large nuclei with irregular nuclear contours and significant mitotic activity (>10 mitoses/10 HPF) in addition to focal tumor necrosis, in contrast to JAZF1 ESS, which lacked a nested growth pattern, were composed of cells with small round/oval nuclei, and typically had <5 MF/10 HPF. In 7 of the 11 uterine tumors, there was an additional cytologically bland and mitotically weakly active spindle cell component with a fibrous/fibromyxoid stroma (ESS, fibromyxoid variant). Two metastatic tumors (pulmonary) also contained round cell and spindle cell components, whereas 1 metastasis (vaginal) was composed solely of the spindle cell component. In both primary and metastatic tumors, the spindle cells were diffusely positive for estrogen and progesterone receptors and CD10, in contrast to the round cell areas, which were negative. Clinically, 10 of 12 patients with YWHAE-FAM22 ESS presented with FIGO stages II to III disease, in contrast to only 4 of 16 patients with JAZF1 ESS presenting with stages II to III disease (P<0.05). Tumors with YWHAE-FAM22 rearrangements constitute a distinct group of ESS, which is associated with high-grade morphology and aggressive clinical behavior compared to JAZF1 ESS. Thus, their distinction from typical JAZF1 ESS is important for prognostic and therapeutic purposes.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.forename: Adrian
authors.initials: A
authors.lastname: Mariño-Enriquez
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ou
authors.forename: Meijun
authors.initials: M
authors.lastname: Zhu
authors.forename: Rola H
authors.initials: RH
authors.lastname: Ali
authors.forename: Sarah
authors.initials: S
authors.lastname: Chiang
authors.forename: Frédéric
authors.initials: F
authors.lastname: Amant
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: Paola
authors.initials: P
authors.lastname: Dal Cin
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fletcher
authors.forename: Marisa R
authors.initials: MR
authors.lastname: Nucci
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D018203:Sarcoma, Endometrial Stromal / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; C430460:JAZF1 protein, human; D009363:Neoplasm Proteins; C482983:YWHAE protein, human