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YWHAE-NUTM2A/B Translocated High-grade Endometrial Stromal Sarcoma Commonly Expresses CD56 and CD99

YWHAE-NUTM2A/B translocated high-grade endometrial stromal sarcoma is an uncommon and clinically aggressive uterine mesenchymal neoplasm which is sometimes associated with a low-grade fibromyxoid component. Although the diagnosis is confirmed using molecular techniques, it is possible to make the diagnosis based on the characteristic morphology and the immunophenotype; the latter typically includes diffuse positive staining of the high-grade component with cyclin D1 and CD117 and negative staining with CD10 and hormone receptors. Especially in a small biopsy specimen, in cases without a low-grade component or when presenting with extrauterine disease, the differential diagnosis may be wide and potentially include “small round cell tumors” such as a high-grade neuroendocrine carcinoma and a tumor in the Ewing family. In this study, we report consistent CD56 and CD99 immunoreactivity in YWHAE-NUTM2A/B translocated high-grade endometrial stromal sarcoma. We stained 20 of these neoplasms (10 molecularly confirmed and 10 where diagnosis was based on the morphology and immunophenotype) with CD56 and CD99; in one case, CD56 staining was not performed. Nineteen of 19 (100%) and 17 of 20 (85%) were positive with CD56 and CD99, respectively. Staining was usually diffuse with membranous and cytoplasmic immunoreactivity. Pathologists should be aware that YWHAE-NUTM2A/B translocated high-grade endometrial stromal sarcoma is commonly positive with CD56 and CD99; as well as potentially assisting in diagnosis, positivity with these markers may also result in consideration of other neoplasms in the differential diagnosis.