SMARCA4-deficient undifferentiated uterine sarcoma (malignant rhabdoid tumor of the uterus): a clinicopathologic entity distinct from undifferentiated carcinoma
2018
Small cell carcinomaof the ovary, hypercalcemic type is a rare, aggressive malignancy which usually occurs in young women and is characterized by mutations in
SMARCA4, with few other alterations. We recently encountered uterine tumors with morphologic, immunohistochemical, and genetic similarities to
small cell carcinomaof the ovary, hypercalcemic type. Herein we report the clinicopathologic and molecular features (using a targeted
massively parallel sequencing[MPS] assay) of these tumors. The cases were diagnosed on cervical and
endometrial biopsies(n = 2, 34, and 29 years) or hysterectomy and
bilateral salpingo-oophorectomy(n = 3, 25, 33, and 58 years). The tumors were composed of sheets of large atypical
epithelioid cellswith prominent
rhabdoidmorphology, indistinguishable from the “large cell” variant of
small cell carcinomaof the ovary, hypercalcemic type. In three cases, the ovaries were pathologically examined to exclude a primary ovarian malignancy. Immunohistochemically, four of four cases showed
SMARCA4loss, and were negative or only focally positive for keratins, EMA, and
claudin-4. One of three cases was positive for WT-1. Targeted MPS was successfully performed on 4 of 5 tumors, and showed recurrent mutations in
SMARCA4, with few other alterations. Of the cases diagnosed on hysterectomy, all had extensive
lymphovascular invasion, extra-uterine spread, and marked infiltrative growth. These tumors were uniformly aggressive; all patients died of disease (median survival 7 months, range 1–43 months). We propose this entity be called “
SMARCA4-deficient undifferentiated
uterine sarcoma(malignant
rhabdoidtumor of the uterus)”, a term which describes both the tumor’s underlying molecular abnormality and its morphology. Its unique clinicopathologic and molecular features differentiate it from other related malignancies, including undifferentiated endometrial carcinoma,
small cell carcinomaof the ovary (hypercalcemic type), and
epithelioid sarcoma. We review and discuss previously reported “
rhabdoidtumors of the uterus;” while they are a heterogenous group of tumors, some of them are likely examples of this entity. Correctly identifying cases of
SMARCA4-deficient
uterine sarcomafrom histologic mimics is important as it may have prognostic, predictive, and germline implications.
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