Tumors with NUTM1 fusions occur predominantly in the thoracic cavity and head and neck region. However, recent literature expanded the location of NUTM1-translocated malignancy to soft tissue, brain, and visceral organs. In this study, we describe the first series of six NUTM1-translocated carcinomas and sarcomas occurring in the genitourinary tract. The sites of origin were kidney (n = 2), bladder (n = 3), and penis (n = 1). All tumors occurred in adulthood (range: 30-78 years). The histologic features were heterogeneous, showing epithelial, spindle cell, or primitive small blue round cell morphology. Glandular architecture, keratinization, rhabdoid cells, or myxoid-to-edematous stromal component were also noted. In three cases, features were in keeping with a carcinoma (two from kidney and one from bladder), whereas the remaining three were classified as malignant undifferentiated neoplasm (MUN)/sarcoma. Fusion partners detected in four cases tested by either FISH and/or RNA sequencing were BRD4 in two kidney tumors, MXD1 in a bladder sarcoma, and MXD4 in a penile sarcoma. NUT immunostain showed diffuse spiculated positivity in five cases. Immunopositivity for various cytokeratins was noted in two tumors. The outcome of NUTM1-rearranged genitourinary malignancy was dismal: four of five cases with follow-up developed distant metastasis, and three suffered disease-specific death. In conclusion, NUTM1-rearranged carcinoma and sarcoma can affect the genitourinary tract, including kidney, bladder, and penis. Histologic features and keratin immunoexpression are highly variable. A NUTM1-fusion positive malignancy may be included in the differential diagnosis of a MUN of the genitourinary tract given the dismal outcome and the existing BET-targeted therapy for tumors with BRD3/4::NUTM1 fusion.
Keywords: NUT; NUT carcinoma; NUTM1; genitourinary tract.
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