NUTM1‐fusion positive malignant neoplasms of the genitourinary tract: A report of six cases highlighting involvement of unusual anatomic locations and histologic heterogeneity. Issue 9 (27th April 2022)

• Record Type: Journal Article
• Authors: Xu, Bin; Chen, Jie‐Fu; Sarungbam, Judy; Tickoo, Satish; Dickson, Brendan C.; Reuter, Victor E.; Antonescu, Cristina R.
• Is Part Of: Genes, chromosomes & cancer. Volume 61:Issue 9(2022)
• Page Start: 542
• Page End: 550
• Publication Date: 2022-04-27
• Subjects: genitourinary tract -- NUT -- NUT carcinoma -- NUTM1; Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.23046
• Languages: English
• ISSNs: 1045-2257

Abstract

Abstract: 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.