NUTM1-fusion positive malignant neoplasms of the genitourinary tract: A report of six cases highlighting involvement of unusual anatomic locations and histologic heterogeneity Journal Article
| Authors: | Xu, B.; Chen, J. F.; Sarungbam, J.; Tickoo, S.; Dickson, B. C.; Reuter, V. E.; Antonescu, C. R. |
| Article Title: | NUTM1-fusion positive malignant neoplasms of the genitourinary tract: A report of six cases highlighting involvement of unusual anatomic locations and histologic heterogeneity |
| 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. © 2022 Wiley Periodicals LLC. |
| Keywords: | adult; clinical article; aged; middle aged; oncoprotein; genetics; histopathology; case report; cell cycle protein; cell cycle proteins; gene; nuclear protein; neoplasm proteins; transcription factor; tumor marker; transcription factors; cell heterogeneity; nuclear proteins; sarcoma; tumor protein; gene fusion; oncogene proteins, fusion; carcinoma; repressor protein; repressor proteins; soft tissue neoplasms; soft tissue tumor; genitourinary tract; basic helix loop helix leucine zipper transcription factor; basic helix-loop-helix leucine zipper transcription factors; nut; humans; human; male; female; article; nut carcinoma; brd4 protein, human; biomarkers, tumor; urogenital tract carcinoma; nutm1; anatomical location; nutm1 gene; mxd1 protein, human |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 61 |
| Issue: | 9 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2022-09-01 |
| Start Page: | 542 |
| End Page: | 550 |
| Language: | English |
| DOI: | 10.1002/gcc.23046 |
| PUBMED: | 35430756 |
| PROVIDER: | scopus |
| PMCID: | PMC9271589 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 August 2022 -- Source: Scopus |
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