NUT Carcinoma: Clinicopathologic features, pathogenesis, and treatment

Abstract

NUT carcinoma (NC) is a rare, aggressive subtype of squamous cell carcinoma defined by rearrangement of the NUTM1 (aka NUT) gene. NC is driven by NUT‐fusion oncoproteins resulting from chromosomal translocation, most commonly BRD4‐NUT. This is a nearly uniformly lethal cancer affecting patients of all ages, but predominantly teens and young adults. The cell of origin is unknown, but NC most commonly arises within the thorax and head and neck. NC typically consists of sheets of monomorphic primitive round cells that can exhibit focal abrupt squamous differentiation. Diagnosis of NC is easy, and can be established by positive NUT nuclear immunohistochemical staining. Though characterization of the NUTM1‐fusion gene is desirable by molecular analysis, it is not required for the diagnosis. The increasingly widespread availability of the NUT diagnostic test is leading to increasing diagnoses of this vastly underdiagnosed disease. The NUT midline carcinoma registry (http://www.NMCRegistry.org) serves as a central repository that has provided the main source of clinical and outcomes data for NC. Currently there is no effective therapy for NC, however small molecules directly targeting the BRD4 portion of BRD4‐NUT, termed BET bromodomain inhibitors, have shown activity.

Primary malignant epithelioid and rhabdoid tumor of bone harboring ZNF532‐NUTM1 fusion: the expanding NUT cancer family

“…1 Histologically, NC shows a high grade poorly differentiated morphology, with solid sheets of round to epithelioid tumor cells, brisk mitoses, tumor necrosis, and abrupt foci of squamous differentiation in 33% to 40% of cases. 1 Histologically, NC shows a high grade poorly differentiated morphology, with solid sheets of round to epithelioid tumor cells, brisk mitoses, tumor necrosis, and abrupt foci of squamous differentiation in 33% to 40% of cases.…”

SMARCB1 (INI‐1) and NUT immunoexpression in a large series of head and neck carcinomas in a Brazilian reference center

“…To date, about 73 cases of SMARCB1 (INI-1)-deficient sinonasal carcinoma (SDSC) have been reported, [1][2][3][4][5] representing between 3% to 6% of all sinonasal carcinomas. 11,12 To date, approximately 51 head and neck NUT carcinomas have been reported. Recently, 12 SMARCB1 (INI-1)-deficient sinonasal adenocarcinomas have been reported.…”

“…Recently, 12 SMARCB1 (INI-1)-deficient sinonasal adenocarcinomas have been reported. [11][12][13] Initially described in children and adolescents, it is now clear that NUT carcinoma can develop in all ages, without gender distinction, although its true incidence remains unclear. Moreover, we have recently reported a rare case of SMARCB1 (INI-1)intact myoepithelial carcinoma with rhabdoid features in the maxillary sinus, expanding the clinicopathological spectrum of sinonasal carcinomas.…”

“…6 These findings indicate that the histomorphological spectrum of SMARCB1 (INI-1)-deficient tumors are broader than initially described. 11,12 To date, a standard treatment for NUT carcinoma has not been established and a multimodal approach including surgery, chemotherapy and radiation therapy is currently adopted in the clinical practice, 11,12 whereas some SMARCB1 (INI-1)-deficient carcinomas appear to show enhanced radiochemosensitivity. 7 Noteworthy, SMARCB1 (INI-1)-deficient carcinomas in extrasinonasal location are extremely rare.…”

“…Moreover, we have recently reported a rare case of SMARCB1 (INI-1)intact myoepithelial carcinoma with rhabdoid features in the maxillary sinus, expanding the clinicopathological spectrum of sinonasal carcinomas. 2,6,[11][12][13][14] In this context, the correct diagnosis of these cases is fundamental. 1,[8][9][10] Nuclear protein in testis (NUT) carcinoma is a rare and aggressive poorly differentiated carcinoma, often affecting the head and neck region (especially the nasal cavity and paranasal sinuses).…”