<p>NUT midline carcinoma of the head and neck: current perspectives</p>

Abstract

: NUT midline carcinoma (NMC) is a rare and aggressive subtype of squamous carcinoma that typically arises from midline supradiaphragmatic structures, frequently from the head and neck area. NMC is genetically driven by a chromosomal rearrangement involving the NUT gene, which forms oncoproteins considered major pathogenic drivers of cellular transformation. Diagnosis of NMC has been made remarkably easier with the availability of a commercial antibody against NUT, and can be established through positive nuclear immunohistochemical staining. Although NMC remains an underrecognized malignancy, in recent years there has appeared to be increasing awareness of disease and frequency of diagnosis in adults. To date, a standard treatment for head and neck NMC has not been established and a multimodal approach with systemic chemotherapy, surgery and radiation therapy is currently adopted in clinical practice. Recently, BET inhibitors and histone deacetylase inhibitors have emerged as two promising classes of targeted agents, currently investigated in clinical trials for adults with head and neck NMC. At the same time, combination approaches and novel targeted agents, such as next-generation BET inhibitors and CDK9 inhibitors, have shown preclinical activity. The present review explores the clinical pathological characteristics of NMC of the head and neck and presents the current state of the art on diagnosis, prognosis, and treatment of this rare but lethal disease.

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

“…32 Similar with the current series, other study evaluated 155 poorly differentiated malignant tumors of the upper respiratory tract, including sinonasal, nasopharyngeal and neuroendocrine carcinomas, as well as nonepithelial malignant tumors, being detected four NUT carcinomas. 11,34,35 By considering SMARCB1 (INI-1)-deficient carcinoma, some of these cases survive for several years following multimodal therapy (especially nonmetastatic cases under aggressive adjuvant radiochemotherapy), suggesting enhanced chemosensitivity. Three and one case were previously diagnosed as poorly differentiated SCC and SNUC, respectively.…”

“…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).…”