A young adult presented with severe nasal congestion and was found to have a destructive 2.0 cm nasal cavity soft tissue mass by CT scan. The mass was biopsied, and microscopic examination revealed a malignant neoplasm composed of predominantly undifferentiated cells with a high nuclear-to-cytoplasmic ratio, a monotypic appearance, and abundant tumor necrosis. Immunohistochemically, tumor cells are strongly positive for AE1/AE3, p63, and the stain in Panel C of below figure.
1. The speckled nuclear pattern of staining in Panel C is a specific surrogate marker for a rearrangement involving which gene?
A. SMARCB1
B. EWSR1
C. NUTM1
D. IDH2
2. True or False: This is an extremely aggressive malignancy; however, some fusion partners have an overall better prognosis than others.
NUT Carcinoma
NUT carcinoma is a rare and aggressive epithelial malignancy, accounting for 1% of all head and neck carcinomas. In the head and neck, NUT carcinomas predominantly involve the sinonasal tract.
A rearrangement involving theNUTM1 gene defines this NUT carcinomas. Specifically, the most common rearrangement is BRD4::NUTM1 which are associated with a poor overall survival rate. Rarely, non-BRD4::NUTM1 fusions are present, which have a comparatively improved prognosis.
Histologically, NUT carcinoma grows as nests and sheets of undifferentiated appearing monotypic cells with high mitotic activity and necrosis. Occasionally, abrupt squamous differentiation can occasionally be seen next to the undifferentiated predominant component (Panel B – arrow).
The differential diagnosis of high-grade malignancies of the sinonasal tract with cytokeratin immunoreactivity include SWI/SNF complex-deficient sinonasal carcinoma (SMARCB1 or SMARCA4-deficient), squamous cell carcinoma, certain salivary carcinomas, neuroendocrine carcinomas, adamantinoma-like Ewing sarcoma, and sinonasal undifferentiated carcinoma, among others.
Reference
- Bishop JA, Thompson LDR, Loney EL, et al. NUT Carcinoma. In: WHO Classification of Tumours Editorial Board. Head and neck tumours [Internet; beta version ahead of print]. Lyon (France): International Agency for Research on Cancer; 2022 [cited 2024 Feb 12]. (WHO classification of tumours series, 5th ed.; vol. 9). Available from: https://tumourclassification.iarc.who.int/chapters/52/19
Quiz Answers
Q1 = C. NUTM1
Q2 = True
Melad N. Dababneh, MBBS
Head and Neck Pathology Fellow
Cleveland Clinic
