ABSTRACT

Objective

To expand the clinicopathological, immunohistochemical, and molecular spectrums of head and neck NUT carcinoma (HN-NC) of rare sites and explore potential prognostic factors and treatments.

Materials and Methods

HN-NCs were confirmed by NUT immunostaining, fluorescence in situ hybridization and/or next generation sequencing. Immunohistochemistry for therapeutic markers and follow-up were performed.

Results

Fifteen HN-NCs were collected. Most involved major salivary gland (n = 7) and oral mucosa (n = 5). Other sites included mandible (n = 1), and maxilla (n = 2). Nine out of 13 harbored BRD4::NUTM1 fusion while the others carrying rare ZNF532::NUTM1, novel CCNT2::NUTM1 and WHSC1L1::NUTM1 fusion respectively. Microscopically, three unusual morphologies were observed, resembling differentiated papillary squamous cell carcinoma, myoepithelial carcinoma and small round cell malignancy, respectively. SOX2, PRAME, c-MYC, EGFR showed positive staining in around half cases. During the average follow-up time of 12.8 months, 3/13 patients suffered recurrence, 5 had distant metastasis and 5 died of disease. Integrating with published reports, Kaplan–Meier method revealed that tumor site was associated with overall survival (p = 0.039), and fusion gene type was associated with disease-free survival (p = 0.039).

Conclusions

HN-NCs had dismal prognosis, especially those originating from oral mucosa. HN-NC should be included in the differential diagnosis when encountering poorly differentiated/undifferentiated malignancies or carcinomas with squamous differentiation.