Expanding the Morphological, Immunohistochemical, and Molecular Spectrums of NUT Carcinoma at Rare Sites of Head and Neck Region.

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.