Sinonasal NUT carcinoma: clinicopathological and cytogenetic analysis with autopsy findings

Nuclear protein in testis (NUT) carcinoma is a rare malignant neoplasm with an undifferentiated morphology. Its diagnosis is often difficult, especially as the sinonasal tract gives rise to many tumors with undifferentiated morphologies. Not many cases of sinonasal NUT carcinomas have been reported, and its clinicopathological features have not been sufficiently clarified. In this study, we performed a clinicopathological study of 4 patients with sinonasal NUT carcinoma, including wide-ranging immunohistochemical tests and cytogenetic analyses using fluorescence in situ hybridization and DNA sequencing. Autopsy findings were obtained from 2 patients. Patients' ages ranged from 9 months to 66 years (median, 37 years). Three cases involved the nasal cavity; of these, 2 also involved the ethmoid sinus. One case only involved the frontal sinus. Histologically, all cases revealed undifferentiated small round cell morphology and necrosis with indistinct cell borders, vesicular chromatin, and distinct nucleoli. All patients received chemoradiotherapy; 3 died of disease 10 to 15 months after their diagnoses, while one was lost to follow-up. The 2 autopsied patients showed multiorgan metastases; interestingly, one showed cartilaginous differentiation in a metastatic lesion. Immunohistochemically, all cases were diffusely positive for NUT, p63, and Myc, and were focal for p40. The cells variably expressed epithelial markers, and CD34 was positive in one patient. Cytogenetically, all showed BRD4-NUT fusion genes, but one had a different breakpoint in each exon. Finally, a literature review indicated that sinonasal NUT carcinoma tends to involve frontal and ethmoidal sinuses more frequently than other sinonasal cancers.