A rare Japanese case with a NUT midline carcinoma in the nasal cavity: a case report with immunohistochemical and genetic analyses.

Background: NUT (nuclear protein in testis) midline carcinoma (NMC) is a recently described aggressive malignancy that is genetically defined by rearrangements of the NUT locus at 15q14. In approximately two-thirds of cases, the characteristic t(15;19) results in the fusion oncogene BRD4-NUT. Only 10 sinonasal NMCs have been documented, none of which were Japanese cases.

Case Presentation: An 18-year-old woman was admitted because of a rapidly progressing tumor in the nasal cavity. A biopsy revealed an undifferentiated neoplasm without squamous differentiation. The tumor cells had round to oval nuclei with vesicular chromatin, prominent nucleoli, and scant cytoplasm. Immunohistochemical staining demonstrated a strong positivity for vimentin and NUT, with focal CD138 and only spotty EMA and cytokeratin AE1/AE3 staining. Cytogenetic and fluorescence in situ hybridization analyses revealed a t(15;19) and BRD4-NUT gene rearrangement. Direct sequencing identified the in-frame fusion of exon11 of BRD4 with exon2 of NUT. The patient was transferred to another hospital for chemoradiotherapy.

Conclusion: We herein describe the first Japanese case with an NMC of the sinonasal cavity, providing detailed and unambiguous cyto- and molecular genetic information on BRD4-NUT-rearrangement. The accumulation of cases with well-documented genetic data should provide clues to the treatment of this tumor entity.