Midline Carcinoma with NUT Rearrangement

Abstract

Objective: 1) Report the clinicopathologic features of a rare, midline carcinoma. 2) Review the literature on NUT midline carcinoma and associated treatment protocols. Method: Case report with review of the literature on NUT midline carcinoma. Results: A 23-year-old Chinese man presented with a 10-day history of enlarging nontender cervical lymphadenopathy, dysphagia, and dysarthria. Clinical examination demonstrated right tongue atrophy and a 6-cm ipsilateral level III neck mass. CT of the neck with contrast revealed an infiltrating hypopharyngeal lesion and bilateral necrotic cervical lymphadenopathy. At microlaryngoscopy, the patient was noted to have a friable postcricoid mucosal lesion that on multiple biopsies revealed only necrosis. Cytogenetic analysis of a lymph node biopsy demonstrated chromosomal rearrangements consistent with a translocation between chromosomes 15 and 19, ie, t(15;19), resulting in the fusion oncogene BRD4-NUT consistent with diagnosis of NUT midline carcinoma (NMC). NMC is a newly recognized entity identified by the presence of chromosomal rearrangements involving the nuclear protein in testis (NUT) gene on chromosome 15q14. The clinical course is rapid and fatal and to date there is not a well-established treatment protocol. NMC is likely under-diagnosed and should be considered within the differential diagnoses in all poorly differentiated and undifferentiated midline carcinomas, particularly in young adult, nonsmokers. The patient presented is currently under treatment. Conclusion: Accurate and prompt diagnosis of this rapidly progressing carcinoma is crucial to improving prognosis and identifying effective treatment regimens.