Oral and oropharyngeal NUT carcinoma: a multicentre screening study of poorly differentiated oral cancer

Abstract

Background and aimsNuclear protein testis (NUT) carcinoma (NC) is a rare and highly aggressive tumour characterised by chromosomal rearrangement of the nuclear protein testis family member 1 (NUTM1) gene, also known as the NUT gene. NC occurs mainly in the head and neck, mediastinum and lung. In general, primary NC in the oral cavity is extremely rare and reported sporadically.MethodsA total of 111 formalin‐fixed and paraffin‐embedded specimens of poorly differentiated oral and oropharyngeal tumours were collected from 10 hospitals. NUT protein IHC staining was performed on these samples, and fluorescence in‐situ hybridisation (FISH) and RNA sequencing detection were further carried out for NUT IHC‐positive cases.ResultsThe expression of NUT protein in tumour cells was detected in five cases (five of 111, 4.5%). The tumours in these cases were located in the oral floor, lip, base of the tongue, gingiva and hard palate. FISH detection results showed BRD4::NUT rearrangement in three patients and a non‐BRD4::NUT rearrangement pattern in two patients. RNA sequencing results confirmed BRD4::NUT rearrangement in two cases.ConclusionsTo our knowledge, this is the first and largest retrospective study of oral NC, and we found that NC is easily misdiagnosed as poorly differentiated oral squamous cell carcinoma (SCC) or poorly differentiated carcinoma. The morphology and immunophenotype of four NC cases were similar to SCC, and abrupt keratinisation was observed in three cases. Therefore, it is necessary to detect NUT protein for NC screening in oral malignant tumours with these morphologies, especially for young patients who are more likely to be misdiagnosed with other types of cancer.