NUT carcinoma of the upper respiratory tract: Two case reports and literature review

NUT carcinoma is a rare and highly aggressive malignancy characterized by the rearrangement of the NUTM1 gene. It typically arises in midline structures, including the respiratory tract. Due to its rarity and poor prognosis, early diagnosis and effective treatment remain challenging. This report presents two cases of NUT carcinoma occurring in the respiratory tract, additionally, a review of the literature is provided to enhance understanding of this disease. Both patients were young females, one tumor was located in the larynx and the other in the left main bronchus. Endoscopic forceps biopsy samples revealed tumor growth beneath the superficial mucosal epithelium, arranged in sheets, cords, or nests with extensive necrosis. The tumor cells were uniform in size, with eosinophilic cytoplasm, ill-defined borders, and round or oval nuclei showing hyperchromasia and a high nuclear-to-cytoplasmic ratio. One case showed focal areas with squamous differentiation. Immunohistochemically, tumor cells were positive for P40, P63, and NUT, and fluorescence in situ hybridization detected NUT gene rearrangement, confirming the diagnosis of NUT carcinoma. One patient experienced rapid disease progression despite receiving chemotherapy and died within five months. Another patient declined further treatment after diagnosis. NUT carcinoma is a rare and aggressive malignancy of the respiratory tract with a poor prognosis. Early diagnosis through molecular testing is crucial for appropriate management. However, diagnosis is often delayed until advanced stages, contributing to low survival rates. Increased awareness of this tumor among clinicians and pathologists may facilitate earlier detection and potentially improve patient outcomes.