A man in his early 20s presented with progressive dyspnea and a cough producing mucus and tissue fragments. He is a non-smoker but has a history of occasional vaping. Imaging revealed a midline thoracic mass abutting the central airways with extensive mediastinal lymphadenopathy. A bronchoscopic biopsy was performed. The biopsy demonstrated sheets of tumor cells infiltrating a desmoplastic stroma (Figure 1, 4×). The neoplastic cells appeared relatively monotonous with focal keratinization (Figure 2, 10×; Figure 3, 20×). Notably, there were areas of abrupt squamous differentiation with keratin "pearls" (Figures 4 and 5, 20×). By immunohistochemistry, the tumor cells were diffusely positive for p40 and negative for TTF-1, and no intracytoplasmic mucin was identified on special stains. Given the patient's age and the unusual presentation, additional studies were performed: a NUT antibody immunostain showed speckled nuclear positivity, and molecular testing confirmed a BRD4::NUTM1 gene fusion, establishing the diagnosis.

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