Unveiling the enigmatic primary pulmonary NUT carcinoma with WHSC1L1::NUTM1-rearrangement : a case-based insight and contemporary literature review

Abstract NUT carcinoma (NC) is a rare, aggressive, and genetically defined epithelial malignancy characterized by rearrangements involving the NUTM1 gene, most commonly BRD4::NUTM1 fusions. Although classically and initially described as involving midline location, especially the sinonasal region of children and young adults, NC has been found to have myriad localizations and age affliction, with primary pulmonary involvement being exceedingly uncommon. A 60-year-old female presented with a non-productive cough, weight loss, and anorexia. Imaging revealed a right upper lobe lung mass with mediastinal involvement and subcarinal lymphadenopathy. Biopsy demonstrated an undifferentiated carcinoma with focal abrupt keratinization and immunohistochemically the tumor exhibited strong positivity for p40 and NUT protein, confirming the diagnosis of NC. PD-L1 testing revealed a tumor proportion score (TPS) of 70%. Next-generation sequencing identified a rare WHSC1L1::NUTM1 fusion. The patient was treated with paclitaxel and carboplatin with partial thoracic response; however, new skeletal metastases developed, and she was transitioned to palliative care.