Primary pulmonary NUT carcinoma in an older adult with paraneoplastic hypercalcemia: A rare case report

Background: NUT carcinoma is a rare and highly aggressive malignancy characterized by rearrangement of the NUTM1 gene. It most commonly affects children and young adults and typically arises in midline structures such as the mediastinum, lung, and head and neck region. Due to its rarity and histologic overlap with poorly differentiated squamous cell carcinoma, it is frequently misdiagnosed, leading to delays in appropriate management. Reports in older adults remain scarce, and atypical clinical features may further complicate recognition. Case Presentation: We report the case of a 60-year-old male who presented with a three-week history of persistent cough, hemoptysis, weight loss, fever, and night sweats. Imaging revealed a large centrally located pulmonary mass with mediastinal lymphadenopathy. Endobronchial biopsy with immunohistochemical staining confirmed the diagnosis of NUT carcinoma. The patient was also found to have paraneoplastic hypercalcemia at presentation. He was treated with concurrent chemoradiotherapy followed by immunotherapy; however, the disease demonstrated rapid progression with subsequent metastatic spread despite multimodal therapy. Management ultimately shifted to palliative care. Discussion: This case highlights several uncommon aspects of NUT carcinoma, including presentation in an older adult and the presence of hypercalcemia as a possible paraneoplastic manifestation. It underscores the importance of considering NUT carcinoma in the differential diagnosis of poorly differentiated thoracic malignancies regardless of patient age. Early use of NUT-specific immunohistochemistry is critical to avoid misclassification and guide management. Despite aggressive treatment, prognosis remains poor, emphasizing the need for improved diagnostic awareness and targeted therapies. Conclusion: NUT carcinoma should be suspected in aggressive midline tumors even in older patients. Prompt immunohistochemical testing can facilitate accurate diagnosis, while recognition of atypical presentations such as hypercalcemia may aid early detection. Increased awareness of this rare entity is essential to improve diagnostic accuracy and future therapeutic outcomes.