Large cell neuroendocrine tumor of the lung: Case report of an uncommon tumor and brief literature review

Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare and aggressive malignancy accounting for approximately 1–3% of all lung cancers. Its rarity, combined with morphologic overlaps with other high-grade thoracic tumors, makes diagnosis and management challenging. We report the case of a 71-year-old male, a heavy smoker with a 45-pack-year history, who presented with a six-week history of progressive dyspnea, productive cough with hemoptysis, and significant weight loss. Imaging identified a 5.0 cm FDG-avid central right upper lobe mass with ipsilateral mediastinal nodal involvement, staged as IIIA disease. Following multidisciplinary tumor board review, the patient underwent right upper lobectomy with mediastinal lymph node dissection. Histopathology confirmed LCNEC with a Ki-67 proliferation index of 75%, and molecular profiling revealed co-mutations of TP53 and STK11 with loss of RB1 expression. The tumor was classified as an NSCLC-like subtype (non-small cell lung carcinoma). He received adjuvant cisplatin and etoposide and remained disease-free for 30 months before developing metastatic recurrence involving the liver, adrenal glands, and cerebellum. Subsequent systemic therapy proved refractory, and the patient died 19 weeks after recurrence, with an overall survival of 39 months. This case illustrates the diagnostic complexity, aggressive biology, and the critical role of multidisciplinary decision-making in managing resectable LCNEC, while underscoring the urgent need for evidence-based therapeutic strategies in this underrepresented tumor type.