William Le, Megana Tirupathi, Luke Oh, Michael Diaz, Sreelatha Tirupathi
Combined lung carcinomas containing both non-small cell and high-grade neuroendocrine components are rare and diagnostically challenging due to intratumoral heterogeneity. We report a 61-year-old never-smoking woman with pleuritic chest discomfort and chronic cough. Computed tomography (CT) and positron emission tomography (PET)/CT demonstrated a left upper-lobe pulmonary nodule with intensely FDG-avid hilar and mediastinal lymphadenopathy. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of FDG-avid lymph nodes was nondiagnostic. Given persistent clinical and radiologic concern for malignancy, the patient underwent video-assisted thoracoscopic surgery (VATS) for definitive diagnosis. Pathology revealed a rare triple-component malignancy composed of adenocarcinoma, large-cell neuroendocrine carcinoma, and small-cell lung carcinoma, with metastatic neuroendocrine carcinoma involving mediastinal lymph nodes and pleura, consistent with stage IVA disease. The patient was subsequently treated with platinum-etoposide-based systemic therapy, with immunotherapy planned as part of her treatment course. This case highlights that nondiagnostic minimally invasive sampling does not exclude malignancy and underscores the importance of radiologic-pathologic concordance, awareness of sampling limitations, and timely escalation to additional tissue acquisition, including surgical biopsy when appropriate.