A 60-year-old man presents to the emergency department with a 3-month history of persistent cough, unintentional weight loss of 12 kg, and intermittent hemoptysis. He denies fever or night sweats. He has a history of chronic obstructive pulmonary disease and a 40-pack-year smoking history. He uses a tiotropium inhaler. Vital signs are within normal limits. Physical examination reveals diminished breath sounds bilaterally and no lymphadenopathy. A chest X-ray shows a 4 cm central mass in the right hilar region. Serum sodium is 128 mEq/L. Bronchoscopy-guided biopsy reveals small, densely packed cells with nuclear molding, scant cytoplasm, and positive immunohistochemistry for chromogranin and synaptophysin.
Which of the following is the most likely diagnosis?
The correct answer is:
D) Small cell lung carcinoma
This patient’s presentation, including heavy smoking history, central hilar mass, rapid symptom progression (cough, weight loss, hemoptysis), and hyponatremia from syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characteristic of small-cell lung carcinoma. Biopsy shows small blue cells with nuclear molding and scant cytoplasm, confirming neuroendocrine origin, with positive chromogranin and synaptophysin staining. Small cell lung carcinoma arises centrally from neuroendocrine cells, is strongly associated with smoking cigarettes, and frequently presents with paraneoplastic syndromes like the syndrome of inappropriate antidiuretic hormone due to ectopic hormone secretion, leading to hyponatremia.
Answer choice A: Adenocarcinoma, is incorrect. Adenocarcinoma is the most common lung cancer, typically occurring at the lung periphery, and is less smoking-associated. It is most typically central in location, and SIADH is uncommon. On biopsy, it features glandular patterns and mucin without neuroendocrine markers.
Answer choice B: Bronchoalveolar carcinoma, is incorrect. Bronchoalveolar carcinoma is peripheral, mimics pneumonia, and lacks small cell morphology, neuroendocrine markers, or central mass association.
Answer choice C: Large cell carcinoma, is incorrect. Large cell carcinoma is a non-small cell type with large cells and prominent nucleoli, lacking neuroendocrine features or chromogranin/synaptophysin positivity. Paraneoplastic syndromes, like SIADH, are not typical.
Answer choice E: Squamous cell carcinoma, is incorrect. Squamous cell carcinoma is smoking-related and often central in location, presenting with similar symptoms as small cell lung carcinoma, but histology shows keratin pearls and intercellular bridges without neuroendocrine markers. It may cause hypercalcemia via parathyroid hormone-related peptide, but rarely presents with SIADH.
Key Learning Point
Small cell lung carcinoma is a high-grade neuroendocrine tumor linked to smoking, featuring small cells with nuclear molding and positive chromogranin/synaptophysin. Central location, rapid metastasis, and paraneoplastic syndromes (e.g., the syndrome of inappropriate antidiuretic hormone hyponatremia) distinguish it from other lung cancers.
