Which lung cancer type is most strongly associated with paraneoplastic manifestations such as SIADH and Lambert-Eaton syndrome?

• A. Adenocarcinoma
• B. Squamous cell carcinoma
• C. Small cell carcinoma
• D. Large cell carcinoma

Answer: (C)

Paraneoplastic phenomena in lung cancer arise from tumor hormone production or immune effects. The strongest link to SIADH and Lambert-Eaton syndrome is small cell carcinoma. Its neuroendocrine nature allows ectopic hormone secretion, such as antidiuretic hormone, leading to SIADH with hyponatremia and low serum osmolality. It also triggers autoimmune processes against presynaptic voltage-gated calcium channels, causing Lambert-Eaton myasthenic syndrome, with proximal muscle weakness and autonomic features. This combination is classic for this cancer type. Other lung cancers can have paraneoplastic effects, but they don’t present this characteristic pair as reliably (for example, squamous cell often causes hypercalcemia via PTHrP), so small cell carcinoma is the best fit.