Hypercalcemia due to PTHrP is classically associated with which cancer?

• A. Small cell carcinoma of the lung
• B. Renal cell carcinoma
• C. Osteosarcoma
• D. Squamous cell carcinoma of the lung

Answer: (D)

Hypercalcemia from cancer is often due to humoral factors secreted by the tumor, most classically a peptide that mimics PTH. This PTH-related peptide raises calcium by stimulating bone resorption and increasing renal calcium reabsorption, with endogenous PTH suppressed. Among the cancers listed, squamous cell carcinoma of the lung is the classic source of PTHrP, leading to this type of hypercalcemia. The other tumors are more associated with different paraneoplastic syndromes or mechanisms (for example, small cell carcinoma often secretes ACTH or ADH), and osteosarcoma is not typically linked to PTHrP-driven hypercalcemia. So the best answer is squamous cell carcinoma of the lung.