A 58-year-old man with squamous cell carcinoma of the lung develops hypercalcemia. Biopsy of the tumor reveals strong immunopositivity for PTHrP. Which mechanism best explains the hypercalcemia in this case?
- A Osteolytic bone metastases secreting RANKL
- B Tumor-derived 1,25-dihydroxyvitamin D overproduction
- C Ectopic secretion of PTHrP causing increased osteoclast activity ✓
- D Ectopic PTH secretion from chief cell differentiation within the tumor
Correct answer: C. Ectopic secretion of PTHrP causing increased osteoclast activity
Explanation
Squamous cell carcinoma of the lung is the classic cause of humoral hypercalcemia of malignancy (HHM) via ectopic PTHrP secretion. PTHrP binds PTH receptors in bone and kidney, stimulating osteoclast-mediated bone resorption and renal calcium reabsorption. Ectopic 1,25-D production occurs in granulomatous disease and lymphoma, not squamous carcinoma; true ectopic PTH is extremely rare.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.