USMLE PRACTICE QUESTION OF THE WEEK

Question for December 12, 2025

A 70-year-old man with a 60-pack-year smoking history is admitted for hemoptysis and progressive shortness of breath. He has a chronic cough but reports worsening over the past 2 months. Physical exam reveals decreased breath sounds and dullness to percussion over the right upper lung. CT chest shows a 6-cm cavitary lesion with irregular borders. Bronchoscopy reveals necrotic tissue obstructing the right mainstem bronchus. Biopsy demonstrates malignant squamous cells with keratin pearls. His serum calcium is 12.3 mg/dL, and creatinine is 1.0 mg/dL.

Which of the following is the most likely mechanism for this patient's hypercalcemia?

A. Bone metastases with osteolysis

B. Increased calcitriol production

C. Vitamin D intoxication

D. Primary hyperparathyroidism

E. Increased parathyroid hormone-related peptide

Get Detailed Explanation

Correct Answer:

E. Increased parathyroid hormone-related peptide

Correct Answer Explanation:

This patient has squamous cell carcinoma of the lung, which often secretes PTHrP, leading to hypercalcemia without elevated PTH or vitamin D. Bone metastases are more typical of breast/prostate cancers. Calcitriol production is characteristic of lymphomas.

Further Insight:

Squamous cell carcinoma is strongly linked to smoking and classically central in location.
Paraneoplastic syndromes are high-yield associations: SIADH (small cell), PTHrP (squamous).