A 58-year-old man with a lung mass has elevated serum calcium (12.8 mg/dL) but no bone metastases on imaging. PTH-rP is elevated. The tumor histology shows cells with intercellular bridges and abundant pink cytoplasm. Which molecular alteration is MOST characteristic of this tumor type?
- A SOX2 amplification at 3q26 ✓
- B EGFR exon 19 deletion
- C ALK rearrangement
- D KRAS codon 12 mutation
Correct answer: A. SOX2 amplification at 3q26
Explanation
The clinical scenario describes squamous cell carcinoma of the lung (intercellular bridges, pink cytoplasm) causing humoral hypercalcemia of malignancy via PTH-rP secretion. Squamous cell carcinoma characteristically shows amplification of the SOX2 oncogene at chromosome 3q26, which is a key molecular driver in squamous differentiation. EGFR deletions and ALK rearrangements are features of adenocarcinoma, and KRAS mutations are also more common in adenocarcinoma.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.