A 65-year-old heavy smoker develops a centrally located lung mass on CXR. Biopsy shows small blue cells with nuclear molding, scant cytoplasm, 'salt and pepper' chromatin, and neuroendocrine markers (synaptophysin, INSM1, CD56) positive. TTF-1 is positive. SCLC is diagnosed. Which oncogene amplification most frequently drives SCLC and what is the key treatment implication?
- A KRAS G12C mutation — responsive to sotorasib
- B FGFR1 amplification — responsive to erdafitinib
- C ALK fusion — responsive to alectinib
- D MYC family amplification (MYC, MYCL, MYCN) — especially MYCL; no direct druggable target yet but predicts aggressive biology and CDK inhibitor trials ✓
Explanation
Small cell lung carcinoma (SCLC) is characterized by near-universal RB1 and TP53 loss (biallelic). MYC family amplification (MYCL1 amplified in ~18%, MYCN in ~4%, MYC in ~5%) is the most frequent oncogene amplification and defines an aggressive subgroup with shorter survival. Currently no direct MYC inhibitor is clinically approved, but high MYC expression predicts sensitivity to Aurora kinase inhibitors (alisertib) and is being studied. KRAS, FGFR1, and ALK alterations are characteristic of non-small cell lung cancer, not SCLC. SCLC first-line treatment is platinum-etoposide + anti-PD-L1 (atezolizumab/durvalumab).
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.