Synchronous Small Cell and Adenocarcinoma of the Lung Integrating Morphology and Molecular Profiling: A Case Report.
Robin Chang, Alejandro S Mendoza, Swikrity U Baskota
✦ AI-curated · Sources linked
Case in brief
A 61-year-old woman had two synchronous right upper-lobe tumors, both staged pT1bN0M0: a combined small cell lung carcinoma (SCLC) with adenocarcinoma, and a separate invasive adenocarcinoma. Core biopsy of the combined tumor showed only adenocarcinoma morphology. Profiling found shared TP53 C135Y, RB1 Q344, and KRAS G12C alterations at markedly different variant allele frequencies (about 46% in one tumor versus about 3% in the other), plus a dominant KRAS G12V alteration unique to the second tumor. Integrated findings favored independent primaries over intrapulmonary metastasis. The SCLC component determined adjuvant cisplatin-etoposide treatment.
What made this case unusual
The combined SCLC was undersampled on core biopsy, which showed only adenocarcinoma. Despite overlapping alterations, discordant variant allele frequencies and a tumor-specific KRAS G12V supported separate primary tumors rather than clonal spread.
Diagnostic / clinical pearl
In synchronous lung tumors, interpret molecular overlap alongside variant allele frequencies, tumor-specific alterations, histology, and clinical findings; shared mutations alone may not establish intrapulmonary metastasis.