Late-Onset Li-Fraumeni Syndrome-Like Phenotype Presenting With Synchronous Lung Adenocarcinoma and Ovarian High-Grade...

Li-Fraumeni syndrome is classically defined by germline TP53 mutations and early-onset malignancies, yet the clinical spectrum has expanded to include atypical and late-onset presentations that challenge standard diagnostic criteria. We report the case of a 53-year-old female diagnosed with synchronous high-grade serous ovarian carcinoma and lung adenocarcinoma. Somatic analysis identified TP53 driver mutations in both tumors, including a specific F341Y variant, despite negative comprehensive germline testing. This discordance suggests a mosaic somatic mutation or a Li-Fraumeni-like phenotype distinct from classic inheritance patterns. This case illustrates the complexities of diagnosing hereditary cancer syndromes in patients with multiple primary malignancies and highlights the importance of integrating tumor genomic profiling with germline analysis to ensure accurate risk stratification and clinical management.