Late-Onset Li-Fraumeni Syndrome-Like Phenotype Presenting With Synchronous Lung Adenocarcinoma and Ovarian High-Grade Serous Carcinoma: A Case Report

TL;DR

A 53-year-old woman with two cancers shows a Li-Fraumeni-like syndrome without typical genetic mutations, highlighting the need for genomic profiling in complex cancer cases.

Contribution

This case presents a late-onset Li-Fraumeni-like phenotype with TP53 mutations in tumors but no germline mutations, suggesting non-classic inheritance patterns.

Findings

Synchronous ovarian and lung cancers showed TP53 mutations without germline TP53 mutations.

The F341Y TP53 variant was identified in both tumors, suggesting a somatic mosaic mutation.

The case highlights the importance of integrating tumor and germline genomic data for accurate diagnosis.

Abstract

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.

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