ArticleAmerican journal of cancer research2026
Sequential triple primary malignancies in the larynx, lung, and liver with discordant p53 expression patterns: a case report.
Article in American journal of cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Sequential triple primary malignancies are very uncommon. Distinguishing new primary tumors from metastases in cancer survivors is a diagnostic challenge. This case illustrates how comprehensive immunohistochemistry (IHC), particularly p53 expression patterns as a surrogate for TP53 gene status, can determine clonal independence. A 71-year-old male ex-smoker presented with three malignancies over 4 years. First, laryngeal squamous cell carcinoma (pT1bN0M0) showed complete loss of p53 staining (null pattern, truncating mutation). Four years later, lung adenocarcinoma (pT1bN1M0; TTF-1+/Napsin A+) showed strong, diffuse p53 nuclear positivity (missense mutation pattern). One month later, intrahepatic cholangiocarcinoma (pT1N0M0; CK7+/CK19+/TTF-1-) showed wild-type p53 (scattered weak positivity). Divergent p53 IHC patterns (two mutant phenotypes and one wild-type) indicated three independent primaries. The patient recovered well after each curative-intent surgery. Meticulous IHC profiling and careful interpretation of p53 staining patterns are crucial for distinguishing multiple primary cancers from metastatic disease.
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