Challenging Metastatic Melanoma to the Lung With p40 Expression: A Diagnostic Pitfall, Case Report

p40 immunohistochemistry is a cornerstone of histopathological examination for non-small cell lung carcinoma. p40 is an isoform of p63 and is reported to be highly specific for the diagnosis of squamous cell carcinoma. Very rare pitfalls are reported for this antibody, and p40 is typically negative in melanoma. A 66-year-old patient was admitted for multiple hemorrhagic brain tumors evocative of secondary tumors. On imaging, a 26 mm lung tumor was detected, and a biopsy of the lung tumor was performed. The tumor was stained by melanic markers and diffusely stained by p40 and p63. Molecular analysis found a somatic p.Asn581Ser (c.1742A>G) point mutation in exon 15 of BRAF and a p.Arg80Ter (c.238C>T) germline variant of CDKN2A , a predisposing mutation to melanoma. This case report highlights the importance of clinical, pathologic, and molecular correlation.