Non‐Small Cell Lung Carcinoma With Bilayered Architecture and TP53 Alteration: A Diagnostic Pitfall and a Potential Distinct Entity

ABSTRACT

The presence of a continuous basal cell layer is generally regarded as a defining feature of bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT), and preservation of this bilayered architecture is commonly used as a surrogate marker of benign behavior. We report a 1.1‐cm pulmonary nodule detected in a 75‐year‐old never‐smoker that exhibited marked high‐grade cytologic atypia in both luminal and basal cells. Immunohistochemical analysis demonstrated diffuse strong P53 expression and an increased proliferative index (Ki‐67 approximately 10%). Targeted next‐generation sequencing revealed a pathogenic TP53 mutation (p.A161T). Despite the intact basal layer, the diffuse high‐grade cytology and shared strong P53 expression in both compartments indicate that this lesion represents a fully malignant carcinoma rather than a benign BA/CMPT. In practice, it can only be classified as non‐small cell lung cancer (NSCLC), NOS, with a distinctive bilayered phenotype. This case emphasizes that a preserved basal cell layer does not always equate to benignity, and it highlights a rare tumor type that may mimic BA/CMPT, carrying a risk of underdiagnosis. Integrating cytology, immunophenotype, and molecular findings is crucial for correct classification.