Non-small cell lung carcinoma and its mimics on cytology and small biopsy samples: a practical approach aligned with...

Accurate classification of lung tumors in cytology specimens and small biopsies remains a diagnostic challenge because of limited cellularity, preanalytical variables, and significant morphologic overlap among entities. This review summarizes key cytomorphologic characteristics and practical immunocytochemical strategies, and common diagnostic pitfalls encountered in the evaluation of non-small cell lung carcinoma, small cell lung carcinoma, neuroendocrine tumors, secondary pulmonary neoplasms, and uncommon thoracic entities in endobronchial ultrasound-guided transbronchial needle aspiration and fine-needle aspiration samples. Particular emphasis is placed on the appropriate use of limited immunohistochemical panels to optimize tumor subtyping while preserving material for molecular testing. Diagnostic challenges such as crush artifact, necrosis, reactive mimics, overlapping morphologic patterns, and the risk of misclassification of rare tumors are addressed with practical guidance for differential diagnosis. By integrating morphologic assessment with ancillary testing, cytopathologists can achieve accurate tumor subtyping, distinguish mimics, and provide precise diagnoses that guide clinical management and selection of targeted therapies.