Characterization of Nonsmall Cell Lung Carcinoma in Limited Biopsy Samples and Identifying Optimal Immunohistochemical Marker Combinations in Resource-Constrained Setup: An Institutional Experience

Abstract

Abstract Background The incorporation of immunohistochemical markers in the analysis of small biopsy samples, as outlined in the fourth edition of the World Health Organization Blue books, represents a noteworthy advancement in the diagnosis of advanced-stage lung carcinoma. This improved the histological classification for poorly differentiated nonsmall cell lung carcinomas (NSCLCs), especially in small biopsy specimens. Despite challenges in obtaining viable cells from diminutive tumor samples, a focused immunohistochemical panel effectively distinguishes histological types in most NSCLC. This preserves tissue for subsequent molecular testing. Material and Methods This study examined 130 consecutive lung biopsy cases initially diagnosed as NSCLC, including various biopsy types (transbronchial, endobronchial, ultrasound-guided, computed tomography-guided). Carcinomas were categorized based on specific characteristics, such as glands and/or mucin for adenocarcinomas, keratinization and/or intercellular bridges for squamous cell carcinomas, and recognition of poorly differentiated NSCLC. Cases lacking clear morphological attributes underwent reclassification using immunohistochemical markers (TTF1, Napsin A, p63, and p40). Results TTF1 exhibited superior sensitivity (97.56%) and specificity (96.77%) for adenocarcinoma compared with Napsin A, with sensitivity and specificity at 90.24 and 93.3%, respectively. p63 and p40 demonstrated 100% sensitivity for squamous cell carcinoma, with p40 being more specific than p63 (100% vs. 82.92%). Using TTF1 and p63 as a conventional panel, 87% of cases were subtyped. However, the combination of TTF1 and p40 achieved accurate classification in 94.66% (71/75) of cases, and all four markers allowed subtype identification in 97.2% (73/75) of cases. Conclusion In a resource-constrained setting, subtyping NSCLC in small biopsy can be effectively accomplished using a minimal panel consisting of TTF1 and p40 immunohistochemical markers.