Minimalistic Immunomarker Approach for the Diagnosis of Non Small Cell Lung Carcinoma with Emphasis on Tumours with Ambiguous Morphology

Abstract

Introduction: Diagnosing Non Small Cell Lung Carcinoma (NSCLC) by morphology on small biopsy specimens are on demand. With major advances in molecular testing of lung cancers and introduction of targeted therapies, accurate subtyping of NSCLC has become essential. Immunophenotyping with various immunomarkers is helpful in identification of different tumour subtypes. As sparing material for molecular testing is mandatory, a minimalistic Immunohistochemistry (IHC) based diagnostic approach is warranted by means of reliable and accessible immunomarkers. In this study, one immunomarker Thyroid Transcription Factor (TTF1) for glandular and protein40 (p40) for squamous differentiation was applied to maximise the proportion of accurately subtyped NSCLC on small biopsy specimens. Aim: To find utility of TTF1/p40 minimalistic immunopanel in subtyping NSCLC especially those with ambiguous morphology. Materials and Methods: This retrospective observational study was conducted from 15 December 2020 to 5 March 2021 in a tertiary care hospital in which 93 (mean age 64.8 years, Male:female ratio 4.8:1) consecutive lung biopsies from suspected lung carcinoma obtained from January 2019 to December 2020 were studied. The morphological diagnosis and diagnosis after application of TTF1 and p40 minimalistic immunopanel was evaluated using chi-square test. The p-value <0.01 was considered significant. Results: Based on morphology, only 21 (22.5%) cases out of 93 cases of NSCLC were characterised into Adenocarcinoma (ADC) and Squamous Cell Carcinoma (SCC), whereas 72 (77.4%) were grouped as NSCLC ambiguous type. With addition of IHC (p40 and TTF1), the latter category reduced to 10 (10.7%) which constituted final NSCLC Not Otherwise Specified (NOS) category and a sum of 79 (84.9%) cases were accurately subtyped into SCC and ADC. Significance of adding TTF1/p40 immunopanel in the diagnosis of non small cell carcinoma was found to be very significant(p-value<0.001) p40 showed 100% sensitivity and 92.6% specificity for SCC where as TTF1 showed sensitivity of 92.59% and 100% specificity for ADC. Conclusion: Study showed that a minimalistic approach using only two antibodies (p40 and TTF1) might help in subtyping NSCLC especially those with ambiguous morphology and reduction of category of NSCLC NOS significantly and contribute in sparing material for molecular testing.