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CC BY 4.0 · Avicenna J Med 2024; 14(03): 158-166
DOI: 10.1055/s-0044-1791560
Original Article

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

Ankita Grover
1   Department of Pathology, Goyal Hospital and Research Centre Pvt. Ltd, Jodhpur, Rajasthan, India
,
Md Ali Osama 
2   Department of Pathology, Lady Hardinge Medical College, New Delhi, India
,
Shashi Dhawan 
3   Department of Histopathology, Sir Gangaram Hospital, New Delhi, India
› Author Affiliations Funding The authors received no financial support for the research, authorship, and/or publication of this article.
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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.

Keywords

lung - immunohistochemistry - nonsmall cell - squamous - adenocarcinoma

Guarantor of Submission

The corresponding author is the guarantor of submission.


Ethics Statement

All procedures performed in the current study were approved by the Ethics Committee of Sir GangaRam Hospital, New Delhi, India (EC/03/14/649). Informed consent was waived by the Institutional Review Board.


Data Availability Statement

The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.


Authors' Contributions

A.G.: contributed with idea, design, acquisition of data, studying of collected data, data analysis, interpretation of data, and drafting the article.


M.A.O.: took part in design, concept, studying of collected data, interpretation of data, drafting the article, revising the article revising the article, and also shared final approval.


S.D.: took part in conceptualization, design, studying of collected data, interpretation of data, revising the article, and shared final approval.




Publication History

Article published online:
11 October 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Deo SVS, Sharma J, Kumar S. GLOBOCAN 2020 report on global cancer burden: challenges and opportunities for surgical oncologists. Ann Surg Oncol 2022; 29 (11) 6497-6500
    CrossrefPubMedSearch in Google Scholar
  • 2 Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 2008; 83 (05) 584-594
    CrossrefPubMedSearch in Google Scholar
  • 3 Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res 2016; 5 (03) 288-300
    CrossrefPubMedSearch in Google Scholar
  • 4 Al-Saleh K, Quinton C, Ellis PM. Role of pemetrexed in advanced non-small-cell lung cancer: meta-analysis of randomized controlled trials, with histology subgroup analysis. Curr Oncol 2012; 19 (01) e9-e15
    CrossrefPubMedSearch in Google Scholar
  • 5 Ocque R, Tochigi N, Ohori NP, Dacic S. Usefulness of immunohistochemical and histochemical studies in the classification of lung adenocarcinoma and squamous cell carcinoma in cytologic specimens. Am J Clin Pathol 2011; 136 (01) 81-87
    CrossrefPubMedSearch in Google Scholar
  • 6 Travis WD, Brambilla E, Noguchi M. et al. Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med 2013; 137 (05) 668-684
    CrossrefPubMedSearch in Google Scholar
  • 7 Xiao Y, Liu P, Wei J, Zhang X, Guo J, Lin Y. Recent progress in targeted therapy for non-small cell lung cancer. Front Pharmacol 2023; 14: 1125547
    CrossrefPubMedSearch in Google Scholar
  • 8 Zhang R, Shao F, Wu X, Ying K. Value of quantitative analysis of circulating cell free DNA as a screening tool for lung cancer: a meta-analysis. Lung Cancer 2010; 69 (02) 225-231
    CrossrefPubMedSearch in Google Scholar
  • 9 Petersen I. The morphological and molecular diagnosis of lung cancer. Dtsch Arztebl Int 2011; 108 (31-32): 525-531
    PubMedSearch in Google Scholar
  • 10 Pelosi G, Sonzogni A, Viale G. The classification of lung carcinoma: time to change the morphology-based approach?. Int J Surg Pathol 2010; 18 (03) 161-172
    CrossrefPubMedSearch in Google Scholar
  • 11 Kadota K, Nitadori J, Rekhtman N, Jones DR, Adusumilli PS, Travis WD. Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using immunohistochemical analysis. Am J Surg Pathol 2015; 39 (09) 1170-1180
    CrossrefPubMedSearch in Google Scholar
  • 12 Rekhtman N, Ang DC, Sima CS, Travis WD, Moreira AL. Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens. Mod Pathol 2011; 24 (10) 1348-1359
    CrossrefPubMedSearch in Google Scholar
  • 13 Zhang P, Han YP, Huang L, Li Q, Ma DL. Value of napsin A and thyroid transcription factor-1 in the identification of primary lung adenocarcinoma. Oncol Lett 2010; 1 (05) 899-903
    CrossrefPubMedSearch in Google Scholar
  • 14 Righi L, Graziano P, Fornari A. et al. Immunohistochemical subtyping of nonsmall cell lung cancer not otherwise specified in fine-needle aspiration cytology: a retrospective study of 103 cases with surgical correlation. Cancer 2011; 117 (15) 3416-3423
    CrossrefPubMedSearch in Google Scholar
  • 15 Mukhopadhyay S, Katzenstein AL. Subclassification of non-small cell lung carcinomas lacking morphologic differentiation on biopsy specimens: Utility of an immunohistochemical panel containing TTF-1, napsin A, p63, and CK5/6. Am J Surg Pathol 2011; 35 (01) 15-25
    CrossrefPubMedSearch in Google Scholar
  • 16 Wang BY, Gil J, Kaufman D, Gan L, Kohtz DS, Burstein DE. P63 in pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors. Hum Pathol 2002; 33 (09) 921-926
    CrossrefPubMedSearch in Google Scholar
  • 17 Turner BM, Cagle PT, Sainz IM, Fukuoka J, Shen SS, Jagirdar J. Napsin A, a new marker for lung adenocarcinoma, is complementary and more sensitive and specific than thyroid transcription factor 1 in the differential diagnosis of primary pulmonary carcinoma: evaluation of 1674 cases by tissue microarray. Arch Pathol Lab Med 2012; 136 (02) 163-171
    CrossrefPubMedSearch in Google Scholar
  • 18 Ao MH, Zhang H, Sakowski L. et al. The utility of a novel triple marker (combination of TTF1, napsin A, and p40) in the subclassification of non-small cell lung cancer. Hum Pathol 2014; 45 (05) 926-934
    CrossrefPubMedSearch in Google Scholar
  • 19 Goldstein NS, Thomas M. Mucinous and nonmucinous bronchioloalveolar adenocarcinomas have distinct staining patterns with thyroid transcription factor and cytokeratin 20 antibodies. Am J Clin Pathol 2001; 116 (03) 319-325
    CrossrefPubMedSearch in Google Scholar
  • 20 Bishop JA, Teruya-Feldstein J, Westra WH, Pelosi G, Travis WD, Rekhtman N. p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. Mod Pathol 2012; 25 (03) 405-415
    CrossrefPubMedSearch in Google Scholar
  • 21 Zhang K, Deng H, Cagle PT. Utility of immunohistochemistry in the diagnosis of pleuropulmonary and mediastinal cancers: a review and update. Arch Pathol Lab Med 2014; 138 (12) 1611-1628
    CrossrefPubMedSearch in Google Scholar