Effect of Increased Sampling on Prognostic Parameters in Large (>3 cm) Lung Tumors: A Study on Macroscopic Standardization
Sampling Density in Large Lung Tumors
DOI:
https://doi.org/10.5281/zenodo.21227833Keywords:
Lung Neoplasms, Gross Examination, Biopsy, Lymphatic MetastasisAbstract
Objective: Adequate macroscopic sampling is vital for accurate staging in non-small cell lung carcinomas. This study compares the concordance of 1 (standard) versus 2 blocks per centimeter sampling on detecting tumor subtype, lymphovascular invasion, and perineural invasion in lung tumor resections with a diameter greater than 3 cm.
Methods: Twenty lung resection specimens with a tumor diameter greater than 3 cm, processed between 2016 and 2019, were included. Samples were taken at 1 block per centimeter followed by a 2nd block per centimeter using a double-blind method. Two pathologists evaluated histological type, lymphovascular invasion, and perineural invasion. Fisher’s Exact, Cohen’s Kappa concordance coefficient, the McNemar test, and the Mann-Whitney U test were used for statistical analysis.
Results: Cases comprised 80% squamous cell carcinoma and 20% adenocarcinoma. Squamous cell carcinoma cases had significantly larger mean diameters (p=0.029). Histological subtyping showed complete concordance (100%; κ=1.000). High concordance (κ=0.857) was observed for perineural invasion. Lymphovascular invasion detection showed only moderate concordance (κ=0.500); lymphovascular invasion was identified in 10% of cases with standard sampling versus 25% with extended sampling. This 2.5-fold increase in detection did not reach statistical significance on paired testing in this pilot cohort (McNemar p=0.25).
Conclusion: Sampling 1 block per centimeter is sufficient for histological subtyping. However, standard sampling shows reduced sensitivity for lymphovascular invasion, a critical prognostic factor. We recommend taking at least 2 samples per centimeter in tumors larger than 3 cm to reduce the risk of false-negative lymphovascular invasion reporting and to support accurate staging and appropriate adjuvant treatment decisions.
References
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
Tupper HI, Sarovar V, Banks KC, et al. Time to surgery in early-stage non-small cell lung cancer: defining the optimal diagnosis-to-resection interval to reduce mortality. J Thorac Cardiovasc Surg. 2025;169(6):1563-1572. doi:10.1016/j.jtcvs.2024.11.040
Travis WD, Asamura H, Bankier AA, et al. The IASLC Lung Cancer Staging Project: proposals for coding T categories for subsolid nodules and assessment of tumor size in part-solid tumors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol. 2016;11(8):1204-1223. doi:10.1016/j.jtho.2016.03.025
Goldstraw P, Chansky K, Crowley J, et al. The IASLC Lung Cancer Staging Project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11(1):39-51. doi:10.1016/j.jtho.2015.09.009
The Royal College of Pathologists. Dataset for Histopathological Reporting of Lung Cancer. G048. 6th ed. The Royal College of Pathologists; 2018.
College of American Pathologists. Protocol for the Examination of Resection Specimens From Patients With Primary Non-Small Cell Carcinoma, Small Cell Carcinoma, or Carcinoid Tumor of the Lung. Version 4.4.0.0. College of American Pathologists; 2021.
Mollberg NM, Bennette C, Howell E, Backhus L, Devine B, Ferguson MK. Lymphovascular invasion as a prognostic indicator in stage I non-small cell lung cancer: a systematic review and meta-analysis. Ann Thorac Surg. 2014;97(3):965-971. doi:10.1016/j.athoracsur.2013.11.002
Higgins KA, Chino JP, Ready N, et al. Lymphovascular invasion in non-small-cell lung cancer: implications for staging and adjuvant therapy. J Thorac Oncol. 2012;7(7):1141-1147. doi:10.1097/JTO.0b013e3182519a42
Nicholson AG, Tsao MS, Beasley MB, et al. The 2021 WHO classification of lung tumors: impact of advances since the 2015 classification. J Thorac Oncol. 2022;17(3):415-428. doi:10.1016/j.jtho.2021.11.003
Schuchert MJ, Abbas G, Awais O, et al. Anatomic segmentectomy for the solitary pulmonary nodule and its relation to lymphovascular invasion. Ann Thorac Surg. 2010;90(2):545-552. doi:10.1016/j.athoracsur.2010.04.053
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung Cancer. Version 3.2024. Accessed November 30, 2025. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
Demir A, Gunluoglu MZ, Kara HV, Buyukpinarbasili N, Dincer SI. Prognostic factors in resected T3 non-small cell lung carcinoma: perineural invasion as a new prognostic factor. Thorac Cardiovasc Surg. 2008;56(2):93-98. doi:10.1055/s-2007-965059
Kiliçgün A, Turna A, Sayar A, Solak O, Urer N, Gürses A. Very important histopathological factors in patients with resected non-small cell lung cancer: necrosis and perineural invasion. Thorac Cardiovasc Surg. 2010;58(2):93-97. doi:10.1055/s-0029-1186240
Downloads
Published
How to Cite
License
Copyright (c) 2026 Hanife Gülnihal Özdemir, Şermin Çoban Kökten
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The Avicenna Anatolian Journal of Medicine operates under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
