The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015

J Thorac Oncol. 2022 Mar;17(3):362-387. doi: 10.1016/j.jtho.2021.11.003. Epub 2021 Nov 20.


The 2021 WHO Classification of Thoracic Tumours was published earlier this year, with classification of lung tumors being one of the chapters. The principles remain those of using morphology first, supported by immunohistochemistry, and then molecular techniques. In 2015, there was particular emphasis on using immunohistochemistry to make classification more accurate. In 2021, there is greater emphasis throughout the book on advances in molecular pathology across all tumor types. Major features within this edition are (1) broader emphasis on genetic testing than in the 2015 WHO Classification; (2) a section entirely dedicated to the classification of small diagnostic samples; (3) continued recommendation to document percentages of histologic patterns in invasive nonmucinous adenocarcinomas, with utilization of these features to apply a formal grading system, and using only invasive size for T-factor size determination in part lepidic nonmucinous lung adenocarcinomas as recommended by the eighth edition TNM classification; (4) recognition of spread through airspaces as a histologic feature with prognostic significance; (5) moving lymphoepithelial carcinoma to squamous cell carcinomas; (6) update on evolving concepts in lung neuroendocrine neoplasm classification; (7) recognition of bronchiolar adenoma/ciliated muconodular papillary tumor as a new entity within the adenoma subgroup; (8) recognition of thoracic SMARCA4-deficient undifferentiated tumor; and (9) inclusion of essential and desirable diagnostic criteria for each tumor.

Keywords: Adenocarcinoma; Cancer; Immunohistochemistry; Lung; Molecular pathology; Pathology; Squamous cell carcinoma.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma of Lung*
  • Adenocarcinoma* / pathology
  • Adenoma*
  • Carcinoma, Squamous Cell*
  • DNA Helicases
  • Humans
  • Lung Neoplasms* / pathology
  • Nuclear Proteins
  • Transcription Factors
  • World Health Organization


  • Nuclear Proteins
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases