The 2021 World Health Organization Classification of Tumors of the Pleura: Advances since the 2015 Classification

J Thorac Oncol. 2022 Jan 10;S1556-0864(22)00026-0. doi: 10.1016/j.jtho.2021.12.014. Online ahead of print.


Significant changes in the 2021 World Health Organization (WHO) Classification of Tumors of the Pleura and Pericardium since the 2015 WHO Classification include: 1) Pleural and pericardial tumors have been combined in one chapter whereas in the 2015 WHO, pericardial tumors were classified with cardiac tumors; 2) Well-differentiated papillary mesothelioma (WDPM) has been renamed well-differentiated papillary mesothelial tumor (WDPMT) given growing evidence that these tumors exhibit relatively indolent behavior; 3) Localized and diffuse mesothelioma no longer include the term "malignant" as a prefix; 4) Mesothelioma in situ (MIS) has been added to the 2021 classification since these lesions can now be recognized by loss of BAP1 and/or MTAP by immunohistochemistry and/or CDKN2A homozygous deletion by FISH; 5) The three main histologic subtypes (i.e. epithelioid, biphasic and sarcomatoid) remain the same but architectural patterns, cytologic and stromal features are more formally incorporated into the 2021 classification based on their prognostic significance; 6) Nuclear grading for epithelioid diffuse mesothelioma is introduced and it is recommended to record this and other histologically prognostic features in pathology reports; 7) BAP1, EZH2 and MTAP immunohistochemistry have been shown to be useful in separating benign mesothelial proliferations from mesothelioma; 8) Biphasic mesothelioma can be diagnosed in small biopsies showing both epithelioid and sarcomatoid components even if the amount of one component is less than 10%; and 9) The most frequently altered genes in diffuse pleural mesothelioma include BAP 1, CDKN2A, NF2, TP53, SETD2 and SETB1.

Keywords: World Health Organization classification; mesothelioma; pleura.

Publication types

  • Review