Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart

Abstract

W orld Health Organization (WHO) Classifications of Tumors have historically provided a global standard for tumor diagnosis. Familiarity with these classifications is essential for clinicians because they provide the foundation for accurate patient diagnosis and optimal medical management. In addition, the diagnostic terminology and criteria recommended by the WHO should be incorporated into study design of clinical trials and molecular studies such as The Cancer Genome Atlas (TCGA). WHO Classifications are periodically updated to incorporate important advances to make them relevant to current knowledge and clinical practice. The 2015 WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart has just been published 1 and the Journal of Thoracic Oncology will be publishing a series of articles summarizing key points about the new classification outlining the major changes from the 2004 classification. 2-4 † The International Association for Research on Cancer (IARC) under the leadership of Dr. Hiroko Ohgaki coordinated this project and was the publisher of this book. IARC hosted a consensus meeting in Lyon, France, April 24-26, 2014, where all major changes in the classification from the 2004 book were discussed and approved (Figure).The 2015 WHO Classification features the incorporation of many exciting new advances in thoracic tumor diagnosis and classification. It was formulated by a multidisciplinary group of international experts with broad international representation.The primary changes in the lung classification, which are highlighted in the first paper in this series, 3 relate to lung cancer where over the past decade remarkable progress in genetics and therapy has had a major impact on tumor classification. These most significant changes are consequent to the 2011 IASLC/ATS/ERS Classification 5 including recommendations for routine molecular testing and use of immunohistochemistry, a new approach to small biopsies and cytology and a novel way of subtyping of surgically resected lung adenocarcinomas that has provided a powerful new tool for identifying prognostic and molecular correlations. Large scale genomic studies from the TCGA 6,7 and Clinical Lung Cancer Genome Project 8 provided a strong genetic foundation for reclassification of squamous cell carcinoma, adenocarcinoma and large cell carcinoma. These changes have major clinical relevance as histologic type and genetics are now driving personalized medicine for lung cancer patients. New concepts in adenocarcinoma classification with lepidic versus invasive patterns are also having an impact on the approach to tumor size measurement for TNM staging of small tumors ≤3cm and therefore the surgical management of patients. Support from the IASLC, through their Pathology Committee and by providing multidisciplinary input, contributed greatly to the development of this classification. 5,9

Blastomatoid pulmonary carcinosarcoma: A rare case report and review of the literature

“…Sarcomatoid carcinomas are estimated to account for only 0.1–0.4% of all lung cancers, and of these, only 4% are pulmonary carcinosarcomas 1, 7. According to the recent World Health Organization (WHO) classification of lung tumors, carcinosarcoma is defined as a malignant tumor that consists of an admixture of non‐small cell lung carcinoma and sarcoma‐containing heterologous elements 1, 8.…”

“…According to the recent World Health Organization (WHO) classification of lung tumors, carcinosarcoma is defined as a malignant tumor that consists of an admixture of non‐small cell lung carcinoma and sarcoma‐containing heterologous elements 1, 8. Koss et al .…”

“…Those authors divided pulmonary adenocarcinomas of the fetal lung into low‐ and high‐grade forms, and low‐grade adenocarcinomas of fetal lung type (L‐FLACs) are also known as well‐differentiated fetal adenocarcinomas (WDFAs) in the WHO classification at present 10. Currently, both L‐FLACs/WDFAs and H‐FLACs are included as a subtype of adenocarcinoma in the WHO classification 11. Although both groups show similar histological findings, H‐FLACs show high nuclear atypia and typically lack morules 12.…”

“…The pathogenesis of these two groups has been discussed, and the up‐regulation of the Wnt signaling component, including gene mutations of beta catenin, is suggested to be important for L‐FLACs/WDFAs but not for H‐FLACs 2, 7, 12. Furthermore, immunohistochemical analyses have demonstrated aberrant nuclear and cytoplasmic staining of beta catenin in the epithelial cells of L‐FLACs/WDFAs, while membranous staining in H‐FLACs 2, 3, 11, 12. These findings with ancillary techniques support our diagnosis in the present study.…”

“…Blastomatoid pulmonary carcinosarcoma is one of the rarest histologic types of carcinosarcoma of the lung 1. Although there have been only a few reports on this histologic type so far, there might be some cases in which a definitive diagnosis of blastomatoid pulmonary carcinosarcoma was not obtained 2, 3, 4, 5.…”