MTE02.01 Update on WHO Classification and Staging of Lung Cancer

Abstract

The most significant changes in the 2015 WHO classification of the lung tumors include classification criteria for small biopsy and cytology specimens, use of immunohistochemistry, integration of molecular testing, adoption of the IASLC/ATS/ERS adenocarcinoma classification and a strict definition of large cell carcinoma limited to surgical resection specimens only. 1,2 Tumors that show unequivocal morphology of adenocarcinoma or squamous cell carcinoma on a small specimen should be diagnosed without immunohistochemistry. Immunohistochemical work up of poorly differentiated tumors should be limited to TTF-1and p40/p63, while neuroendocrine markers should be used only if morphologically indicated. This approach should reduce the diagnosis of NSCC, NOS to less than 5% and preserve tissue for molecular testing. 1,2 Major changes in the adenocarcinoma classification for resected specimens include addition of adenocarcinoma in situ (AIS) to preinvasive group that already includes atypical adenomatous hyperplasia. Minimally invasive adenocarcinoma (MIA) defined as a solitary, lepidic predominant adenocarcinoma presenting measuring in gross size 3 cm or less and with invasion of ≤ 5 mm was added as a new category. These tumors are also recognized by the 8th edition of the AJCC staging of lung cancer and include Tis(adenocarcinoma) and T1a-mi. T stage of non-mucinous lepidic predominant adenocarcinomas is based on the microscopic size of invasion, but gross size should be recorded in the pathology reports. Multifocal ground glass opacities/lung nodules most frequently present as MIAs and should be classified by the T category of the lesion with the highest T along with the number of lesions (#) or simply (m) for multiple indicated in parentheses, and with a single N and M category that applies to all of the multiple tumor foci. This approach should be applied to grossly or microscopically identified lesions occurring in the same or in different ipsilateral or contralateral lobes.3 For non-lepidic adenocarcinoma T stage is determined by gross size in 1.0 cm increments as each size subgroup carries prognostic significance. Former mucinous BAC are reclassified as invasive mucinous adenocarcinoma, excluding tumors that meet criteria for AIS or MIA. Signet ring and clear cell carcinomas are considered to represent cytologic variants rather than specific subtypes. Invasive adenocarcinomas should be subtyped by semi-quantitatively estimating the percentage of the various subtypes in 5% increments. 1,2 Reproducibility for lung adenocarcinoma predominant subtypes among pulmonary pathologists was good to moderate (κ-values 0.44 to 0.72).4 For untrained pathologists, κ-values were lower ranging from 0.38 to 0.47, but these improved after a training session and particularly for individual reviewer. 5 The 2015 WHO classification defines large cell carcinomas based on morphology, as carcinomas without morphologic evidence of glandular, squamous or neuroendocrine differentiation, and also based on null immunophenotype and genotype. 1This change in definition reflect what was already happening in the pathology practice. According to National Cancer Institute (NCI) Surveillance Epidemiology and End Results registry the diagnosis of large cell carcinoma started to decline about the time that TTF-1 was introduced into clinical diagnosis. 6 Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. Lyon: International Agency for Research on Cancer, 2015. Travis WD. Et al. The 2015 World Health Organization Classification of Lung Tumors Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol 2015; 10 (9); 1243-1260 Frank C. Detterbeck, MD et al. The IASLC Lung Cancer Staging Project: Summary of Proposals for Revisions of the Classification of Lung Cancers with Multiple Pulmonary Sites of Involvement in the Forthcoming Eighth Edition of the TNM Classification . J Thorac Oncol 2016;11(5): 639-650 Thunnissen E, Beasley MB, Borczuk AC, et al. Reproducibility of histopathological subtypes and invasion in pulmonary adenocarcinoma. An international interobserver study. Mod Pathol 2012;25:1574–1583. Warth A, Cortis J, Fink L, et al.; Pulmonary Pathology Working Group of the German Society of Pathology. Training increases concordance in classifying pulmonary adenocarcinomas according to the novel IASLC/ ATS/ERS classification. Virchows Arch 2012;461:185–193. Lewis DR, Check DP, Caporaso NE, Travis WD, Devesa SS. US lung cancer trends by histologic type. Cancer 2014;120:2883–2892. lung carcinoma- WHO classification- staging