The New Taxonomy of Lung Adenocarcinoma Stemming from a Multidisciplinary Integrated Approach: Novel Pathology Concepts and Perspectives

Abstract

Lung cancer is the leading cause of morbidity and death all over the world and a significant burden on healthcare resources of most countries.1 Among the diverse histologic subtypes, adenocarcinoma (AD) is the most common type of lung cancer in both males and females in most countries, even in young people,2 and in tumors detected in screening low-dose computed tomography programs.3,4 The characteristic mixture of multiple subtypes has been a major source of inconsistency in subclassification in the past, hence the axiom, the more tumor categories, the more difficulties in the diagnosis. Therefore, new diagnostic criteria and uniform and consistent terminology are needed to improve accuracy and permit correlations between pathology and multiple patient characteristics including clinical features, tumor staging, molecular signatures, prognostic and predictive markers, and imaging data. Morphology still remains an agreed-on gold standard for AD, but a global rethinking of its histopathologic basis by exploiting an integrated multidisciplinary approach could really improve our diagnostic, prognostic, and predictive capabilities. The issue of accurate subtyping of poorly differentiated tumors and limited diagnostic material for predictive purposes is strictly intermingled with this scenario and often presents a difficult challenge,5 because most lung cancer patients are discovered with locally advanced or metastatic disease, so cytology or biopsy samples are the only available material. Therefore, in the past, the term “non-small cell lung cancer, not otherwise specified” has been encouraged6 mainly due to the lack of a clinical reason to classify more precisely. This situation has led to the uncomfortable feeling that histopathology is a finite and imperfect source of diagnostic, prognostic, or predictive information in lung cancers and that molecular studies are more important than histology for prognosis and prediction. For these reasons, this new multidisciplinary classification of AD that is presented in the Journal under the aegis of three outstanding scientific communities devoted to lung cancer, namely the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society, represents an extraordinary, meritorious, and almost herculean effort by Dr. William D. Travis,7 which surely will contribute to address many contemporary issues and questions on the subject of pulmonary AD through a close integration of pathologic, clinical, molecular, and radiologic data. There are several innovative aspects of this classification. First, it relies on a multidisciplinary approach with integration of clinical, radiologic, molecular, and imaging features. Second, there is a completely new proposal to provide diagnostic criteria and terminology in small biopsies and cytology, a problem not addressed in previous World Health Organization classifications. Third, for patients with advanced lung AD, epidermal growth factor receptor mutation assessment is recommended, so small biopsy and cytology specimens need to be processed strategically not only for diagnosis but also to