Clinical relevance of the new IASLC/ERS/ATS adenocarcinoma classification

Abstract

In 2011, recommendations for a multidisciplinary classification of lung adenocarcinoma were published under the auspices of the International Association for the Study of Lung Cancer, the American Thoracic Society and the European Respiratory Society. The review was considered necessary due to emerging data on the radiological features, genetics and therapeutic approaches to lung adenocarcinoma, all underpinned by expanding the knowledge of the pathology of this common tumour. The existing WHO classification of 2004 was not really fit for this multidisciplinary focus on the disease. This review describes the recommendations made on the reporting of surgically resected lung cancers according to their predominant pattern, and argues the case for replacing the term bronchioloalveolar carcinoma (WHO 1999 and 2004 definition) with adenocarcinoma in situ and for the introduction of minimally invasive adenocarcinoma. There is also a discussion of diagnosis of non-small-cell lung carcinomas in the small biopsy or cytology setting, a practice that was inadequately addressed in WHO 2004, yet this is much more relevant to most pathologists' daily practice because 85% or so of adenocarcinomas are never resected. Predictive immunohistochemistry, used correctly, can reduce non-specific diagnosis to less than 10% of the cases. Finally, there is an overview of the emerging data on therapeutically relevant lung adenocarcinoma genetics, considering targetable mutations that are now the focus of much activity. The clinical relevance of these changes is discussed.

Implications of Evolving Medical Science for Proof of Lung Cancer Causation

“…One of the more common presentations denominated BAC has been a peripheral lung tumor with a lepidic growth pattern, little or no invasion into surrounding lung parenchyma, and almost 100% five-year survival when surgically resected (38). Lepidic growth refers to tumor cells that line alveolar walls and replace normal bronchioloalveolar epithelium while conserving alveolar architecture (20). A so-called "ground glass" appearance on CT studies has also been commonly associated with BAC (11).…”

“…The micropapillary subtype is new to the revised classification owing to significant research conducted in recent years indicating that it is an important variant associated with aggressive growth and poor prognosis, even when representing only a relatively small percentage of total tumor volume (40). The solid adenocarcinoma subtype, more common than micropapillary adenocarcinoma, is also associated with aggressive growth and poor patient outcome (20). The precision required in the revised adenocarcinoma classification to parse lung tumor surgical resection specimens in 5% increments stands in marked contrast to the imprecise small cell/NSCLC dichotomy that has been commonly used by surgical pathologists with poorly differentiated small biopsies to determine suitability for surgical intervention.…”

“…Small biopsy specimens pose a heightened risk of missing one histological type or the other that co-exist in such tumors (3). The insistence on the part of the authors of the revised classification that surgical pathologists avoid whenever possible the generic NSCLC classification in favor of an adenocarcinoma/squamous cell carcinoma distinction stems from recent advances in the treatment of lung adenocarcinoma that require a clearer diagnosis as their starting point (20). Such treatments include the folate antimetabolite pemetrexed and the monoclonal antibody bevacizumab for cases of advanced adenocarcinoma.…”

“…Such treatments include the folate antimetabolite pemetrexed and the monoclonal antibody bevacizumab for cases of advanced adenocarcinoma. Prior to the use of these drugs, however, a diagnosis of squamous cell carcinoma must be excluded to help ensure treatment efficacy (pemetrexed, when used with cisplatin) and to avoid possible fatal hemorrhaging (bavacizumab) (3,20). Other advances in the treatment of adenocarcinoma are based on the presence of so-called genetic "driver mutations" or chromosome rearrangements identified when molecular testing is conducted on tumor specimens.…”

“…While the strength of the association between lung cancer and most other risk factors might be weaker than the association between lung cancer and cigarette smoking, relative risks used for such comparisons are determined in population studies that cannot serve as the basis for a determination of the complex interactions that occur among exogenous and endogenous lung cancer risk factors in the case of a specific individual (19). Moreover, the presence of a specific risk factor in an individual's history -even cigarette smoking as a risk factor for the development of lung cancer -does not mean that risk factor was part of the causal mechanism responsible for the development of the disease (19)(20)(21). No methods currently exist to accurately characterize the complex biological mechanisms that give rise to lung cancer and most other diseases with long development times and multiple risk factors (19,22,23).…”