International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary

The American Thoracic Society is a cosponsor of a newly published lung adenocarcinoma classification. An international multidisciplinary panel of experts was formed. A systematic review was performed and recommendations were graded by strength and quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The classification addresses both resection specimens and small biopsies/cytology. The terms bronchioloalveolar carcinoma and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ and minimally invasive adenocarcinoma for small solitary adenocarcinomas with pure lepidic growth and predominant lepidic growth with ≤ 5 mm invasion, respectively. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic, acinar, papillary, and solid patterns; micropapillary is added. In the new aspect of this classification that provides guidance for small biopsies and cytology specimens, non-small cell lung carcinomas (NSCLC), in patients with advanced stage disease, are to be classified into more specific types, such as adenocarcinoma or squamous cell carcinoma, whenever possible, for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for EGFR mutations, because the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy, and (3) squamous histology is a risk factor for life-threatening hemorrhage with bevacizumab therapy. NSCLC- not otherwise specified by light microscopy alone should be studied with immunohistochemistry and/or mucin stains. This classification is intended to support clinical practice as well as research investigation and clinical trials.