At the beginning of 2011, the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society (IASLC, ATS, ERS) joined forces to publish new international multidisciplinary classification criteria for lung adenocarcinoma in the Journal of Thoracic Oncology (J Thorac Oncol. 2011, 6: 244C285). Proposed new classification The new classification criteria for lung adenocarcinoma present, for the first time, separate classification methods for surgical resection specimens, small biopsies, and cytology. Approximately 70% of lung cancers are diagnosed on the basis of small biopsies and cytology, so the new classification criteria provide more detailed guidelines for small biopsies and cytology specimens. If the pathologist is unable to classify the tumor definitively on the basis of light microscopy, further classification should be done with the help of immunohistochemistry and/or histochemical staining, etc., with a note in the pathology report that the classification was derived on the basis of immunohistochemistry or histochemical staining performed. The term histologically indeterminate NSCLC (NSCLC-NOS) should be used as sparingly as possible. In addition, the new classification criteria have specific requirements for specimens. The diagnosis of AIS, MIA, or large cell carcinoma should not be made in small biopsies or cytology specimens. This is because such diagnoses must be made on the basis of a comprehensive sampling of the tumor. The new classification also suggests that a coordinated approach to biopsy tissue specimens is essential, especially for small biopsies and cytology specimens, and that as much high quality tissue as possible should be available for molecular studies. Conceptual updates of the new classification criteria 1. The new classification recommends that the names bronchoalveolar carcinoma (BAC) and mixed adenocarcinoma no longer be used, but be replaced by adenocarcinoma in situ (AIS) and microinfiltrating adenocarcinoma (MIA). AIS and MIA usually present as non-mucinous or very rare mucinous subtypes, and patients with radical surgery have a disease-specific survival rate of 100% or nearly 100%, respectively. Infiltrative adenocarcinoma can be classified into subtypes of squamous, follicular, papillary, and solid growth patterns, with a new subtype of “micropapillary growth pattern” recommended because of its association with poor prognosis. The former WHO classification of clear cell adenocarcinoma and indolent cell adenocarcinoma were included in the subtype of solid growth. 3. The variants of invasive adenocarcinoma include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid adenocarcinoma, fetal adenocarcinoma, and intestinal adenocarcinoma. Intestinal type is a newly proposed subtype, which should be morphologically differentiated from adenocarcinoma of gastrointestinal origin. 4. A comprehensive and detailed histological diagnostic model is advocated for invasive adenocarcinoma, instead of classifying it as a mixed subtype in general. Example of diagnostic pattern: lung adenocarcinoma with a predominantly solid growth pattern, 10% with an alveolar-like growth pattern, and 5% with a papillary growth pattern; in the previous WHO classification, a tumor component (a particular growth pattern) was considered a constituent component only when it accounted for 10%, whereas the new classification recommends that it should be described in the diagnosis as soon as it reaches 5%. Clinical rationale for the new classification criteria For progressive NSCLC, it should be subdivided into more definite types, such as adenocarcinoma or squamous carcinoma, whenever possible. The rationale is as follows: 1. Epidermal growth factor receptor (EGFR) mutation status should be tested for adenocarcinoma or NSCLC-NOS because it predicts EGFR-tyrosine kinase inhibitor (TKI) efficacy; 2. Adenocarcinoma is an effective and strong predictor of pemetrexed therapy compared with squamous carcinoma; 3. Potentially fatal major bleeding can occur in patients with squamous carcinoma treated with bevacizumab.