New classification of lung adenocarcinoma (Reprint)

Specimen classification covers surgical specimens, small biopsies, and cytology specimens. The term “BAC, mixed adenocarcinoma” is no longer used. For surgical specimens, new concepts have been introduced: adenocarcinoma in situ (AIS) refers to small isolated adenocarcinoma with simple volvulus-like growth; and microinvasive adenocarcinoma (MIA) is mainly volvulus-like growth but infiltrates ≤5 mm. . With the use of comprehensive histologic staging (CHS), invasive adenocarcinoma subtypes are mainly classified as volvulus-like growth (corresponding to the majority of previous mixed adenocarcinomas with non-mucinous BAC), follicular, papillary, and solid; a new histologic subtype of micro papillae has been added. Other less invasive adenocarcinoma variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), glioid adenocarcinoma, fetal adenocarcinoma, and intestinal adenocarcinoma. This classification provides guidance for small biopsies and cytologic specimens, and approximately 70% of lung cancers are definitively diagnosed by such criteria. Patients with advanced non-small cell lung cancer (NSCLC) require definitive pathologic staging, such as adenocarcinoma or squamous cell carcinoma, whenever possible because (1) adenocarcinoma or other non-specific types of NSCLC require testing for epidermal growth factor receptor (EGFR) mutation status, and such mutations predict the efficacy of EGFR tyrosine kinase inhibitors, (2) adenocarcinoma is an effective predictor of pemetrexed efficacy compared to squamous cell carcinoma, and (3) potentially, adenocarcinoma is an effective predictor, and (3) potentially fatal hemorrhage can occur in patients with squamous cell carcinoma treated with bevacizumab. If the tumor cannot be classified by light microscopy, then special tests such as immunohistochemistry and/or mucin staining are used for further tumor classification. The use of terms such as unclassified (NOS) NSCLC should be minimized. CONCLUSION: The new classification is based on multidisciplinary collaboration, including diagnosis of lung adenocarcinoma by clinical, molecular biology, imaging and surgical routes, but most of all based on histology. This classification helps to support clinical practice, research investigations, and clinical trials. Because EGFR mutations are a valid predictor of efficacy and progression-free survival in advanced lung adenocarcinoma treated with EGFR-TKI, we recommend that patients with advanced lung adenocarcinoma should be routinely tested for EGFR mutation status. This implies the need for coordinated management of tissue specimens, especially for small biopsies and cytology specimens, in order to provide as many high-quality tissue specimens as possible for molecular biology studies. The measurement of T-stage size in primary, lymph node and metastasis (TNM) staging has been adjusted to include (1) pathology: based on the infiltrative component in areas of infiltrative tumor with vascular wall-like growth, or (2) imaging: to determine the size of the solid component in “partially solid lesions”.