The new IASLC-ATS-ERS lung adenocarcinoma classification: what the surgeon should know

Abstract

In 2011, a new histologic classification of lung adenocarcinomas was proposed from a joint working group of the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society, based on the recommendation of an international and multidisciplinary panel. This classification proposed a method of comprehensive histologic subtyping (lepidic, acinar, papillary, micropapillary, and solid pattern) based on semiquantitative assessment of histologic patterns (in 5% increments), with the ultimate goal of choosing a single, predominant pattern. Prognostic subsets could then be described for the classification. Patients with completely resected adenocarcinoma in situ and minimally invasive adenocarcinomas experienced low risk of recurrence. Patients with micropapillary or solid predominant tumors have a high risk of recurrence or cancer-related death. Patients with acinar and papillary predominant tumors comprise an intermediate-risk group. Herein, we review the outline of the proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society classification, a summary of published validation studies of this new classification, and then discuss the key surgical issues; we mainly focused on limited resection as an adequate treatment for early-stage lung adenocarcinomas, as well as preoperative and intraoperative diagnoses. We also review the published studies that identified the importance of histologic subtypes in predicting recurrence, both rates and patterns, in early-stage lung adenocarcinomas. This new classification for the most common type of lung cancer is useful for surgeons, as its implementation would require only hematoxylin-and-eosin histology slides, which is the common type of stain used in hospitals. It can be implemented with routine pathology evaluation and with no additional costs.

Keywords: histologic classification; limited resection; lung adenocarcinoma; micropapillary; small lung nodules.

Figure 1. Histologic subtyping for surgeon

Resected lung nodules that are diagnosed as adenocarcinoma are first classified based on the degree of lepidic growth pattern. Tumors with lepidic predominant growth are composed of 3 groups: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive adenocarcinoma (LEP). AIS is defined as a ≤3 cm tumor with a pure lepidic pattern (no invasion). MIA is defined as a ≤3 cm tumor with ≤5 mm stromal invasion. LEP is defined as a tumor that is >3 cm in total size and/or >5 mm in invasive size with a non-mucinous lepidic predominant pattern. Each histologic pattern % is recorded in 5% increments. When showing conventional lung adenocarcinoma morphology, non-lepidic predominant invasive adenocarcinomas are classified into acinar (ACI), papillary (PAP), micropapillary (MIP), or solid subtype (SOL) on the basis of predominant histologic pattern. Variant histologies included invasive mucinous, colloid, fetal and enteric subtype. AIS, adenocarcinoma in situ; MIA, minimally invasive adenocarcinoma; LEP, lepidic; MIP, micropapillary; SOL, solid; ACI, acinar; PAP, papillary

Figure 2. Major histologic subtypes of lung adenocarcinoma

All pictures are intermediate magnification images (x200, hematoxylin and eosin staining). LEP growth pattern shows that tumor cells appeared to replace normal pneumocytes on alveolar walls. ACI adenocarcinoma shows malignant glands invading a fibrous stroma. PAP adenocarcinoma consists of cuboidal tumor cells growing along fibrovascular cores in a papillary configuration. MIP growth pattern shows small papillary clusters in airspace without fibrovascular cores. SOL adenocarcinoma consists of sheets of tumor cells with abundant cytoplasm. Invasive mucinous adenocarcinoma shows columnar cells filled with abundant mucin invading with an ACI pattern. LEP, lepidic; ACI, acinar; PAP, papillary; MIP, micropapillary; SOL, solid

Figure 3. Prognosis and histologic pattern distribusion according to the new IASLC/ATS/ERS classification

AIS and MIA had 100% disease free survival rate in all studies except for the study from Yeh et al. Among invasive adenocarcinoma subtypes, LEP-predominant invasive adenocarcinoma has better prognosis as compared with other subtypes. In contrast, MIP and SOL-predominant subtypes generally have poorer prognosis than the others. In all studies, ACI and PAP subtypes account for the majority of histologic subtype distribution. In most studies their survival rates are similar or lower than those of AIS/MIA or LEP subtypes and higher than those of SOL or MIP subtypes. AIS, adenocarcinoma in situ; MIA, minimally invasive adenocarcinoma; DFS, disease-free survival; LEP, lepidic; MIP, micropapillary; SOL, solid; ACI, acinar; PAP, papillary †Russell et al was the only study included that used a study endpoint of overall survival (OS). *5-yr DFS rate could not be applied because of a small number of patients in MIP group.

Figure 4. Prognosis based on presence or absence of MIP component

In all studies, the survival rate of patients with MIP component is lower than those without MIP component. The distribution of patients with MIP component is not small, although the percentage of MIP-predominant adenocarcinoma is very low. MIP, micropapillary; OS, overall survival; DFS, disease free survival

Figure 5. Published evidence for selecting the extent of surgical resection for clinical stage IA lung adenocarcinoma

AIS, adenocarcinoma in situ; MIA, minimally invasive adenocarcinoma; C/T ratio, consolidation to tumor size ratio; TDR, tumor disappearance ratio; LEP, lepidic; MIP, micropapillary; SOL, solid