Invasive size is an independent predictor of survival in pulmonary adenocarcinoma

Abstract

Current classification of pulmonary adenocarcinoma includes noninvasive bronchioloalveolar carcinoma, mixed subtype adenocarcinoma, and several patterns of invasive carcinoma. The extent of invasion in mixed subtype adenocarcinoma is variable, and prior studies suggest that estimates of extent of desmoplasia or invasion and gross tumor size are predictors of survival. Pathologic review of 178 consecutive primary lung adenocarcinoma resections from 1997 to 2000 was performed blinded to outcome. Lymph node metastases were not present in adenocarcinomas with less then 0.6 cm of invasion. In multivariate analysis and in strata adjusted for stage, measurement of linear extent of invasion was significantly associated with survival whereas gross size measurement alone was not. Significant differences in median survival were observed when patients were divided into noninvasive, microinvasive (<0.6 cm invasion), and invasive subcategories. In conclusion, among lung adenocarcinomas, histologic assessment of invasive growth may provide valuable prognostic information, and tumors with invasion under 0.6 cm have a more indolent clinical course after resection.

Figure 1. Histology of pre-invasive bronchioloalveolar carcinoma and invasion in AdCa

(A) BAC shows irregularly collapsed slightly thickened alveolar walls. (B) Alveolar walls are lined by uniform low columnar neoplastic cells. (C) Microinvasive AdCa with a predominant BAC/lepidic pattern and a solid area (arrowhead). (D) The solid area in (C) shows irregular glands amidst a fibroblastic stroma. (E) Irregular angulated glands in a fibrous stroma within an invasive focus. (F) The extent of the invasive focus (black circle) seen in (E). The black line represents the linear measurement of invasive size. (A-F, Hematoxylin and eosin stain - Original magnification - Panel A × 10, Panel C, F × 5, Panel B, D and E × 150).

Figure 2. Distribution and survival times of patients by pathologic staging

(a) Kaplan Meier curves of patient survival by pathologic stage and median survival (b) Comparison of stage distribution of patients using existing pathologic staging with the proposed IASLC staging projected for year 2009 implementation.

Figure 3. Survival curves by invasive size parameter, all patients

Kaplan Meier curves showing survival of patients divided into 4 groups based in invasiveness with BAC (solid black), Microinvasive (dotted black), Mixed subtype (dash dot) and invasive (solid gray). The median survival is recorded by group. Log rank testing was performed between all categories and only significant statistical comparisons are reported.