Atypical adenomatous hyperplasia of the lung : Implications for the pathogenesis of peripheral lung adenocarcinoma

• Published in: American journal of clinical pathology Vol. 111; no. 5; pp. 610 - 622
• Main Authors: KITAMURA, H, KAMEDA, Y, ITO, T, HAYASHI, H
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Society of Clinical Pathologists 01.05.1999
• Subjects: Adenocarcinoma - etiology; Adenoma - pathology; Biological and medical sciences; Cell Differentiation - physiology; Gene Expression - physiology; Humans; Hyperplasia; Lung - pathology; Lung Neoplasms - etiology; Medical sciences; Pneumology; Terminology as Topic; Tumors of the respiratory system and mediastinum; Adenocarcinoma; Human; Lung disease; Premalignant lesion; Respiratory disease; Adenomatous hyperplasia; Hyperplasia; Malignant tumor; Adenoma; Review; Electron microscopy; Carcinogenesis; Bronchopulmonary; Periphery; Pathology; C-Onc gene; Bronchus disease; Atypical; Molecular biology; Morphometry; Protooncogene; Tumor suppressor gene; Bronchioloalveolar carcinoma
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1093/ajcp/111.5.610

Bronchioloalveolar lung carcinoma (BAC) exhibits many features that distinguish it from bronchogenic carcinomas. For early detection, therapy, and prevention of BAC, it is essential to understand its pathogenesis. Development of BAC appears to be stepwise, and the earliest lesion to be recognized is atypical adenomatous hyperplasia (AAH), the proliferative lesion of atypical epithelial cells along the alveolar septa. Our review of the studies of AAH revealed that certain populations of AAH cells exhibit active proliferation, aneuploidy, 3p and 9p deletions, K-ras codon 12 mutation, and disruption of the cell cycle control, but p53 gene aberrations are rare and telomerase activation is absent. We emphasize that AAH is an alveolar intraepithelial neoplasia. This allows more precise analyses of the process and mechanism of the development of BAC. Furthermore, AAH could serve as a surrogate end-point biomarker in future chemoprevention trials. The criteria for the diagnosis of AAH and related lesions should be established as early as possible.