Current status of small peripheral adenocarcinomas of the lung and their importance to pathologists Jose ´ I. Lo ´pez, MD a, * , Thomas V. Colby, MD b , Adi F. Gazdar, MD c a Department of Pathology, Hospital de Basurto, The Basque Country University, Bilbao, 48013 Spain b Department of Pathology and Laboratory Medicine, Mayo Clinic Scottsdale, Scottsdale, AZ 85259, USA c Department of Pathology, University of Texas Southwestern Medical Centre, Dallas, TX 75235, USA Abstract There has been a large amount of work done recently on small peripheral stage I adenocarcinomas that come to resection. Radiological (including proportion of ground glass opacity) and pathological features of these lesions (predominant bronchioloalveolar component, central scar with or without invasion b 0.5 cm) have been shown to be prognostically favorable with cure rate approaching 100% in some series. Most of these studies emanate from Japan. The relevance of these studies to other parts of the world, particularly North America, is discussed in light of the fact that some recent chemotherapeutic studies with gefitinib have shown increased response in individuals of Asian origin, suggesting that some genetic differences may be significant. The relevance of these findings to pathologists and the pathological study of small peripheral adenocarcinomas from elsewhere in the world are discussed. D 2005 Elsevier Inc. All rights reserved. Index word: Lung cancer; Adenocarcinoma; Pathology; Bronchioloalveolar carcinoma; Nonmucinous bronchioloalveolar carcinoma; Atypical adenomatous hyperplasia 1. Background Lung cancer is one of the most common malignancies and is a health problem worldwide. It is one of the few malignancies that continue to show an increasing incidence, with up to 70 per 100 000 inhabitants affected and nearly 160 000 annually in the United States [1]. The origin of most of these neoplasms is directly related to tobacco smoking [2]. Many other putative etiologic agents are also implicated including genetic predisposition, diet, occupational expo- sures, and air pollution [3]. Lung carcinomas generally pursue a dismal clinical course, often presenting in advanced stage at the time of diagnosis with a brisk evolution to death. Only 14% of patients with lung cancer in the United States survive after 5 years [1]. The death rate from lung cancer in the United States and Canada steadily increased during the 20th century, and only in the last few years has there been any tendency toward decline in the death rate [1]. In developing countries, the death rate continues to accelerate. Non – small cell lung carcinomas account for approximately 80% of lung cancers [4], and adenocarcinoma is the most common histologic subtype [5]. 2. Why is lung cancer such a bad cancer? The poor prognosis in lung cancer is related to many factors among which are the peculiarities of the pulmonary microanatomy, with a weak barrier effect to local neoplastic growth and invasion, and a high density of lymphatics, the involvement of which can lead to regional spread and distant seeding. The adverse effect of immunosuppression and the influence of inhaled carcinogens are also factors as is the long asymptomatic period between the initial development of the tumor and its actual clinical presenta- tion, often as in advanced stage disease. These features are particularly true for peripheral adenocarcinomas because common signs of lung cancer including cough, hemoptysis, and other sentinel symptoms usually do not appear in early curative stages. Traditionally, many of the small peripheral tumors have been difficult to identify with conventional chest x-rays, cytologic evaluation, and bronchoscopy. 1092-9134/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2004.12.011 * Corresponding author. Annals of Diagnostic Pathology 9 (2005) 115 – 122