Early Lung Cancer With Lepidic Pattern

Adenocarcinoma in Situ, Minimally Invasive Adenocarcinoma, and Lepidic Predominant Adenocarcinoma

Wilko Weichert; Arne Warth


Curr Opin Pulm Med. 2014;20(4):309-316. 

In This Article

Abstract and Introduction


Purpose of Review. This review gives a comprehensive overview on recent developments in the classification of neoplastic lung lesions with lepidic growth patterns, comprising the adenocarcinoma (ADC) precursor lesions atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA) as well as lepidic predominant adenocarcinoma (LPA).

Recent F indings. The concept of a continuum between the precursor lesions AAH and AIS to MIA and frankly invasive ADC is backed by a wealth of recent data showing a gradual decrease in overall survival from 100% for AAH, AIS, and MIA to moderately lower rates for LPA. Further, it has been shown that the morphologic categorization of these tumors can be done with reasonable reliability and that nonmucinous lepidic tumors show distinct molecular alterations with high rates of epidermal growth factor receptor mutations. Importantly, lepidic tumor growth is also mirrored by specific characteristics in computed tomography images, arguing for a combined assessment of histomorphology and imaging data for an optimized classification of lepidic neoplasms.

Summary. The validity and clinical importance of the novel concept of ADC precursor lesions and LPA have been confirmed by clinical, radiological, morphological, and molecular data. Thereby, it has evolved into a valuable tool to aid in clinical decision-making.


Adenocarcinoma (ADC) is the most common subtype of lung cancer. Over the last decade, clinical, radiological, and pathological efforts including molecular and morphological analyses have revealed multiple novel disease classifiers. These findings need to be translated and integrated into the clinical setting in order to improve patients' outcome.

Morphology-based categorization of ADC has recently gained attention, as clinically relevant findings have been put forward in this field. To account for this, in 2011, a revised classification for pulmonary ADC was introduced by joint international, multidisciplinary lung cancer specialists representing the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS).[1] Major aspects of this classification comprise a revised concept of ADC precursor lesions and a semi-quantitative assessment of ADC growth pattern. This classification has been validated independently in different cohorts worldwide and was proven to be an important, in some studies even stage-independent, predictor of survival.[2–14] First studies indicate that the classification is reproducibly applicable.[15–17] Most recently, retrospective analysis of more than 6000 resected ADCs of the Japan lung cancer registry underscored the independent prognostic impact of histomorphological subtyping.[18] In advanced tumor stages, the semi-quantitative assessment of growth pattern was also suggested to be of predictive value for adjuvant treatment.[12,19] However, there are also some conflicting data claiming that assessment of growth patterns does not add relevant prognostic information to established staging systems.[20] In this review, we focus on the most recent findings and clinical implications of the IASLC/ATS/ERS classification of ADC with emphasis on tumors with lepidic growth, which comprise the ADC precursor lesions atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) as well as minimally invasive adenocarcinoma (MIA) and lepidic predominant adenocarcinoma (LPA).