ABSTRACT
INTRODUCTION: Multifocal lung adenocarcinoma (MFLA) is becoming increasingly recognized as a distinct subset of lung cancer, with unique biology, disease course, and treatment outcomes. While definitions remain controversial, MFLA is characterized by the development and concurrent presence of multiple independent (non-metastatic) lesions on the lung adenocarcinoma spectrum. Disease progression typically follows an indolent course measured in years, with a lower propensity for nodal and distant metastases than other more common forms of non-small cell lung cancer. AREAS COVERED: Traditional imaging and histopathological analyses of tumor biopsies are frequently unable to fully characterize the disease, prompting interest in molecular diagnosis. We highlight some of the key questions in the field, including accurate definitions to identify and stage MLFA, molecular tests to stratify patients and treatment decisions, and the lack of clinical trial data to delineate best management for this poorly understood subset of lung cancer patients. We review the existing literature and progress toward a genomic diagnosis for this unique disease entity. EXPERT OPINION: Multifocal lung adenocarcinoma behaves differently than other forms of non-small cell lung cancer. Progress in molecular diagnosis may enhance potential for accurate definition, diagnosis, and optimizing treatment approach.