Clinical implications of genetic heterogeneity in multifocal pulmonary adenocarcinomas

Multifocal pulmonary adenocarcinomas are increasingly encountered in clinical practice, in part due to the increased availability and improvement in the thoracic imaging. Recognized as a distinct entity in the upcoming 8^th edition of American Joint Commission on Cancer (AJCC) staging system, multifocal adenocarcinomas exhibit several unique features such as the characteristic appearance of multiple ground glass opacities or nodules in computerized tomography (CT). Recent studies have suggested that the vast majority of these malignant lesions are genetically independent even when occurring synchronously in a single patient. For instance, the pattern of epidermal growth factor receptor (EGFR) mutations in multifocal pulmonary adenocarcinomas can vary from one lesion to another. This observation has several important clinical implications. These include the potential need to perform multiple molecular tests on multiple lesions, the possible role of molecular marker such as EGFR mutation in the staging of questionable multiple lung cancers, and the justification for empirical use EGFR inhibitors for multifocal adenocarcinomas among high-prevalence population when no known mutation has been detected.