Small Peripheral Pulmonary Adenocarcinoma: Morphologic and Molecular Update

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The dichotomous histopathologic separation of lung carcinoma into “small cell” and “nonsmall cell” categories is validated by marked clinical and biologic differences between these groups of tumors. However, nonsmall cell carcinoma represents a heterogenous group of tumors, and the subclassification of nonsmall cell lung carcinoma at the molecular, morphologic, and epidemiologic levels has led to the promise of precise treatment and better prognostication. Histomorphologic aspects of small peripheral adenocarcinomas that represent good prognosis include pure bronchioloalveolar carcinoma, minimal invasion within a mixed invasive and lepidic growth pattern tumor, and minimal scar within a lepidic growth pattern tumor. Activating mutations and increased gene copy number of the epidermal growth factor receptor protein and locus, respectively, have been shown to help predict responsiveness to small molecule receptor tyrosine kinase inhibitors in lung adenocarcinoma. These important concepts of morphology and molecular pathology are reviewed, and recommendations for application of these concepts to the practice of surgical pathology are provided.

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