Pulmonary small cell carcinoma: Review, common and uncommon differentials, genomics and management

Lung cancer is the leading cause of cancer-related death worldwide. It is divided into sub-categories based upon morphology, immunostaining pattern, biology, molecular profile, and/or treatment options. Up until the early 2000s when driver mutations with targeted therapies were identified in a subset of adenocarcinomas, the most critical distinction of lung carcinomas was driven by differences in treatment between small cell carcinoma (SCC) and nonsmall cell lung carcinoma (NSCLC). The distinction between SCC and NSCLC remains critical in the 21st century for management, especially for advanced stage cancer. In the vast majority of cases, morphological features are sufficient to separate SCC from other types of lung cancers. In some instances, however, cytomorphological features and immunohistochemical overlap with other tumors, limited sample availability, and/or crush artifact pose diagnostic challenges. The aim of this review is to highlight salient features of SCC and ancillary studies to distinguish it from common and uncommon potential mimickers, as well as provide updates in genomics and management.