Update on small cell carcinoma and its differentiation from squamous cell carcinoma and other non-small cell carcinomas

Small cell lung cancer (SCLC) comprises 14% of all lung cancers, and >30 000 new cases are diagnosed per year in the United States. SCLC is one of the most distinctive malignancies in the entire field of oncology with characteristic clinical properties, responsiveness to specific chemotherapy, genetic features and a highly reliable pathological diagnosis. SCLC is defined by light microscopy, and the most important stain is a good-quality hematoxylin and eosin (H&E)-stained section. The vast majority of cases can be diagnosed on H&E alone; however, in problem cases, immunohistochemistry can be very helpful in making the distinction from other tumors. Cytology is also a powerful tool, often being more definitive than small biopsies with scant tumor cells, crush artifact and/or necrosis. As virtually all SCLCs present in advanced stages, most patients are diagnosed based on small biopsy and cytology specimens. Historically, there has been significant evolution in the histological subclassification of SCLC dating from 1962 when Kreyberg proposed the oat cell and polygonal cell types. The current subclassification recognizes only two subtypes: pure SCLC and combined SCLC. Pathologists need to do their best to make a diagnosis of SCLC or other histological types of lung cancer and this can be achieved in most cases. This review will address some of the diagnostic problems that occur in the minority of cases and outline practical ways to address them. Brief reference will be made to other neuroendocrine lung tumors with an overview of the molecular pathogenesis of this spectrum of tumors. Modern Pathology (2012) 25, S18-S30; doi:10.1038/modpathol.2011.150