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

Abstract

Small cell lung cancer (SCLC) comprises 14% of all lung cancers, and 430 000 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 goodquality 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.

Fibroblast growth factor receptor 1 (FGFR1) amplification is a potential therapeutic target in small-cell lung cancer

“…1 Thus, morphological features, eg, size of nuclei, nucleus/cytoplasm ratio, chromatin structure and nuclear molding, were evaluated on H&E slides. To confirm the diagnosis ancillary immunohistochemical stainings were made, eg CD56, synaptophysin, chromogranin A and cytokeratins as well as TTF1 (thyroid transcription factor 1).…”

“…1 It typically occurs in heavy smokers, is a rapidly progressive disease and most patients present at first diagnosis with advanced stage disease. The median survival ranges from 23 months for limitedstage disease down to 8 months for extensive-stage disease.…”

“…The median survival ranges from 23 months for limitedstage disease down to 8 months for extensive-stage disease. 1 Over the last 30 years, medical treatment for advanced SCLC has mainly remained unchanged, consisting of a platinum-based chemotherapy regimen with optional radiation therapy depending on tumor stage. 2 Although targeted therapeutic options have been established for pulmonary adenocarcinomas, including EGFR (epidermal growth factor receptor) and ALK (anaplastic lymphoma kinase) inhibitors, 1,3,4 and recently also for squamous cell carcinomas, 5,6 small-cell carcinomas still lack therapeutically exploitable genetic alterations.…”

Application of Immunohistochemistry in the Diagnosis of Pulmonary and Pleural Neoplasms

“…126 Small cell lung carcinoma can be easily recognized by its distinct morphology. 127,128 The neoplastic cells usually form sheets and nests. Cytologically, they are small (less than 3 times the diameter of a resting lymphocyte), hyperchromatic, and round to fusiform; they contain inconspicuous nucleoli, finely granular chromatin, and scant cytoplasm.…”

Extrapulmonary neuroendocrine small and large cell carcinomas: a review of controversial diagnostic and therapeutic issues

“…Among them, the issue of high grade, poorly differentiated NE carcinomas (NEC) was briefly addressed (FAQ #4) with regard to their occurrence in several extrapulmonary organs, as either small cell carcinomas (SCC) or large cell NECs (LCNEC), apparently very similar to their well-known respective pulmonary counterparts [2,3]. In the literature, the occurrence of extrapulmonary poorly differentiated NECs (EPNEC) has been reported in single case reports (see review [4]), and only recently were relatively large series collected and analyzed from both clinical and pathological perspectives [5].…”