Small cell lung cancer (SCLC) represents approximately 15% of lung cancer cases, with the remaining cases classified as non-SCLC. SCLC is characterized by an aggressive clinical course, with most patients presenting with advanced or metastatic disease at diagnosis.
Tobacco smoking remains the predominant risk factor for SCLC, with the vast majority of cases occurring in current or former smokers and only a small minority arising in never-smokers. Additional risk factors include older age, residential radon exposure, and occupational exposures such as asbestos and diesel engine emissions. Environmental factors, including long-term exposure to ambient air pollution, may play a role in a subset of cases, especially among individuals without a history of smoking.
Although Down syndrome is associated with an increased risk for certain hematologic malignancies, individuals with Down syndrome generally have a lower incidence of most solid tumors.
Learn more about the epidemiology of SCLC.
TP53 and RB1 are key tumor suppressor genes involved in genomic stability, apoptosis, and cell cycle regulation, and are biallelically inactivated in most SCLC tumors. Additionally, SCLC exhibits marked transcriptional and phenotypical heterogeneity. This plasticity is thought to promote rapid metastatic spread and facilitate the emergence of acquired resistance to therapy.
FMR1, BRCA2, and OPRM1 are not commonly associated with SCLC.
Learn more about the pathophysiology of SCLC.
SCLC is usually characterized on light microscopy by small- to intermediate-sized tumor cells. The cells have minimal cytoplasm as well as round to spindle-shaped nuclei. They also have granular chromatin and inconspicuous or absent nucleoli. These histologic features are considered typical for SCLC.
Learn more about the histology of SCLC.
CT of the chest and abdomen should be carried out in patients with SCLC. Brain MRI is also routinely recommended. FDG PET-CT is useful in selected cases, especially in limited-stage SCLC or if curative treatment is considered, but it is not yet recommended routinely.
Learn more about SCLC guidelines.
Initial therapy for SCLC often consists of platinum and etoposide chemotherapy, along with chemoimmunotherapy. According to researchers, treatment resistance with chemotherapy tends to develop quickly, often "leading to poor overall survival and limited efficacy of subsequent therapies, especially for platinum-resistant disease." Further, recent studies report that median progression‑free survival generally remains short. Concurrent use of immune-related targeting can help improve survival in this population.
Learn more about SCLC management.
Editor's Note: This article was created using several editorial tools, including generative AI models, as part of the process. Human review and editing of this content were performed prior to publication.
