This is a highly aggressive, undifferentiated carcinoma which grows rapidly and metastasizes early:
- is a high-grade neuroendocrine carcinoma arising predominantly in current or former smokers (1)
- cigarette smoking is the primary risk factor for development of small cell lung cancer (SCLC), as 95% of patients diagnosed with SCLC have a history of tobacco use (2)
- is a dose-dependent relationship between the degree of smoke exposure and the relative risk of lung cancer (3)
- dosage of smoke depends on the type of cigarette, duration of inhalation, and presence of a filter
- makes up about 15% of lung cancer cases (1)
The tumour contains dense core granules similar to the argentaffin cell granules of the gastrointestinal tract and actively secretes hormones and hormone like products. The granules bear close resemblance to secretory granules of the amine precursor uptake and decarboxylation - APUD - system.
Three types are distinguishable histologically:
- oat cell tumour - characterised by uniform small - to - medium sized, closely packed cells arranged in strands, clusters, or singly, with dark-staining nuclei and a high nuclear:cytoplasmic ratio. A crush artefact is commonly seen in biopsies.
- intermediate cell tumour - similar to the oat cell type but the cells are more fusiform in nature
- combined oat cell tumour - has definite areas of squamous and glandular differentiation
Clinical presentation of SCLC:
- may present with respiratory symptoms such as
- cough (40%),
- shortness of breath (34%)
- hemoptysis (10%)
- metastases with corresponding local symptoms (30%) such as pleuritis or bone pain
- most common sites of metastasis include the contralateral lung, the brain, liver, adrenal glands and bone (1)
- about 60% of patients with SCLC may be asymptomatic at diagnosis
A number of paraneoplastic syndromes are associated with these tumours, including the Eaton-Lambert myasthenic syndrome, SIADH, Cushing's syndrome due to excess ACTH, and carcinoid syndrome from biogenic amines.
Small cell lung cancer is classified into limited stage (LS-SCLC; 30%) vs extensive stage (ES-SCLC; 70%) based on whether the disease can be treated within a radiation field that is typically confined to 1 hemithorax but may include contralateral mediastinal and supraclavicular nodes (2).
Management principles of SCLC
LS-SCLC
- for patients with LS-SCLC, surgery or concurrent chemotherapy with platinum-etoposide and radiotherapy is potentially curative in 30% of patients (2)
- median survival for LS-SCLC has reached up to 55.9 months with the addition of durvalumab, an immunotherapy
ES-SCLC
- first-line treatment for ES-SCLC is combined treatment with platinum-etoposide chemotherapy and immunotherapy with the programmed cell death 1 ligand 1 (PD-L1) inhibitors durvalumab or atezolizumab followed by maintenance immunotherapy until disease progression or toxicity (2)
- initial rates of tumor shrinkage are 60% to 70% with platinum-etoposide and immunotherapy treatment, the median overall survival of patients treated for ES-SCLC is approximately 12 to 13 months, with 60% of patients relapsing within 3 months
- second-line therapy for patients with ES-SCLC includes (2)
- DNA-alkylating agent lurbinectedin (35% overall response rate; median progression-free survival, 3.7 months) and
- a bispecific T-cell engager against delta-like ligand 3, tarlatamab (40% overall response rate; median progression-free survival, 4.9 months)
Reference:
- Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers. 2021 Jan 14;7(1):3.
- Kim SY, Park HS, Chiang AC. Small Cell Lung Cancer: A Review. JAMA. 2025;333(21):1906–1917.
- Basumallik N, Agarwal M. Small Cell Lung Cancer. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.