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small cell carcinoma of the lung (SCLC, oat cell carcinoma)

Etiology: 1) tumor originates from neuroendocrine cells 2) Kulchitsky cell hypothesized cell of origin, although not proven Epidemiology: 1) 25% of bronchogenic carcinomas 2) smokers & uranium miners are at risk Pathology: 1) generally metastatic cancer at the time of diagnosis [5] 2) histologic classification [3]: a) small cell carcinoma b) mixed small & large cell carcinoma c) combined small cell carcinoma (neoplastic squamous &/or glandular components) 3) histological features a) scant cytoplasm b) small, hyperchromatic nuclei with fine chromatin c) indistinct nucleoli d) diffuse sheets of cells 4) invades tracheobronchial tree 5) spreads submucosally & later breaks through mucosa 6) < 20% of tumors are peripheral 7) brain metastases (30%) Genetics: - rearrangement 1p32 RLF with L-MYC - chromosomal deletion 3p13-23 - other implicated genes - ROBO1, HTATIP2, ITGA9, c-MYC, INSM1, CCKBR, USP4 Clinical manifestations: 1) cough 2) hemoptysis 3) chest pain 4) hoarseness 5) dyspnea [5] 6) associated syndromes: a) SIADH b) Cushing syndrome c) Lambert-Eaton myasthenic syndrome d) superior vena cava syndrome e) cortical cerebellar degeneration [5] (rare) f) limbic encephalitis [5] (rare) g) peripheral neuropathy [5] (rare) 7) hyperpigmentation from melanocyte-stimulating hormone (MSH) Laboratory: 1) serum chemistries: a) chem 7 1] serum K+: hypokalemia (increased ACTH) 2] serum Na+: hyponatremia (SIADH) b) serum Ca+2: NOT associated with hypercalcemia c) serum phosphorous d) liver function tests (LFTs) 2) serum osmolality & urine osmolality 3) complete blood count (CBC) 4) serum calcitonin & serum procalcitonin - increased secretion of calcitonin (70%) 5) serum ACTH: increased ACTH 6) 24 hour urinary free cortisol (Cushing syndrome) 7) antineuronal nuclear antibody (ANNA-1) may be positive 8) bone marrow biopsy & aspiration 9) immunohistochemistry: - NSE: + in 95% of pulmonary neuroendocrine tumors of all types - chromogranin A: + 20-50% of small cell carcinomas - synaptophysin: + 80-100% - CK7: + 10% - CD57: + 20-50% - CEA: + 100% - low molecular weight keratins (CAM5.2, 34betaH11, AE1/AE3): + 90% - high molecular weight keratins: - Special laboratory: 1) bronchoscopy may show thickened mucosa 2) biopsy of metastatic deposits identified on radiographs establishes diagnosis [5]* 3) skin test for tuberculosis 4) barium swallow if esophageal symptoms are present 5) pulmonary function studies including arterial blood gas (ABG) if signs/symptoms of respiratory insufficiency are present 6) electrocardiogram 7) overnight dexamethasone suppression test (Cushing syndrome) * needle aspiration rather than biopsy of lymph node diagnostic according to ref [5] Radiology: 1) chest X-ray a) unilateral, rapidly enlarging hilar or peripheral mass b) widening of mediastinum 2) computed tomography of thorax & abdomen & pelvis (chest CT, abdominal CT, CT of pelvis) a) hilar hilar or peripheral mass confirming chest X-ray finding b) mediastinal lymphadenopathy 3) MRI of brain (even if no symptoms) 4) whole body radionucliide bone scan or positron emission tomography (PET scan) [5,6] Staging: 1) limited: no universal definition - includes confined to one hemithorax/mediastinum/supraclavicular nodes or limited to one radiation field 2) extensive: distant metastases - TNM staging system for non-small cell carcinomas not commonly used - survival not usually affected by small differences in amount of local/regional tumor - ref [14] recommends TNM staging system 3) defer further staging procedures if distant metastasis is documented [6] 4) see pretreatment staging for patients with lung cancer Differential diagnosis: -> neuroendocrine neoplasms encompass a spectrum: a) bronchial carcinoid with excellent prognosis after resection b) malignant/atypical carcinoid or well-differentiated neuroendocrine carcinoma c) small cell carcinoma Management: 1) tumor responds to radiation & chemotherapy [5] 2) even patients with poor performance status benefit from chemotherapy [6] - effect of chemotherapy on quality of life & in patients with poor prognosis is unknown [10] 3) early palliative care consult for metastatic lung cancer - concurrent chemotherapy & palliative care can improve quality of life & increase life expectancy 20% [5,18] 4) platinum-based combination chemotherapy - 5-6 cycles of chemotherapy suggested [5] 5) active chemotherapeutic agents: a) carboplatin or cisplatin (carboplatin with favorable toxicity profile) [17] b) etoposide c) cyclophosphamide d) doxorubicin e) vincristine f) oral topotecan may be an option for relapse (do not use IV topotecan) [7] (NGC NICE) g) addition of lurbinectedin (Zepzelca) to atezolizumab (Tecentriq) as 1st-line maintenance therapy for advanced-stage small cell lung cancer improves progression-free & overall survival [19] 6) surgical candidates (rare to uncommon) - single small primary tumor [5] - absence of lymph node involvement - invasive staging of the mediastinum with endobronchial ultrasound vs mediastinoscopy to rule out occult disease - adjuvant chemotherapy (without radiation if surgical margins negative) 7) limited stage disease - combination chemotherapy (cisplatin + etoposide) + radiation therapy 8) if complete clinical response to chemotherapy, add prophylactic cranial irradiation; decreases frequency of brain metastases & prolongs survival [5,6,15] 9) extensive stage disease: combination chemotherapy a) carboplatin or cisplatin + etoposide [5,6] + immunotherapy [5] b) cisplatin + ironotecan (conflicting reports) [6] c) radiation therapy of no benefit [5] 10) whole brain radiation therapy - prophylaxis for patients who respond to chemotherapy - symptomatic brain metastases 11) routine chest radiation therapy does not improve survival [5] 12) monthly intravenous bisphosphonate (pamidronate, zoledronate) decreases skeletal-related events see National Cancer Institute - Small Cell Lung Cancer Treatment [7] Prognosis: - most aggressive of pulmonary tumors without treatment: median survival ~2-4 months

Interactions

disease interactions

Related

chromosomal deletion 3p13-23 (SCC lung) distinguishing features of small cell carcinoma pretreatment staging for patients with lung cancer

General

carcinoma of the lung neuroendocrine carcinoma small cell carcinoma

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 769
  2. NCI CancerNet PDQ Statement http://www.cancer.gov/cancerinfo/types/lung http://www.cancer.gov/cancerinfo/pdq/treatment/small-cell-lung/healthprofessional/
  3. Hirsch FR et al Histopathologic classification of small cell lung cancer. Changing concepts and terminology. Cancer 62:973-7, 1988 PMID: 2842029
  4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 552-561
  5. Medical Knowledge Self Assessment Program (MKSAP) 14, 15, 16 17, 18, 19. American College of Physicians, Philadelphia 2006, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  6. Samson DJ, Seidenfeld J, Simon GR Evidence for management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007 Sep;132(3 Suppl):314S-323S. PMID: 17873177
  7. Stinchcombe TE, Gore EM. Limited-stage small cell lung cancer: current chemoradiotherapy treatment paradigms. Oncologist. 2010;15(2):187-95 PMID: 20145192
  8. Hanna N, Bunn PA Jr, Langer C et al Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. PMID: 16648503
  9. Slotman B, Faivre-Finn C, Kramer G et al Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16;357(7):664-72. PMID: 17699816
  10. Agra Y, Pelayo M, Sacristan M et al Chemotherapy versus best supportive care for extensive small cell lung cancer. Cochrane Database Syst Rev. 2003;(4):CD001990. PMID: 14583943
  11. Meert AP, Paesmans M, Berghmans T et al Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis. BMC Cancer. 2001;1:5. Epub 2001 Jun 19. PMID: 11432756
  12. Nair BS, Bhanderi V, Jafri SH. Current and emerging pharmacotherapies for the treatment of relapsed small cell lung cancer. Clin Med Insights Oncol. 2011;5:223-34. PMID: 21836818
  13. Pignon JP, Arriagada R, Ihde DC et al A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med. 1992 Dec 3;327(23):1618-24. PMID: 1331787
  14. Vallieres E, Shepherd FA, Crowley J et al The IASLC Lung Cancer Staging Project: proposals regarding the relevance of TNM in the pathologic staging of small cell lung cancer in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol. 2009 Sep;4(9):1049-59 PMID: 19652623
  15. Socha J, Kepka L. Prophylactic cranial irradiation for small-cell lung cancer: how, when and for whom? Expert Rev Anticancer Ther. 2012 Apr;12(4):505-17. PMID: 22500687
  16. Jett JR, Schild SE, Kesler KA, Kalemkerian GP. Treatment of small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May;143(5 Suppl):e400S-e419S. PMID: 23649448
  17. Azar I, Yazdanpanah Y, Jang H et al Comparison of Carboplatin With Cisplatin in Small Cell Lung Cancer in US Veterans. JAMA Netw Open. 2022;5(10):e2237699. PMID: 36264573 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797497
  18. Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  19. Jazz Pharmaceuticals Jazz Pharmaceuticals Announces Statistically Significant Overall Survival and Progression-Free Survival Results for Zepzelca® (lurbinectedin) and Atezolizumab Combination in First-Line Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer. News Release. Oct 15, 2024 https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-statistically-significant-overall
  20. National Cancer Institute - Small Cell Lung Cancer Treatment http://www.nci.nih.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional

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OMIM 182280 images related to small cell carcinoma of the lung