Lung tumor
Other carcinoma
Small cell carcinoma

Topic Completed: 1 September 2012

Revised: 31 January 2019, last major update September 2012

Copyright: (c) 2003-2018,, Inc.

PubMed Search: small cell carcinoma[title] lung
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Cite this page: Jain D. Small cell carcinoma. website. Accessed April 23rd, 2019.
Definition / general
  • Also called oat cell carcinoma
  • 10-20% all of lung carcinoma, 45,000 new cases per year in US
  • Usually men, median age 60 years, 99% occur in smokers, very aggressive with early mediastinal lymph node involvement
  • Apparently derived from primitive cells of basal bronchial epithelium with partial differentiation towards neuroendocrine cells
  • Associated with paraneoplastic syndromes due to production of ACTH (Cushing's syndrome), ADH (hyponatremia), calcitonin (hypocalcemia), gonadotropins (gynecomastia), parathyroid hormone (hyperparathyroidism), serotonin (carcinoid syndrome); also encephalomyelitis, Lambert-Eaton syndrome, sensory neuropathy
  • Two subtypes: pure or combined (Mod Pathol 2012;25:S18)
  • Biopsies often crushed
  • Cytology may be helpful
  • Diagnosis based on H&E, not the presence of neuroendocrine markers
Prognostic factors
  • Poor prognostic factors: elevated serum LDH, alkaline phosphatase, albumin, hemoglobin, white blood count
  • Chemotherapy, radiation
  • Cure rates of 15-25% for limited disease
  • Most live 1 year
  • Preoperative chemotherapy and surgery if T1-2, N0-1, M0
Gross description
  • Usually central / hilar
  • White-tan, soft, friable, extensive necrosis
  • Peripheral nodules have fairly well-defined border and fleshy cut surface
Gross images

Images hosted on other servers:

Central tumor

Spreading along bronchi

Microscopic (histologic) description
  • Sheets, ribbons, clusters, rosettes or peripheral pallisading of small to medium sized (2-4x neutrophils) round / oval cells with minimal cytoplasm, salt and pepper chromatin without prominent clumps, hyperchromatic, indistinct nucleoli, nuclear molding, smudging, frequent mitotic figures
  • Azzopardi phenomena (basophilic nuclear chromatin spreading to wall of blood vessels), indistinct cell borders
  • Stroma is scanty, vascular, delicate
  • No glands, replacement of epithelium is less common than subepithelial growth
  • Necrosis and apoptotic debris are common
  • More cytoplasm is present in cells in metastases or resections than in small biopsies
  • May have larger cells with similar morphology, small mixtures of squamous cell carcinoma or adenocarcinoma (Am J Surg Pathol 2002;26:1184)
  • Rarely scattered giant cells, prominent nucleoli
Microscopic (histologic) images

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Flow, H&E, stains (not necessarily lung)

Positive stains
  • Pan-keratin (100%, dot like pattern), TTF1 (89%); also neuron specific enolase (77%), CD117 (75%, 50% after chemotherapy, Mod Pathol 2003;16:1041), chromogranin (58%, may be weak), synaptophysin (57%), calretinin (49%), thrombomodulin (27%), keratin5 (27%), CD57 / Leu7 (variable), gastrin releasing peptide, N-CAM / CD56, bcl-2 (variable)
Negative stains
  • CD3, CD20, CD45, CD99 / MIC2, pancreatic polypeptide, vimentin, mesothelin, p63
Flow cytometry description
Electron microscopy description
  • Occasional round, membrane bound, dense core neurosecretory granules, 100-200 nm in diameter
  • May have bundles of tonofibrils
  • May form glandular spaces
Differential diagnosis
  • Atypical carcinoid tumor: less nuclear atypia, < 20 mitotic figures per 10 HPF, no extensive necrosis, more intense neuroendocrine staining
  • Metastatic small cell carcinoma
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