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Lung tumor

Other Carcinoma

Small cell carcinoma

Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 23 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.


● 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

Central tumor

Spreading along bronchi

Micro 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

Micro images

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

Virtual slides

Various slides

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

● CD56+ (neural cell adhesion molecule), CD45-, which differentiates from lymphoma (Arch Pathol Lab Med 2003;127:461)

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

End of Lung tumor > Other carcinoma > Small cell carcinoma

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