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Small Cell Lung Cancer (SCLC):Diagnosis, Treatment and Natural History Gary L.Weinstein M.D. SCLC Lung cancer epidemiology SCLC Pathology Tumor markers Genetics Clinical course Staging Treatment SCLC, factoids 15 – 25 % of all lung cancers Almost exclusively in smokers Distinguished from NSCLC by: Rapid doubling time High growth fraction Early development of wide-spread mets SCLC, factoids (cont’d) Considered highly responsive to “chems and beams” BUT…usually relapses within 2 years despite treatment Overall, only 3 –8 % of all patients survive more than 5 years Most common malignancy associated with Neurologic paraneoplastic syndromes SCLC, pathology Most recent (1999) WHO classification Classical small cell carcinoma Large cell neuroendocrine cancer Combined small cell carcinoma with some NSCLC Cells are approx. 2 X’s the size of normal lymphocytes SCLC, pathology SCLC, pathology SCLC, clinical presentation Typically arise centrally Most common presentation is a large hilar mass with bulky mediastinal LAN Common symptoms cough, SOB, wt loss Approx. 70 % with overt mets at presentation Commonly spread to liver, adrenals, bone and brain Can present with paraneoplastic syndome SCLC, tumor markers 3 main groups: Neural, Epithelial, Neuroendocrine Epithelial: virtually all SCLCs are immunoreactive for Keratin and Epithelial Membrane Antigen 1 or more markers of Neural/Neuroendocrine differentiation found in approx. 75 % of SCLCs SCLC, tumor markers Leads to expression of dopa decarboxylase, calcitonin, neuron-specific enolase, chromogranin A, CD-56 (a neural cell adhesion molecule) gastrin releasing peptide and insulin-like growth hormone Occasionally patients produce antibodies that cross-react with both the SCLC cells and the CNS ? cerebellar degeneration syndromes SCLC cells can produce a number of polypeptide hormones including ACTH and Vasopressin Neurologic Paraneoplastic Syndromes Lung cancer, Paraneoplastic Syndromes SCLC, genetics Development of lung cance