1. Small Cell Lung Cancer (SCLC): Diagnosis, Treatment and Natural History Gary L.Weinstein M.D.

2. SCLC Lung cancer epidemiology SCLC –Pathology –Tumor markers –Genetics –Clinical course –Staging –Treatment

28. 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

29. 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

30. 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

31. SCLC, pathology

32. SCLC, pathology

33. 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

34. 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

35. 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

36. Neurologic Paraneoplastic Syndromes

37. Lung cancer, Paraneoplastic Syndromes

38. SCLC, genetics Development of lung cancers occur through stimulation of proliferation and mutagenesis, occurring over YEARS and resulting from exposure to tobacco and other carcinogens

39. SCLC, genetics The most common genetics of SCLC are: –P53 mutation is present in 75 -90 % –Loss of heterozygosity of c-somes 9p and 10q in the majority –Deletion of 3p  inactivation of as many as 3 tumor suppressor genes –Loss of the retinoblastoma gene function is nearly ubiquitous –Activation of telomerase in approx. 90 % (allows cells to divide forever)

55. The End Questions?