1、Small Cell Lung Cancer(SCLC):Diagnosis,Treatment and Natural HistoryGary L.Weinstein M.D.SCLC Lung cancer epidemiology SCLC Pathology Tumor markers Genetics Clinical course Staging TreatmentSCLC,factoids 15 25%of all lung cancers Almost exclusively in smokers Distinguished from NSCLC by:Rapid doubli
2、ng time High growth fraction Early development of wide-spread metsSCLC,factoids(contd)Considered highly responsive to“chems and beams”BUTusually relapses within 2 years despite treatment Overall,only 3 8%of all patients survive more than 5 years Most common malignancy associated with Neurologic para
3、neoplastic syndromesSCLC,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 Xs the size of normal lymphocytesSCLC,pathology SCLC,pathology SCLC,clinical presentation Typically
4、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 syndomeSCLC,tumor markers 3 main groups:Neural,Epithe
5、lial,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 SCLCsSCLC,tumor markers Leads to expression of dopa decarboxylase,calcitonin,neuron-specific enolase,chro
6、mogranin 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 includin
7、g ACTH and Vasopressin Neurologic Paraneoplastic Syndromes Lung cancer,Paraneoplastic Syndromes SCLC,genetics Development of lung cancers occur through stimulation of proliferation and mutagenesis,occurring over YEARS and resulting from exposure to tobacco and other carcinogensSCLC,genetics The most
8、 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)The EndQuestions?
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