Small Cell Lung Cancer (SCLC): Diagnosis, Treatment and Natural History

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Small Cell Lung Cancer (SCLC)Diagnosis,
Treatment and Natural History

• Gary L.Weinstein M.D.

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SCLC

• Lung cancer epidemiology
• SCLC
• Pathology
• Tumor markers
• Genetics
• Clinical course
• Staging
• Treatment

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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

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SCLC, 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
  paraneoplastic syndromes

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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 Xs the size of normal
  lymphocytes

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SCLC, pathology
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SCLC, pathology
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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

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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

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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

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Neurologic Paraneoplastic Syndromes
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Lung cancer, Paraneoplastic Syndromes
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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

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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)

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The End
Questions?