Transcript Small Cell Lung Cancer: Diagnosis, Treatment and Natural

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 crossreact 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 cancers occur through
stimulation of proliferation and
mutagenesis, occurring over YEARS and
resulting from exposure to tobacco and
other carcinogens
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)
The End
Questions?