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Evolution of NeoplasiaThe Uterine Cervix As a Model
Raj C. Dash, MD
Duke University Medical Center
Durham, North Carolina
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What Medschool Class are You in ?
1 2
98%
2%
1. MS2014
2. MS 2015
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Q: How do we screen for cervical cancer?
A) Blood te
st
B) X-ra
y or CT...
C) Dire
ct exam...
D) S
lide te
st
0%
54%
46%
0%
1. A) Blood test
2. B) X-ray or CT-imaging
3. C) Direct examination (colposcopy)
4. D) Slide test
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Cancer of the Uterine Cervix
• History of Cervical Ca Screening Techniques – 1925 - Hans Hanselman introduces colposcope. – 1926 - Aureli Babes publishes on cytologic screening. Little
publicity. – 1928 - Papanicolaou presents findings on cytologic
screening. – 1941 - Papanicolaou publishes on cytologic screening.
Widely read and accepted – 1955 - Scheffey introduces colposcopy to the US.
• Dramatic decrease in mortality rate due to effectiveness of the Papanicolaou cytologic test in detecting precancerous lesions.
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What site has highest incidence rate of cancer in women?
1 2 3 4
94%
4%1%1%
1. A) Cervix/Uterus
2. B) Pancreas
3. C) Thyroid
4. D) Ovary
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What site has the highest death rate of cancer in women?
1 2 3 4
16%
31%
1%
52%
1. A) Cervix/Uterus
2. B) Pancreas
3. C) Thyroid
4. D) Ovary
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Incidence Rate
Death Rate
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Cervical Cancer Epidemiology
• 20,000 new cases per year
• 7,600 deaths per year
• 3.5% of all female deaths per year
• 50 million women undergo Pap testing in the U.S. / year.
• 3.5 million (7%) are diagnosed with a cytological abnormality requiring additional follow-up or evaluation. JAMA. 2002;287:2120-2129.
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Cervical Cancer Screening
• Epidemiologic Proof for Cervical Ca Screening - Why we do it... • MacGregor (1976):
– Screened women - invasive cancer rate = 30-50/100,000 – Unscreened women - invasive cancer rate = 310/100,000
• Fidler (1968): – Screened women - invasive cancer rate = 5/100,000 – Unscreened women - invasive cancer rate = 29/100,000
• Walton (1976): – Strong correlation between screening intensity and cervical cancer
mortality (R=0.72) • Adami (1994):
– "Cytologic screening reduces mortality from cervical cancer by earlier diagnosis of invasive disease" Cancer 1994; 73:140-7.
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Cervical Intraepithelial Neoplasia (CIN)
• Represents a continuum of morphologic changes with relatively indistinct boundaries– Dysplasia: abnormal cell growth
• Will not invariably progress to cancer– May spontaneously regress– Risk of progression to cancer increases with the
severity of the “changes” observed• Associated with viral infection?
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Which virus is most closely associated with development of cervical cancer?
1 2 3 4 5
7%
93%
0%0%0%
1. A) HIV
2. B) HPV
3. C) Hep B
4. D) Hep C
5. E) None of the above
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HPV
• Human Papilloma Virus (HPV)– 10 x risk increase of cervical neoplasia, found in 90% of CIN
– Low Risk (6,11,42,43,44)– High Risk (16,18,31,33,35,39,45,51,52,56,58,59,68)– DiGene Hybrid Capture® HPV DNA Test (3/99)
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Nomenclature
• Tumors are composed of proliferating neoplastic cells (clones) and supportive stroma of connective tissue and blood vessels.
• Tumors are named according to their neoplastic component.
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Malignancy Nomenclature
• Carcinoma: malignant neoplasia arising from epithelial tissue.
• Sarcoma: malignant neoplasia arising from mesenchymal (connective) tissue.
• Lymphoma: malignant neoplasm arising from lymphoid tissue.
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Nomenclature
• Carcinoma– Squamous cell carcinoma: derived from squamous
epithelium.– Adenocarcinoma: derived from glandular epithelium.
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Malignant Characteristics
• Rapid, Autonomous Growth– “Anaplasia” (uncontrolled growth bearing little similarity to
cell of origin, implies progression beyond severe dysplasia, beyond well-differentiated malignancy; often associated with “poor differentiation”)
• Locally invasive
• Potential for metastatic spread– Lymphovascular invasion
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Squamous Cell Neoplasia
Traditional Pathology Nomenclature
Current Pathology Nomenclature (CIN)
Bethesda System Nomenclature (SIL)
Squamous atypia Squamous atypia ASCUS
Condyloma Condyloma Low Grade SIL
(HPV effect)
Mild Dysplasia CIN I Low Grade SIL
(HPV effect)
Moderate Dysplasia CIN II High Grade SIL
Severe Dysplasia CIN III High Grade SIL
Carcinoma in-situ CIN III High Grade SIL
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Quick Quiz: Severe Dysplasia matches…
1 2 3 4 5
4% 5%
59%
15%17%
1. A) LSIL / CIN I
2. B) LSIL / CIN II
3. C) LSIL / CIN III
4. D) HSIL / CIN II
5. E) HSIL / CIN III
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Quick Recap: What cytologic criteria is LEAST important to identify neoplasia?
A) Nucle
ar siz.
..
B) Nucle
ar to ...
C) Cyto
plasm (..
.
D) N
uclear c
on...
E) N
uclear c
hr...
10%3% 4%
21%
63%
1. A) Nuclear size
2. B) Nuclear to cytoplasm size ratio
3. C) Cytoplasm (cell) size
4. D) Nuclear contours
5. E) Nuclear chromasia