Download Video Microscopy Tutorial 15 - American Society of Cytopathology

 Video Microscopy Tutorial 15 Anal Cytology: An Overview Teresa Darragh, MD There are no disclosures necessary. Teresa M. Darragh, MD Hologic: Research supplies for anal cytology; Research Support, Advisory Board: OncoHealth; Other Financial or Material Interest
Anal Cytology: An Overview
Video Microscopy Tutorial #15
Sunday, November 4, 2012
Teresa M. Darragh, MD
UCSF
Departments of Pathology and
Obstetrics, Gynecology & Reproductive Sciences
Conflict of interest
• Faculty Disclosures: Teresa M. Darragh, MD
• Hologic: Research supplies for anal cytology
• OncoHealth: Advisory Board
Tutorial Objectives
• Overview of anal cancer:
– Basic epidemiology & pathology
– Identify at-risk groups for HPV-related
neoplasia of the anal canal
• Anal cytology
– Specimen adequacy
– Negative findings, including organisms
– Abnormal findings
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Anal Cancer in U.S., 2011 Estimates
• New cases in 2011: 5820
– 3280 ♀
– 2140 ♂
• Deaths in 2011: 770
– 470 ♀
– 300 ♂
• SEER: Significant increase 2003-2007
– Both sexes have seen an increase in
incidence
– Rise has been more pronounced in men.
American Cancer Society: www.cancer.org
SEER: http://seer.cancer.gov
Anal Cancer in U.S.
• New cases in 2011: 5820
– 3680 ♀
– 2140 ♂
• Deaths in 2011: 770
– 470 ♀
– 300 ♂
Estimated new cases
and deaths from anal
cancer in the US in 2012:
New cases: 6,230
Deaths: 780
• SEER: Significant increase 2003-2007
– Both sexes have seen a significant
increase in incidence
American Cancer Society: www.cancer.org
SEER: http://seer.cancer.gov
Anal Cancer Rates by Birth Cohort
Coming of age:
• Sexual
revolution
• HIV epidemic
Simpson J A D , Scholefield J H BMJ 2011;343:bmj.d6818
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Anal Cancer: Who is at risk?
• Men who have sex with men (MSM)
• Patients with HIV disease
• Other causes of immunosuppression
– Solid organ transplantation
– ? Other causes of immunosuppression, e.g.
• Chronic steroid therapy
• Cancer chemotherapy
• Women with HSIL / cancer
• Multifocal HPV-related disease
• Vulvar / perianal > cervix
Anal Cancer and Cervical Cancer
• Cervical cancer in US:
– prior to Pap screening
• Cervical cancer in US:
– currently
• Anal cancer:
– women, general pop.
• Anal cancer:
– HIV- MSM*
• Anal cancer:
– HIV+ MSM*
• 40-50 / 100K
• 8 / 100K
• 1.8 / 100K
• 35 / 100K
• Estimated 70 +/ 100K
*MSM = men who have sex with men
Anal Cancer and Cervical Cancer
• Common risk factors
– Sexual intercourse
• Vaginal
• Anal
• HPV infection
– High-risk HPV
– HPV 16 and 18
• >90% of anal cancers
– HPV-related
– Especially HPV 16
• Anatomic
commonality:
– Transformation zones
– Regions of active
squamous metaplasia
– Vulnerable to high-risk
HPV
• Morphologic similarity
– Precursor lesions
• HSIL and LSIL
• CIN vs AIN
– Cancer: Squamous
cell carcinoma
3
Netter Presenter Image Copyright 2003,
Icon Learning Systems. All rights reserved.
Cervix and Anus:
Lesions morphologically similar
Low grade
High grade
Cervix
Anus
HPV-related Lesions of the
Cervix and Anal Canal
SIMILARITIES >> DIFFERENCES
Diagnostic approaches similar
4
Anal Cancer: Screening and
Diagnosis
HPV-related lesions of the anogenital tract
•
•
•
•
Anal Cytology
Digital anal-rectal examination (DARE)
High resolution anoscopy (HRA)
HRA-directed anal biopsy
Anal Cytology: Bethesda 2001
Recommendations
• Relatively “new tool”
– Screen for HPV-related lesions of anal canal
– Screen “high-risk” individuals
•
•
•
•
Engage in anal intercourse, esp. MSM
HIV disease
?Immunodeficiency / Immunosuppression
? HSIL+, vulva > cervix
• Use Bethesda System terminology
– Diagnostic criteria similar to GYN cytology
– HPV-related changes parallel those for GYN cytology:
LSIL, HSIL, ASC-US, ASC-H
– Guidelines for specimen adequacy
Anal Cytology: Technique
• Use moistened Dacron
swab – NOT pre-scored!
• Insert into canal until
resistance is met
– Above anal verge to distal
rectum
– Do not use pre-scored
swab!
• Rotate / apply pressure to
walls of canal while
removing sampling device
• Liquid-based cytology or
direct smear
5
Anal Cytology: Goal
• Sample entire anal canal
• Anal transition zone
– Analogous to cervical TZ
– Squamous metaplasia
• Non-keratinized
squamous mucosa
• Keratinized squamous
mucosa
Netter Presenter Image Copyright 2003,
Icon Learning Systems. All rights reserved.
Anal Cytology:
Normal components
• Transformation Zone
components:
– Rectal columnar cells
– Squamous metaplasia
• Nucleated squamous
cells
• Anucleate squames
Anal Cytology: Specimen Adequacy
• Liquid vs conventional pap
–
–
–
–
Better cell preservation
↑ Cellular harvest
↓ Bacteria / fecal contamination
↓ Mechanical / air-dry artifacts
• Minimum cellularity:
– 2000-3000 nucleated
squamous cells
.........
• ThinPreps (20 mm):
– 1 to 2 nucleated cells / hpf
• SurePath (13 mm):
– 3 to 6 nucleated cells / hpf
– > 6/hpf (Arain et al)
6
Anal Cytology: Specimen adequacy
Satisfactory
Unsatisfactory
Anal Cytology:
2001 Bethesda System
• Negative for intraepithelial lesion
or malignancy
– Organisms
– Other non-neoplastic findings (e.g.
reactive cellular ∆)
• Epithelial Cell Abnormalities
– Squamous cell
– Glandular Cell
Anal Cytology:
Reparative Changes
7
Anal Cytology: Bugs
• Similar to Pap tests
– Herpes
– Candida
Anal Cytology: Bugs
• Unique to anal cytology
– Local infection vs “passing through”
– Ameba, pinworm, strongyloides
2001 Bethesda System:
Epithelial Cell Abnormalities
• Squamous cell abnormalities
– Atypical squamous cells
• of undetermined significance (ASC-US)
• Cannot exclude HSIL (ASC-H)
– Low grade SIL (LSIL)
– High grade SIL (HSIL)
– Squamous cell carcinoma
• Glandular cell abnormalities
8
Low grade  High grade  Cancer
Anal LSIL
Low Grade Lesions
• Caused by both high-risk
and low-risk viral types
• Most of these will
spontaneously regress,
if immunocompetent
• Productive HPV infections
• In general, close clinical
observation without
treatment is recommended
9
Anal HSIL
High Grade Lesions
• Caused by high-risk
viral types
• Most will persist or
progress
• With time, become
integrated HPV
infections
• Goal: Treat
precancer before it
has the opportunity to
develop into cancer
Anal Squamous Cell Carcinoma
10
Anal Squamous Cell Carcinoma
• Invasive cancer
• Associated with high
grade lesions
• No defined
counterpart to cervical
microinvasion
• T1 = 2 cm or less
• Not subdivided
ARC: Atypia
• Atypical squamous cells that quantitatively
or qualitatively that are not sufficiently
atypical to warrant an interpretation of
LSIL or HSIL
• ASC-US
– Suggestive of low grade SIL
• ASC-H
– Cannot exclude high grade SIL
Atypical Squamous Cells
ASC-US
ASC-H
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Anal Cytology:
Sensitivity and Specificity
Sensitivity*
Specificity*
HIV+
81%
63%
HIV-
50%
92%
*Includes ASCUS
Palefsky et al, J AIDS & Hum Retrovir
1997, 14:415-22.
Anal HPV Testing?
• No FDA-approved HPV test for anus
• Laboratories need to validate for this site
• Screening and triage
– Mixed reports of usefulness
– High negative predictive value
– High prevalence in at-risk populations
– ? Usefulness and cost-effectiveness
Screening for AIN
Anal Cytology Screening
Negative
ASC-US
Repeat q year (HIV+)
Repeat q 2-3 yr (HIV-)
LSIL
HSIL
High-resolution
Anoscopy with biopsy
No lesions seen
Low grade AIN
Follow q 6 months
or Tx if symptomatic
High grade AIN
Treat
Chin-Hong and Palefsky. HIV/AIDS 2002;35:1127-1134
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High-resolution Anoscopy:
A, B, C’s +V
• Anal Colposcopy
–Acetowhite
lesions
–Borders
–Contour changes
–Vascular
changes
Low Grade
High Grade
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Anal Squamous Cell Carcinoma
Anal cytology:
Who should we screen?
•
•
•
•
•
1.
2.
3.
4.
5.
All HIV+ MSM (with good prognosis)
All HIV- MSM (esp. over age 40)
All HIV+ men regardless of sexual orientation
All HIV+ women
?? Other causes of immunosuppression
• Renal transplant patients: increased incidence
• Other causes of immunosuppression
• 6. ?? Women with HSIL/cancer
• vulvar/perianal > cervix
• 7. ?? All with perianal condyloma
The Bad News
• The incidence of AIN and
anal cancer is high among
HIV-seropositive women
and MSM (both HIV- and
HIV+)
• HAART has limited positive
effect on HPV-related
neoplasia
• Evidence is mounting that
the incidence of anal
cancer will continue to rise
among HIV-positive MSM
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The Good News
• At-risk men and women should
be considered for screening
and treatment of AIN
– Treatment is improving!
• At-risk men and women should
be screened for anal cancer
with a digital rectal exam
– Early detection of anal cancer has
real benefits
• HPV vaccines have the
potential to prevent anal HPV
infection and ultimately, anal
cancer
Quadrivalent HPV vaccine
• December 28, 2010
• FDA Approves New Indication for Gardasil to
Prevent Anal Cancer and AIN
• The U.S. Food and Drug Administration today
approved use of the vaccine Gardasil for the
prevention of anal cancer caused by HPV types 16
and 18, and for the prevention of anal intraepithelial
neoplasia (AIN), grades 1, 2, and 3 (anal dysplasias
and precancerous lesions) caused by HPV types 6,
11, 16, and 18, in persons aged 9 to 26 years.
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