Cervical Pathology Case Studies

1
Cervical PathologyCase Studies

• Charles Dunton, MDCourse Director
• Professor of Obstetrics and GynecologyJefferson
  Medical College
• Director, Division of Gynecologic OncologyAlbert
  Einstein Medical Center

2
Initial Presentation

• A 30-year-old patient presents for her first Pap
  smear in 3 years. She is asymptomatic with
  normal menses. Regarding her medical history,
  she is G4P4, a cigarette smoker, and has no
  relevant history of treatment or other abnormal
  cytology. Her cervical cytology slide is seen in
  Figure 1.

Figure 1
3
The Correct Cytologic Diagnosis for This Slide Is
Differential Diagnosis

• A. ASC-NOS
• B. ASC-H
• C. LGSIL
• D. HGSIL
• E. AGUS

Figure 1
4
The Correct Cytologic Diagnosis for This Slide Is
Differential Diagnosis

• B. ASC-H Correct
• The 2001 Bethesda System1 added a new category
  of ASC-H Atypical Squamous Cells, Cannot
  Exclude HSIL2. With a diagnosis of ASC-H, the
  cytopathologist is communicating to the
  clinician an equivocal finding. This diagnosis
  should only account for 5-10 of all ASC
  cases.3,4, 5
• While the interpretation is not highly
  reproducible, it does have a high predictive
  value for CIN 2 and 3.

Figure 1
5
The Correct Cytologic Diagnosis for This Slide Is
Differential Diagnosis

• A. ASC-NOS Incorrect
• The cells seen here have an increased
  nuclearcytoplasmic ratio.
• C. LGSIL Incorrect
• A low grade SIL is incorrect. There would be
  more abundant cytoplasm with enlarged nucleus or
  perinuclear halos showing HPV effect in low grade
  SIL.

Figure 1
6
The Correct Cytologic Diagnosis for This Slide Is
Differential Diagnosis

• D. HGSIL Incorrect
• High-grade SIL is incorrect however, if you
  chose this category having not seen the rest of
  the slide, the answer could be correct. These
  cells show typical findings for high-grade
  cells, but due to the paucity of cells on the
  entire slide, the most accurate diagnosis would
  be ASC-H.

Figure 1
7
The Correct Cytologic Diagnosis for This Slide Is
Differential Diagnosis

• E. AGUS Incorrect
• These cells are squamous in origin. They do not
  show the typical features of a glandular lesion
  such as rosetting.

Figure 1
8
Given a Cytologic Diagnosis of ASC-H, the
Preferred Management Option at This Time Is
Management

• A. Reflex HPV-DNA testing
• B. Repeat cytology
• C. Colposcopy
• D. Loop excision  

9
Given a Cytologic Diagnosis of ASC-H, the
Preferred Management Option at This Time Is
Management
Answer 2

• C. Colposcopy Correct
• The diagnosis of ASC-H requires colposcopy to
  detect high-grade lesions. The risk of CIN 2 and
  3 associated with this diagnosis has been
  reported to range from 24 to 94 in various
  studies. The risk of invasion is 0.1-0.2.6
• Published reports do not suggest that
  intermediate triage such as HPV DNA testing is
  useful, and repeat cytological testing would be
  inappropriate. Due to the equivocal nature of
  ASC-H, loop excision is not indicated prior to
  colposcopic diagnosis.7

10
Colposcopy of This Patient Can Be Seen in Figures
2-4. Which of the Following Findings Regarding
the Colposcopic Examination Are True?
Diagnostic Study
Figure 2 Image without filter

• A. Satisfactory examination
• B. Atypical vessels
• C. Acetowhite areas
• D. Nodularity

Figure 3 Image with filter
Figure 4 High resolution image
11
Colposcopy of This Patient Can Be Seen in Figures
2-4. Figures 2-4 Indicate the Following
Findings
Diagnostic Study
Figure 2 Image without filter

• B. Atypical vessels Correct
• The area seen in the colposcopy appears flat.
  There are numerous atypical vessels in a
  background of acetowhite changes. The entire
  squamo-columnar junction is not visible.
• C. Acetowhite areas Correct
• The area seen in the colposcopy appears flat.
  There are numerous atypical vessels in a
  background of acetowhite changes. The entire
  squamo-columnar junction is not visible.

Figure 3 Image with filter
Figure 4 High resolution image
12
These Findings (i.e., Atypical Vessels and
Acetowhite Areas) Are Best Described As
Diagnostic Study
Figure 2 Image without filter

• A. Invasive cancer
• B. Metaplasia and cervicitis
• C. High grade CIN
• D. HPV changes

Figure 3 Image with filter
Figure 4 High resolution image
13
These Findings (i.e., Atypical Vessels and
Acetowhite Areas) Are Best Described As
Diagnostic Study
Figure 2 Image without filter

• A. Invasive Cancer Correct
• The presence of atypical vessels should alert the
  clinician to the possibility of invasive cancer.
• Other warning signs of invasion include areas of
  necrosis, large lesions, nodularity, ulceration,
  invasive cytology, lesions extending to the canal
  and a positive endocervical curettage.

Figure 3 Image with filter
Figure 4 High resolution image
14
The Pathology From a Biopsy at 6 OClock is Seen
in Figure 5. Based on This Pathology, Your
Initial Diagnosis Is
Final Diagnosis

• A. CIN 3
• B. AIS
• C. Squamous cell carcinoma
• Invasion 1 mm
• D. Squamous cell carcinoma
• Invasion 5 mm

15
The Pathology From a Biopsy at 6 OClock is Seen
in Figure 5. Based on This Pathology, the
Correct Diagnosis is
Final Diagnosis

• C. Squamous cell carcinoma - Invasion 1 mm
  Correct
• The pathology shown in Figure 5 demonstrates
  full-thickness dysplasia and invasion below the
  basement membrane. In this slide, the invasion is
  minimal.

16
For this Patient, the Correct Management Option
at This Time Is
Treatment

• A. Simple hysterectomy for "microinvasion
• B. Radical hysterectomy for cervical cancer
• C. Cold knife conization
• D. Loop excision

17
The Correct Management Option Is
Treatment
Answer 6

• C. Cold knife conization Correct
• The diagnosis of microinvasion cannot be made on
  a colposcopic biopsy.8 In this case, it would
  appear that a significant invasion is present.
  Excisional biopsy is necessary to discover the
  depth of invasion. Cold knife conization is
  preferred in order to most accurately determine
  depth of invasion and margin status without
  thermal artifact.
• Radical hysterectomy maybe necessary, depending
  on results of the cone biopsy.

18
Summary

• After a colposcopy and directed biopsy is it
  necessary to exclude significant disease? HPV DNA
  triage for ASC-H has not been studied and is not
  recommended. It has been found to be highly
  effective in patients with ASC-US in triaging
  patients to colposcopy. A finding of ASC-H should
  be further investigated with diagnostic testing.
• The cytologic finding of ASC-H is associated with
  true cancer precursors in a significant number of
  cases. Colposcopy and directed biopsy are
  necessary to exclude significant disease.
  Treatment should be based on the histologic
  findings. With this cytologic category, if no
  lesions are found, close cytologic surveillance
  is warranted. Recommendations call for repeat
  cytology at 6 and 12 months or HPV DNA testing at
  12 months.9 The authors of the 2001 Bethesda
  report state, "However, the equivocal nature of
  the ASC-H designation should encourage
  comprehensive review of all pathology and
  colposcopic findings prior to performing a
  diagnostic loop electrosurgical excision
  procedure in women with negative histology
  results.10

19

• 1. American Society for Colposcopy and Cervical
  Pathology (ASCCP) Web site. Consensus Guidelines.
  Available http//www.asccp.org/consensus/about.sht
  ml March 2003.
• 2. Solomon D, Davey D, Kurman R, et al. The 2001
  Bethesda System terminology for reporting
  results of cervical cytology. JAMA.
  2002287(16)2114-2119.
• 3. Sherman ME, Tabbara SO, Scott DR, et al.
  ASCUS, rule out HSIL cytologic features,
  histologic correlates and human papillomavirus
  detection. Mod Pathol. 199912335-343.
• 4. Quddus MR, Sung CJ, Steinhoff MM, et al.
  Atypical squamous metaplastic cells
  reproducibility, outcome, and diagnostic features
  on ThinPrep Pap test. Cancer. 20019316-22.
• 5. Sherman ME, Tabbara SO, Scott DR, et al.
  ASCUS, rule out HSIL cytologic features,
  histologic correlates and human papillomavirus
  detection. Mod Pathol. 199912335-343.
• 6. Wright TC Jr, Cox JT, Massad LS, Twiggs LB,
  Wilkinson EJ. 2001 Consensus Guidelines for the
  management of women with cervical cytological
  abnormalities. JAMA 2002 Apr 24287(16)2120-9.
• 7. Solomon D, Davey D, Kurman R, et al. The 2001
  Bethesda System terminology for reporting
  results of cervical cytology. JAMA.
  2002287(16)2114-2119.
• 8. Holtz DO, Dunton C. Traditional management of
  invasive cervical cancer. Obstet Gynecol Clin
  North Am. 200229(4)645-657.
• 9. Wright TC Jr, Cox JT, Massad LS, Twiggs LB,
  Wilkinson EJ. 2001 Consensus Guidelines for the
  management of women with cervical cytological
  abnormalities. JAMA 2002 Apr 24287(16)2120-9.
• 10. Solomon D, Davey D, Kurman R, et al. The 2001
  Bethesda System terminology for reporting
  results of cervical cytology. JAMA.
  2002287(16)2114-2119.