Cervical Pathology Case Studies

1
Cervical PathologyCase Studies

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

2
Initial Presentation

• A 24-year-old G0P0 presents for her first pap
  smear in 3 years. There is no previous history
  of abnormal smears. She has smoked in the past
  but stopped one year ago. She has no history of
  STDs. She is using oral contraceptives.

3
Your Diagnosis Is
Differential Diagnosis

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

4
Your Diagnosis Is
Differential Diagnosis
Answer 1

• A. ASC-US Correct
• This Pap smear was read as atypical squamous
  cells of undetermined significance (ASC-US).
• Note the normal cells present with small nuclei
  and abundant cytoplasm. The more eosinophilic
  cell to the right of the screen has a slightly
  enlarged nucleus, approximately 2 to 3 times the
  size of normal nuclei. There is, however,
  abundant cytoplasm.

5
Given the Diagnosis of ACS-US, Preferred
Management Is to
Management

• A. Colposcopy
• B. HPV-DNA reflex testing
• C. Repeat cytology in 4-6 months
• D. Cryotherapy

6
Given the Diagnosis of ACS-US, Preferred
Management Is to
Management
Answer 2

• B. HPV-DNA reflex testing Correct
• Previously, the 1994 guidelines would have
  allowed any of the other three answers to be
  acceptable management. The new 2001 Consensus
  Guidelines, commonly referred to as the ASCCP
  Guidelines, have suggested that HPV-DNA reflex
  testing on liquid-based cytology is the
  preferred management. As these Guidelines are set
  up on evidence-based medicine, preferred
  management is considered the option that is best,
  or one of the best, when there are multiple
  other options.
• HPV-DNA testing for high-risk virus (types 16,
  18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and
  68) is shown to identify women with high grade
  CIN.
• This is a sensitive test when used in conjunction
  with cervical cytology. While it is not a highly
  sensitive test, HPV-DNA testing can decrease
  referral to colposcopy by approximately 50 and
  will maintain a high sensitivity for pickup of
  true cancer precursors. The Consensus Guidelines
  recommended this to be the preferred management
  option when using triage testing.

American Society for Colposcopy and Cervical
Pathology (ASCCP) Web site. Consensus Guidelines.
Available http//www.asccp.org/consensus/about.sh
tml October 7, 2002.
7
Given the Diagnosis of ACS-US, Preferred
Management Is to
Management
Answer 2 continued

• Answer A Colposcopy is an acceptable option.
• Answer C Repeat Cytology in 4 to 6 months is
  also an acceptable option. If option C is used,
  women should undergo repeat cytologic testing at
  4 to 6 month intervals until two consecutive
  negatives for intraepithelial lesions or
  malignancy results are obtained. Should a repeat
  ASC-US or greater cytologic abnormality be found,
  the woman should be referred for a colposcopy.
• If the patient is referred for an immediate
  colposcopy and no lesions were found, the patient
  should be followed up with repeat cytology at 12
  months. Prior therapy without a histologic
  diagnosis of dysplasia is inappropriate.

8
What Are the Colposcopic Findings?
Diagnostic Study

• 1. Faint acetowhite, geographic borders, fine
  mosaic patterns
• 2. Acetowhite lesion, well defined margins,
  coarse mosaic and punctation
• 3. Dense acetowhite, atypical vessels
• 4. Satellite lesions

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9
What Are the Colposcopic Findings?
Diagnostic Study
Answer 5A

• 2. Acetowhite lesion, well defined margins,
  coarse mosaic and punctation Correct
• These colposcopic photographs show a lesion at 12
  o'clock with a well-defined margin. There is, of
  course, punctation and mosaic patterns and
  acetowhite lesion. There are no atypical vessels
  present. Satellite lesions are not seen.

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10
What Is Your Colposcopic Impression?
Diagnostic Study

• 1. Squamous Metaplasia
• 2. CIN 1, HPV
• 3. CIN2, CIN3
• 4. Invasive Squamous cell cancer

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11
What Is Your Colposcopic Impression?
Diagnostic Study
Answer 5B

• 3. CIN2, CIN3 Correct
• The colposcopic findings here are suggestive of a
  high grade CIN, CIN 2-3. There is no evidence
  that this is an invasive lesion

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12
The Most Appropriate Area for Biopsy Is
Diagnostic Study

• 1. 3 o'clock
• 2. 6 o'clock
• 3. 9 o'clock
• 4. 12 o'clock

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13
The Most Appropriate Area for Biopsy Is
Diagnostic Study
Answer 5C

• 4. 12 o'clock Correct
• It would be most appropriate to biopsy the lesion
  near the transformation zone at 12 o'clock.

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14
Your Diagnosis Is
Diagnosis

• A. Squamous Metaplasia
• B. CIN 1
• C. CIN3
• D. Invasive Squamous cell cancer

15
Your Diagnosis Is
Diagnosis
Answer 6

• C. CIN3 Correct
• Here is seen the colposcopically directed biopsy.
  Note the full thickness change in the squamous
  epithelium and lack of invasion of the basement
  membrane. These findings are consistent with a
  CIN 3 lesion.

16
Management Options for This Patient Include
Treatment

• A. Observation
• B. Loop excision
• C. Cryotherapy
• D. Cold-Knife Conization

17
Management Options for This Patient Include
Treatment
Answer 7

• B. Loop excision Correct
• Observation is not appropriate for high-grade
  dysplasia. This is a true cancer precursor and
  requires treatment.
• Loop excision would be the author's preferred
  treatment plan, though cryotherapy and cold knife
  conization have their advantages and
  disadvantages. I would prefer a Loop excision for
  treatment of this high-grade lesion with
  satisfactory colposcopy. Since I would plan a
  Loop excision procedure when I first saw this
  patient, I would not necessarily perform an
  endocervical curettage at initial diagnosis.

18
Management Options for This Patient Include
Treatment
Answer 7 continued

• Cryotherapy is certainly appropriate. However,
  given a satisfactory colposcopy, an endocervical
  curettage would need to be performed prior to
  performing cryotherapy.
• Cold knife conization would be appropriate
  however, this generally requires more anesthesia
  than a Loop excision does.

19
Summary

• This case demonstrates the use of HPV-DNA reflex
  testing in the management of low-grade
  abnormalities.
• The ALTS trial,1 a randomized prospective trial
  of repeat cytology HPV-DNA testing and immediate
  colposcopy in women with atypical squamous cells
  of undetermined significance (ASC-US),
  demonstrated that the most cost effective method
  for follow-up of these patients was HPV-DNA
  testing. This testing gives a high sensitivity
  for the detection of high-grade lesions with
  reasonable referral for colposcopic examination.
• 2001 Consensus Guidelines made this the preferred
  option. If the patient does not have liquid-based
  cytology, she is required to return for an
  additional office visit and HPV testing. It is
  the author's opinion, based on results from
  numerous studies,2,3,4,5,6 that liquid-based
  cytology increases the sensitivity of the Pap
  smear and has the added advantage of being able
  to do HPV-DNA testing, along with chlamydial
  testing.
• Concerning the management of high-grade lesions,
  acceptable treatments include cryotherapy, Loop
  excision procedures, cold knife conization, and
  laser treatments. All of these modalities have
  their advantages and disadvantages.

20
Summary(continued)

• Cryotherapy is less effective with large
  high-grade lesions and certainly requires
  endocervical curettage before its performance.
  Cold knife conization is highly successful
  however, generally requires more anesthesia than
  a Loop excision procedure, which may be an
  office-based procedure under local anesthesia.
  Laser therapy, again, requires lasers that need
  to be calibrated and maintained and the cost of
  laser is higher than the cost of a loop excision
  procedure, if one considers the cost of the
  equipment.
• Women with atypical squamous cells have a 5-17
  chance of having CIN 2-3 confirmed by biopsy. In
  fact, if all cases of high grade CIN are
  considered, the most likely preceding diagnosis
  is atypical squamous cells. Therefore, additional
  follow-up and testing must be performed on these
  women. HPV-DNA typing decreases the number of
  colposcopic exams and allows for high sensitivity
  to discover patients with true precancerous
  lesions.

21

• 1. The Atypical Squamous Cells of Undetermined
  Significance/Low-Grade Squamous Intraepithelial
  Lesions Triage Study (ALTS) Group. Human
  papillomavirus testing for triage of women with
  cytologic evidence of low-grade squamous
  intraepithelial lesions Baseline data from a
  randomized trial. Journal of the National Cancer
  Institute 2000 92(5)397-402.
• 2. Belinson J, Qiao YL, Pretorius R, Zhang WH,
  Elson P, Li L, Pan QJ, Fischer C, Lorincz A,
  Zahniser D Shanxi Province cervical cancer
  screening study A cross-sectional comparative
  trial of multiple techniques to detect cervical
  neoplasia. Gynecol Oncol 2001 83439-44.
• 3. Corkill M, Knapp D, Martin J, Hutchinson ML
  Specimen adequacy of ThinPrep sample preparations
  in a direct-to-vial study. Acta Cytol
  19974139-44.
• 4. Lee KR, Ashfaq R, Birdsong GG, Corkill ME,
  McIntosh KM, Inhorn SL Comparison of
  conventional Papanicolaou smears and a
  fluid-based, thin-layer system for cervical
  cancer screening. Obstet Gynecol 199790278-284.
• 5. Diaz-Rosario LA, Kabawat SE Performance of a
  fluid-based, thin-layer Papanicolaou smear method
  in the clinical setting of an independent
  laboratory and an outpatient screening population
  in New England. Arch Pathol Lab Med 1999 123(9)
  817-21.
• 6. Guidos BJ, Selvaggi SM Use of the ThinPrep
  Pap Test in clinical practice. Diagn Cytopathol
  19992070-73.