The Plaintiff / Patient Perspective on the Interpretation and Management of Cervical Cytology

1
The Plaintiff / Patient Perspective on the
Interpretation and Management of Cervical
Cytology

• Jerry I. Meyers, Esq.
• Of Meyers Kenrick Giuffre, LLC

2
A Significant Problem

• 4,900 U.S. women die of cervical cancer every
  year.
• 15,700 U.S. women are diagnosed with cervical
  cancer every year.

Austin RM American Society of Cytopathology
3
That is Nearly 100 Preventable.

• 1961 incidence rate of cervical cancer 33 per
  100,000 women.
• 1987 8.3 per 100,000 women.
• Between 1961 and 1987, the percentage of women
  receiving pap smears at least every three years
  increased from 10 20 to 80.

American Cancer Society, Koss LG Linder J.
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The Role of Cytopathology in Reducing Cancer
Mortality and Morbidity

• 50 million pap smears are performed in the U.S.
  every year
• 1/1000 high-grade S.I.L.
• 1,140 NNS Number Needed to Screen each year for
  ten years to prevent one death from cervical
  cancer.
• To prevent one death 228,000

Benedet JL, Anderson GH, Matisic JP Does not
include the cost of gynecological services
Kosary CL, Reis LAG, Miller BA, Hankey BF, Harras
A, Edwards BK
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The 1987 Van der Graaf Study

• In 1987, Van der Graaf, Y., et al., reported
  striking findings concerning screening errors in
  cervical cytology.
• In a screened population of 165,185 women, 555
  women demonstrated "moderate dysplasia" or a
  higher lesion, three years after a negative
  screening.
• An examination of the slides previously read as
  negative showed that the adequate smears all were
  misread. Fully 1/3 represented "dysplasia" or a
  carcinoma in situ.

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Interpreting the Van der Graaf Study

• The Good News
• Assuming all the facts of the study, none of the
  women in the study died because a slide was
  under-read.

• The Bad News
• The study cohort involved an obviously
  unrepresentative population (so many high-grade
  lesions, no high-grade cancers described)
• The false negative rate was unacceptably high

7
The Secret Is Public

• November 1987 Maryland Virginia and District of
  Columbia come under criticism
• Error rate 30 to 40
• Cytologists finishing 250 slides per day at home

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88 CLIA Amendments Follow Senate Investigation

• Limits on slides read per day
• Expanded mission of health care financing
  administration to regulate cytology labratories
• Mandatory cytology proficiency testing (PT)
• 18 years later April 2006 standards mandated in
  1988 will finally be implemented

DeBoy JM, MPH, PhD, Jarboe BR, CT,
Government-Mandated Cytology Proficiency Testing
Practical, Equitable and Defensible Standards
Paxton A
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The Recent MIME PT

• 10 slide test- not comprehensive enough
• Test not administered frequently enough

Probability of Passing one Test out of Two

Competence Levels
Unacceptable Acceptable
Slides in Test Set 75 80 85 90 95 97.5
10 .42 .85 .89 .93 .99 1
20 .17 .45 .64 .90 .99 1
30 .08 .23 .54 .88 1 1
40 .04 .15 .46 .84 1 1.00
Table from Proficiency Testing in
Cytopathology A Personal Perspective by Timothy
OLeary http//www.phppo.cdc.gov/mlp/pdf/EQA/go200
2/ODYSSEY1.pdf With Permission
10
Plaintiffs Perspective Patients Perspective

• The acceptable false negative rate for
  cytopathology labs ranges from 5 to 20 and even
  25.
• A labs overall false-negative score is the
  cumulative average of the individual scores of
  each cytotechnologist, so there can be a
  significant variance between the performance of
  different cytologists within a given lab.

Frable WJ, Naryshkin S.
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Koss invasive cancer is rarely preceded by
truly negative serial Pap smears when available
for the 2 to 3 years prior to the diagnosis of
invasive cancer being made.
My clients are victims of the refusal to support
and implement proficiency testing
Koss LG
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Culpable vs. Non-Culpable False Negatives

• The mere fact that abnormal cells exist on a
  slide does not mean that the slide interpreter is
  culpable for the delay in diagnosis
• A false negative slide should only result in
  liability if the slide, given currently accepted
  standards of interpretation, should have been
  interpreted otherwise
• Single cell cases are extremely rare

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The Single Cell Slide
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False Negatives

• Definition A false negative slide is a slide for
  which neoplastic change was not located and
  reported, where the slide in fact demonstrates
  evidence of such change.

Not sampling false negatives
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Location Errors

• Potential abnormalities requiring a closer look
  must be examined with a higher power objective
  for neoplasia to be ruled out.

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Interpretive Errors

• Interpretive errors of therapeutic consequence
  are rarely made if one rigorously accepts and
  applies the standards for interpretation and
  reporting established by the Bethesda System.

The cytologist who reported this pap test as
negative properly interpreted these cells as
representing a high grade lesion when they were
shown to her.
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False Positive

• Pathologist over-reads a slide and decides there
  is a high grade lesion when there is not.

More centrally located flat sheet is area of
interest. The nuclei are larger than normal but
not hyperchromatic. Compared to sheet at bottom,
the ratios are higher.
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Why is the Performance Gap Between Various Labs
so Large?

• 1. Time Requirements
• 2. Proficiency Standards
• Motivational Factors

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1. Time Requirements

• CLIA limits the quantity of slides screened
  daily, but the limits are not related to the
  actual analysis time required by the particular
  set of slides, which varies by

American Society of Cytopathology
20

• Sample preparation
• Overall sample cellularity
• Blood
• Inflammation or other obscuring factors
• Clinical history
• Complexity of findings
• Cytologists experience
• Cytologists state of mind

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2. Proficiency Standards and the False Negative
Rate

• Cytolology labs are allowed significant variation
  in slide analysis and interpretation from
  employee to employee while maintaining an
  obtainable qualitative endpoint, a 5 false
  negative rate
• Experts apparently claim that a 5 false negative
  rate is irreducible, given current technology and
  circumstances
• Conversely, a 5 false negative rate and lower IS
  obtainable
• Yet, many cytotechnology labs still report 20
  rates unflinchingly

Wang SE, Ritchie MJ, and Atkinson, BF, 1997
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3. Motivation

• What currently motivates cytopathologists and
  cytotechnologists?
• Meeting business expectations of the laboratory,
  created by reinbursement vs. cost considerations
• 2. Scientific and professional personal
  standards
• Which behavior will be rewarded when the second
  interest conflicts with the first?
• What is the role of accountability as a
  motivational factor?
• Accountability In civil courts vs. internal
  quality control

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Reimbursement Levels

• The problem is driven by reimbursement levels
• 1997 Medicare reinbursement for a pap smear less
  than 8
• Today Around 15
• Answer 1 Do fewer pap smears per hour/day and
  reduce the false negative rate, thereby
  justifying a further increase in the rate of
  reinbursement
• Answer 2 Accept an obviously inadaquate
  reinbursement rate, and make pap smears the loss
  leader in your facility
• Answer 3 Obtain higher reinbursement rates, but
  do nothing to reduce the false negative rates

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• Under CLIA specifications, the pathologist is
  penalized if they dont consistently
  differentiate on a reliable basis between
  low-grade and high-grade cases. This sounds very
  clear cut, but we know from the Pap program and
  other data that about 10 to 20 percent of high-
  and low-grade cases may easily be classified in
  the other category - R. Marshall Austin, M.D.,
  from Past Now Present with Cytology PT by Anne
  Paxton, CAP Jan 2005 website.

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If there was a single feature by which the
categorical distinction had to be made and
reported, it would be very easy for mistakes to
be made, and they would occur frequently.
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Why not Enforce the Bethesda System Criteria?

• If you dont want the government to set standards
  such as MIME or otherwise, you must police
  yourself

Although occasional borderline cases occur,
attention to morphologic features usually
supports classification as either LSIL or HSIL
The Bethesda System for Reporting Cervical
Cytology, 2004.
D Solomon and R. Nayar. The Bethesda System
for Reporting Cervical Cytology, 2nd
Ed., Springer-Verlag New York 2004, 107.
27
Critical Differences between LSIL and HISL

• LSIL
• Cytologic changes confined to mature cells
• Contour of nuclear membranes slightly irregular
  at most
• Cytoplasmic ratio only slightly larger than
  normal

• HISL
• Cytologic changes affect smaller, less mature
  cells
• Contour of nuclear membranes is always quite
  irregular
• Marked increase in the nuclear/cytoplasmic ratio
  over LSIL
• Hyperchromatic clusters must be carefully
  assessed

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How can deaths and increased morbidity of
advanced disease be avoided?

• Increase patient and physician compliance with
  screening recommendations
• Reduce barriers to the economically disadvantaged
  and uninsured receiving screening
• Establish rather than dilute standards of
  abnormal cell location and interpretation
• Establish reimbursement policies that focus on
  quality rather than quantity

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• Guarantee communication of vital historical and
  clinical data between the clinician and the
  service laboratory
• Issue no report on a Pap smear specimen if
  necessary historical data has not confidently
  been obtained
• Issue no report on a Pap smear specimen without a
  concurrent review of the patient record within
  the service laboratory and a comparison of
  slides, if indicated
• Utilize the accumulation of statistical data
  concerning the interpretation of Pap smears on a
  monthly basis to identify and act upon areas of
  concern
• Implement all CLIA 88 proficiency testing
  protocols

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Requisition 1 9/26/91
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Requisition 2 11/22/92
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9/26/91
11/22/92
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• Barbara Smith died at age 32, leaving three
  children to be raised by other family members. I
  believe that her death was avoidable. I believe
  she was a preventable cancer death. She is the
  reason for my interest in this type of
  litigation. Barbara was one of those women who
  really didnt have the three or four years to
  wait for a diagnosis to be made.

Name changed to protect anominity of
patient/client