Section 1 -

Gynecologic Cytopathology: History and Medical Legal Issues William J. Frable

Since widespread introduction of the Papanicolaou smear in the early 1950s for the detection of cervical cancer and its precursor lesions, the death rate for cervical cancer has dropped in the United States and Canada by more than 70%. Currently there are an estimated 14,000 new cases per year of invasive cervical cancer and 4500 deaths from this disease within the United States [1]. Death rates in countries around the world where widespread and systemic screening for cervical cancer has not been employed remain at high levels and often constitute the first or second cause of death from cancer among women in those countries. It is generally believed that the "Pap" smear is still the single most effective screening test for cancer ever devised. Screening for cervical cancer has had the added benefit of dramatically increasing the biologic knowledge of the disease and its cause, human papilloma virus, and has led to development of increasingly sophisticated technology to improve the effectiveness of detection and treatment of precursor lesion of the cervix. Against this backdrop of successful screening, detection and treatment of cervical cancer has been a somewhat sorry history of poor performance of individuals and laboratories offering gynecologic cytology services. Initial Federal government regulations to improve overall clinical laboratory performance and with some focus on cytology were implemented as far back as the late 1960's. Personnel standards, laboratory inspections and even proficiency testing in cytology were put in place and to a limited extent were carried out by the Centers for Communicable Disease (CDC), but the effort was hampered by lack of sufficient funding [2]. The consolidation of laboratory services into large commercial ventures mixed with the small outpatient laboratory establishments competing for business with hospital laboratories led to exploitation of the Pap smear as a loss leader. Despite concern over quality control in the cytology laboratory and efforts to improve quality by major cytology and pathology organizations, matters came clearly into focus with the publications of the famous Wall Street Journal articles exposing shoddy laboratory practices in cytology in late 1987 [3, 4]. These exposes plus the long-term promotion of the Pap smear as a fail-safe test against death from cervical cancer caught the attention of Congress leading to the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88). CLIA88 focused strongly on cytology laboratory practices including mandated annual proficiency testing for all those engaged in the practice of gynecologic cytology [5]. CLIA 88 regulations, particularly the look-back provision, and the adverse publicity of the Wall Street Journal articles shortly came to the attention of plaintiff's attorneys. The latter were beginning to discover who pathologists are what they do. The Doctors Company, a medical malpractice insurer, who provide risk coverage for a large number of pathologists noted the relatively rapid upward trend in malpractice claims against pathologists in a number of areas in anatomic pathology but with a particular severity for gynecologic cytology [6]. This risk peaked during the late 1990s largely due to educational efforts of the major cytopathology and pathology societies to improve laboratory performance in cytology and to educate the clinicians and the public about the performance of the Pap smear as a screening test. An additional impact can also be attributed to the introduction of testing for human papilloma virus that can be performed on liquid based cervical cytology samples and the parallel introduction of liquid based cytologic preparations, and an array of imaging technology to improve the sensitivity and specificity of the Pap smear [7]. The latest analysis of claims from the Doctors Company, between 2000 and 2003 reveals that in total numbers of cases of alleged malpractice against pathologist, the three leaders are: 1. miss diagnosis of breast lesions, 2. pigmented skin lesions and 3. cervical cytology. In terms of severity, indemnity plus loss adjustment, pigmented skin lesions (melanoma) ranks first at $757,140.00, followed by cervical cytology at $686,599.00 and breast lesions, $203,192.00 [8]. Thus, missing cervical cancer or a precursor lesion on a Pap smear poses significant risk for violation of standard of care. These cases are difficult to defend, as the plaintiffs are appealing victims to a jury, being young an either badly injured or dead. However, pathologists still remain at low risk overall in frequency of claims, 8.3% per year or approximately 1 claim per pathologist every 12 years [8]. To prevail in a medical malpractice case the plaintiff must prove to the satisfaction of a jury the there was practice below the standard of care (negligence), that the negligence caused the injury and that there are damages (loss of life, severe disability, pain and suffering). In the miss interpretation of a Pap smear the injury, often death or significant disability from cervical cancer and the associated pain and suffering are rather obvious. Plaintiff's case therefore turns on violation of the standard of care, and that results from expert testimony. Pap smear cases are usually of two types, most commonly (approximately 85% of the cases), the cytotechnologists failed to detect the abnormal cells on the smear, while the remaining cases are failure of the pathologist to recognize cells in the screened smear at a significant level of abnormality, an interpretative error. In recent years and in the writer's experience these latter cases seem to be increasing in frequency. Plaintiff's pathology experts will present testimony that the abnormal cells could be easily recognized and should routinely be identified on screening of the smears and if identified should be reported as significantly abnormal, leading to an early diagnosis of cervical cancer. It may be established by the plaintiff that the laboratory lacks adequate quality control and/or is not accredited or out of compliance with Federal or State laboratory regulations (CLIA 88). Plaintiff will also attempt to establish that the Pap smear as a screening test should identify nearly all-precancerous or early cancers of the cervix and that the expected cure rate with limited therapy is nearly 100%. Regardless of significant clinical errors that are often present in these cases, plaintiff will usually not present experts who testify that there were violations of the standard of care in managing and treating the patient. Therefore, the liability for most Pap smear claims usually falls entirely on the laboratory and or the pathologist. There has been relatively little comment in the literature on the definition of expert testimony in cases of cervical cytology. One expert cytopathologist in conducting a teleconference some years ago opined, "the standard of care is difficult to define. Would I expect to find these kinds of cells in my daily practice with a high degree of probability? If the answer is yes, then I think that can be defined as the standard of practice" [9]. A plaintiff's attorney, speaking during the same teleconference made the following remarks. "The legal community perceives the false negative rate as comparing laboratory to laboratory. We don't perceive it from the legal community as a way of actually defending a particular Pap smear result. You have to get a retrospective review which many times seem to imply that the test is perfect, but the test is really what the next ten people in a row would interpret this as and what they would see in terms of abnormal cells. If it was a fifty-fifty split that might in essence not be a breach of the standard of care" [9]. It should be noted that within the legal framework, the term more probable than not means simply only slightly more than fifty percent. Therefore, when an attorney uses this phase in questioning an expert, the expert is answering in terms of slightly better than a coin flip. This writer does not seriously believe that the practice of pathology and medicine is conducted on the basis of flipping coins. The biased nature of any retrospective review is well known to pathologists who serve as experts in medical malpractice cases. Some however choose to ignore this issue. In an effort to both defend allegations of practice below the standard of care in Pap smear cases, leaders in the cytopathology and greater pathology community, the American Society of Cytopathology and the College of American Pathologists have developed guidelines for the review of Pap smears in the context of litigation. These guidelines have been endorsed by the majority of members of both organizations as well as other pathology organizations at the State and National level and the American Society of Cytotechnologists. These guidelines are currently available on the website for the American Society of Cytopathology and can be downloaded [10]. In addition to the guidelines members of the profession have offered to conduct blinded reviews of Pap smear slides that are the subject of litigation, in a statistically valid manner and to simulate as closely as possible the normal working conditions in the cytology laboratory. The results of those reviews have been introduced into evidence at trial in a number of Pap smear cases. The methodology and results have also been independently validated [11, 12]. Through examination of data from large numbers of pathologists and cytotechnologists in the gynecologic cytology performance improvement program of the College of American Pathologists , it has also been demonstrated that there are certain features of some cervical cytology smears that make them difficult to consistently recognize as abnormal [13]. The writer has conducted some experiments in respect to the bias nature of retrospective review of Pap smears, first during a lecture on the subject of Pap smear litigation at the annual meeting of the American Society of Cytology in 1996 and at several subsequent workshops on cytology sponsored by the American Society of Clinical Pathologists. In the first instance single photos of normal and reactive cells were presented to the audience in the context that they represented findings in a retrospective review that led to litigation, and in the second experiments using photos taken from rescreening of Pap smears retrieved from the authors negative file. All cases currently have not less than a 10-year negative clinical and Pap smear follow-up. In both experiments, significant numbers of participants submitted answers that there were abnormal cells in all cases, ranging from atypical squamous or glandular cells of undetermined significance all the way to outright caner. Eileen Hewer, a senior cytotechnologists quality control officer in a large cytology laboratory in the United Kingdom conducted a similar experiment among cytotechnologists using photos from standard cytology textbooks illustrating benign and reactive cells from cervical smears. The results were almost identical to those of the writer. I do not believe there is anyway to eliminate this inherent and pervasive bias in the retrospective review of Pap smear cases except by the statistically valid blinded review as described by Holladay . This method has also been used to adjudicate and or settle cases based on the results and therefore may avoid the long and expensive litigation process [13]. The more general defense strategy is to show that the Pap smear is a screening test with false negative and false positive rates. While most cytopathologists believe that the Pap smear is 80% sensitive in detecting cervical cancer and precursor lesions, epidemiology studies show that the sensitivity is only about 60% [14]. The defense will also challenge the context and outcome bias of the retrospective review of Pap smears in litigation as noted above and may be able to establish that the Pap smears in question are not routinely or easily detected in a statistically valid blinded review. The plaintiff's attorney will vigorously object to introducing evidence of the blinded review and the judge may rule that the standard of care is what that particular practitioner, cytotechnologist/pathologist, did at the time of the examination of the Pap smears in question. It is important to remember that the legal system of the United States treats cases individually. The defense may show that the there is a well established and well documented quality control program in place in the cytology laboratory and that the laboratory is appropriately accredited, participates in quality improvement programs and complies with all appropriate laboratory regulations of CLIA88. Documentation is the key to this defense. Some defense attorneys will argue that this strategy potentially opens up to discovery all aspects of the laboratory operation rather than just the question of the Pap smear or smears at issue in the particular case. Proactively, laboratories should take steps to reduce risk from miss interpreted pap smears. The following are suggestions to reduce that risk. Educate clinicians through presentations, procedure manual, and information on the Pap smear report that the Pap smear is a screening test with known false positive and negative results and that it has a relatively modest sensitivity. Discourage clinicians from taking Pap smears during menstrual periods. Encourage clinicians to provide complete clinical information related to the examination of the cervix, to biopsy even minimally suspicious lesions of the cervix, and to not rely only on the Pap smear to detect cervical cancer or precancerous lesions. Use a recognized terminology for reporting Pap smears. Educate clinicians about the terminology you are using and what they should expect from your reports. Have a comprehensive well-documented quality control program in place. Work closely with the cytotechnologists and where there is more than one in the laboratory insure that they communicate with each other and are working together. Establish criteria for hierarchical review of Pap smears beyond abnormalities required by CLIA 88, for example, smears that contain blood, particularly broken down blood, smears containing small cells, and any smear with hyperchromatic crowded groups of cells. Be aggressive in reporting Pap smears. Remember it is a screening test. Identify clinicians who provide inadequate information or poor quality specimens. Attempt remedial education for them. Avoid, if possible, the pathologist performing the 10% rescreen of negatives; particularly late in the day, when tired and anxious to leave work. Be particularly careful about the five-year look back regulation and the issuing of amended reports. The focus of the amended report is on current patient care. That care is the result of the current Pap smear report in the vast majority of cases. Therefore, amended reports are seldom required. Careless management of this regulation essentially guarantees litigation [15]. References Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ: Cancer Statistics 2006. CA Cancer J Clin 2006;56:106-130. Inhorn SL: Government legislation affecting Cytology Laboratories. Acta Cytol 1976; 20:197-202. Bogdanich W. The Wall Street Journal 1987 Nov 2; p. 1. Ebid. 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