Julia Dahl, MD

Clinical laboratory tests and anatomic pathology diagnoses affect the vast majority of treatment decisions made by clinical physicians in nearly every medical discipline, impacting nearly every person seeking medical care. Many clinical laboratory tests are automated, performed by calibrated machines, reducing factors of human error and subjectivity. Errors made during the process of handling specimens in the anatomic pathology laboratory have recently been reported in the media (Roche, 2005). Subsequently, specimen handling processes in anatomic pathology, as well as quality assurance measures and safeguards, are under increasing scrutiny by patients, referring physicians, insurers, and the media. In addition to standard laboratory specimen handling processes, anatomic pathology remains critically dependent upon an individual physician — the pathologist — to perform an interpretation of microscopic tissue characteristics and to select specific language to convey each diagnosis. Referral of a patient's tissue for pathologic evaluation remains a physician consultation.

The practice of anatomic pathology involves the subjective interpretation of objective data. The objective data, contained in the characteristics of the cells, organization of tissues, and relationship to the organ on the whole, are preserved for the initial examination on histologic slides, within paraffin blocks, and, more recently in digital image archives. As pathology material is retained in a continuously observable format (the histologic slide or digitized image), an important method of assessing the quality of pathology services is the use of second opinion "quality assurance" consultation. The consistent utilization of intra- and extra-departmental consultation to assess and report the diagnostic accuracy, completeness of information (clinical history and reporting of pertinent prognostic features), and consistency of terminology conveyed within each pathology report to clinicians and patients is but one measurement of quality performance in pathology.

Changes in the pathology interpretation (the diagnosis) can drastically alter the clinician's treatment plan and the patient's prognosis. As in all disciplines of medicine, the goals of anatomic pathology are to conform to the ethical principles of beneficence and non-maleficence: the obligation to help and not to harm patients (Tomaszewski, et al., 2000). To this end, pathologists are obligated to provide accurate and timely diagnoses, to protect patients from wrong diagnoses, and to reduce the diagnostic variability that can have a major impact on patient therapy and management.

Guidelines for intra-departmental and extra-departmental consultation have been established and disseminated by the College of American Pathologists. They have been required to achieve and maintain certain types of laboratory accreditation (Sarewitz, n.d.). These guidelines, while providing a baseline opportunity for preventing the most costly (and damaging to patient) pathology medical errors, appear to have failed to encourage quality assurance activities that result in optimal diagnostic accuracy, consistency in terminology, and timely care for patients.

Over the last two decades, several studies have been published documenting the rates of diagnostic discrepancy in surgical and cytopathology (Lind et al., 1995). A discrepancy is defined as: when one pathologist renders a diagnosis and another pathologist looks at the same material and renders a different opinion/diagnosis. Major discrepancies are those discrepancies that result in (prospective review) or would have resulted in (retrospective review) alteration of treatment and/or prognosis, while minor discrepancies are those that have diagnostic disagreement but do not lead to treatment alteration.

A subset of these quality assurance studies report the rate of discrepancy observed during intradepartmental review, where the disagreement between the original diagnoses rendered by general pathologists (both within community hospitals and within academic centers) and by other general and possibly subspecialty pathologists within their own institutions are recorded, as shown in Table 1.

Tissue/organ System	Major	Minor	# Cases Reviewed	Parameter Reported	Author
Surgical pathology	1.2%	Not Reported	2,694	Intradepartmental prospective review, all cases	Lind, et al., 1995
	1.7%	Not Reported	2,694	Intradepartmental retrospective review previous six months, all cases	Lind, et al., 1995
	0.96%	2.2%	3,000	Intradepartmental prospective review, surgical cases	Whitehead, et al., 1984
	.08%	8.88%	5,000	Intradepartmental prospective blinded review, biopsy cases	Renshaw, et al., 2003
Gynecologic oncology	4.7%	3.4%	295	Intradepartmental retroprospective review	Selman, et al., 1999

TABLE 1. Discrepancies Observed During Intradepartmental Review

Other studies have reported the rates of diagnostic discrepancy observed between the original diagnosis rendered by general pathologists (both within community hospitals and within academic centers) and the diagnoses rendered by pathologists with subspecialty expertise within a particular organ system or type of tissue, at the time of inter-institutional review (Table 2, pg. 52). This type of extra-departmental consultation may be requested by the original pathologist, or may be a consultation not requested by the original pathologist, but required prior to definitive therapy as the standard of care within the treating institution.

Tissue/organ System	Major	Minor	# Cases Reviewed	Parameter Reported	Author
Surgical pathology	1.4%	Not Reported	6,171	Inter-institutional review, prior to therapy.	Kronz, et al., 1999
Dermatopathology	1.4%	5.1%	589	Inter-institutional blinded retrospective review.	Trotter, et al., 2003
Endocrine/thyroid	18.0%	Not Reported	66	Inter-institutional consultive review requested by pathologist.	Hamaday, et al., 2005
Head and neck	7.0%	Not Reported	814	Inter-institutional review, prior to therapy.	Westra, et al., 2002
Breast	7.8%	40.0%	340	Inter-institutional review, prior to therapy.	Staradub, et al., 2002
Gynecologic - endometrial	23.6%	Not Reported	182	Inter-institutional review, prior to therapy.	Jacques, et al., 1998
Gynecologic - all	5.1%	Not Reported	*6,171	Inter-institutional review, prior to therapy.	Kronz
Gynecologic oncology	2.0%	14.0%	720	Inter-institutional review, prior to therapy.	Santoso, et al.,1998
Genitourinary - bladder	11.0%	7.0%	97	Inter-institutional review, prior to therapy.	Coblentz, et al., 2001
Genitourinary - prostate	1.0%	1.7%	3,251	Inter-institutional review - missed lesions.	Kronz
Serosal surfaces	9.5%	Not Reported	*6,171	Inter-institutional review, prior to therapy.	Kronz
Gastrointestinal	7.5%	10.4%	106	Inter-institutional review, prior to therapy.	Hahm, et al., 2001
Hepatic (liver)	6.8%	28.4%	88	Inter-institutional review, prior to therapy.	Hahm
Hepatic (liver)	28.0%	37.6%	125	Inter-institutional consultive review requested by pathologist.	Bejarano, et al., 2001
Gastrointestinal - inflammatory	45.0%	Not Reported	119	Inter-institutional retrospective review - limited to classification of IBD.	Farmer, et al., 2000
*As a subset of "Surgical pathology"

TABLE 2. Discrepancies Observed in Extra-Departmental Consultation

These extra-departmental consultation studies document the results of review of case material sent by the originating institution to the referral institution for confirmation of diagnosis in which the diagnoses rendered by the referral institution is rendered primarily by pathologists with subspecialty expertise in each organ system being reviewed. In all but two of these studies, the cases were referred as a part of the "standard of care" review of pathology materials prior to definitive therapy for the patient within the referral institutions, and not at the request of the original pathologist with a query or diagnostic uncertainty.

While these studies underscore significant rates of discrepancy, it is important to regard the considerable case selection bias toward neoplastic conditions, as these conditions most frequently result in patient referral for additional therapy. Nonetheless, inter-institutional review performed by experienced subspecialty pathologists detects a significant rate of diagnostic discrepancy in pathology diagnoses, and a substantially higher rate of diagnostic discrepancy than intradepartmental consultation among general surgical pathologists. This appears to reveal a significant rate of diagnostic error that is not suspected by general pathologists, although unconfirmed by large-scale, systematic study.

This rate of diagnostic discrepancy may not accurately reflect the broad distribution of pathology diagnoses rendered for the distribution of patients evaluated with tissue biopsy in daily pathology practice. The majority of biopsies performed in the United States are performed for the evaluation of potential or confirmed inflammatory conditions, rather than neoplastic processes. The three studies (Hahm, et al., 2001; Bejarano, et al., 2001; Farmer, et al., 2000) that primarily focused on inflammatory conditions documented major discrepancies between general pathologists and subspecialty gastrointestinal and hepatic pathologists. These rates are significantly higher than the rates reported for neoplastic conditions, ranging between 6.8% and 45% of cases reviewed by expert subspecialty pathologists. This is several times higher than the "self-detected" rates of discrepancy within intradepartmental consultation by general pathologists, and substantially higher than the rates of discrepancy reported for neoplastic conditions.

Quality Assurance Consultation
The experience of the pathologist has an impact on the precision of the pathology findings. Pathologists choosing to practice within a distinct subspecialty (organ system) acquire a fund of knowledge during fellowship training that extends beyond anatomic and clinical pathology residency training. Additionally, subspecialty pathologists, when defining their practice exclusively within their area of expertise (accepting specimens limited to their area of specialty) may review significantly greater numbers of cases over a shorter period of time as compared to general pathologists — complementing the deeper fund of knowledge with rapidly acquired experience measured in tens to hundreds of thousands of cases.

Within a general pathology setting, an individual pathologist may review a total of 6,000 cases each year — distributed among each of the organ systems: 30% gastrointestinal, 25% skin, 20% urologic, 15% breast and gynecologic, and 10% a mixture of the remaining organ systems. That translates to an approximate case experience of 1,800 gastrointestinal; 1,500 skin; 1,200 urologic; 900 breast and gynecologic; and 600 other cases each year. For comparison, experienced gastrointestinal pathologists who selectively practice gastrointestinal pathology may review 10,000 cases each year — with all 10,000 cases gastrointestinal specimens. The level of experience and expertise between general pathologists and subspecialty pathologists broadens with each year of practice.

Subspecialty Sign-Out
Many academic centers, in an effort to increase quality and reduce diagnostic inaccuracy, have adopted partial or complete subspecialty pathologist sign-out of cases. This distribution and review of cases represents a significant cultural and system change from the general pathologist-driven pathology practice, in which "every pathologist signs out every type of case." Many clinicians accept subspecialty sign-out as the "gold standard" for review and diagnosis in pathology. With subspecialty sign-out, the patient and clinician experience the benefit of pathologists practicing with a limited, but specialized skill set, generally complemented by the use of standardized terminology common to both the pathologist and the clinician specialist. Subspecialty pathologist review of cases may result in consistent adherence to established diagnostic criteria, pathologists' ability to correlate objective pathologic tissue data with subjective and objective clinical information, and the ability to provide a "common language" to facilitate ease of communication of the pathology report.

Consultative Review
Consultative review of pathology materials (second opinions) is an essential component of total quality assurance programs in diagnostic surgical pathology and cytopathology (Tomaszewski, et al., 2000; Sarewitz, n.d.). This key aspect in the assurance of patient safety for tissue- and cytology-based diagnoses is likely to be the most accurate and cost-effective when a program combines:

• prospective intradepartmental review of cases,
  
  
• retrospective intradepartmental review of diagnoses rendered,
  
  
• selected utilization of inter-institutional second opinions referred to pathologists with subspecialty expertise within specific organ systems and disease categories, and
  
  
• mandatory review of pathology materials in which the diagnosis was reported at external institutions when patients are referred for definitive therapy within the "home" institution (Tomaszewski, et al., 2000; Sarewitz, n.d.).

While these components of quality assurance programs may appear "self-evident" or universally accepted, self-reporting surveys of academic and community hospitals demonstrate that each of these measures is performed consistently within the pathology departments of only 30% to 65% of institutions (Gupta & Layfield, 2000).

The elements of quality assurance consultation essential within your department, institution, or organization can be assessed by compiling and/or requesting specific reports of consultation activities by pathologists:

Intra-departmental consultation

• Policies to incorporate:
  • Mandatory second pathologist review when indicated by current standard of care (any malignancy, high grade dysplasia in Barrett's, any dysplasia in IBD, and others).
    
    
  • Consensus conference activities within the department to set standards and "thresholds" for diagnosis.
    
    
  • Prospective documented and confidential peer review of challenging cases — recording minor and major discrepancies within the department.
    
    
  • Retrospective review of 2% of all cases, randomly selected, or selected by organ system for systematic review.
• Inquiries to the pathologist and department:
  • Which pathologists have subspecialty expertise in which organ systems and/or disease? Is this formal or informal training?
    
    
  • Is the intradepartmental consultation directed to pathologists with subspecialty expertise or distributed among the pathologists in another manner?
    
    
  • What are the rates of minor and major discrepancies among the pathologists?
    
    
  • How are the discrepancies resolved?

Extra-departmental (Inter-institutional review)

• Policies to institute:
  • Mandatory review of any outside pathology materials upon which a definitive therapy is planned within a referral institution.
    
    
  • External consultation by subspecialty pathologists required on no less than 0.5% of all cases. Within a community hospital with 20,000 cases each year, this results in 100 cases for consultation each year; roughly 2 cases per week.
• Inquiries to the pathologist and department:
  • What is the ratio of inter-institutional consultation performed (a) at the request of the patient, (b) at the request of the clinician, (c) at the request of the treating institution and (d) at the request of the pathologist rendering the original diagnosis?
    
    
  • Does the pathology department utilize a specific set of preferred consultants who are recognized experts within each subspecialty?
    
    
  • Alternately, do the referral cases get "sent to the university," without specifying a consultant pathologist?
    
    
  • What is the rate of diagnostic agreement? Minor disagreement? Major disagreement? With the consulting pathologist?
    
    
  • How are these discrepancies resolved?

Summary
Because therapeutic decisions are based on the presumed reliability of the pathology diagnosis, a misdiagnosis can result in unnecessary, harmful and aggressive therapy, or inadequate treatment. The financial cost of errant pathology diagnoses in terms of unnecessary treatment, wrong treatment, repeat physician visits and procedures, lost income, and morbidity and death has not been collectively documented, but is estimated to be substantial. Despite the fact that several studies have demonstrated the cost-efficiency of expert consultation second opinions in pathology, reimbursement for inter-institutional consultation has been reduced or excluded by some third party payers during the age of managed care and cost containment. Considering the coming wave of pay for performance and evidence-based outcome measures, the effect of errant pathology diagnoses on the ability of clinical physicians to meet the performance standards has yet to be determined.

Increased demand for medical care is quickly outpacing supply of services. To meet the increasing demand without compromising quality, integration of subspecialty pathologists within general pathology practices, utilization of subspecialty pathology services, or liberal utilization of expert consultation by experienced subspecialty pathologists within other institutions may increase the baseline diagnostic accuracy of pathology evaluations. In the era of consumerism, advocating increased access to subspecialty care for both patients and clinicians referring their patients to pathologists, who can demonstrate measurable outcomes, can provide a real means of reducing costs, improving efficiency, and providing exemplary care.

References

Bejarano, P. A., Koehler, A., & Sherman, K. E. (2001). Second opinion in liver biopsy interpretation. American Journal of Gastroenterology, 96(11), 3158-3164.

Coblentz, T. R., Mills, S. E., & Theodorescu, D. Impact of second opinion pathology in the definitive management of patients with bladder carcinoma. Cancer, 91(7), 1284 — 1290.

Farmer, M., Petras, R. E., Hunt, L. E., & Janosky, J. E. (2000). The importance of diagnostic accuracy in colonic inflammatory bowel disease. American Journal of Gastroenterology, 95(11), 3184 — 3188.

Gupta, D., & Layfield, L. J. (2000). Prevalence of inter-institutional anatomic pathology slide review: A survey of current practice. American Journal of Surgical Pathology, 24(2), 280 — 284.

Hahm, G. K., Niemann, T. H., Lucas, J. G., & Frankel, W. L. (2001). The value of second opinion in gastrointestinal and liver pathology. Archives of Pathology Laboratory Medicine, 125(6), 736 — 739.

Hamady, Z. Z., Mather, N., Lansdown, M. R., & Davidson L. (2005). Surgical pathological second opinion in thyroid malignancy: Impact on patient management and prognosis. European Journal of Surgical Oncology, 31(1), 74 — 77.

Jacques, S. M., Qureshi, F., Munkarah, A., & Lawrence, W. D. (1998). Inter-institutional surgical pathology review in gynecologic oncology: I: Cancer in endometrial curettings and biopsies. International Journal of Gynecological Pathology, 17(1), 36 — 41.

Kronz, J. D., Westra, W., Epstein, J. I. (1999). Mandatory second opinion surgical pathology at a large referral hospital. Cancer, 86(11), 2426 — 2435.

Lind, A. C., Bewtra, C., Healy, J. C., & Sims, K. L. (1995). Prospective peer review in surgical pathology. American Journal of Clinical Pathology, 104(5), 560-6.

Renshaw, A. A., Cartagena, N., Granter, S. R., & Gould, E. W. (2003). Agreement and error rates using blinded review to evaluate surgical pathology of biopsy material. American Journal of Clinical Pathology, 119(6),797-800.

Roche, W. F., Jr. (2005, December 2). Lab mistakes threaten credibility, spur lawsuits: Some top medical facilities are scrutinized as errors mount and oversight is questioned. Los Angeles Times.

Santoso, J. T., Coleman, R. L, Voet, R. L., & Bernstein, S. G. (1998). Pathology slide review in gynecologic oncology. Obstetrics & Gynecology, 91(5pt1), 730-734.

Sarewitz, S. J. (n.d.). Laboratory accreditation program inspection checklists. College of American Pathologists. www.cap.org.

Selman, A. E., Neimann, T. H., Fowler, J. M., & Copeland, L. J. (1999). Quality assurance of second opinion pathology in gynecologic oncology. Obstetrics & Gynecoogy, 94(2), 302 — 306.

Staradub, V. L., Messenger, K. A., Hao, N., & Wiley, E. L. (2002). Changes in breast cancer therapy because of pathology second opinions. Annals of Surgical Oncology, 9(10), 982-987.

Tomaszewski, J. E., Bear, H. D., Connally, J. A., et al. (2000). Consensus conference on second opinions in diagnostic anatomic pathology: Who, what and when. American Journal of Clinical Pathology, 114(3), 329-335.

Trotter, M. J., & Bruecks, A. K. (2003). Interpretation of skin biopsies by general pathologists: Diagnostic discrepancy rate measured by blinded review. Archives of Pathology and Laboratory Medicine, 127(11), 1489-1492.

Westra, W. H., Kronz, J. D., & Eisele, D. W. (2002). The impact of second opinion surgical pathology on the practice of head and neck surgery: A decade experience at a large referral hospital. Head & Neck Surgery, 24(7), 684-693.

Whitehead, M. E., Fitzwater, J. E., Lindley, S. K., Kern, S. B., et al. (1984). Quality assurance of histopathologic diagnoses: A prospective audit of three thousand cases. American Journal of Clinical Pathology, 81(4), 487 — 91.