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The current and ideal state of anatomic pathology patient safety.

Investigations of anatomic pathology inter-observer variability and secondary review methods to detect error have not shown that there has been a significant decrease in error rates since the Institute of Medicine (IOM) seminal report in the 1990s. (1-2) Why?

Formal and informal methods of root cause analysis of anatomic pathology error have revealed the importance of optimizing work processes to decrease error frequency as well as to improve quality in the IOM domains of timeliness, efficiency, effectiveness, patient centeredness, and equity. (3) Using Spear and Bowen's concept of lean work, (4) anatomic pathology testing consists of a large number of steps, or individual activities and hand-offs, from the pre-pre-analytic phase involving test choice to the post-post-analytic phase incorporating the test diagnosis into clinical decision making. The anatomic pathology laboratory sits in the middle of the testing cycle.

An anatomic pathology diagnostic error occurs because of a failure in one or several of the steps in the testing pathway. For example, a diagnostic error may result when the wrong procurement procedure is ordered, an inadequate sample is obtained, a specimen is lost in

transport, a pathologist renders an incorrect interpretation, or a clinician does not receive a report. Use of this frame has contributed to the development of a team approach to understanding anatomic pathology diagnosis and error, as both clinical practitioners and laboratory personnel need to be involved in improvement activities. Although diagnostic errors have an active component, a large number of latent system factors contribute to failures.

Accuracy and precision

For the pathologist interpretation step, an anatomic pathology diagnostic error may be classified into one of two categories: an error of accuracy or an error of precision. (2)

An error in diagnostic accuracy is an anatomic pathology diagnosis that does not correspond to the patient's disease. (5) An example is if a patient has lung cancer and the anatomic pathology diagnosis is benign lung. Based on the testing pathway model, the cause of this error could be secondary to a failure in any of a number of steps, such as those that involve the clinical sampling, processing, or interpretation activities or hand-offs.

An error in diagnostic precision is an anatomic pathology diagnosis that differs among pathologists who examine the same specimen. An example is if two pathologists examine the same lung biopsy tissue specimen and one pathologist renders a diagnosis of adenocarcinoma and the other pathologist renders a diagnosis of no malignancy identified. This specific error in precision also is an error in accuracy for at least one of the diagnoses, as both diagnoses cannot represent the true state of disease. In some circumstances, both pathologists are inaccurate.

Both errors in accuracy and precision fall within the IOM definition of error. (1) In the medical literature, many anatomic pathologists have preferred to use terms such as disagreement or discordance instead of "error in precision." The use of these terms highlights a unique aspect of physician decision making, which is outlined below.

When an anatomic pathologist examines a slide or a diagnostic image, she or he uses the cognitive steps of the process known as pattern recognition. In the current model of anatomic pathology education, trainees learn in an apprenticeship-based environment in which more experienced pathologists first teach diagnostic criteria.

Diagnostic criteria

A criterion describes a specific characteristic of: 1) cells (e.g., morphologic features of color, texture, and amount of cytoplasm); 2) the arrangement of cells (e.g., small clusters, sheets, or gland-like structures); and 3) the tissue architecture or the relationship of cellular and non-cellular components (e.g., invasion, necrosis, or microcalcification).

The combination of criteria is referred to as the pattern of a specific disease. All diseases have pattern spectra, reflecting variability of criteria levels of expression. For example, for the population of patients who have a squamous cell carcinoma, tumors will show different degrees of keratinization across the population of cells. Malignancies generally share similar patterns, although the differentiation of malignancies and other diseases requires the identification of specific patterns.

Pathologists sometimes use other data, in addition to visual observations of hematoxylin and eosin slides or images, to render a diagnosis. These data include clinical history, surgical findings, molecular testing results, and visual observation of other ancillary tests such as histochemical and immunohistochemical studies.

In the first stages of learning, a novice pathologist examines a slide slowly and carefully to identify criteria and patterns. As a pathologist becomes more experienced, the criteria and patterns are identified more rapidly. The process of pattern recognition involves the use of a cognitive heuristic or a mental shortcut that associates the criteria and pattern with a specific disease. Heuristics are simple, efficient rules which explain how people make decisions, come to judgments, and solve problems, typically when facing complex problems or incomplete information.

Cognitive processes: slow and fast thinking

Kahneman described two cognitive processes: slow thinking and fast thinking. (6,7) Slow thinking consists of a rational, deliberate, methodical, and logical process of thinking. Novices practice slow thinking as they learn the process of recognizing criteria and patterns and associating these patterns with specific diseases. Fast thinking is the rapid process of quickly making associations, which all people use most of the time, each day. Experienced pathologists generally use fast thinking in their pattern recognition process.

If experienced pathologists encounter a challenging case, they may move from fast thinking to slow thinking and more rationally analyze the criteria and patterns of a case. In this example, they may recognize that the pattern they see does not readily correspond to a specific disease "mental map" and they need to think more carefully about the information before rendering a definitive diagnosis.

In 2011, our research team was funded by the Agency for Healthcare Research and Quality (AHRQ) to study the use of simulation in anatomic pathology education. We found that the cause of many anatomic pathologist cognitive errors was secondary to failure in several specific cognitive process steps. Fast and slow thinking failures are different causes of diagnostic interpretation error in precision (agreement) and in accuracy (truth).

Mental maps

Pathologists generally learn different mental maps of image criteria-pattern association with disease due to the differing experts from whom they initially trained. This lack of standardization results in errors in precision and accuracy. For example, my mental map image criteria/pattern of cancer micro-invasion may be different from another pathologist's mental map. This is one reason why even pathologist experts sometimes lack precision.

In this frame, a pathologist may use slow thinking to make a diagnosis, but disagree with another pathologist who may also use slow thinking because of differences in the mental maps. This type of error is inherently related to system issues as it reflects the lack of standardized development and application of criteria.

Second, we found that failures in experienced pathologist fast thinking resulted in errors in accuracy and precision. These failures were often the result of bias, or quickly making the incorrect association between criteria-pattern and disease. In the AHRQ project, we found that fast thinking errors were associated with specific biases, which included anchoring bias (paying attention to only certain criteria and ignoring others), overconfidence bias, and do no harm bias. We derived a list of more than 30 biases, although the majority of errors were secondary to a limited subset.

In the field of patient safety, most medical errors are slips or mistakes in processes that go unnoticed or unchecked. In the process of slow thinking, errors are less common as one rationally reviews cognitive associations. In the process of fast thinking, errors are more frequent as mental processes and associations are less checked.

As much of medical practice outside of anatomic pathology involves the association of patterns (e.g., signs, symptoms, physical findings, testing results, etc.) the concepts of non-standard criteria (mental maps) and bias also may be contributing factors to medical cognitive failures in general.

Interestingly, errors secondary to bias and to failures of standardizing mental maps are closely linked to a number of latent factors involving specimen quality, environment (e.g., workload and stress), and educational methods. In fact, even though diagnostic errors had a cognitive component, in all cases, multiple system components easily could be identified that contributed to the error.

Solutions on a system level

Regarding the question asked in the beginning, we conjecture that the rate of anatomic pathology error has remained constant because the solutions to the problem need to be implemented on a system level, as individual pathologists are not equipped and lack the capacity to change system factors.

Potential solutions to these cognitive causes of error include traditional methods of dealing with non-standard (cognitive) work and bias. Teamwork has been shown to reduce both sources of error.

Published inter-observer variability studies repeatedly show that knowledge of specific criteria is critical for accurate diagnosis for specific subspecialty areas in anatomic pathology. These criteria were developed and are recognized by experts in these subspecialty areas. However, a proposed solution (often made by experts) is to develop referral networks to subspecialists, rather than to provide other formats to decrease error. These other formats include the development of checklists, paradigm shifts in education, use of digital imaging consultation for specific scenarios, and other best practices to limit the number of cases sent for consultation and efficiently use existing practices. These solutions generally will need to be implemented at the highest level of care (Level D). (3)

For non-standard work, or the application of non-standard criteria in this scenario, checklists have been shown to be helpful. Checklists will need to be developed by large groups of pathologists based on evidenced-based outcomes of criteria application, rather than on expert opinion. Our team also is studying how pathologist team sign-out may lower the probability of error by creating real-time consensus and the application of similar mental maps over time.

Kahneman and Tversky reported the use of reference class forecasting as a method to lessen the influence of bias. (6-7) Reference class forecasting may involve the study of case sets in which bias is prevalent in order to determine interventions that would limit bias. The practice of team sign-out is based on such an intervention, as other team members, who feel free to speak up when an error is occurring, may recognize cognitive biases in others.

In a more ideal state of anatomic pathology, slow thinking and fast thinking pathologist cognitive errors would be decreased through a number of mechanisms. Slow thinking errors could be reduced through a system-based approach of pathologist teams reaching consensus on the agreement and application of diagnostic disease image criteria. Although experts have reached diagnostic consensus for some diseases in a number of subspecialties, the widespread application of these criteria to practice settings will need to occur through dissemination plans involving educational changes and other support mechanisms. Digital imaging support is one such mechanism that could have a large impact on standardizing image criteria.

Fast thinking errors also could be addressed through a team approach to decrease specific types of bias with the use of mechanisms such as bias checklists and secondary review processes. These mechanisms could introduce slow thinking in specific parts of the diagnostic process.

In summary, the changes necessary to decrease anatomic pathology error involve process changes within anatomic pathology laboratories to affect the technical components of care and changes within pathology systems that will affect training and the components of pathologists' cognitive work.


(1.) Kohn LT, Corrigan JM, Donaldson MS. To err is human: building a safer health system. Washington, DC: National Academy Press, 1999.

(2.) Raab SS, Grzybicki DM, Quality in cancer diagnosis. CA Cancer J Clin. 2010;60:139-65.

(3.) Institute of Medicine. Crossing the quality chasm: a new health system for the 21st century. Washington, DC: National Academy Press, 2001.

(4.) Spear SJ, Bowen HK. Decoding the DNA of the Toyota production system. Harv Bus Rev. 1999;77:97-106.

(5.) Raab SS, Grzybicki DM, Janosky JE, Zarbo RJ, Meier FA, Jensen C, et al. Clinical impact and frequency of anatomic pathology errors in cancer diagnosis. Cancer. 2005;104:2205-13.

(6.) Kahneman D, Tversky A, editors. Choices, values and frames. New York: Cambridge University Press, 2000.

(7.) Kahneman D. Thinking, fast and slow. New York: Farrar, Straus and Giroux, 2011.

This article was originally published in the journal Diagnosis2014;1:95-7, and is reprinted with permission.


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Upon completion of this article, the reader will be able to:

1. Identify the specialized sub-populations of cells and explain the importance of multimarker phenotyping of such cells in situ in FFPE tumor sections.

2. List and describe the four methodologies that have been incorporated together into an application that provides the per-cell quantification needed in situ in FFPP sections.

3. Compare the images provided to help ascertain the advantages of using "tissue cytometry" imaging.

4. Differentiate between the anatomic pathology diagnostic errors of accuracy and precision.

5. Explain the two cognitive processes known as slow thinking and fast thinking as they apply to anatomic pathology, and discuss ways to decrease these pathologist cognitive errors.

Stephen Spencer Raab, MD, is a member of the Department of Pathology, University of Washington, Seattle, WA, and the Department of Laboratory Medicine, Memorial University of Newfoundland and Eastern Integrated Health Authority, St. John's, NL, Canada.
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Title Annotation:CE story: Anatomic pathology
Author:Raab, Stephen Spencer
Publication:Medical Laboratory Observer
Geographic Code:1USA
Date:Jun 1, 2014
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