Delay in Malignancy Diagnosis Reflects Systemic Failures.
A 32-year-old man presented to the hospital with a comminuted midshaft femoral fracture after a bicycle accident. Imaging suggested the fracture was pathologic. The next day, the patient was taken to the operating room and an open biopsy specimen was submitted to pathology for intraoperative consultation. Frozen section examination of the tissue by the bone pathologist was inconclusive, with potential concern for neoplasm. Given the lack of a final diagnosis, the patient was placed in traction with superficial wound closure and deferred femoral stabilization. Five days later, the bone pathologist responsible for the case contacted the orthopedic surgery service to inform them that atypical cells warranted further evaluation by immunohistochemistry, and that more time was needed to establish the diagnosis. The bone pathologist then went on vacation for several days but did not document his discussions with the orthopedic surgery service or inform his colleagues about the status of the case or his concern for neoplasm.
The day after the bone pathologist’s conversation with the orthopedic surgeon, another individual from the orthopedic surgery service contacted a supervising surgical pathologist, requesting a final diagnosis to allow for discontinuation of traction and surgical resolution of the fracture. The supervising pathologist had the impression that finalization of the pathologic diagnosis was urgently needed. Because the bone pathologist was on vacation, the biopsy specimen was re-evaluated by the supervising pathologist, who lacked specific expertise in bone pathology. After reviewing published materials, the supervising pathologist rendered a benign pathologic diagnosis of “exuberant fracture callus,” without showing the images to another pathologist. Without questioning the discrepancy between the radiographic findings and the final pathologic diagnosis, the surgical team proceeded with intramedullary nailing of the femoral fracture. Shortly after the bone pathologist returned from vacation, he voiced concern to the supervising pathologist and the orthopedic surgery team that the patient’s fracture was secondary to osteosarcoma. To resolve the discrepancy, the biopsy materials were sent in consultation to a nationally recognized bone pathologist, and the diagnosis of “osteosarcoma with high-grade features” was received several days later. Given this new diagnosis, it was evident the patient had undergone the incorrect surgical procedure, although the long-term ramifications of this error remained unclear.
by Hang Mieu Ha, DO and Kristin Alexis Olson, MD
In this case, a confluence of individual decisions and system failures resulted in the wrong surgical procedure being performed. Care for the patient began appropriately with radiographic imaging and an intraoperative consultation through open biopsy of the fracture site. However, this procedure was followed by a series of events that increased the likelihood for harm, including the inability to provide a definitive diagnosis at the time of frozen section examination, the subsequent delay in establishing the final diagnosis, the presence of only one bone pathologist in the department without cross coverage for leave, the lack of documented communication history between the bone pathologist and the orthopedic surgery team, the lack of effective communication and proper handoff within the surgery and pathology teams, the commission of a diagnostic error by a pathologist lacking expertise in bone pathology, and the willingness of the surgical team to overlook the discrepancy between the initial radiologic findings and the pathologic diagnosis without further inquiry.
Approach to Improving Safety & Patient Safety Target
The Three Phases of Error in Pathology
As with clinical laboratory testing, the surgical pathology test cycle consists of pre-analytic, analytic, and post-analytic phases.1 The most common source of error is the pre-analytic phase, which includes the steps that occur before a specimen is received by the pathology department, such as specimen collection, labeling, transport, and processing. The analytic phase encompasses specimen analysis, report generation, and turnaround time. Finally, the post-analytic phase entails the conveyance of pathology results to the clinical team and the impact of those results on clinical management.
Errors that occur in the analytic phase of surgical pathology differ from those in the analytic phase of clinical laboratory testing. In the latter setting, a “correct” result is based on a scientifically validated gold standard. In contrast, the surgical pathology diagnosis is a synthesis of the individual pathologist’s observations, knowledge base, clinicopathologic reasoning, and prior training and experience. The subjectivity of this process leads to greater interobserver variation in surgical pathology diagnoses. Because scientifically validated gold standards for surgical pathology diagnosis often do not exist, the “correct” result is the most precise diagnosis.2 In other words, the correct diagnosis is the most reproducible, or the one with which most experienced pathologists will concur. Therefore, for particularly challenging or high-stakes diagnoses, a common practice in surgical pathology is to seek intradepartmental consensus or, if necessary, extramural consultation.
For this patient, the pre-analytic phase was uneventful. The analytic phase began with an intraoperative consultation with frozen section examination of the femur biopsy. Although it can be compromised by processing artifact or sampling error, the frozen section examination offers rapid diagnosis of surgeon-selected specimens with correct diagnoses rendered for 96% to 98% of cases in two retrospective studies, and for 86% to 96% of bone tumors in three other studies.3-7 In this instance, however, a definitive diagnosis was not provided at the time of frozen section examination. This prolonged the analytic phase and resulted in postponement of the planned surgical procedure.
Turnaround Time: What Is Reasonable?
The ensuing five-day interval between the frozen section examination and the next communication from the bone pathologist to the orthopedic surgery team was longer than ideal. At our institution, the current standard turnaround time for uncomplicated, routine biopsy cases is 48 hours or two working days after receipt in the laboratory, which is consistent with a College of American Pathologists (CAP) recommendation.8 However, there is no broad consensus on the appropriate turnaround time for a complicated biopsy or surgical resection, given the additional time commonly needed for decalcification, ancillary studies (e.g., immunohistochemical stains), consultations with other pathologists, or additional sampling of resection specimens.9
When a patient’s circumstances are particularly urgent or a clinical encounter or procedure is imminently scheduled, the physician managing the patient’s care should initiate discussion of the anticipated timing of the final report with the pathologist. The Association of Directors of Anatomic and Surgical Pathology (ADASP) and CAP also encourage healthcare organizations to develop policies and procedures for prompt, preferably physician-to-physician conveyance of “urgent diagnoses” and “significant, unexpected diagnoses.”10 As one author observes, “There are situations where a pathologist has to pick up the phone and call.”11 Active, timely communication among all members of the clinical care team remains a cornerstone of safe and high-quality healthcare.
Effective Communication Is Often Both Oral and Written
While effective communication is a boon to patient care, miscommunication contributes to adverse patient outcomes.12 In discussing this patient’s pathology findings, the bone pathologist and surgeon primarily relied on oral communication. Oral communication is fast, efficient, and allows for immediate response to clarifying questions, but it does not allow for later review or provide accessibility to other individuals to ensure shared and consistent understanding. Therefore, a significant barrier to effective communication in this case was the lack of standardized written documentation of all oral communication, beginning with the frozen section and extending to the start of the bone pathologist’s vacation.
Subspecialty Pathology: Diagnostic Boon or Burden?
Within academic and large private practice surgical pathology groups, there has been increasing adoption of subspecialization service models. Touted benefits of subspecialization include increased efficiency, speed, quality, and accuracy of reports; improved communication and collaboration between pathologists and their clinical counterparts; and enhanced resident training.13 Early studies suggest that quality assurance metrics are improved and fewer discrepant results occur when cases are completed by subspecialty pathologists.13-14
However, this subspecialty model comes at a cost. As pathologists move from the generalist model to the subspecialist model, subspecialists lose familiarity and comfort with the diagnostic criteria, current terminologies, and most recent guidelines applicable to specimen types that are under the purview of other subspecialties. For pathology groups to avoid the problem of cross-coverage between specialties and the associated risk of diagnostic error, at least two subspecialists must be hired for each service with faultless coordination of their leave time to ensure uninterrupted subspecialty service coverage. This coordination may be challenging to accomplish and maintain, given the volume of cases on each service (which may be too few or too many for the number of pathologists) and the relatively small number of pathology subspecialists in the labor pool at any given time. In this case, only one bone pathologist was on staff due to the relatively low volume of bone cases. As a result, cross coverage was provided by a pathologist lacking subspecialty training in bone pathology. The result, unfortunately, was this patient’s osteosarcoma being mistaken for an exuberant bone callus – a diagnostic pitfall that has been reported in the literature.15-16
For a first-time diagnosis of malignancy, many institutions require intradepartmental review with concordance before case completion. Similarly, if significant disparity exists between the intraoperative consultation diagnosis and the final pathology diagnosis, CAP guidelines require reconciliation and documentation in the pathology report. To accomplish this, the responsible pathologist should seek intradepartmental consensus or external expert consultation to settle the diagnostic disagreement. The same approach to case review is not required or typically used for benign diagnoses, which are more common. Therefore, it is easier to prevent the issuance of an incorrect diagnosis of malignancy, but more difficult to prevent an incorrect diagnosis of benign disease.
Systems Change Needed
Consistency in Documentation
Adherence to a standardized frozen section examination protocol to ensure consistency in reporting and documentation helps to underpin surgical pathology communication, patient safety, and quality improvement efforts. At our institution, all intraoperative consultation diagnoses are incorporated into a designated section of the pathology report with a time stamp of communication with the surgeon. These diagnoses are conspicuously flagged to alert the responsible pathologist to the presence of a preliminary diagnosis and the need for reconciliation of the frozen and permanent sections. We recommend that the surgical team also document intraoperative consultation results within the operative report. In addition, other preliminary impressions can be entered into the pathology report before finalization, allowing for an ongoing shared understanding with other pathologists that may become involved with the case before its completion. Following these guidelines would have been particularly helpful in this case, as they would have bridged communication gaps and provided for better continuity of care between pathologists and surgeons on the team.
Clarity in Patient Care Handoffs
All pathology groups must have clear policies and procedures surrounding the transition of case responsibility when pathologists go on leave. Cases should not remain in limbo, awaiting the return of a specific pathologist before the case is completed. One pathology residency program published a standardized, structured handoff tool to decrease the risk of miscommunication; a similar tool could be implemented for all pathologists, including those practicing independently.17
Reducing Diagnostic Error
Establishing a “double-reading” protocol for all cases with significant clinical implications can help to decrease risks of analytic errors, particularly in the setting of cross-coverage.18 Utilizing technology to create digital slide images for remote review by other pathologists may also be helpful, allowing for rapid second opinions and collaboration across locations.
In this situation, there was no second pathologist with expertise in bone pathology, so one approach to cross-coverage of the bone pathology service would be to distribute all bone pathology cases to the “pathologist of the day,” who would confer with at least one another pathologist when reviewing the case. Cases in which the two pathologists are not in agreement should be sent out for review by an extramural consultant with expertise in bone pathology. In addition, because radiographic correlation is so important for bony lesions, tripartite consultation involving an orthopedic oncologist, a pathologist, and a radiologist is useful for collaborative planning of diagnostic and treatment strategies for bone lesion cases. The outcome of such a consultation should be documented within the pathology report.
Diagnostic error in surgical pathology, although unusual, can have significant implications for patient care. As in all fields of medicine, clear and consistent communication and documentation remain essential components of effective teamwork. It is important that policies, procedures, and other systems be designed to support the determination of the correct diagnosis and the documentation of all communication related to the case.
Take Home Points
Establishing a timely and correct pathology diagnosis is the goal for all patients, with hospitalized patients and similarly urgent situations requiring special prioritization in the pathology workflow.
Subspecialty surgical pathology service models offer many benefits but create specific cross-coverage and patient care handoff needs that must be anticipated and accounted for by the organization.
Written documentation of important communications among members of the health care team, including intraoperative consultation diagnoses, should be available in the electronic health record for all parties to review.
- If pathologic diagnoses are discordant with radiographic findings or the clinical impression, that discordance should be discussed and resolved before any definitive procedures are performed or final care decisions are made.
Hang Mieu Ha, DO
Department of Pathology and Laboratory Medicine
UC Davis Health
Kristin Alexis Olson, MD
Associate Dean of Curriculum and Medical Education
Professor and Vice Chair of Pathology and Laboratory Medicine
UC Davis Health
- Hollensead SC, Lockwood WB, Elin RJ. Errors in pathology and laboratory medicine: consequences and prevention. J Surg Oncol. 2004;88:161-181. [Available at]
- Sirota RL. Defining error in anatomic pathology. Arch Pathol Lab Med. 2006;130(5):604-606. [Free full text]
- Ferreiro JA, Myers JL, Bostwick DG. Accuracy of frozen section diagnosis in surgical pathology: review of a 1-year experience with 24,880 cases at Mayo Clinic Rochester. Mayo Clin Proc. 1995;70(12):1137-114. [Available at]
- Holaday WJ, Assor D. Ten thousand consecutive frozen sections. A retrospective study focusing on accuracy and quality control. Am J Clin Pathol. 1974;61(6):769-777. [Available at]
- Fahad S, Umer M. Diagnostic accuracy of frozen section in musculoskeletal tumors. IJS: Oncology. 2021;6(1):10–17. [Free full text]
- Bhaker P, Mohan H, Handa U, et al. Role of intraoperative pathology consultation in skeletal tumors and tumor-like lesions. Sarcoma. 2014;2014:902104. [Free full text]
- Estrada-Villaseñor EG, Cedillo ED, González LML, et al. Accuracy of intraoperative consultation for bone tumors: experience in an orthopedic hospital. J Orthop Sci. 2007;12(2):123-126. [Available at]
- College of American Pathologists QCDR Measure: Turnaround Time (TAT) - Biopsies. Accessed September 20, 2023. [Free full text (PDF)]
- Patel S, Smith JB, Kurbatova E, et al. Factors that impact turnaround time of surgical pathology specimens in an academic institution. Hum Pathol. 2012;43(9):1501-1505. [Available at]
- Nakhleh RE, Myers JL, Allen TC, et al. Consensus statement on effective communication of urgent diagnoses and significant, unexpected diagnoses in surgical pathology and cytopathology from the College of American Pathologists and Association of Directors of Anatomic and Surgical Pathology. Arch Pathol Lab Med. 2012;136(2):148-154. [Free full text]
- Lehr, HA, Bosman FT. Communication skills in diagnostic pathology. Virchows Arch. 2016;468: 61–67. [Available at]
- The Joint Commission, Sentinel Event Data 2022 Annual Review. Accessed September 4, 2023. [Free full text]
- Liu Y, Kessler M, Zander DS, et al. Trends in extramural consultation: comparison between subspecialized and general surgical pathology service models.Ann Diagn Pathol. 2016;24:20-24. [Available at]
- Conant JL, Gibson PC, Bunn J, et al. Transition to subspecialty sign-out at an academic institution and its advantages. Acad Pathol. 2017;4:2374289517714767. [Free full text]
- Binesh F, Sobhan M, Moghadam RN, et al. Exuberant callus formation misdiagnosed as osteosarcoma: a case report. Chin Ger J Clin Oncol. 2013;12:137–139. [Available at]
- Sadoghi P, Leithner A, Clar H, et al. The threat of misdiagnosis of primary osteosarcoma over the age of 60: a series of seven cases and review of the literature. Arch Orthop Trauma Surg. 2010;130(10):1251-1256. [Available at]
- Rogers TS, Wilcox R, Harm SK. Design and implementation of a pathology-specific handoff tool for residents. Acad Pathol. 2019;6:2374289519839186. [Free full text]
- Nakhleh RE, Nosé V, Colasacco C, et al. Interpretive Diagnostic Error Reduction in Surgical Pathology and Cytology: Guideline From the College of American Pathologists Pathology and Laboratory Quality Center and the Association of Directors of Anatomic and Surgical Pathology. Arch Pathol Lab Med. 2016;140(1):29-40. [Free full text]