| Abstract|| |
Objective: To determine the frequency and magnitude of discrepancies in the surgical pathological diagnosis of soft tissue lesions on review and second opinion in a histopathology center. Study Design: Cross-sectional, observational. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from April 2006 to May 2007. Materials and Methods: All the cases of soft tissue as well as bone lesions, irrespective of age and gender, which were referred for second opinion or review after being reported elsewhere, were included in the study. A panel of antibodies of soft tissue, epithelial and lymphoid markers was applied according to the requirements of each case. The cases were categorized as category A where there was concurrence between initial diagnosis and diagnosis at review. Category B included cases where there was disagreement in the specific diagnostic entity as per WHO classifications without therapeutic implications. Category C was cases where the category of benign or malignant diagnosis remained the same but there was disagreement in the specific diagnosis with definite therapeutic implications. Category D had diagnosis of benign changed to malignant while category E had cases where diagnosis of malignancy was changed to a benign lesion. Results: During the study period, 34 cases of soft tissue lesions were received for review and second opinion. The mean age of the patients was 39 22 years and immunohistochemistry was performed in 21 (62%) of 34 cases. Concurrence between the review and initial diagnosis was seen in 18 (53%) cases (category A). Discrepancy in the diagnosis at review and initial consultation was seen in 16 (47%) cases. There were four (11.8%) cases that were placed in category B as the diagnosis of benign and malignant remained the same but the specific diagnostic entity was changed. Category C included eight (23.5%) cases where the review diagnosis changed the therapeutic modality despite the benign or malignant category remaining unchanged. All the cases in this category required immunohistochemistry as diagnosis of metastatic carcinoma was changed to sarcoma in two cases and diagnosis of sarcoma was changed to carcinoma in three cases. There was only one (2.9%) case in category D where a benign diagnosis was changed to malignant on review and three (8.8%) cases reported as malignant had a revised diagnosis of benign lesion, placing them in category E. Conclusion: In the absence of a quality assurance regulatory body to monitor and overlook the professional competence of practicing surgical pathologists, a mandatory review and second opinion should be undertaken whenever a major therapeutic endeavor is to be undertaken, regardless of the cost for the ultimate benefit of the patient.
Keywords: Immunohistochemistry, medical errors, second opinion, surgical pathology
|How to cite this article:|
Sharif MA, Hamdani SR. Second opinion and discrepancy in the diagnosis of soft tissue lesions at surgical pathology. Indian J Pathol Microbiol 2010;53:460-4
|How to cite this URL:|
Sharif MA, Hamdani SR. Second opinion and discrepancy in the diagnosis of soft tissue lesions at surgical pathology. Indian J Pathol Microbiol [serial online] 2010 [cited 2020 May 26];53:460-4. Available from: http://www.ijpmonline.org/text.asp?2010/53/3/460/68277
| Introduction|| |
Demands placed on histopathologists have risen because of the complexity in surgical pathology reports as per guidelines mentioning the prognostic parameters and resection margins where indicated.  Surgical pathologists are physicians, but they are humans too. They have as great a capacity for error and susceptibility to subjective distractions as other practitioners of the art of medicine. Clinicians believe that pathologists have all the ingredients to produce a statement of absolute truth given only a piece of the patient's tissue, but even more dangerous to the mankind is a pathologist who also believes in this concept. 
It is important for the pathologist to know the limitations of his specialty and to be aware of its strength and potential weaknesses. Neither pride nor the pressures should force a pathologist to make a decision about a disease process that he does not recognize. A mismatch can result in mutilation or death of the patient. A very fortunate aspect of histopathology, although considered a curse by some, is the fact that material on which diagnosis is made is of permanent nature and can be reevaluated by different observers at different times.  Diagnostic errors in histopathology are important in terms of cost, disability and patient suffering. 
The Institute of Medicine, in its report in 1999, cited medical error as a cause of death in some 40,000-98,000 Americans each year.  This brings the medical practices affecting patient safety under scrutiny. The methodology of diagnosis has also come under audit, and diagnostic failure is the most common cause of medical malpractice claims among hospitals.  Studying cases of "missed" diagnosis has a pivotal role in medical education, research and quality assurance.  Blinded reviews and second opinion are among the methods used to identify the area of disagreement in clinical and surgical pathology diagnosis. Second opinion is a patient safety practice as an institutional protocol before starting any major therapeutic endeavor. 
The Royal College of Pathologist has classified diagnostic discrepancies/error into categories to evaluate response to an expression of concern about doctor's performance and as a matter of duty of care review. In the context of duty of care review, the potential impact on clinical care is obvious and has a vital component. 
Soft tissue lesions are tricky to diagnose but important to recognize because of therapeutic implications. A multidisciplinary team of doctors decides the most effective treatment and a misdiagnosis may cause a major catastrophy or even a loss of limb. In our country, there is absence of external quality assurance programmes and many laboratories do not have the necessary ancillary techniques, including immunohistochemistry, which are required at times to reach a conclusive diagnosis.  Keeping this in mind, we undertook this study to ascertain the magnitude (frequency) of discrepancies in the diagnosis of soft tissue lesions on review and second opinion in our set-up.
| Materials and Methods|| |
This study was carried out at a referral institute from April 2006 to May 2007. Our institute is a referral laboratory with an annual histopathology workload of approximately 26,000 surgical biopsy specimens. It receives samples from Armed Forces Hospital establishments, Northern Punjab, North West Frontier Province and from adjoining civil and private hospitals in our region.
All the cases of soft tissue as well as bone lesions, irrespective of age and gender, which were referred to the Histopathology Department of this institute for second opinion or review after being reported elsewhere, were included in the study. Those cases that did not have their previous histopathology report mentioning the diagnosis were excluded from the study.
The cases were reviewed in a systematic manner. Initially, the cases were seen independently by a senior registrar and then by the consultant histopathologist.
Ancillary techniques including immunohistochemistry and special stains for periodic acid Schiff (PAS) and reticulin were performed whereever required. A panel of antibodies of soft tissue, epithelial and lymphoid markers was applied using the antigen-antibody immunoperoxidase technique according to the requirements of each case. Soft tissue antibodies comprised smooth muscle actin, myogenin for muscles, S-100 for neural and fat and CD-99 for neuroectodermal differentiating sarcomas. Epithelial membrane antigen and cytokeratin were used as epithelial markers while leucocyte common antigen (LCA), CD-20 and CD-3 were used as lymphoid markers. Intradepartmental consultation was carried out in those cases where diagnostic difficulty arose due to any reason.
The selected cases of soft tissue lesions were categorized keeping in view their implications on patient management. The categories were:
- Category A: concurrence between initial diagnosis and diagnosis at review.
- Category B: category of benign or malignant diagnosis remained the same but there was disagreement in the specific diagnostic entity as per WHO classifications without therapeutic implications.
- Category C: category of benign or malignant diagnosis remained the same but there was disagreement in the specific diagnosis, which had definite therapeutic implications.
- Category D: initial diagnosis of benign lesion was changed to malignant on review.
- Category E: initial diagnosis of malignancy was changed to a benign lesion on review.
Discrepancy: Difference in opinion between the original consultation diagnosis and interpretation at review.
Magnitude: Degree/severity of difference in opinion graded according to the categories described above with respect to implications on patient management.
Data were entered in SPSS vesion 16.0 and statistical analysis was performed to determine the mean age and frequency of the discrepancy and percentage of cases in each category.
| Results|| |
During the study period, 34 cases of soft tissue lesions were received for review and second opinion. The male to female ratio was 1.13:1. The mean age of the all the patients was 39 22 years, with a range of 2-85 years, whereas the mean age of malignant cases was 43 19 years. Immunohistochemistry was carried out in 21 (62%) out of 34 cases.
Concurrence between the review and initial diagnosis was seen in 18 (53%) cases (category A) while immunohistochemistry was performed in 10 (55.6%) of the 18 category A cases to confirm the diagnosis.
Discrepancy in the diagnosis at review and initial consultation was seen in 16 (47%) cases. Major diagnostic discrepancy was seen in 12 (35.2%) cases, which had different therapeutic implications, and among these, four (11.8%) cases had an altogether reversal in diagnosis from benign to malignant and vice versa. There were four (11.8%) cases that had a change in the nomenclature without any effect on treatment modalities. The discrepancy cases were categorized accordingly to determine the magnitude of discrepancy.
There were four (11.8%) cases that were placed in category B as the diagnosis of benign and malignant remained the same but the specific diagnostic entity was changed. The cases in this category included benign lesions like Schwannoma, nonossifying fibroma and chronic synovitis. Similarly, a high-grade sarcoma was reassigned a diagnosis of pleomorphic liposarcoma. However, this reviewed diagnosis did not affect the therapeutic intervention in these cases.
Category C included eight (23.5%) cases where the review diagnosis would change the therapeutic modality and patient care despite the benign or malignant category remaining unchanged. Interestingly, all the cases in this category were malignant and the confirmation of diagnosis required the ancillary technique of immunohistochemistry by applying specific antibody markers in all the cases. [Table 1] shows the discrepancy between initial and review diagnosis in category C cases. A diagnosis of metastatic carcinoma was changed to sarcoma in two cases while a diagnosis of sarcoma was changed to carcinoma in three cases. A small round cell tumor initially reported as malignant non-Hodgkin lymphoma was changed to primitive neuroectodermal tumor/Ewing sarcoma by application of immunohistochemistry antibody markers for LCA, CD-99, CD-3 and CD-20, further aided by PAS stain [Figure 1]. Similarly, angiosarcoma was reassigned a diagnosis of plasma cell tumor after negativity for CD-31 and CD-34 and positivity for CD-79a and kappa antibodies.
There was only one (2.9%) case in category D where a benign diagnosis was changed to malignant on review. A diagnosis of dermatofibroma was changed to liposarcoma in a 50-year-old male patient supported by positive immunohistochemical stains for S-100 for liposarcoma.
|Figure 1 :Photomicrograph showing the primiti ve neuroectordermal tumor (a) that was initi ally reported as malignant lymphoma (H and E, ×200 magnifi cati on). Periodic acid Schiff stain showing cytoplasmic|
positi vity (b) while immunohistochemistry shows CD-99 positi vity (c) and leucocyte common anti gen negati vity (d) by the tumor cells (anti gen– anti body peroxidase method, ×200 magnifi cati on)
Click here to view
There were three (8.8%) cases that were reported initially as malignant but had a diagnosis of benign lesion on review. The discrepancy revealed one inflammatory lesion reported as liposarcoma. Furthermore, two cases reported as benign neoplasms were diagnosed as malignant. [Table 2] shows the cases in categories D and E with major diagnostic discrepancy, where a diagnosis of benign and malignant was reversed altogether.
|Table 2 :Comparison of initi al and review diagnosis in categories D and E|
Click here to view
| Discussion|| |
The large majority of soft tissue tumors are benign, with a very high cure rate after excision. Malignant mesenchymal neoplasms account for <1% of the overall human burden of malignant tumors, but they are life-threatening and pose a significant diagnostic and therapeutic challenge as there are more than 50 histological subtypes of soft tissue sarcomas associated with unique clinical, prognostic and therapeutic features. Given the prognostic and therapeutic importance of accurate diagnosis, a biopsy is mandatory and appropriate to establish malignancy and assess the tumor grade and specific subtype of sarcoma. Subsequent to diagnosis, a treatment plan is tailored according to the lesion's predicted pattern of growth, risk of metastasis and likely sites of spread. Thus, the basic building block of the treatment protocol is the correct surgical pathology diagnosis based on the biopsy. 
Discrepancies are evaluated by second opinion or review whenever there is substance of concern about a doctor's performance or to identify those patients whose care might be suboptimal and to rectify deficiency in care. Pretreatment institutional review is an endeavor toward the same goal, with an aim to ensure uniformity of diagnosis and grading to allow comparison with subsequent material from the same patient. 
Quality assurance programs in surgical pathology are challenging because of the subjective interpretation of the test result.  The WHO classification of soft tissue tumors addressed the problems relating to the use of specific nomenclature for standardization and uniformity in diagnostic entities and grading of lesions. However, variation of terminology does not indicate a mistake.  This fact was kept under consideration in the evaluation of cases in the present study as well.
The benefits of interinstitutional consultations in surgical pathology have been documented for prostate,  soft tissue,  female genital tract  and brain biopsies.  Significant discrepancies ranging from 0.26 to 5.8% have been seen, which emphasizes the diagnostic accuracy as a result of this practice.  The present study shows the agreement in the initial and review diagnosis in 53% of the cases. An earlier study on lymphoid lesions had shown an agreement of 28% of the cases, which was alarming as compared to Western studies.  Abt et al.  documented a discrepancy rate of 9% out of 777 cases, and only 5.8% had a change in treatment because of this review. Similarly, 1.3% discrepancy was seen in a review of 535 prostate biopsies.  Tsung et al.  demonstrated 35 (5.2%) out of 673 cases having a difference in opinion. In this study, absolute agreement with initial consultation was seen in 53% of the cases, but 65% of the cases did not have any change in therapeutic modality and 35% of the patients had a change in treatment protocol as a result of this review. An earlier study in England had shown an agreement in diagnosis of sarcomas up to 76% out of 450 cases, emphasizing the role of second opinion to ensure appropriate treatment. 
The Association of Directors of Anatomic and Surgical Pathology allows 2% as the acceptable threshold for clinically significant disagreement following review. , However, the disagreement rates of our study of 35% for soft tissue lesions and 72% for lymphoid lesions  is well beyond the acceptable threshold of patient safety practices.
The current trends and advances in histopathology require the use of immunohistochemistry for the definitive diagnosis in selective cases. Immunohistochemistry has become an indispensable tool for the practice of histopathology.  Lack of ancillary techniques including immunohistochemistry has been attributed as one of the causes of a higher discrepancy rate in our set-up.  The present study also showed 11 out of 16 cases with discrepancy in diagnosis requiring immunohistochemistry to reach a conclusive and specific diagnosis. Moreover, 10 out of 18 cases with concurrence with initial diagnosis also required the same to be sure of the diagnosis. However, in the absence of any regulatory body and quality assurance programmes, there is no bar or hesitancy on the practicing histopathologist to defer and not to report any such case that requires referral to another facility for specialized tests as immunohistochemistry.
In the current era of cost-effectiveness, the above inferences demand a mandatory review. Diagnostic alteration can lead to deletion, addition or alteration of treatment with a consequent modification of cost. The benefits of revised appropriate diagnosis and subsequent specific therapy on the quality of life have been well documented. Moreover, the cost of performing wrong diagnostic and therapeutic procedures outweighs the cost of doing the review and cost alone should never be the primary determinant of patient care. 
Unsafe care is one of the prices we pay for not having organized systems of care without clear lines of accountability. Provision of care to patients by a collection of loosely affiliated organizations and providers makes it difficult to implement guidelines and enforce quality assurance programs. Despite the cost pressures, liability constraints, resistance to change and other seemingly insurmountable barriers, it is simply not acceptable for patients to be continuously harmed by the same healthcare system that is supposed to offer healing and comfort. In the absence of a quality assurance regulatory body to monitor and overlook the professional competence of practicing surgical pathologists, a mandatory review and second opinion should be undertaken whenever a major therapeutic endeavor is to being planned regardless of the cost of review for the ultimate benefit of the patient.
| References|| |
|1.||Sharif MA, Mushtaq S, Mamoon N, Jamal S, Luqman M. Clinicians responsibility in pre-analytical quality assurance in histopathology. Pak J Med Sci 2007;23:720-3. |
|2.||Rosai J. Introduction. In: Rosai J, editor. Rosai and Ackerman's Surgical Pathology. London, UK: Mosby; 2004. p. 1-24. |
|3.||Baker GR, Norton P. Patient safety and healthcare error in the Canadian healthcare system. Ottawa, Canada: Health Canada; 2002. p. 1-167. |
|4.||Kohn LT, Corrigan JM, Donaldson MS. To err is human: building a safer health system. Washington, DC: National Academy Press; 1999. |
|5.||Landrigan CP, Rothschild JM, Cronin JW. Effect of reducing interns' work hours on serious medical errors in intensive care units. N Engl J Med 2004;351:1838-48. |
|6.||Foucar E. Classification of error in anatomic pathology: a proposal for an evidence-based standard. Semin Diag Pathol 2005;22:139-46. |
|7.||The College's Professional Standards Unit and the Specialty Advisory Committee on Histopathology. Review of the categorization of discrepancies in histopathology. London: Royal College of Pathologist; 2008. |
|8.||Ahmad Z, Qureshi A, Khurshid A. Will histopathology survive in Pakistan. J Clin Pathol 2009;62:575. |
|9.||Fletcher CD, Rydholm A, Singer S, Sundaram M, Coindre JM. Soft tissue tumors: Epidemiology, clinical features, histopathological typing and grading. In: Fletcher CD, Unni KK, Mertens F, editors. World Health Organisation classification of tumors. Pathology and genetics, tumors of soft tissue and bone. Lyon (France): IARC Press; 2002. |
|10.||Kwon JS, Francis JA, Qiu F, Weir MM, Ettler HC. When is a pathology review indicated in endometrial cancer? Obstet Gynecol 2007;110:1224-30. |
|11.||Rickert RR. Quality assurance goals in surgical pathology. Arch Pathol Med Lab 1990;114:1157-62. |
|12.||Epstein JI, Walsh PC, Sanfilippo F. Clinical and cost impact of second-opinion pathology. Am J Surg Pathol 1996;20:851-7. |
|13.||Harris M, Hartley AL, Blair V, Birch JM, Banerjee SS, Freemont AH, et al. Sarcomas in northwest England: I. Histopathological peer review. Br J Cancer 1991;64:315-20. |
|14.||Selman AE, Niemann TH, Fowler JM, Copeland LJ. Quality assurance of second opinion pathology in gynecologic oncology. Obstet Gynecol 1999;94:302-6. |
|15.||Inouye L, Langford LA, Fuller GN, Bruner JM. Diagnostic discrepancies in a neuropathology consultation practice; 500 consecutive cases. Mod Pathol 1996;9:165A. |
|16.||Hamdani SN, Sharif MA, Mushtaq S, Mamoon N, Khadim MT. Second opinion in pathology of lymphoid lesions- An audit. Pak J Med Sci 2008;24:798-802. |
|17.||Abt AB, Abt LG, Olt GJ. The effect of inter-institution anatomic pathology consultation on patient care. Arch Pathol Lab Med 1995;119:514-7. |
|18.||Tsung JS. Institutional pathology consultation. Am J Surg Pathol 2004;28:399-402. |
|19.||Association of Directors of Anatomic and Surgical Pathology. Quality control in pathology: Recommendations on quality control and quality assurance in anatomic pathology. Am J Surg Pathol 1991;15:1007-9. |
|20.||Association of Directors of Anatomic and Surgical Pathology. Consultations in surgical pathology. Am J Surg Pathol 1993;17:743-5. |
|21.||Qazi JI, Mubarak M. Histopathology in present arena. J Pak Med Assoc 2009;59:1-2. |
Muhammad Ashraf Sharif
House 107, Street 110, Sector G-11/3, Islamabad
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]