June 2004, Volume 54, Issue 6

Original Article

Diagnostic Surgical Pathology: the importance of Second Opinion in a Developing Country

Z. Ahmed  ( Department of Pathology and Microbiology. The Aga Khan University Hospipital, Karachi )
N. Yaqoob  ( Department of Pathology and Microbiology. The Aga Khan University Hospipital, Karachi )
S.Muzaffar  ( Department of Pathology and Microbiology. The Aga Khan University Hospipital, Karachi )
N. Kayani  ( Department of Pathology and Microbiology. The Aga Khan University Hospipital, Karachi )
S. Pervez  ( Department of Pathology and Microbiology. The Aga Khan University Hospipital, Karachi )
S. H. Hasan  ( Department of Pathology and Microbiology. The Aga Khan University Hospipital, Karachi )

Introduction

While the basic aim of the practice of surgical pathology is to provide accurate diagnosis, it is equally essential to prevent an erroneous diagnosis, which can result in serious errors in the treatment and prognosis of the patient. In Pakistan, surgical pathology is still evolving as a science and it is only now that clinicians are becoming aware of the importance of an accurate surgical pathology diagnosis for the treatment of their patients. In a developing country like Pakistan where most centers lack the facilities and expertise that are needed to function as modern surgical pathology units, the Section of Histopathology at the Aga Khan University Hospital is serving as the major referral center for diagnostic surgical pathology. While the overwhelming majority of surgical pathology cases which we report are those which are sent primarily to us, a new trend is being observed which is represented by cases that are sent to us for second opinion by clinicians and in some cases by the primary pathologists themselves.             The purpose of this study is to review the cases sent to Section of Histopathology, Aga Khan University for second opinion and see whether there are significant differences in the original outside diagnosis and the subsequent diagnosis submitted by us.

Materials and Methods

 All consecutive cases for second opinion in the form of paraffin blocks, which were received over a nine-month period i.e., from 1st November 2001 to 31st July 2002, were included in the study. The primary submitted diagnosis in each case was compared with the diagnosis submitted by us. The use of immunohistochemistry in 54.16% cases was noted. It was assumed that the blocks we received for second opinion were the same ones on which the original diagnosis was submitted.

Results

 Over the 9 month study period, a total of 381 cases were received for second opinion. In 336 cases (88.18%), the initial surgical pathology diagnosis was provided. In 45 cases (11.81%) initial surgical pathology diagnosis was not provided. In 204 out of 336 cases (60.71%) initial diagnosis
Table1. Commonest organ systems on which second opintion was sougt.
1 Lymph Nodes 72 21.42
2 Soft Tissues 65 19.34
3 GIT* 52 15.47
4 Bones and Joints 30 8.92
5 Breast 30 8.92
6 Female genital tract** 27 8.03
7 Head and Neck*** 27 8.03
* Includes liver, gall bladder andbiliary tract, pancreas, and salivary glands. ** Includes vulva, vagina, cervix, endometrium, ovaries, and placenta. *** Includes jaws and oral cavity, nose, paranasal sinuses, nasopharynx, larynx, eyes and ocular adnexae.
Table2. Lymph nodes cases.
S. No. Submitted Diagnosis Second opinion Diagnosis
1 Chornic granulomatous inflammation with caseation necrosis. T.B Peripheral T cell NHL (LCA, T positive)
2 Non Hodgin's Lymphoma Reactive folicular Huperplasia.
3 Chornic granulmatous inflammation T.B. Reactive lymphadenitis not T.B. nonspecific
4 Hodgkin's lymphoma mixed cellularity Anaplastic large cell (kil) lymphoma
5 Non Hodgkin's lymphoma Chronic Granulomatous inflammation T.B.
6 Non Hodgkin's lymphoma Reactive lumphadenitis
7 D/DT cell NHL/Hodgkin's disease Diffuse large cell NHL of B phenotype (LCA, B positive)
8 Hodgkin's lymphoma mixed cellularity Diffuse large cell NHL of B phenotype (LCA, B positive)
9 Metastatic Carcinoma Diffuse large cell NHL of B phenotype (LCA, B positive)
10 Hodgkin's lymphoma Atypical lymphoid hyperplasia
11 Non Hodgkin's lymphoma Non-specific reactive lymphadenitis
12 Follicular lymphoma Reactive folicular hyperplasia
13 Reactive lymphadenitis Diffuse large cell NHL of B phenotype (LCA, B positive)
14 D/D reactive lymphadenties Hodgkin's lymphoma Diffuse large cell NHL of B phenotype (LCA, B positive)
15 Hodgkin's lymphoma Non-specific reactive lymphadenitis
16 Non Hodgkin's lymphoma Reactive follicular hyperplasia
17 Follicular lymphoma Reactive follicular hyperplasia
18 Non Hodgkin's lymphoma Reactive follicular hyperplasia
19 Chronic granulomatous inflammation T.B Atypical lymphoid hyperplasia
20 Malignant undifferentiated neoplasm Chronic granulomatous inflammation T.B
21 Non Hodgkin's lymhoma Metastatic carcinoma (CK MNF, CAM 5.2 positive LCA negative)
22 Reactive lymhadenitis Diffuse large cell NHL of B phenotype (LCA, B positive)
and AKU diagnosis were the same. In 120 cases (35.71%), AKU diagnosis was different from the initial diagnosis. In 12 cases, we could not give a diagnosis due to the presence of marked fixation/processing artifact.             Immunohistochemistry was performed in 125 out of 336 cases (37.20%). Out of the 120 cases in which the initial diagnosis and AKU diagnosis were different, Immunohistochemistry was performed in 65 cases (54.16%).             Table 1 lists the commonest organ systems on which second opinion was sought, while tables 2 to 10 list the cases with differences in diagnosis belonging to various organ systems.

Discussion

  The Section of Histopathology at the Aga Khan University Hospital, Karachi is the largest center of histopathology in Pakistan. In 2001, over 28,000 cases of surgical pathology and over 14,000 cases of cytopathology were reported. The section has the services of six full time academic pathologists with diverse background along with ten to twelve fellows and residents.             The section acts as the major referral center for histopathology in the country and specimens for primary diagnosis as well as second opinion are received from all over the country through laboratory collection points of the Aga Khan University Hospital located in all important cities and towns of the country. The section is equipped with the latest state of the art Immunohistochemistry and Molecular labs, and is playing a leading role in the development and advancement of diagnostic histopathology in the country.             Pakistan being a developing country, there are very few laboratories, which can function as modern surgical pathology units. Facilities like Immunohistochemistry are restricted to a handful of centers in the entire country. Moreover, clinicians, especially in small towns and cities are only now becoming aware of the importance of an accurate surgical pathology diagnosis. With this increased awareness and recognition of surgical pathology as a major science, sensitivities of clinicians towards surgical pathology diagnosis are also increasing and more and more cases are being received by us in which a second opinion is sought.
Table3. Soft tissue eases.
S. No. Submitted dianosis Second opinion diagnosis
1 Fumngal linfection Neurofiborma (S 100 protein positive)
2 Soft Tissue sarcoma Diffiuse large cell NHL of B cell phenotype (LCA pan B positive)
3 Mailgnant peripheral nerve sheath tumor Metastatic carcinorma (CK MNF and CAM 5.2 positive)
4 lipsarcoma Malignant peripheral nerve sheath tumor, (Vimentin S 100 protein positive)
5 Lipoma Ewing's sarcoma/ PNET (Vimentin, MIC 2 positive)
6 Hemangiopericytoma Fibrosarcoma
7 Fibrosarcoma Leiomyosarcoma (Vimentin, ASMA, Desmin positive)
8 Fibrosarcoma Leiomyoma ( Vimentin, ASMA positive)
9 Fibrosarcoma Synovial sarcoma (CK MNF, CAM 5.2 EMA, Vimentin positive)
10 Malignant peripheral Nerve sheath tumor Malignant Melanoma, (Vimentin, S100 protein, HMB 45 positive)
11 Small roung blue cell tumor DVD PNET/ Neuroblastoma NHL, (LCA pan B positive)
12 Myxoid liposarcoma Malignant peripheral nerve sheath tumor (Vimentin, S100 protein positive)
13 Liposarcoma Malignant peripheral nerve sheath tumor (Vimentin, S100 protein positive)
14 Non Hodgkin's Lymphoma Yolk Sac Tumor (CK MNF CAM 5.2, AFP positive)
15 Fibrosarcoma Malignant peripheral nerve sheath tumor high grade (Vimentin, S100 protein positive)
16 Fibrosarcoma Synovial sarcoma (CK MNF CAM 5.2, EMA, Vimentin positive)
17 Alveolar soft part sarcoma Malignant Melanoma (Vimentin, ASMA positive)
18 Pleomorphic liposarcoma Leiomyosarcoma, (Vimentin, ASMA positive)
20 Angiosarcoma Diffuse large cell NHL of B phenotype (LCA, B positive)
21 Fibrosarcoma Nodular fascitis
22 Malignant Melanoma Nodular Tenosynow itis
23 Rhabdomysarcoma Ewing' sarcoma/PNET (MIC 2 positive desmin negative)
24 Fibroma Fibrosarcoma Grade II
25 Tuberculosis Pilomatrixoma
26 Myxoid liposarcoma Benign Adipose tissue
27 Metastatic amelanotic melanoma Metastatic carcinoma CK MNF, AE 1 / AE3 positive
28 Angiosarcoma Benign Fibrous histiocytoma (Vimentin, CD 68 positive)
29 Soft wissue sarcoma Malignant melanoma (Vimentin, S100 protein, HMB 45 positive)
            The concept of second opinion in surgical pathology is well established. The American Society of Clinical Pathologists (ASCP) has recognized second opinion as an important component of total quality assurance programs in diagnostic surgical pathology and cytopathology.1 The Association of Directors of Anatomic and Surgical Pathology has developed recommendations for consultations in surgical pathology.2 Numerous studies in literature have noted the usefulness and efficacy of second opinions in diagnostic surgical pathology.3-7 An analysis of our results shows that in 35.71% cases, the second opinion diagnosis submitted by us was different from the original submitted diagnosis. This is a significantly high figure. The results also show that the differences in diagnosis in most cases were major, having significant implications for the treatment and prognosis of the patient. It must always be kept in mind, however, that a difference between primary and secondary diagnosis does not prove that the latter is correct and studies in literature have demonstrated that diagnostic disagreements occur between experts. 8             There is a great variation in the results from different studies looking at second opinions in diagnostic surgical pathology. Krontz et al.5 reported a 1.4% discrepancy rate for all organ systems while Abt et al.3 reported a 1.3% overall discrepancy rate. These are very low discrepancy rates. However, Malhotra et al .7 reported a discrepancy rate
Table 4. Gastrointestinal tract cases.
S. No. Submitted Diagnosis Second opinion Diagnosis
1 Esophagus Squamous cell carcinoma Esophagus: mild non specific inflammation
2 Chronic hepatitis with cholestasis Liver: Hemosiderosis
3 Pancreas: extra-rena wilm's tumor Pancreas papillary-solid epithelial tumor (Vimentin, NSE, Chromogranin positive)
4 Liver: liver tumor not further specified Liver: vascular malformation
5 Liver Teratoma Liver: hemangiondothelioma, (Vimentin, CD31 positive)
6 Rectum: Ganglion cells not seen Rectum ganglion cells seen
7 Small intestine: Non Hodkin's lymhoma (Immunoblastic) Small intestinal inflammatory infectious process (Typhoid, Yersinia etc)
8 Gall bladder: Adencorcinoma Gall bladder: Xanthogranulomatous cholecystitis.
9 Liver: reactive fibrosis Liver: Metasatic adencarcinoma lung possible site of primary (CK AE1/AE, CAM 5.2 and CK positive)
10 Gall bladder: Adencorcinoma Gall bladder: Xanthogranulamatous cholecystits.
11 Colon: ulcerative colitis with dysplasia, grade II (moderate) Non specific inflammationno dysplasia
12 Stomach: undifferentiated malignant tumor Stomach: Benign gastric tissue
13 Colon: Adenocarcinoma Colon: non specific inflammation and granulation tissue formation
14 Partid: Adenoid cystic carcinoma Parotid mucoepidermoid carcinoma, low grade.
15 Small Intestine: diffuse large cell non Hodgkin's lymphoma Small intestine: Burkitt's lymphoma, (LCA, B positive)
16 Small intestine ki1 or Hodgkin's lymphoma Small intestine T cell Non Hodgkin's lymphoma (LCA, Pan T positive, Ki 1 negative)
17 Jejunum: Fibroma Jejunum: Neurofibroma, (Vimentin, S100 positive)
Table 5. Skin cases.
S. No. Submitted Diagnosis Second Opinion Diagnosis
1 Malignant Melanoma Compound Melanocytic nevus
2 Squamous cell carcinoma Basal Cell Carcinoma
3 Squamous cell carcinoma Bowen's Disease
4 Malignant Melanoma Angiosarcoma (CD 31, Ulex Europeus, vimentin positiv, HMB 45 ngative)
5 Kaposi, Sarcoma Lobular capillary Hemangioma
6 Rperipheral T cell lymphoma Anaplastic large cell (kil 1) lymphoma (Ki 1 positive)
7 Non Hodgkin's Lymphoma T cell pseudolyphoma
of 11.6% among 275 cases. Our overall discrepancy rate was very high 35.71% among 336 cases (results). Various western studies have however, reported high discrepancy rates for specific organ systems.             Harris et al. 9 reported a 24% discrepancy rate for bone and soft tissue sarcomas. Our study showed 36.66% discrepancy rate for bone and joint cases (results). However, these include both neoplastic and non neoplastic cases. Jacques et al. 10,11 reported a 23.6% discrepancy rate for endometrial biopsies. Our study showed an 18.51%discrepancy rate for all female genital tract cases (results) and as shown in table 8, 4 out of 5 cases were ovarian in origin Epstein et al.12 reported a 9.1% discrepancy rate for prostatic biopsies. Our study showed a 38.46% discrepancy rate for all male genital tract cases (results) and as shown in Table 9, 4 out of 5 cases were prostatic in origin. Kim et al.13 reported a 16.7% and 27.3% discrepancy rate for Hodgkin's and non-Hodgkin's lymphomas respectively. Our study showed a 30.55% discrepancy rate for lymph node cases, both neoplastic and non neoplastic (results).             Bruner et al.14 reported an 8.8% discrepancy rate for
Table 7. Head and neck cases.
S. No. Submitted diagnosis Second opinion diagnosis
1  Nose Liposarcoma Malignant Melanoma (Vimentin, S100Protein HMB 45positive)
2 Nasopharynx: Nasopharyngeal carcinoma Large cell NHL of B phenotype (LCA, B positive)
3 Hard Palate sarcoma Diffuse large cell NHL of B phenotype (LCA, B positive)
4 Cheek: Non Hodgkin's lymphoma Neuroblastoma ( NSE, S100 protein positive, LCA negative)
5 Ehomoid Sinus Chronic granulomatous inflammation T.B No fungus seen. Chronic granulomatous inflammation fungus positive no T.B
6  Nose: Plasmacytoma Peripheral T cell Non Hodgkin's lymphuma (PTCL)(LCA, T positive)
7 Nose malignant neoplasm D/D carcinoma/ NHL Malignant Melanoma, (Vimentin, S100 protein, HMB 45 positive)
8 Parapharyngeal area: Heman giopericytoma   Solitary fibrous tumor (Vimentin, CD 34 positive)
9  Ethmoid Sinus: Malignant neoplasm D/D rhabdomyosarcoma poorly differentiated Carcinoma, (CK MNF, CK CAM 5.2 positive)
10 Vocal cord: Carcinoma Inflammatory pseudotumor (Vimentin, ASMA positive cytokeratins negative)
11  Cheek Carcinoma Diffuse large cell non Hodgkin's lymphoma of B phenotype, LCA B positive)
12 Oral cavity: poorly differentiated carcinoma Diffuse large cell Non Hodgkin's lymphoma of B phenotype (LCA, B positive)
Table 8. Female genital tract cases.
   
S.No. Submitted diagnosis Second opinion diagnosis
1 Cervix Dysplasia Sqyamous metaplasia and non-specific inflammation No dysplasia
2 Overy: Bordeline serous tumor Endometriotic Cyst
3 Overy: Sertoli leydig cell tumor Gramulosa cell tumor, (Vimentin, ASMA, S100 protein, MIC 2 positive)
4 Overy: Malignant tumor Benign ovarian tissue
5 Ovary: poorly differentiated carvinoma Dysgerminoma
Table 9 Male genital tract cases.
   
S.No. Submitted diagnosis Second opinion diagnosis
1 Prostate: Adenocarvinoma Atypical adenomatous hyperplasia
2 Prostate: Adenocarvinoma Rhabdomysosarcoma. (Vementin, Desmin pisitive Keratins negative)
3 Prostate: Adenocarvinoma Transitional cell carcinoma (PSA negative)
4 Testis: Seminoma Benign testicular tissue
5 Prostate: sqyamous cell carcinoma Infarction with squamous metaplasia
Table 10. Miscellaneous cases with difference in diagnosis.
S.No. Submitted diagnosis Second opinion diagnosis
1 Lung: Pulmonary blastoma Orfanizing pneumoia
2 Glomus Jugulare: Glomus Jugulare tumor Choroid plexus papilloma (Kerains, EMA pisitive)
3 Breast: Mammary dysplasia Severe chronic non-specific inflammation and fat necrosis
4 Breast: Mammary dysplasia ProstateAdenocarcinoma (PSA positive)
5 Urinary bladder: Transitional cell carcinoma, grade III prostate Adenocarcinoma (PSA positive)
6 Pleura: malignant mesothelioma Reactive mesothelial cells
7 Thyroid: Follicular carcinoma Papillary carcinoma
8 Thyroid: Papillary carcinoma Medullary carcinoma (CK MNF, CK, CAM 5.2,S100 protein NSE, chromofranin pisitice Thyroglobin negative)
9 Kidney: soindle cell carcinoma Leiomyosarcoma, (Vimentin, ASMA positive: cytokeratins negative)
10 Breast infiltrating ductal carcinoma Fibrocystic disease
11 Kidney: Renal cell carcinoma Xanthogranulomatous pyelonephritis
12 Brain:Desmoplastic Medulloblastoma Neuroblastoma, (GFAP, NSE, Chromgranin positive)
neuropathology cases. In our study, neuropathology cases for second opinion were very few except for one case (Table 10). Our study also showed high discrepancy rates of 53.84%, 44.44% and 32.69% for skin, head and neck (excluding neuropathology) and gastrointestinal tract cases (results). Malhotra et al.7 reported a 7% discrepancy rate in skin cases. As shown in Table 10, significant diagnostic differences were also seen in breast and thyroid cases.             It was concluded from the study that a second opinion for determining a diagnosis of difficult cases by histopathology examination, is highly recommended. This practice is implemented worldwide

References

1.Tomaszewski JE, Bear HD, Connally JA, et al Consensus conference on second opinions in diagnostic anatomic pathology. Who, what and when. Am J Clin Pathol 2000;114:329-35.
2.Consultation in surgical pathology. Association of Directors of Anatomic and Surgical Pathology. Am J Surg Pathol 1993;17:743-5.
3.Abt AB, Abt LG, Olt GJ. The effects of inter institution anatomic pathology consultation on patient care. Arch Pathol Lab Med 1995;119:514-17.
4.Gupta D, Layfield LJ. Prevalence of inter institutional anatomic pathology slide review: a survey of current practice, Am J Surg Pathol 2000;24:280-4.
5.Kronz JD, Westera WH, Epstein JI. Mandatory second opinion surgical pathology at a large referral hospital Cancer 1999;86:2426-35.
6.Lind AC, Bewtra C, Healy JC, et al. Prospective peer review in surgical pathology. Am J Clin Pathol 1995;104:560-6.
7.Malhotra R, Massimi G, Woda BA. Inter institutional surgical pathology consultation and its role in patient management. Mod Pathol 1996;9:(165 A) 1-2.
8.Ackerman AB Discordance among expert pathologists in diagnosis of melanocytic neoplasms. Hum Pathol 1996; 27:1115-16 .
9.Harris M, Hartley Al, Blair V, et al. Sarcomas in north west England: I Histopathological peer review. Br J Cancer 1991:64: 315-20.
10.Jacques SM, Qureshi F, Mankarah A, et al. Inter institutional surgical pathology review in gynecologic oncology I: cancer in endometrial curettings and biopsies. Int J Gynecol Pathol 1998;17:36-41.
11.Jacques SM, Qureshi F, Mankarah A, et al. Inter institutional surgical pathology review is gynecologic oncology II: endometrial cancer in hysterectomy specimens. Int J Gynecol Pathol 1998;17:42-5.
12.Epstein JI, Walsh PC, Sanfilippo F. Clinical and cost impact of second opinion pathology: review of prostate biopsies prior to radical prostatectomy. Am J Surg Pathol 1996;20:851-7.
13.Kim H, Zelman RJ, Fox MA, et al. Pathology panel for lymphoma clinical studies: a comprehensive analysis of cases accumulated since its inception. J Natl Cancer Inst 1982;68:43-67.
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Abstract

Objective:
                To review the cases sent to the section of histopathology, Aga Khan Universty (AKU) for second opinion and see whether there are significant differences in the original outside diagnosis and the subsequent diagnosis submitted by us.

Methods:
                A retrospective study of all consecutive cases for second opinion in the form of paraffin blocks from 1st Novemver 2001 to 31st July 2002. The primary submitted diagnosis in each case was compared with the subsequent AKU diagnosis.

Results:
                The study included a total of 381 cases. However, in 45 cases (11.81%), initial histopathological diagnosis was not provided. Out of the remaining 336 cases, there were differences between the original diagnosis and the subsequent AKU diagnosis in 120 cases (35.71%). Out of these 120 cases, immunohistochemistry was performed in 65 cases (54.16%) only.

Conclusion:
                In a developing country like Pakistan, where few laboratories are equipped to function as modern histopathology units, second opinion on difficult cases is very important. Worldwide, the concept of second opinion in surgical pathology is well established (JPMA 54:306;2004).

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