|Year : 2017 | Volume
| Issue : 2 | Page : 401-408
Histopathologic review of 400 biopsies and resection specimens of trunk and extremity-based soft tissue tumors
R Badanale1, B Rekhi1, NA Jambhekar1, A Gulia2, J Bajpai3, S Laskar4, N Khanna4, G Chinnaswamy3, A Puri2
1 Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
3 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
4 Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||21-Feb-2018|
Dr. B Rekhi
Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
AIMS: To review various pathologic parameters in diagnosed cases of trunk and extremity-based soft tissue tumors (STTs), in order to identify concordance rate between initial biopsy and resection specimen and discrepancies between initial and review diagnosis, by a specialist pathologist. MATERIALS AND METHODS: Over a 2-year-period, 400 retrospectively diagnosed STTs (553 specimens) including referral and “in-house” cases were studied. The reviewing specialist pathologist was blinded to the initial diagnoses. Discordances including discrepancies and deficiencies were defined as major and minor. Major discrepancies included those that could lead to significant treatment changes. True discrepancies were those related to sampling issues between the biopsies and resection specimens. Deficiencies relating to tumor subtyping, sarcoma grading, documentation of tumor size, and marginal status (in resections) were subdivided as major and minor. RESULTS: Most cases (328, 82%) were sarcomas (most common, synovial sarcoma; most common Stage, III), followed by benign tumors (36, 9%) (most common, schwannoma) and intermediate malignancies (32, 8%) (most common, fibromatosis). Within STTs, liposarcomas, neural tumors, and undifferentiated pleomorphic sarcomas were relatively more frequently associated with discrepancies. Percentage of cases with major discordances between the referral reports (100 cases) and review diagnosis was 60%. Percentage of cases with major discordances between the specialist and other oncopathologists was 11%. True discrepancies were observed in 20 (5%) cases. The association of type of specimen with the rate of discordance was not significant (P = 0.114). CONCLUSIONS: Diagnoses of STTs are fraught with errors mostly from general pathologists, followed by nonspecialist oncopathologists. These findings reinforce the need for reporting of STTs, especially sarcomas, by specialist pathologists.
Keywords: Diagnostic discrepancies, sarcomas, review of soft tissue tumors, specialist oncopathologist
|How to cite this article:|
Badanale R, Rekhi B, Jambhekar N A, Gulia A, Bajpai J, Laskar S, Khanna N, Chinnaswamy G, Puri A. Histopathologic review of 400 biopsies and resection specimens of trunk and extremity-based soft tissue tumors. Indian J Cancer 2017;54:401-8
|How to cite this URL:|
Badanale R, Rekhi B, Jambhekar N A, Gulia A, Bajpai J, Laskar S, Khanna N, Chinnaswamy G, Puri A. Histopathologic review of 400 biopsies and resection specimens of trunk and extremity-based soft tissue tumors. Indian J Cancer [serial online] 2017 [cited 2021 Sep 27];54:401-8. Available from: https://www.indianjcancer.com/text.asp?2017/54/2/401/225801
| » Introduction|| |
Soft tissue sarcomas (STSs) constitute <1% of overall adult cancers and nearly 15% of all pediatric malignancies. These are complex, heterogeneous, and diagnostically challenging tumors, associated with mortality rates exceeding 50% and even higher morbidity rates, as a result of recurrences and metastasis, making their accurate pretreatment pathologic evaluation, crucial, for appropriate management., Although surgery with radiation therapy has been considered as the most common modality of treatment, certain sarcomas, mostly in pediatric patients and some in adults, are treated with specific chemotherapy regimens and are associated with variable chemosensitivity, respectively.
At our institution, between 300 and 400 new cases of STS are diagnosed, with an average 2.1% frequency rates in males and 1.2% in females. General pathologists working outside specialist centers gain limited experience in the diagnosis of these rare tumors.
Among various diagnostic modalities, fine needle aspiration cytology (FNAC) is useful in identifying recurrent and metastatic lesions as well as for triage, with its limited scope in diagnosis of primary tumors, restricted at specialized, high volume centers.
At times, there is a challenge in diagnosing these tumors with limited biopsy sample, by a nonspecialized pathologist, which can result in inappropriate medical management, in more than 70% patients.,, At present, all soft tissue tumors (STTs) at our center are primarily diagnosed with a biopsy specimen. Trucut core needle biopsy is a safe diagnostic modality of choice for diagnosis of STSs, with an accuracy rate up to 98%, with contrasting results from some other studies.,,,,,
Histopathologic review and second opinion by a pathologist, who specializes in STSs, are crucial, before initiating a definite treatment in these cases. These reviews are necessary to identify reasons of diagnostic discrepancies and for future learning.
We reviewed and analyzed various pathologic parameters, in diagnosed cases of STTs from our department, over a period of 2 years (2010 and 2011), with respect to the currently accepted World Health Organization (WHO) classification of STTs, in order to identify the degree of concordance between the initial biopsy and resection specimens, wherever the latter was performed and between the initial and review diagnosis.
| » Materials and Methods|| |
A retrospective analysis of 400 diagnosed cases of STTs, including referral and “in-house,” from the trunk and extremity sites, over a 2-year-duration (years 2010 and 2011), was undertaken after approval from the Institutional Ethics Committee. Clinical details were obtained using electronic medical records and case files. Cases, in which biopsies were performed, with or without subsequent resections, were included in the study.
All 400 cases included biopsies either performed at Tata Memorial Hospital or at other hospitals. Of 553 specimens, there were 400 biopsy specimens (331 trucut, 38 incisional, and 31 excisional) and 153 were resection specimens, including 66% R0, 14.9% R1, 5.6% R2, and 13.5% Rx type. R0 resection was referred to the one with gross and microscopically free margins; R1 referred to a resection with grossly free, but microscopically positive margins; R2 referred to a resection with grossly and microscopically positive resection margins. Cases, in which marginal status was not known, were referred as Rx.
Hematoxylin and eosin-stained slides were available in all the cases. Cases with suboptimal or uninterpretable tissue sections, with unavailable slides for a review, and the ones with biopsy specimens, which were either nonrepresentative, or inadequate for a diagnosis, were excluded from the study. The principal investigator (B.R) was blinded during histopathologic review of cases.
Histopathologic observations during the review included histopathologic tumor type, histopathologic grade and stage, the latter two parameters in cases of sarcomas. The WHO 2002 and 2013 classification of tumors of soft tissue and bone was used as a reference for classification of STTs., Grading in sarcomas was based on the French Fédération Nationale des Centres de Lutte Contre Le Cancer sarcoma grading system., Grading was considered as “nonapplicable” in (1) benign lesions and intermediate malignancies and (2) when there was insufficient material for grading.
The review diagnosis was compared with the initial diagnosis on biopsy and resection, whenever the latter was available.
Among 400 cases, there were 400 biopsies and 153 resection specimens, together forming 553 specimens that were evaluated for diagnostic concordance.
Diagnostic discrepancies were defined as true, major, or minor and deficiencies were defined as major or minor. A concordance code, namely, C1, C2, or C3, was offered in each case with biopsy and subsequent resections. These were defined as follows: C1: Concordant, C2: Minor discordance, C3: Major discordance.
Major discrepancies were defined as those that could lead to a significant change in the treatment, such as those leading to under- or over-treatment, and were subdivided into six categories: (1) malignant to malignant (where there was a significant difference in the management of exact subtype of the STS); (2) malignant to benign; (3) benign to malignant; (4) major discrepancies related to grading of a STS, including tumors in which there was any change of grade between Grades 2 and 3 and Grade 1; (5) incorrect marginal status in resection specimens of STSs, and (6) others, for example, benign or intermediate malignancy to benign, but resulting in significant management change; missed mention of residual viable tumor in posttherapy cases, etc.
Minor discrepancies were divided into those related to diagnosis, classification, or grading of STSs, wherein the discrepancy was not associated with any significant change in the management.
True discrepancies were defined as the discrepancies between initial biopsy and resection specimen, due to sampling issue considering tumor heterogeneity within STTs.
Deficiencies were related to (1) STT typing, (2) grading of sarcomas, (3) lack of mention of marginal status, (4) noncategorization of a tumor (benign or malignant), and (5) lack of mention of tumor size during grossing of resection specimens.
Deficiencies were classified as major, such as those related to sarcoma grading, margin status, and noncategorization of a tumor, and minor, such as those related to tumor typing and tumor size. There were cases with both, discrepancies and deficiencies. Considering together the discrepancies and deficiencies, a concordance code was offered in every case.
In case any addenda (additional information or revised diagnosis) were given by the specialist pathologist after the initial report, as well as after discussion in the multidisciplinary meetings, these were also noted.
| » Results|| |
Of the 400 cases, there were 253 (63.2%) males and 147 (36.8%) females (M:F = 1.7:1), with their age ranging from 1 to 82 years (median=40.5 years). Three hundred and eighty-six (96.5%) tumors were deep-seated and 14 (3.5%) tumors were superficial. Site-wise, common tumor locations were extremities (n = 182, 40.5%), limb girdles (n = 35, 8.75%), retroperitoneum (n = 53, 13.25%), and the chest wall (n = 33, 8. 25%). Tumor (T) size was known in 274 (68.5%) cases and varied from 1 to 38 cm (average = 9). T-size was ≥ 5 cm seen in 231 (84.3%) cases.
On histopathologic examination, of 400 cases, there were 328 STSs; 36 benign STTs; 32 intermediate malignancies and 2 of pseudosarcomatous lesions (nodular fasciitis). In terms of exact histopathologic subtypes of STSs, synovial sarcoma was the most common STS (n = 64, 16%), followed by a leiomyosarcoma (n = 45, 11.3%), Ewing sarcoma (n = 38, 9.5%), liposarcoma (n = 32, 8.5%), malignant peripheral nerve sheath tumor (MPNST) (n = 26, 6.5%), high-grade undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (MFH) (n = 26, 5.5%), and a rhabdomyosarcoma (RMS) (n = 21, 5.3%).
Discrepancies and deficiencies in the referral reports
Of 124 cases where case files were available, 100 cases were accompanied with the referral diagnoses, initially formed at the referring hospitals or laboratories, in the form of an FNAC (n = 40), biopsy (n = 20), or resection specimens (n = 6). In 10 cases, the diagnostic modality was not mentioned. Of 100 cases, 65 showed diagnostic discrepancies, including 46 major and 19 minor discrepancies. Forty-six major discrepancies included malignant to malignant (16); malignant to benign (7); and benign to malignant (7). Sixteen cases were not offered a definite diagnosis of a sarcoma, from the referring laboratory. On review, these were found to be STSs. There were 15 minor discrepancies related to diagnosis and four discrepancies related to grading of sarcomas. In 22 cases, deficiencies were observed, of which 13 were major and 9 were minor. Grading of sarcoma was not offered in 5 cases and further sub typing was not offered in 2 cases of sarcoma. In 9 cases, sub typing of the STTs was not offered. In six cases, it was not specified whether the tumor was benign or malignant.
Overall, after review, 19 (19%) cases were found to be concordant; 21 (21%) cases with minor discordance (C2) and 60 (60%) cases with major discordance (C3).
Discrepancies and deficiencies in the cases reported within the department, on review
Of 553 specimens, 393 (71%) were found to be concordant. One hundred and sixty (29%) specimens showed discordances. Of the 160 discordances, 61 (11% of total; 38.1% of 160 cases) were major and 99 (18% of total or 61.9% of 160 cases) were minor. Three cases, on review, turned out to be non-STTs. Two of these were chondrosarcomas and a single case was a thymoma. Therefore, these cases were excluded from this study. On univariate analysis, the association of the type of specimens (biopsies vs. resection) and the discordance rate was not found to be significant (P = 0.114) [Table 1].
Diagnostic discrepancies were observed in 111 (20%) specimens, of which 36 were major and 75 were minor. Among 36 major discrepancies, 24 (66.7%) were observed in the biopsies (20 trucut, 3 incisional, and 1 excisional biopsies) and 12 (33.3%) in the resection specimens. Out of 75 minor discrepancies, 57 (76%) were observed in the biopsies (48 trucut, 2 incisional, and 7 excisional) and 18 (24%) in resections. True discrepancies were observed in 20 out of 400 (5%) cases.
Deficiencies were observed in 64 (11.6%) specimens. Major deficiencies were 29 (45.3%) and minor were 35 (54.7%). Of 29 major deficiencies, 21 (72.4%) were observed in biopsies (20 trucut and 1 incisional) and 8 (27.6%) in resection specimens. Of 35 minor deficiencies, 22 (62.9%) were observed in biopsies (18 trucut, 2 incisional, and 2 excisional) and 13 (37.1%) in resections.
Furthermore, 36 major discrepancies were further divided as malignant to malignant (14 specimens [11 biopsies and 3 resections]); malignant to benign (6 specimens [5 biopsies and 1 resection]); and benign to malignant (2 specimens [both biopsies]); discrepancies related to STS grading (3 specimens [all biopsies]); discrepancies related to marginal status (6 specimens). In postchemotherapy cases, mention of the residual viable tumor was missed in two cases. In two cases, the final diagnosis was not categorized as either benign or malignant. Of these, one case was diagnosed with differentials of benign versus malignant entity and other as benign versus intermediate malignancy. In a single case, viable sarcoma was misdiagnosed as a necrotic tumor [Table 2] and [Table 3].
Discrepancy related to diagnosis from benign to malignant (n = 2)
These two cases included major discrepancy in the initial biopsies and a true discrepancy in the resection specimen in one of the cases. Out of these, one of these cases was initially diagnosed as a low-grade spindle cell lesion, which on review was considered as a low-grade spindle cell sarcoma and on resection turned out as a low-grade, de-differentiated liposarcoma. In the second case, the initial biopsy diagnosis was diagnosed as reactive myofibroblastic proliferation, which on review was diagnosed as a low-grade spindle cell sarcoma with myogenic/myofibroblastic differentiation and on resection turned out to be a high-grade myofibrosarcoma.
A total of 75 minor discrepancies were categorized into three groups. Nineteen were diagnostic discrepancies (in 15 biopsies and 4 resection specimens); 39 related to tumor classification (in 32 biopsies and 7 resection specimens) l and 17 minor discrepancies related to grading (13 biopsies and 4 resection specimens).
In most specimens, discrepancies were as a result of an incorrect morphologic subtyping and/or immunohistochemical (IHC) stain interpretation, followed by discrepancies related to sarcoma grading. In one specimen, the reason for discrepancy was a mix-up, wherein a pleomorphic liposarcoma was initially reported as an adamantinoma with sarcomatous transformation.
In 23 (5.8%) cases, addenda were given after the initial reporting as per requested review or discussion in the multidisciplinary joint meetings.
There were 20 cases where there was a difference in diagnosis on the biopsy and the resection specimen, as a result of sampling issues [Table 4] and [Figure 1], [Figure 2], [Figure 3], [Figure 4]. In 23 (5.8%) cases, addenda were given after initial reporting as per requested review or discussion in the joint meetings.
|Table 4: True discrepancies between review diagnosis on biopsy and resection (n=20)|
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|Figure 1: (a) Case of a synovial sarcoma, misdiagnosed as malignant peripheral nerve sheath tumor, on resection (H and E, ×200). (b) Diffuse BCL2 positivity within the tumor cells (DAB, ×200). (c) MIC2 positivity (DAB, ×200). (d) Focal, distinct epithelial membrane antigen positivity within the tumor cells (DAB, ×400). (e) CK7 positivity within the tumor cells (DAB, ×200). (f) Tumor displayed response to chemotherapy, in the form of predominant areas of necrosis and hyalinization (H and E, ×200). DAB = Diaminobenzidine|
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|Figure 2: (a and b) Finely multivacuolated cells of brown adipose tissue, misdiagnosed as a well-differentiated liposarcoma (H and E, ×200). (c) A well-differentiated liposarcoma/atypical lipomatous tumor, missed on biopsy (H and E, ×200). (d) Same case showing distinct atypical stromal cells and lipoblasts (indented tumor nuclei by cytoplasmic vacuoles), noted, on review (H and E, ×400). Inset: S100 protein positivity highlighting adipocytes, including lipoblasts (DAB, ×400). DAB = Diaminobenzidine|
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|Figure 3: (a and b) Case of a schwannoma with degenerative atypia (Ancient schwannoma), misdiagnosed as malignant peripheral nerve sheath tumor (H and E, ×200). (c) Case of a low-grade malignant peripheral nerve sheath tumor, misdiagnosed as an inflammatory myofibroblastic tumor (H and E, ×200). Inset: Higher magnification showing hypercellular tumor areas showing nuclear atypia and interspersed mitotic figures (H and E, ×400). (d) Significant tumor cells showing S100 protein positivity, reinforcing nerve sheath differentiation in this case (DAB, ×200)|
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|Figure 4: (a and b) Case of a malignant peripheral nerve sheath tumor, diagnosed as schwannoma, on biopsy (H and E, ×2000). On review, the biopsy lacked features of malignancy. (c and d) On resection, sarcomatous areas with prominent mitoses seen, juxtaposed with areas of schwannoma (asterix), sampled in the biopsy (H and E, ×400)|
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During review, we encountered limitations in 30 cases for reaching the diagnosis in the form of need for additional IHC stains (25 cases), molecular analysis (3 cases), and additional diagnostic material (2 cases).
| » Discussion|| |
It is known that major diagnostic difficulties in reporting of oncopathology specimens are frequently associated with lymphomas and STSs, by a general pathologist. The benefits of institutional consultations in surgical pathology relating to STTs have been highlighted.
The guidelines for cancer services by the National Institute for Health and Clinical Excellence in 2006 state that all STSs should either be primarily reported or reviewed by a pathologist, who specializes in STTs. An STT or a sarcoma pathologist is the one who regularly reports STTs, which form a significant component of his or her workload. He or she should participate in the soft tissue part of the bone and soft tissue pathology external quality assurance scheme and be part of a properly constituted sarcoma multidisciplinary team.
To the best of our knowledge, there has been no sizable study on the critical evaluation/audit of STTs from our country and continent, except for an occasional account of few cases, emphasizing the necessity and value of reviews and second opinions in the diagnosis of soft tissue lesions.
In this study, the discordant rate between reports from the referring laboratories and review by the sarcoma pathologist was 81%, including 60% major and 21% minor discordances. Apparently, this significant discordant rate was a result of the referral diagnoses established on FNAC specimens in 40% cases. The role of FNAC in the primary diagnosis of STTs is limited. Essentially, few centers, engaged in dealing with large volume of these cases with access to ancillary techniques on cytology specimens, can deal with this challenge. This higher rate of discordance between STTs reported elsewhere and at our institution underpins the value of referring STT for diagnosis at a specialized center, with access to IHC and molecular techniques.
The discordance rate between the cases reported by the various consultants from within our Department and review by the sarcoma pathologist was 29%, including 18% minor and 11% major discordances. The possible reasons for this relatively lower percentage of discordances include ready access for second opinion in certain cases; multidisciplinary meetings; and easy communication regarding challenging cases between the departmental experts and the nonexperts for a specific tumor specialty. However, rates in both the scenarios are beyond the acceptable threshold of patient safety practices. The Association of Directors of Anatomic and Surgical Pathology approves of 2% as the acceptable threshold for clinically significant disagreement following review.,
The rate of discordance, with regard to the specimen type (trucut, incisional and excisional biopsies, and resections), was not found to be significant in this study. Serpell et al. noted high degree of diagnostic accuracy with trucut biopsies in STSs and highlighted the disadvantages of open biopsies.
Considering the “in-house” diagnoses were uniformly based on histopathologic examination, we preferred to compare the rate of discordance (between sarcoma pathologist and other oncopathologists) with the previous studies ,,,,,,,,, [Table 5]. Prescott et al. observed a diagnostic disagreement of 23%, of which 15% were major and 8% minor. Earlier studies ,, comprising analysis of discrepancies or discordances in referral reports of all STTs on histopathologic tissue sections disclosed these rates ranging from 26.6% to 47%. Similar studies ,,,,, on STSs showed diagnostic disagreement between referral and “in-house” cases ranging from 33% to 65%. Major discordances in the earlier studies ranged from 10.9% to 24.4%, compared to 11% in our study and minor discordances ranged from 7.5% to 15.7%, compared to 18% in our study. In the present study, revision in the diagnosis from an STS to non-STS was observed in only 3 cases.
|Table 5: Percentage of discordance/disagreement rates across various studies|
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In 9 (9%) cases, referred from the other hospitals or laboratories, diagnosis of a nonsarcoma was revised to a sarcoma. In the previous studies,,,,,, revision in the diagnoses from a sarcoma to a nonsarcoma was observed from 5% to 18% cases. Revision in grade, as well as lack of details regarding sarcoma grade was observed in 12.5% specimens each, respectively. In the previous studies, discrepancies related to grading ranged from 18.3% to 43% of the total disagreements/discordances ,,, and those related to grading and subtyping, together, formed as 29% of the total disagreements.
Among major discrepancies observed in the present study, while comparing “in-house” reported cases with review by a sarcoma pathologist, revision in the diagnosis from one STS subtype into another was observed in 38.9% specimens, as noted in another by others (39.5%). Reasons for discrepancies in these cases included incorrect morphological and IHC interpretation, along with lack of selection of an optimal panel of IHC markers, which are relatively more specific as well as sensitive. This is very pertinent in our limited resource settings. For example, for diagnosis of a synovial sarcoma, which is the most frequent adult STS, in our settings, an optimal IHC panel includes epithelial markers, CD34, BCL2, MIC2, with an option of TLE1, the latter being highly sensitive, but with limited specificity. Finally, a uniquely sensitive and specific, “weak to absent “expression of INI1 is being utilized for diagnosis of synovial sarcoma and triage for molecular testing. IHC markers, such as myoglobin are useless for substantiating diagnosis of RMS (most common pediatric STS) and should be replaced by more specific skeletal muscle markers, such as MyoD1 and myogenin. Similarly, vimentin is losing its value in the IHC panel of STTs. Errors as a result of IHC misinterpretation and failure to select a proper IHC panel have also been highlighted in previous studies.,, At the same time, during this review, in 15 cases, the diagnoses were limited to spindle cell sarcoma, including grade, due to limitations of additional IHC and molecular testing.
In this study, revision in the diagnosis from malignant to benign formed 14% discrepancies. In the previous three studies,,, this discrepancy constituted 5.2%–15% discrepancies. Discrepancy related to benign to malignant change (8.3%) was well within the range (2.9%–29%) as per previous studies.,,
Within the STS subtypes, various liposarcomas, MPNSTs, undifferentiated pleomorphic sarcomas/MFHs were more frequently misdiagnosed in the present study. Among other studies, gastrointestinal stromal tumor (GIST), leiomyosarcoma, and pleomorphic sarcoma, in one study, and nodular fasciitis, lipoma, and their variants and fibrous histiocytoma and desmoplastic neurotropic melanoma, in another study, were more frequently associated with discrepancies., We excluded GISTs during this study. A single case of an extra-intestinal GIST was misdiagnosed as intermediate-grade leiomyosarcoma, in the present study. We excluded head and neck STTs and therefore did not have many cases of nodular fasciitis in this study. There were only two cases of nodular fasciitis that were correctly diagnosed. During their review, Thway and Fisher  observed that lipoblasts were confused with foamy histiocytes in fat necrosis and vacuolated fibroblasts (pseudolipoblasts), the latter observed in a myxofibrosarcoma. In one of our cases, misinterpretation of brown adipose tissue as “lipoblasts” led to an incorrect diagnosis of a well-differentiated liposarcoma/atypical lipomatous tumor. While lipoblasts are not necessary for diagnosis of a well-differentiated liposarcoma, indentation of an atypical nucleus by its cytoplasmic vacuoles forms an important morphological feature of a true lipoblast. Lack of careful attention toward subtle atypia in stromal cells and fewer lipoblasts can lead to a “missed” well-differentiated liposarcoma as was also noted in our study. Other discrepancies related to lipomatous tumors included lack of sampling of the well-differentiated liposarcomatous component in four specimens, leading to “missed” diagnoses of liposarcomas, especially in locations such as retroperitoneum. A higher index of suspicion for well and de-differentiated liposarcomas, including awareness of spectrum of the latter, is required for its correct diagnosis. It is noteworthy that myxoid liposarcomas are rare in the retroperitoneum.
We also observed schwannomas, including those with degenerative changes, mistaken for MPNSTs. This pseudosarcomatous lesion can be a diagnostic pitfall. Immunohistochemically, within neurogenic tumors, misinterpretation of S100 protein (5 specimens) led to missed diagnoses of MPNST. S100 protein is the most reproducible marker for diagnosing MPNSTs that mostly display its focal staining. In an earlier study, we observed 70.3% positivity for S100 protein within MPNSTs. Discrepancies due to S100 protein immunostaining were also noted by Prescott et al. Nuclear and cytoplasmic expression of S100 protein in tumor cells, rather than in dendritic cells, is acceptable for diagnosing various nerve sheath tumors.
Myogenic differentiation was missed in high-grade pleomorphic sarcomas in four specimens. It is noteworthy that myogenic differentiation in pleomorphic sarcomas is associated with relatively grim prognosis as it is predictive of aggressive clinical behavior among patients with pleomorphic sarcomas.,
Discrepancies related to resection margins were observed in the form of 16.7% major discrepancies (6 specimens). One of the earlier studies on resection margins of resected specimens disclosed 82% of referral resections were with positive margins. A much lower percentage in our study was as a result of most resections with available marginal status from “in-house” operated patients.
Of total discrepancies, we observed minor discrepancies in 67.5% cases, of which 25.3% were diagnostic, 52% were related to classification, and 22.7% were related to sarcoma grading. In a study from Royal Marsden Hospital, minor discrepancies accounted for 59.1% of total discrepancies, of which 52.7% were related to diagnosis, 32.7% were related to classification, and 14.5% were related to grading STSs.
| » Conclusions|| |
The observed clinicopathological profile, including more common occurrence of STTs in adults, including men, in extremity sites, in the present study, was according to the established literature. Synovial sarcoma constitutes as the most common adult sarcoma in our settings. Trucut biopsies constitute as an optimal, safe material for diagnosing STTs. Diagnosis of STTs, especially sarcomas, is fraught with errors mostly from general/referring pathologists, followed by a nonspecialist oncopathologists. Most discrepancies in STT reporting, in this study, were associated with the referral cases and were as a result of errors in the interpretation of morphologic findings and interpretation of IHC markers. Among various tumors, liposarcomas, neurogenic tumors, including MPNSTs, undifferentiated pleomorphic sarcomas were relatively more commonly associated with errors. S100 protein and smooth muscle actin constituted as in appropriately interpreted IHC markers. Optimal diagnostic IHC panel, based on morphological impression, is recommended for objectively identifying relatively chemosensitive adult sarcomas, such as synovial sarcomas.
While the strength of this study is that it forms the largest, detailed audit of STTs, including STSs from our country, as well as one of the largest studies from our continent, the limitations include selection bias, such as exclusion of head and neck tumors and referral bias leading to an overall higher incidence of sarcomas (large-sized, high-stage). Second, the inability to characterize certain STTs in view of lack of access for additional IHC markers.
Finally, high discordance rates between referral and review reports and between reports formulated by nonspecialist oncopathologists versus specialist oncopathologists are suggestive for the need for reporting of STTs by specialist oncopathologists, who has an access to the ancillary techniques. A pathologist specializing in one of the specific areas is more experienced and is more likely to be able categorize details within the complex STTs, more than a routine pathologist.
Similar studies with larger number of cases from our country and continent would further shed additional light on the problematic areas of STT reporting.
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Conflicts of interest
There are no conflicts of interest.
| » References|| |
Rydholm A, Berg NO, Gullberg B, Thorngren KG, Persson BM. Epidemiology of soft-tissue sarcoma in the locomotor system. A retrospective population-based study of the inter-relationships between clinical and morphologic variables. Acta Pathol Microbiol Immunol Scand A 1984;92:363-74.
Potter DA, Glenn J, Kinsella T, Glatstein E, Lack EE, Restrepo C, et al.
Patterns of recurrence in patients with high-grade soft-tissue sarcomas. J Clin Oncol 1985;3:353-66.
Grimer R, Judson I, Peake D, Seddon B. Guidelines for the management of soft tissue sarcomas. Sarcoma 2010;2010, p. 15, doi:10.1155/2010/506182.
Dinshaw KA, Rao DN, Desai PB, Shroff PD. Hospital Based Cancer Registry, Tata Memorial Hospital, Mumbai (Bombay). Individual Registry Data 1984-1993. p. 115-36.
Thomas JM. Surgical biopsy techniques and differential diagnosis of soft tissue tumours. Recent Results Cancer Res 1995;138:25-9.
Rekhi B, Gorad BD, Kakade AC, Chinoy R. Scope of FNAC in the diagnosis of soft tissue tumors – A study from a tertiary cancer referral center in India. Cytojournal 2007;4:20.
] [Full text]
Ray-Coquard I, Thiesse P, Ranchère-Vince D, Chauvin F, Bobin JY, Sunyach MP, et al.
Conformity to clinical practice guidelines, multidisciplinary management and outcome of treatment for soft tissue sarcomas. Ann Oncol 2004;15:307-15.
Pisters PW, Leung DH, Woodruff J, Shi W, Brennan MF. Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 1996;14:1679-89.
Gustafson P, Dreinhöfer KE, Rydholm A. Soft tissue sarcoma should be treated at a tumor center. A comparison of quality of surgery in 375 patients. Acta Orthop Scand 1994;65:47-50.
Serpell JW, Fish SH, Fisher C, Thomas JM. The diagnosis of soft tissue tumours. Ann R Coll Surg Engl 1992;74:277-80.
Kissin MW, Fisher C, Carter RL, Horton LW, Westbury G. Value of Tru-cut biopsy in the diagnosis of soft tissue tumours. Br J Surg 1986;73:742-4.
Ball AB, Fisher C, Pittam M, Watkins RM, Westbury G. Diagnosis of soft tissue tumours by Tru-Cut biopsy. Br J Surg 1990;77:756-8.
Brennan MF. Management of extremity sarcomas. Aust N
Z J Surg 1988;58:693-702.
Mankin HJ, Lange TA, Spanier SS. The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. J Bone Joint Surg Am 1982;64:1121-7.
Collin C, Hajdu SI, Godbold J, Friedrich C, Brennan MF. Localized operable soft tissue sarcoma of the upper extremity. Presentation, management, and factors affecting local recurrence in 108 patients. Ann Surg 1987;205:331-9.
Rekhi B, Desai S, Jambhekar NA. Muskuloskeletal system. Soft tissues. In: Desai SS, Bal M, Rekhi B, Jambhekar NA, editor. Grossing of Surgical Oncology Specimens: A Practical Guide Towards Complete Pathology Reporting. Mumbai: Tata Memorial Hospital; 2011. p. 70-9.
World Health Organization (WHO). Classification of tumors of soft tissue and bone. In: Fletcher CD, Unni KK, Mertens F, editors. Pathology and Genetics of Tumors of Soft Tissue and Bone. 3rd
ed. Lyon: IARC Press; 2002. p. 1-224.
World Health Organization (WHO). Classification of tumors of soft tissue and bone. In: Fletcher CD, Bridge JA, Hogendoorn P, Mertens F, editors. Pathology and Genetics of Tumors of Soft Tissue and Bone. 4th
ed. Lyon: IARC Press; 2013. p. 1-235.
Coindre JM, Trojani M, Contesso G, David M, Rouesse J, Bui NB, et al.
Reproducibility of a histopathologic grading system for adult soft tissue sarcoma. Cancer 1986;58:306-9.
Guillou L, Coindre JM, Bonichon F, Nguyen BB, Terrier P, Collin F, et al.
Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol 1997;15:350-62.
Thway K, Fisher C. Histopathological diagnostic discrepancies in soft tissue tumors referred to a specialist centre. Sarcoma 2009;2009: p. 7, doi:10.1155/2009/741975.
Prescott RJ, Wells S, Bisset DL, Banerjee SS, Harris M. Audit of tumour histopathology reviewed by a regional oncology centre. J Clin Pathol 1995;48:245-9.
Hartley AL, Blair V, Harris M, Birch JM, Banerjee SS, Freemont AJ, et al.
Sarcomas in North West England: II. Incidence. Br J Cancer 1991;64:1145-50.
National Collaborating Centre for Cancer. Improving pathology. In: Guidance on Cancer Services. Improving outcomes for people with Sarcoma. The Manual. National Institute for Health and Clinical Excellence(NICE) London: NICE; 2006. pp. 47-52.
Sharif MA, Hamdani SN. Second opinion and discrepancy in the diagnosis of soft tissue lesions at surgical pathology. Indian J Pathol Microbiol 2010;53:460-4.
] [Full text]
Bonfiglio TA, Corson JM, Fechner RE, Harris NL, LiVolsi VA, Rosai J, et al
. Recommendations on quality control and quality assurance in anatomic pathology. Association of Directors of Anatomic and Surgical Pathology. Am J Surg Pathol 1991;15:1007-9.
Silverberg SG, Corson JM, Dehner LP, Fechner RE, Frable WJ, Kempson RL, et al
. Consultations in surgical pathology. Association of Directors of Anatomic and Surgical Pathology. Am J Surg Pathol 1993;17:743-5.
Arbiser ZK, Folpe AL, Weiss SW. Consultative (expert) second opinions in soft tissue pathology. Analysis of problem-prone diagnostic situations. Am J Clin Pathol 2001;116:473-6.
Ray-Coquard I, Montesco MC, Coindre JM, Dei Tos AP, Lurkin A, Ranchère-Vince D, et al.
Sarcoma: Concordance between initial diagnosis and centralized expert review in a population-based study within three European regions. Ann Oncol 2012;23:2442-9.
Alvegård TA, Berg NO. Histopathology peer review of high-grade soft tissue sarcoma: The Scandinavian Sarcoma Group experience. J Clin Oncol 1989;7:1845-51.
Presant CA, Russell WO, Alexander RW, Fu YS. Soft-tissue and bone sarcoma histopathology peer review: The frequency of disagreement in diagnosis and the need for second pathology opinions. The Southeastern Cancer Study Group experience. J Clin Oncol 1986;4:1658-61.
Baker L, Benjamin R. Histologic frequency of disseminated soft tissue sarcomas in adults. Proc Am Soc Clin Oncol 1978;19:324.
Randall RL, Bruckner JD, Papenhausen MD, Thurman T, Conrad EU 3rd
. Errors in diagnosis and margin determination of soft-tissue sarcomas initially treated at non-tertiary centers. Orthopedics 2004;27:209-12.
Rekhi B, Basak R, Desai SB, Jambhekar NA. Immunohistochemical validation of TLE1, a novel marker, for synovial sarcomas. Indian J Med Res 2012;136:766-75.
] [Full text]
Rekhi B, Vogel U. Utility of characteristic 'Weak to Absent' INI1/SMARCB1/BAF47 expression in diagnosis of synovial sarcomas. APMIS 2015;123:618-28.
Miettinen M. Immunohistochemistry of soft tissue tumours – Review with emphasis on 10 markers. Histopathology 2014;64:101-18.
Simon MA. Biopsy of musculoskeletal tumors. J Bone Joint Surg Am 1982;64:1253-7.
Rekhi B, Navale P, Jambhekar NA. Critical histopathological analysis of 25 dedifferentiated liposarcomas, including uncommon variants, reviewed at a Tertiary Cancer Referral Center. Indian J Pathol Microbiol 2012;55:294-302. [Full text]
Rekhi B, Ingle A, Kumar R, DeSouza MA, Dikshit R, Jambhekar NA. Malignant peripheral nerve sheath tumors: Clinicopathological profile of 63 cases diagnosed at a tertiary cancer referral center in Mumbai, India. Indian J Pathol Microbiol 2010;53:611-8.
] [Full text]
Dei Tos AP. Classification of pleomorphic sarcomas: Where are we now? Histopathology 2006;48:51-62.
Guillou L. Pleomorphic sarcomas: Subclassification, myogenic differentiation and prognosis. Diagn Histopathol 2008;14:527-37.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]