The diagnostic utility of reduced immunohistochemical expression of SMARCB1 in synovial sarcomas: a validation study

Our plain-English summary of The diagnostic utility of reduced immunohistochemical expression of SMARCB1 in synovial sarcomas: a validation study, by J. Ito, N. Asano, A. Kawai, et al (Human Pathology, 2016).

The study

• Authors: J. Ito, N. Asano, A. Kawai, A. Yoshida
• Journal: Human Pathology
• Published: 2016;47(1):32-7
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Synovial sarcoma is a malignant mesenchymal neoplasm of uncertain histogenesis, characterized by a specific SS18-SSX fusion. The diagnosis of synovial sarcoma can be challenging based on morphology and conventional immunohistochemistry alone, and identification of the fusion gene by molecular genetics may be necessary for diagnosis. Several recent studies have demonstrated the diagnostic utility of the reduced expression of SMARCB1 in synovial sarcomas as measured using immunohistochemistry. Therefore, we undertook a validation study using synovial sarcomas and other spindle or round cell tumors that could enter differential diagnosis of monophasic or poorly differentiated synovial sarcomas. Among 36 synovial sarcomas that were successfully evaluated, the expression of SMARCB1 was diffusely reduced in 33 cases (92%) at variable degrees. In contrast, the expression of SMARCB1 was not reduced in any of the 93 evaluable non-synovial sarcoma tumors (5 thymomas, 5 sarcomatoid mesotheliomas, 10 schwannomas, 9 mesenchymal chondrosarcomas, 20 solitary fibrous tumors, 19 Ewing sarcomas, and 25 malignant peripheral nerve sheath tumors). A few schwannomas and malignant peripheral nerve sheath tumors showed mosaic or complete loss of SMARCB1 expression. Reduced expression of SMARCB1 immunoreactivity was therefore found to be highly sensitive and specific for synovial sarcoma, and can be useful for rapidly and accurately confirming the diagnosis of synovial sarcoma. This reduction in SMARCB1 expression likely reflects the BAF47 ejection mechanism of the SS18-SSX fusion product and can therefore be viewed as an indirect visualization of this fusion product.

Copyright © 2015 Elsevier Inc. All rights reserved.

In plain English

This laboratory study tested whether a tissue stain could help pathologists recognise synovial sarcoma, a rare soft-tissue cancer. It did not study asbestos exposure. The authors stained tumour samples from the archives of the National Cancer Center Hospital in Tokyo for the protein SMARCB1. They used 41 synovial sarcomas and 94 other tumours that can look similar under the microscope, including 5 sarcomatoid mesotheliomas. Five synovial sarcomas and one Ewing sarcoma were excluded because the stain failed in normal cells used as controls. Of the 36 synovial sarcomas that could be assessed, 33 (92%) showed reduced SMARCB1 staining. None of the 93 assessable other tumours, including the 5 sarcomatoid mesotheliomas, showed this pattern. A few schwannomas and malignant peripheral nerve sheath tumours showed patchy (mosaic) or complete loss of staining instead. The authors concluded that their results confirmed the practical value of the stain. They cautioned that reading it requires experience, a sensitive staining method, and attention to tissue quality.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory diagnostic validation study using immunohistochemistry (tissue staining) on archived tumour samples
• Who was studied: 41 synovial sarcomas (25 monophasic, 6 biphasic, 10 poorly differentiated) and 94 comparison tumours (5 WHO type A thymomas, 5 sarcomatoid mesotheliomas, 10 schwannomas, 9 mesenchymal chondrosarcomas, 20 solitary fibrous tumours, 20 Ewing sarcomas, 25 malignant peripheral nerve sheath tumours) from the archives of the National Cancer Center Hospital, Tokyo; each sample was from a different patient
• Exposure: No asbestos or other environmental exposure was studied. The 'exposure' was immunohistochemical staining for SMARCB1 using a mouse monoclonal BAF47/SNF5 antibody
• Main results:
  • Among the 36 assessable synovial sarcomas, 33 (92%) showed diffusely reduced SMARCB1 staining
  • Among the 33 synovial sarcomas with reduced staining, the reduction was mild in 13, moderate in 12 and marked in 8
  • Three synovial sarcomas, all with SS18 rearrangement by FISH, showed intact SMARCB1 staining
  • None of the 93 assessable non-synovial sarcoma tumours, a group that included the 5 sarcomatoid mesotheliomas, showed reduced SMARCB1 staining
  • Among the non-synovial sarcoma tumours, 2 schwannomas and 1 malignant peripheral nerve sheath tumour showed mosaic loss of staining
  • A further malignant peripheral nerve sheath tumour showed complete loss of SMARCB1 staining
  • Reduced SMARCB1 staining had a sensitivity of 92% (33/36 cases) and a specificity of 100% (93/93 cases) for diagnosing synovial sarcoma
  • Five synovial sarcomas were excluded because the normal cells used as internal controls did not stain strongly. All five came from unstained slides stored for a long period. One Ewing sarcoma was also excluded for the same reason.
• The authors' conclusion: The authors concluded that their results confirmed the practical value of SMARCB1 staining in diagnosing synovial sarcoma, and that it can be a rapid and reliable tool. They also concluded that interpreting the stain requires care.
• Limitations the authors state:
  • The authors stated that using the stain for diagnosis may require some experience
  • The authors stated that tissue processing or the length of time unstained slides were stored may have caused staining failures, leading to excluded cases
  • The authors noted that staining intensity varied with tumour necrosis or crush damage to the tissue
  • The authors stated that reduced staining must be distinguished from mosaic or complete loss of staining, which carry different diagnostic meanings

Topics

Medical terms in this study, explained in our Lexicon: Synovial Sarcoma, Neoplasm, Immunohistochemistry, Differential Diagnosis, Sarcomatoid, Mesothelioma, Solitary Fibrous Tumor, Sarcoma.

Related studies

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• NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis — J.P. Lai, P.F. Robbins, et al. (2012)
• Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma — M. Miettinen, J. Limon, et al. (2001)
• Synovial sarcoma of the pleura and its differentiation from other primary pleural tumours: a clinicopathological and immunohistochemical review of three cases — A.G. Nicholson, P. Goldstraw, et al. (1998)
• Pleural malignant mesothelioma versus pleuropulmonary synovial sarcoma: a clinicopathological study of 22 cases with molecular analysis and survival data — S. Klebe, S. Prabhakaran, et al. (2018)
• TLE1 is expressed in the majority of primary pleuropulmonary synovial sarcomas — L.S. Lino-Silva, J.P. Flores-Gutiérrez, et al. (2011)

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