Malignant Peripheral Nerve Sheath Tumors with t(X;18). A Pathologic and Molecular Genetic Study

O’Sullivan, Maureen; Kyriakos, Michael; Zhu, Xiaopei; Wick, Mark R.; Swanson, Paul E.; Dehner, Louis P.; Humphrey, Paul A.; Pfeifer, John D.

doi:10.1038/modpathol.3880230

Cited by 46 publications

(42 citation statements)

References 49 publications

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“…The SYT-SSX fusion transcript is specific for a diagnosis of SS and is generally not identified in any other sarcoma 23 except for occasional reports of its detection in malignant peripheral nerve sheath tumor. 24,25 As part of a larger study on malignant small round cell tumors, we have performed RT-PCR for the SYT-SSX fusion transcript in 25 cases of Ewing sarcoma and 12 cases of rhabdomyosarcoma, all of which were negative for this transcript.…”

Section: Discussionmentioning

confidence: 99%

Synovial sarcoma: Diagnosis on fine‐needle aspiration by morphology and molecular analysis

Srinivasan

Gautam

Gupta

et al. 2009

Cancer Cytopathology

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Section: Discussionmentioning

confidence: 99%

Synovial sarcoma: Diagnosis on fine‐needle aspiration by morphology and molecular analysis

Srinivasan

Gautam

Gupta

et al. 2009

Cancer Cytopathology

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“…12,13 Malignant peripheral nerve sheath tumor can be particularly difficult to distinguish from synovial sarcoma, as they share several morphological, immunohistochemical and ultrastructural features. [13][14][15] Some authors have even reported the rare occurrence of a t(X;18) translocation in malignant peripheral nerve sheath tumor, 16 adding further difficulty in differentiating these two tumors. Thus, markers specifically expressed in either one tumor or the other would be extremely useful.…”

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confidence: 99%

Expression of MYCN in pediatric synovial sarcoma

et al. 2007

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Synovial sarcoma accounts for between 6 and 10% of childhood sarcomas and histological diagnosis can be challenging, even for experienced pathologists. Several other tumors enter the differential diagnosis, including malignant peripheral nerve sheath tumor, Ewing sarcoma/primitive neuroectodermal tumor and undifferentiated sarcoma. Several recent reports utilizing expression array techniques have documented expression of the MYCN oncogene in synovial sarcoma. In order to more fully investigate this finding, a series of 12 synovial sarcomas and 29 other sarcomas (four malignant peripheral nerve sheath tumors, 15 Ewing sarcoma/primitive neuroectodermal tumors, 10 undifferentiated sarcomas) were examined for MYCN expression and gene amplification. By RT-PCR, nine of 12 synovial sarcomas (75%) expressed MYCN. Five synovial sarcomas (42%) expressed MYCN at high levels. Of the other sarcomas, one malignant peripheral nerve sheath tumor (25%) and five Ewing sarcoma/primitive neuroectodermal tumors (33%) expressed MYCN at low levels, and all other cases were negative for MYCN. None of the synovial sarcomas had genomic amplification, suggesting that high MYCN expression levels resulted from epigenetic phenomena. Examination of selected downstream targets of MYCN in synovial sarcoma revealed expression of MCM7 (minichromosome maintenance protein 7) in all synovial sarcomas, and expression of nestin (n ¼ 10; 83%), ID2 (inhibitor of DNA binding protein 2) (n ¼ 6; 50%) and MRP1 (multidrug resistance protein 1) (n ¼ 1; 8%) in a subset of synovial sarcomas. Expression of downstream targets did not correlate with expression of MYCN. Neither MYCN nor expression of downstream targets significantly correlated with metastases at presentation, progression-free survival or overall survival in this small series. In summary, high levels of MYCN expression was useful for distinguishing synovial sarcoma from other childhood-spindled cell sarcomas with specificity and sensitivity of 100 and 42%, respectively, in this series. The clinical and biological significance of this finding deserves further study.

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“…t(X;18) (SYT-SSX) fusion gene transcripts were observed in 83 of 86 synovial sarcomas (96% sensitivity) and never detected in any of the 135 tumors of other type that had been examined (100% specificity). Using the same technique on the same kind of material, O'Sullivan et al (5) found (SYT-SSX) fusion gene transcripts in 29 of 34 (85%) synovial sarcomas, but also in 15 of 20 (75%) MPNSTs, 1 of 4 adult fibrosarcomas, 1 of 10 malignant fibrous histiocytomas, 1 of 7 congenital-infantile fibrosarcomas, and 2 of 3 neurofibromas. Based on these results, the authors concluded that the translocation t(X;18) is not specific for synovial sarcoma and, thus, should be used with great caution in the differential diagnosis of spindle cell tumors.…”

Section: Discussionmentioning

confidence: 92%

“…Unfortunately, O'Sullivan et al (5) did not try to confirm their unexpected and provocative results with techniques other than RT-PCR such as in situ hybridization, which could have been applied on paraffin-embedded material as well. They did not ask another independent laboratory to verify their results on the same samples either.…”

Section: Discussionmentioning

confidence: 99%

“…This specificity was recently challenged by O'Sullivan et al (5). These authors detected SYT-SSX fusion gene transcripts not only in synovial sarcomas but also in 15 of 20 malignant peripheral nerve sheath tumors (MPNSTs) as well as in several other types of benign and malignant mesenchymal tumors, thus raising major concerns and controversies regarding t(X;18) specificity.…”

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Malignant Peripheral Nerve Sheath Tumors are t(X;18)-Negative Sarcomas. Molecular Analysis of 25 Cases Occurring in Neurofibromatosis Type 1 Patients, Using Two Different RT-PCR-Based Methods of Detection

et al. 2002

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To verify the absence of the synovial sarcoma translocation t(X;18) (SYT-SSX) in malignant peripheral nerve sheath tumors, 34 tumor samples from 25 neurofibromatosis type 1 patients were examined in two independent laboratories (Bordeaux, France, and Lausanne, Switzerland) using reverse transcriptase polymerase chain reaction (RT-PCR)-based techniques. RNA was extracted from paraffin blocks using standard methods, reverse transcribed, and conventional (in one laboratory) versus real-time (in the other laboratory) PCR performed. Twentyseven tumor samples from 19 patients were negative for the t(X;18) in both laboratories; six additional tumors that were t(X;18)-negative in one laboratory gave noninterpretable results in the other, due to lack of internal positive controls; one case was noninterpretable in both places. In conclusion, malignant peripheral nerve sheath tumors in neurofibromatosis type 1 patients do not bear the synovial sarcoma t(X;18) (SYT-SSX). Laboratories that use PCR-based techniques for diagnostic purposes would benefit from quality assurance programs. KEY WORDS: Malignant peripheral nerve sheath tumor, Neurofibromatosis type 1, RT-PCR, t(X;18). Mod Pathol 2002;15(6):589 -592Most synovial sarcomas bear the translocation t(X;18), which may be detected in formalin-fixed, paraffin-embedded material by reverse transcriptasepolymerase chain reaction (RT-PCR). This technique is particularly useful for consultation cases for which paraffin-embedded material only is available. Several large series have shown that this method is highly sensitive and specific, with virtually no t(X;18) (SYT-SSX) detected in mesenchymal tumors other than synovial sarcomas (1-4). This specificity was recently challenged by O'Sullivan et al. (5). These authors detected SYT-SSX fusion gene transcripts not only in synovial sarcomas but also in 15 of 20 malignant peripheral nerve sheath tumors (MPNSTs) as well as in several other types of benign and malignant mesenchymal tumors, thus raising major concerns and controversies regarding t(X;18) specificity. In a letter to the Editor that strongly disagreed with O'Sullivan et al., Ladanyi et al. (6) regretted that the authors did not attempt to confirm their results using alternative techniques such as Southern blotting, conventional cytogenetics, and/or in situ hybridization. In addition, they reported 145 cases of MPNST that always proved to be t(X;18)-negative in several different laboratories using different techniques, a finding that would strongly support their view.In this article, we report our experience with 34 cases of MPNST that occurred in 25 neurofibromatosis type 1 (NF1) patients. In none of our cases was the t(X;18) (SYT-SSX) detected using two different PCR-based techniques performed in two different laboratories. MATERIALS AND METHODSCases of MPNST occurring exclusively in NF1 patients were retrieved from the files

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Malignant Peripheral Nerve Sheath Tumors with t(X;18). A Pathologic and Molecular Genetic Study

Cited by 46 publications

References 49 publications

Synovial sarcoma: Diagnosis on fine‐needle aspiration by morphology and molecular analysis

Synovial sarcoma: Diagnosis on fine‐needle aspiration by morphology and molecular analysis

Expression of MYCN in pediatric synovial sarcoma

Malignant Peripheral Nerve Sheath Tumors are t(X;18)-Negative Sarcomas. Molecular Analysis of 25 Cases Occurring in Neurofibromatosis Type 1 Patients, Using Two Different RT-PCR-Based Methods of Detection

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