／【Ｋ：】Ｓｅｒｖｅｒ／１６０１０４４６ 新潟県厚生農業協同組合／本文／５１‐３０

五十嵐

０６９‐０７３

2016.02.10 1

Two cases of solitary fibrous tumor and gastrointestinal stromal tumor with an unexpected expression of SYT-SSX
厚生連医誌
fused gene as第a２specific
５巻 marker
１号 for６
９synovial〜７３ sarcoma
２０１
６Case report

Two cases of solitary fibrous tumor and gastrointestinal
stromal tumor with an unexpected expression of SYT-SSX
fused gene as a specific marker for synovial sarcoma
Nagaoka Central General Hospital, Department of pathology ; Pathologist

Toshihiko Ikarashi
AbstractBackground : There were three difficult-to-diagnose fibrous tumors ;（１）synovial sarcoma（SS）,（２）solitary fibrous tumor（SFT）, and（３）gastrointestinal
stromal tumor（GIST）. These tumors could be differentiated pathologically by the following three
viewpoints ; the clinical information especiallywith respect to the favorable site of occurrence, thecharacteristic immunostain, and the genetic analysis. However, SS could arise in unusual sites andthe immunostain was sometimes useless because of
its low discriminating specificity. Consequently SS
could be differentiated from the other tumors onlyby the genetic demonstration of synaptotagminsynovial sarcoma X breakpoint fused gene of t（X；１８）（p１１．
２；q１１．
２）mutual translocation（SYT-SSX fused gene）, but then a problem wasleft in the certainty of this genetic discrimination.
We experienced two non-SS cases positive for
SYT-SSX fused gene confirmed by the reverse
transcriptase-polymerase chain reaction（RT-PCR）
with formalin-fixed paraffin-embedded tissue sections（FFPE）, and reported in this paper.
Case report : Case １：The pathology was SS of monophasic fibrous type, which originated from lung ofan unusual site and diagnosed by the positive
imunostain for epithelial membrane antigen（EMA）and the positive SYT-SSX１fused gene.
Case２, ３: They were identified respectively as serosa-originating SFT and colon-originating GIST
by the positive immunostain for CD３４ and CD１１７（c-kit）. Interestingly SYT-SSX１fused gene wasidentified in both tumors as well as SS.
Conclusion : In the present study, we have demonstrated
that both SFT and GIST can also demonstrate SYT-SSX fused gene regarded as the essential tumor
marker of SS, so that some of these tumors and SS
are reclassified into the fibrous tumor group expressing SYT-SSX fused gene , or the SYT-SSX
fused gene related tumor.
Key words : synovial sarcoma（SS）, solitary fibrous tu-― 69 ―

mor（SFT）, gastrointestinal stromal tumor（GIST）,
immunostain, epithelial membrane antigen（EMA）,CD３
４, CD１１７（c-kit）, fluorescence in situ hybridization（FISH）, reverse transcriptase-polymerase
chain reaction（RT-PCR）, formalin-fixed paraffinembedded tissue sections（FFPE）, synaptotagminsynovial sarcoma X breakpoint fused gene of （t X;１８）（p１１．
２; q１１．
２）mutual translocation（SYTSSX fused gene）, differential diagnosis, specificity, the fibrous tumor group expressing SYT-SSX
fused gene, the SYT-SSX fused gene related tumor

Background
The rare undiagnosable fibrous tumors of borderline malignancy consisted of SS, SFT（hemangiopericytoma, localized fibrous tumor, or fibrous mesothelioma asa synonym）, and GIST. These three tumors could be pathologically differentiated by the favored site of localization, the immunostain for CD３４ and CD１１
７, and SYTSSX fused gene（Table２）.
Although SS was often found in the orthopedic regions, recent references revealed that SS could also develop in several internal organs as an unusual origin. Immunohistochemically EMA, CD３４, and CD１１
７ werestainable in all tumors and their stainability was various
and weak for the definitive diagnosis（Table ２）. In these
diagnostically troublesome tumors the genetic analysis became the most reliable method, and we reexamined about
its differentiating efficacy in this report（１）.
As to our materials and methods, neutral １０％
FFPE was used for immunostain and RT-PCR study. Total ribonucleic acid（RNA）was collected by NucleoSpin!
RNA FFPE（Macherey-Nagel, Germany ; provided by
Takara Bio Inc, Japan）and DNA was amplified byPrimeScript! One Step RT-PCR Kit Ver. ２（Takara BioInc, Japan）. The electrophoretic blotting size of final PCR
products was as follows : SYT-SSX of common type, ９８bp ; SYT-SSX１of one subtype, １１８ bp ; and SYT-SSX２of another subtype,１１８bp（１）.

／【Ｋ：】Ｓｅｒｖｅｒ／１６０１０４４６ 新潟県厚生農業協同組合／本文／５１‐３０

厚生連医誌

第２５巻

五十嵐０６９‐０７３

2016.02.10 1

１号 ６９〜７３ ２０１６

Case report（Table３）
Case１ was５
３ y/o female with left intrapulmonary
carcinoma. She was histologically diagnosed as synovial
sarcoma, monophasic type, on the basis of the presence ofa small focus of epithelial cells of biphasic type and focally positive EMA cells. SS was confirmed by positive
SYT-SSX immunofluorescence in situ hybridization（FISH）study by the pathologic consultation of The Japanese Society of Pathology（＃１４-２６２, ２０１４/０８/２７）. SYTSSX１fused gene was also positive in our RT-PCR study（Figure１）.
Case ２ was ６３ y/o female with huge sphericalmass on serosa involving omentum and mesocolica. She
was immunologically diagnosed as solitary fibrous tumor
by the positive CD３４. Our RT-PCR study revealed SYTSSX１fused gene（Figure２）.
Case ３ was ８
１ y/o male with carcinoma of transverse colon, protuberant-ulcerative tumor with well demarcated expansive growth. He was immunohistologicallydiagnosed as malignant GIST because of positive CD３４and CD１
１
７. Our RT-PCR study, furthermore, showed
SYT-SSX１fused gene（Figure２）.

Discussion
In the pathological differentiation among SS, SFT,and GIST, the following clinical findings were important :the site of origin, the immunostain for EMA, CD３４ andCD１
１７, and the SYT-SSX fused gene（Table２）（１）.
Synovial of SS is a misnomer, because a developmental origin is unknown and a site of origin is unrelated to synovium. As to case １ SS developed in lung,which was an unusual site for SS. In these heterotopicallyoccuring SS the theoretically coexisting epithelial cells
were required to diagnose SS histologically even if there
were few cells among massive fibrous spindle cells. Although positive EMA was the immunohistochemical evidence of SS, the degree of positivity and its reliability ofpositive judgment in non-epithelial spindle cells werelower than that in epithelial cells. The pure fibrous monophasic subtype of ectopic SS or the dedifferentiated subtype of SS was very difficult to diagnose immunologically, and both SFT and GIST could, furthermore, reveal
positive EMA like SS（２,４）. In those situations, the confirmation of SYT-SSX fused gene is necessary to diagnose SS pathologically.
Case ２ was diagnosed as SFT because of the subserosal location as a favorable location and the strong immunostaining for CD３４. Case ３ was diagnosed as GIST
because of the wall of digestive tract as a favorable location and the strong immunostaining for CD３４- and CD
１１
７. The tumor-originating location was, however, often
ambiguous in extramural overgrowing tumors : the tumor
arising from external proper muscle close to subserosa
could not be correctly discriminated from the subserosal
tumor infiltrating into mural wall. CD３
４ could be shownin SS as well as GIST and SFT（３）. In an immunostaining

analysis the decreased staining for CD３
４ and CD１１７, furthermore, disturbed confirming GIST and SFT tumors. In
those situations, the confirmation of SYT-SSX fused genefor SS is useful to rule out SS（１）. Because a reliability ofthis genetic screening has been emphasized, the positive
tumors are automatically classified into SS. However, ourtwo cases of SFT and GIST also showed positive SYTSSX１ fused gene, and the positive cases suggested not
only SS but also other tumors. That being the case, theconfirmation of SYT-SSX１ fused gene was not the sufficient evidence to diagnose SS pathologically.
SYT-SSX fused gene were not diagnostic in ourcases of SFT and GIST, so that the tumors with positive
SYT-SSX fused gene could be reclassified into thebroader category including SS or the fibrous tumorgroup expressing SYT-SSX fused gene named after thisgenetic feature.

Conclusion
SS is not a disease specialized in synovial tissue,
and the demonstration of SYT-SSX fused gene is not themost reliable discriminating marker for SS. Both SS and apart of SFT and GIST could be tentatively grouped together into the fibrous tumor group expressing SYT-SSX
fused gene , or the SYT-SSX fused gene relating tumor, to remove a further meaningless discriminating effort.

Reference
１．Ikarashi T, Hasegawa H. Molecular detection of SYT-SSX fusion gene transcription in monophasic type
synovial sarcoma with the use of formalin-fixed paraffin-embedded specimens − Case report guaranteed by
the chromosomal analysis of incubated cells and an establishment of the most suitable condition in Reverse
Transcription-Polymerase Chain Reaction（RT-PCR）of
SYT-SSX gene-. Niigata-Ken Koseiren Med J ２０００;
１１:３０−４.
２．Martorell M et al. Solitary fibrous tumor of the thighwith epithelioid features : a case report. Diagnostic Pathology２００７;２:１９−２３.
３．Pelmus M et al. Monophasic fibrous and poorly differentiated synovial sarcoma : immunohistochemical reassessment of６０t（X ;１８）
（SYT-SSX）-positive cases.
Am J Surg Pathol２００２;２６:１４３４−４０.
４．Wong NA, Melegh Z. Gstrointestinal stromal tumours can express CD １０ and epithelial membrane antigen but not oestrogen receptor or HMB４５. Histopathology２０１１;５９:７８１−５.

和 文 抄録

症例報告
滑膜肉腫に特異的な SYT-SSX 融合遺伝子の異常発現― 70 ―

／【Ｋ：】Ｓｅｒｖｅｒ／１６０１０４４６ 新潟県厚生農業協同組合／本文／５１‐３０五十嵐

０６９‐０７３

2016.02.10 1

Two cases of solitary fibrous tumor and gastrointestinal stromal tumor with an unexpected expression of SYT-SSX fused gene as a specific marker for synovial sarcomaを認めた弧在性線維性腫瘍と消化管間質腫瘍の２症例

症例報告：第１症例：EMA 陽性の異所性肺原発の単相線維型一部二相型の SS で、SYT-SSX 融合遺伝子が陽性であった。第２、３症例：CD３４強陽性の漿膜原発の SFT と、CD３４と CD１１７が強陽性の消化管固有筋層原発の GIST であった。
２例ともに SYT-SSX 融合遺伝子発現が陽性であった。
結 論：３腫 瘍（SS と SFT と GIST）の 鑑 別 点 と し ての発生部位、免疫染色（EMA、CD３４、CD１１７）、及び SYT-SSX 融合 遺 伝 子 に 関 し て 再 評 価 した。SS に特異的とされる SYT-SSX 融合遺伝子が SFT と GIST の２症例に共通に発現し、この遺伝子発現による病理学的鑑別が困難であることがわかった。SS 及び鑑別が困難な腫瘍を含めたより広義の疾患単位として、暫定的に、『SYT-SSX 融合遺伝子発現線維性腫瘍群』または『SYT-SSX 融合遺伝子関連腫瘍』として捉えることを提唱した。

長岡中央綜合病院、病理部；病理医
いか らしとしひこ

五十嵐俊彦
背景：組織鑑別が困難な境界悪性型線維性腫瘍として以 下 の３腫 瘍 が あ る；す な わ ち、滑 膜 肉 腫（synovial sarcoma, SS）、弧在性線維性腫瘍（solitary fibrous tumor, SFT）、消化管間質腫瘍（gastrointestinal stromal tumor, GIST）である。これらの腫瘍の組織学的鑑別診断の手掛りには３項目がある；すなわち、好発発生部位などの臨床所見と、免疫染色検査における上皮性膜抗原（epithelial membrane antigen, EMA）
、CD３４、CD１１７（c-kit）発現と、そして、遺伝子検査における t（X；１８）（p１１．
２；q１１．
２）相互転座 synaptotagmin-synovial sarcoma X breakpoint fusedgene（SYT-SSX 融合遺伝子）の発現が鑑別点となる（表２）。SS は四肢関節部が好発部位とされ、EMA 陽性により診断される。が、好発以外の異所性に発生する SS が報告されるようになり、EMA の陽性所見が不明瞭な症例においては、SS に特異的とされる SYT-SSX 融合遺伝子の発現が唯一の鑑別診断根拠となった。本論文において、その SYT-SSX 融合遺伝子発現の特異性に関して検討した。SS、SFT、GISTと診断された３症例について、そのホルマリン固定―パラフィン包埋組織切片（formalin-fixedparaffin-embedded tissue sections, FFPE）を材料として、全 ribonucleic acid（RNA）を抽出・精製し、逆転写ポリメラーゼ連鎖反応（reversetranscriptase-polymerase chain reaction, RTPCR）により検討を加えた。その結果、SFT とGIST の２症例にも SS 同様の SYT-SSX 融合遺伝子を確認できたので報告した。

キーワード：滑膜肉腫（synovial sarcoma, SS）、孤在性線維性腫瘍（solitary fibrous tumor, SFT）
、消化管間質腫瘍（gastrointestinal stromal tumor,GIST）、免疫染色、上皮性膜抗原（epithelial mem４、CD１１７（c-kit）、brane antigen, EMA）
、CD３
蛍 光 in situ ハ イ ブ リ ダ イ ゼ ー シ ョ ン（immunofluorescence in situ hybridization, FISH）、
逆転写ポリメラーゼ連鎖反応（reverse transcriptase-polymerase chain reaction, RT-PCR）、ホルマリン固定―パラフィン包埋組織切片（formalin-fixed paraffin-embedded tissue sections, FFPE）、t（X；１８）（p１１．
２；q１１．
２）相互転座 synaptotagmin-synovial sarcoma X breakpoint fused gene 融合遺伝子（SYT-SSX fused gene）、特異性、SYT-SSX 融合遺伝子発現線維性腫瘍群、SYT-SSX
融合遺伝子関連腫瘍、病理学的鑑別診断

Figure１. Electrophoresis of Case１,
１ : SYT-SSX,２: SYT-SSX１,３: SYT-SSX２.
Lane２: SYT-SSX１fused gene is confirmed in１１８bp.

― 71 ―

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厚生連医誌

第２５巻

五十嵐０６９‐０７３

2016.02.10 1１号 ６９〜７３ ２０１６Figure２. Electrophoresis of Case２and３,４-６: Case２,７-９: Case３,４,７: SYT-SSX,５,７: SYT-SSX１,６,９: SYT-SSX２.
Lane５and８: SYT-SSX１fused gene is confirmed in１１８bp.
Table１. Abbreviation list

Table２. Routine differential diagnosis based on references― 72 ―

／【Ｋ：】Ｓｅｒｖｅｒ／１６０１０４４６ 新潟県厚生農業協同組合／本文／５１‐３０五十嵐

０６９‐０７３

2016.02.10 1

Two cases of solitary fibrous tumor and gastrointestinal stromal tumor with an unexpected expression of SYT-SSX fused gene as a specific marker for synovial sarcoma

Table３. Case record（２０１５／０５／３１受付）― 73 ―