Difference between revisions of "STBT5:Solitary fibrous tumour"

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==Definition / Description of Disease==
 
==Definition / Description of Disease==
−
Solitary fibrous tumor (SFT) is a mesenchymal spindle cell neoplasm that can develop at any site in the body, including soft tissue, visceral organs, bone, etc.  It was first described by Klemperer and Rabin in 1992 as a tumor of the pleura. However, since then this entity has been increasingly described from extrapleural sites. A morphologic clue to the diagnosis is the distinctive branching “staghorn” vessels. SFT is characterized by ''NAB2::STAT6'' fusion resulting from a paracentric inversion at chromosome 12q13q13.  
+
Solitary fibrous tumor (SFT) is a mesenchymal spindle cell neoplasm that can develop at any site in the body, including soft tissue, visceral organs, bone, etc.  It was first described by Klemperer and Rabin<ref>{{Cite journal|last=Klemperer|first=Paul|last2=Rabin|first2=Coleman B.|date=1992-01|title=Primary Neoplasms of the pleura. A report of five cases|url=https://onlinelibrary.wiley.com/doi/10.1002/ajim.4700220103|journal=American Journal of Industrial Medicine|language=en|volume=22|issue=1|pages=4–31|doi=10.1002/ajim.4700220103|issn=0271-3586}}</ref> in 1992 as a tumor of the pleura. However, since then this entity has been increasingly described from extrapleural sites. A morphologic clue to the diagnosis is the distinctive branching “staghorn” vessels. SFT is characterized by ''NAB2::STAT6'' fusion resulting from a small paracentric inversion at chromosome 12q13.  
 
==Synonyms / Terminology==
 
==Synonyms / Terminology==
 
Formerly SFTs were categorized as hemangiopericytomas.  
 
Formerly SFTs were categorized as hemangiopericytomas.  
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|-
 
|-
 
|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
−
|<span class="blue-text">EXAMPLE:</span> Cytopenias
+
|
−
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
 
 
|}
 
|}
 
==Sites of Involvement==
 
==Sites of Involvement==
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==Morphologic Features==
 
==Morphologic Features==
 
Morphologically, biopsy or resection specimens will show a bland spindle cell proliferation arranged haphazardly in a background of collagenous stroma. Cells contain ovoid nuclei within eosinophilic cytoplasm with indistinct cell borders. Tumors can vary in cellularity and stromal collagen. On low power, branching, “staghorn” shaped vessels can often be appreciated. Mitotic counts are usually low. Myxoid and lipomatous change have been described. SFT with adipocytic component are referred to as fat-forming (lipomatous) SFTs. There is also a variant known as giant cell rich SFT, which has the classic patternless spindle cell proliferation admixed with multinucleated giant cells. Dedifferentiated SFTs will show conventional SFT transitioning to a high-grade pleomorphic variant. Heterologous elements may be present. Standard immunophenotypic expression of CD34 and STAT6 is often lost in the dedifferentiated component.  
 
Morphologically, biopsy or resection specimens will show a bland spindle cell proliferation arranged haphazardly in a background of collagenous stroma. Cells contain ovoid nuclei within eosinophilic cytoplasm with indistinct cell borders. Tumors can vary in cellularity and stromal collagen. On low power, branching, “staghorn” shaped vessels can often be appreciated. Mitotic counts are usually low. Myxoid and lipomatous change have been described. SFT with adipocytic component are referred to as fat-forming (lipomatous) SFTs. There is also a variant known as giant cell rich SFT, which has the classic patternless spindle cell proliferation admixed with multinucleated giant cells. Dedifferentiated SFTs will show conventional SFT transitioning to a high-grade pleomorphic variant. Heterologous elements may be present. Standard immunophenotypic expression of CD34 and STAT6 is often lost in the dedifferentiated component.  
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==Immunophenotype==
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==Immunophenotype<ref>Goldblum, John R, et al. ''Enzinger & Weiss’s Soft Tissue Tumors''. 7th ed., Philadelphia, PA, Elsevier, 2020, pp. 1133–1147.</ref>==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
−
|Positive (universal)||CD34
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|Positive||CD34
 
|-
 
|-
−
|Positive (universal)||STAT6
+
|Positive||STAT6 (nuclear)
 
|-
 
|-
−
|Negative (universal)||
+
|Positive||BCL2 (30%)
 
|-
 
|-
−
|Negative (subset)||
+
|Positive||CD99 (70%)
 +
|-
 +
|Positive
 +
|EMA (30%)
 +
|-
 +
|Positive
 +
|Actin (20%)
 +
|-
 +
|Negative
 +
|S100
 +
|-
 +
|Negative
 +
|Desmin
 +
|-
 +
|Negative
 +
|Cytokeratins
 
|}
 
|}
 
==Chromosomal Rearrangements (Gene Fusions)==
 
==Chromosomal Rearrangements (Gene Fusions)==
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!Notes
 
!Notes
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
+
|inv(12)(q13q13)||3'STAT6 / 5'NAB2<ref>{{Cite journal|last=Huang|first=Shih‐Chiang|last2=Li|first2=Chien‐Feng|last3=Kao|first3=Yu‐Chien|last4=Chuang|first4=I‐Chieh|last5=Tai|first5=Hui‐Chun|last6=Tsai|first6=Jen‐Wei|last7=Yu|first7=Shih‐Chen|last8=Huang|first8=Hsuan‐Ying|last9=Lan|first9=Jui|date=2016-02|title=The clinicopathological significance of  NAB 2‐ STAT 6  gene fusions in 52 cases of intrathoracic solitary fibrous tumors|url=https://onlinelibrary.wiley.com/doi/10.1002/cam4.572|journal=Cancer Medicine|language=en|volume=5|issue=2|pages=159–168|doi=10.1002/cam4.572|issn=2045-7634}}</ref><ref>{{Cite journal|last=Chmielecki|first=Juliann|last2=Crago|first2=Aimee M|last3=Rosenberg|first3=Mara|last4=O'Connor|first4=Rachael|last5=Walker|first5=Sarah R|last6=Ambrogio|first6=Lauren|last7=Auclair|first7=Daniel|last8=McKenna|first8=Aaron|last9=Heinrich|first9=Michael C|date=2013-02|title=Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors|url=https://www.nature.com/articles/ng.2522|journal=Nature Genetics|language=en|volume=45|issue=2|pages=131–132|doi=10.1038/ng.2522|issn=1061-4036}}</ref><ref>{{Cite journal|last=Robinson|first=Dan R|last2=Wu|first2=Yi-Mi|last3=Kalyana-Sundaram|first3=Shanker|last4=Cao|first4=Xuhong|last5=Lonigro|first5=Robert J|last6=Sung|first6=Yun-Shao|last7=Chen|first7=Chun-Liang|last8=Zhang|first8=Lei|last9=Wang|first9=Rui|date=2013-02|title=Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing|url=https://www.nature.com/articles/ng.2509|journal=Nature Genetics|language=en|volume=45|issue=2|pages=180–185|doi=10.1038/ng.2509|issn=1061-4036}}</ref><ref>{{Cite journal|last=Mohajeri|first=Arezoo|last2=Tayebwa|first2=Johnbosco|last3=Collin|first3=Anna|last4=Nilsson|first4=Jenny|last5=Magnusson|first5=Linda|last6=von Steyern|first6=Fredrik Vult|last7=Brosjö|first7=Otte|last8=Domanski|first8=Henryk A.|last9=Larsson|first9=Olle|date=2013-10|title=Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor|url=https://onlinelibrary.wiley.com/doi/10.1002/gcc.22083|journal=Genes, Chromosomes and Cancer|language=en|volume=52|issue=10|pages=873–886|doi=10.1002/gcc.22083|issn=1045-2257}}</ref><ref>{{Cite journal|last=Vogels|first=Rob JC|last2=Vlenterie|first2=Myrella|last3=Versleijen-Jonkers|first3=Yvonne MH|last4=Ruijter|first4=Emiel|last5=Bekers|first5=Elise M|last6=Verdijk|first6=Marian AJ|last7=Link|first7=Monique M|last8=Bonenkamp|first8=Johannes J|last9=van der Graaf|first9=Winette TA|date=2014-12|title=Solitary fibrous tumor – clinicopathologic, immunohistochemical and molecular analysis of 28 cases|url=https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-014-0224-6|journal=Diagnostic Pathology|language=en|volume=9|issue=1|doi=10.1186/s13000-014-0224-6|issn=1746-1596}}</ref><ref name=":0">{{Cite journal|last=Akaike|first=Keisuke|last2=Kurisaki-Arakawa|first2=Aiko|last3=Hara|first3=Kieko|last4=Suehara|first4=Yoshiyuki|last5=Takagi|first5=Tatsuya|last6=Mitani|first6=Keiko|last7=Kaneko|first7=Kazuo|last8=Yao|first8=Takashi|last9=Saito|first9=Tsuyoshi|date=2015-03|title=Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential|url=https://linkinghub.elsevier.com/retrieve/pii/S0046817714004912|journal=Human Pathology|language=en|volume=46|issue=3|pages=347–356|doi=10.1016/j.humpath.2014.11.018}}</ref>||NA||55-100%
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<span class="blue-text">EXAMPLE:</span> 30% (add reference)
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|Yes
−
|<span class="blue-text">EXAMPLE:</span> Yes
+
|Unknown
−
|<span class="blue-text">EXAMPLE:</span> No
+
|No
−
|<span class="blue-text">EXAMPLE:</span> Yes
+
|Many different breakpoints in the exons and introns are associated with this fusion. Ex: ''NAB2''ex4-''STAT6''ex2; ''NAB2''ex6-''STAT6''ex16/17
−
|<span class="blue-text">EXAMPLE:</span>
 
−
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
 
 
|}
 
|}
 
==Individual Region Genomic Gain / Loss / LOH==
 
==Individual Region Genomic Gain / Loss / LOH==
−
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.'') </span>
+
 
 +
 
 +
Not Applicable
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
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!Notes
 
!Notes
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span>
+
|
−
7
+
|
−
|<span class="blue-text">EXAMPLE:</span> Loss
+
|
−
|<span class="blue-text">EXAMPLE:</span>
+
|
−
chr7:1-159,335,973 [hg38]
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|
−
|<span class="blue-text">EXAMPLE:</span>
+
|
−
chr7
+
|
−
|<span class="blue-text">EXAMPLE:</span> Yes
+
|
−
|<span class="blue-text">EXAMPLE:</span> Yes
 
−
|<span class="blue-text">EXAMPLE:</span> No
 
−
|<span class="blue-text">EXAMPLE:</span>
 
−
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
 
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span>
+
|
−
8
+
|
−
|<span class="blue-text">EXAMPLE:</span> Gain
+
|
−
|<span class="blue-text">EXAMPLE:</span>
+
|
−
chr8:1-145,138,636 [hg38]
+
|
−
|<span class="blue-text">EXAMPLE:</span>
+
|
−
chr8
+
|
−
|<span class="blue-text">EXAMPLE:</span> No
+
|
−
|<span class="blue-text">EXAMPLE:</span> No
 
−
|<span class="blue-text">EXAMPLE:</span> No
 
−
|<span class="blue-text">EXAMPLE:</span>
 
−
Common recurrent secondary finding for t(8;21) (add reference).
 
 
|}
 
|}
 
==Characteristic Chromosomal Patterns==
 
==Characteristic Chromosomal Patterns==
−
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis. Do not delete table.'')</span>
+
 
 +
Not Applicable
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
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!Notes
 
!Notes
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span>
+
|
−
Co-deletion of 1p and 18q
+
|
−
|<span class="blue-text">EXAMPLE:</span> Yes
+
|
−
|<span class="blue-text">EXAMPLE:</span> No
+
|
−
|<span class="blue-text">EXAMPLE:</span> No
+
|
−
|<span class="blue-text">EXAMPLE:</span>
 
−
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
 
 
|}
 
|}
 
==Gene Mutations (SNV / INDEL)==
 
==Gene Mutations (SNV / INDEL)==
−
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.'') </span>
+
There are multiple genes with single nucleotide variations that have been reported only in metastatic solitary fibrous tumor tissues including TP53 and APAF1.<ref name=":1">{{Cite journal|last=Park|first=Hyung Kyu|last2=Yu|first2=Dan Bi|last3=Sung|first3=Minjung|last4=Oh|first4=Ensel|last5=Kim|first5=Mingi|last6=Song|first6=Ji-Young|last7=Lee|first7=Mi-Sook|last8=Jung|first8=Kyungsoo|last9=Noh|first9=Ka-Won|date=2019|title=Molecular changes in solitary fibrous tumor progression|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746689/|journal=Journal of Molecular Medicine (Berlin, Germany)|volume=97|issue=10|pages=1413–1425|doi=10.1007/s00109-019-01815-8|issn=0946-2716|pmc=6746689|pmid=31321477}}</ref>  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
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!Notes
 
!Notes
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
+
|TERT
−
<span class="blue-text">EXAMPLE:</span>
+
|Oncogene
−
 
+
|13-29% <ref name=":3">{{Cite journal|last=Bahrami|first=Armita|last2=Lee|first2=Seungjae|last3=Schaefer|first3=Inga-Marie|last4=Boland|first4=Jennifer M|last5=Patton|first5=Kurt T|last6=Pounds|first6=Stanley|last7=Fletcher|first7=Christopher D|date=2016-12|title=TERT promoter mutations and prognosis in solitary fibrous tumor|url=https://linkinghub.elsevier.com/retrieve/pii/S0893395222023328|journal=Modern Pathology|language=en|volume=29|issue=12|pages=1511–1522|doi=10.1038/modpathol.2016.126}}</ref><ref>{{Cite journal|last=Liu|first=Xiaoli|last2=Bishop|first2=Justin|last3=Shan|first3=Yuan|last4=Pai|first4=Sara|last5=Liu|first5=Dingxie|last6=Murugan|first6=Avaniyapuram Kannan|last7=Sun|first7=Hui|last8=El-Naggar|first8=Adel K|last9=Xing|first9=Mingzhao|date=2013-08|title=Highly prevalent TERT promoter mutations in aggressive thyroid cancers|url=https://erc.bioscientifica.com/view/journals/erc/20/4/603.xml|journal=Endocrine-Related Cancer|volume=20|issue=4|pages=603–610|doi=10.1530/ERC-13-0210|issn=1351-0088|pmc=PMC3782569|pmid=23766237}}</ref><ref>{{Cite journal|last=Killela|first=Patrick J.|last2=Reitman|first2=Zachary J.|last3=Jiao|first3=Yuchen|last4=Bettegowda|first4=Chetan|last5=Agrawal|first5=Nishant|last6=Diaz|first6=Luis A.|last7=Friedman|first7=Allan H.|last8=Friedman|first8=Henry|last9=Gallia|first9=Gary L.|date=2013-04-09|title=TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal|url=https://pnas.org/doi/full/10.1073/pnas.1303607110|journal=Proceedings of the National Academy of Sciences|language=en|volume=110|issue=15|pages=6021–6026|doi=10.1073/pnas.1303607110|issn=0027-8424|pmc=PMC3625331|pmid=23530248}}</ref><ref>{{Cite journal|last=Koelsche|first=Christian|last2=Renner|first2=Marcus|last3=Hartmann|first3=Wolfgang|last4=Brandt|first4=Regine|last5=Lehner|first5=Burkhard|last6=Waldburger|first6=Nina|last7=Alldinger|first7=Ingo|last8=Schmitt|first8=Thomas|last9=Egerer|first9=Gerlinde|date=2014-12|title=TERT promoter hotspot mutations are recurrent in myxoid liposarcomas but rare in other soft tissue sarcoma entities|url=https://jeccr.biomedcentral.com/articles/10.1186/1756-9966-33-33|journal=Journal of Experimental & Clinical Cancer Research|language=en|volume=33|issue=1|doi=10.1186/1756-9966-33-33|issn=1756-9966}}</ref><ref name=":2">{{Cite journal|last=Demicco|first=Elizabeth G.|last2=Wani|first2=Khalida|last3=Ingram|first3=Davis|last4=Wagner|first4=Michael|last5=Maki|first5=Robert G.|last6=Rizzo|first6=Anthony|last7=Meeker|first7=Alan|last8=Lazar|first8=Alexander J.|last9=Wang|first9=Wei-Lien|date=2018-11|title=TERT promoter mutations in solitary fibrous tumour|url=https://pubmed.ncbi.nlm.nih.gov/29985536|journal=Histopathology|volume=73|issue=5|pages=843–851|doi=10.1111/his.13703|issn=1365-2559|pmid=29985536}}</ref>
−
''EGFR''; Exon 20 mutations
+
|
−
 
+
|
−
<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
+
|No
−
|<span class="blue-text">EXAMPLE:</span> TSG
+
|Yes<ref name=":0" /><ref name=":3" /><ref name=":2" /><ref>{{Cite journal|last=Park|first=Hyung Kyu|last2=Yu|first2=Dan Bi|last3=Sung|first3=Minjung|last4=Oh|first4=Ensel|last5=Kim|first5=Mingi|last6=Song|first6=Ji-Young|last7=Lee|first7=Mi-Sook|last8=Jung|first8=Kyungsoo|last9=Noh|first9=Ka-Won|date=2019-10|title=Molecular changes in solitary fibrous tumor progression|url=https://pubmed.ncbi.nlm.nih.gov/31321477|journal=Journal of Molecular Medicine (Berlin, Germany)|volume=97|issue=10|pages=1413–1425|doi=10.1007/s00109-019-01815-8|issn=1432-1440|pmc=6746689|pmid=31321477}}</ref><ref>{{Cite journal|last=Bahrami|first=Armita|last2=Lee|first2=Seungjae|last3=Schaefer|first3=Inga-Marie|last4=Boland|first4=Jennifer M.|last5=Patton|first5=Kurt T.|last6=Pounds|first6=Stanley|last7=Fletcher|first7=Christopher D.|date=2016-12|title=TERT promoter mutations and prognosis in solitary fibrous tumor|url=https://pubmed.ncbi.nlm.nih.gov/27562490|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=29|issue=12|pages=1511–1522|doi=10.1038/modpathol.2016.126|issn=1530-0285|pmc=5731237|pmid=27562490}}</ref>
−
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
+
|No
−
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
+
|
−
|<span class="blue-text">EXAMPLE:</span> ''IDH1'' R123H
+
|-
−
|<span class="blue-text">EXAMPLE:</span> ''EGFR'' amplification
+
|TP53
−
|<span class="blue-text">EXAMPLE:</span> Yes
+
|TSG
−
|<span class="blue-text">EXAMPLE:</span> No
+
|6.3-41%<ref name=":4">{{Cite journal|last=Yao|first=Chen-Chen|last2=Zhou|first2=Jian|last3=Li|first3=Xiao|last4=Yang|first4=Jun|last5=Chen|first5=Gang|last6=Wei|first6=Jia|last7=Fan|first7=Qin-He|last8=Gong|first8=Qi-Xing|date=2023|title=Prognostic analysis of extrameningeal solitary fibrous tumor using the modified Demicco model: a clinicopathologic study of 111 Chinese cases|url=https://pubmed.ncbi.nlm.nih.gov/38239634|journal=Frontiers in Oncology|volume=13|pages=1272090|doi=10.3389/fonc.2023.1272090|issn=2234-943X|pmc=PMC10796168|pmid=38239634}}</ref><ref name=":1" />
−
|<span class="blue-text">EXAMPLE:</span> No
+
|
−
|<span class="blue-text">EXAMPLE:</span> Excludes hairy cell leukemia (HCL) (add reference).
+
|
−
|}Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
+
|No
 +
|Yes<ref>{{Cite journal|last=Machado|first=Isidro|last2=Morales|first2=Gema Nieto|last3=Cruz|first3=Julia|last4=Lavernia|first4=Javier|last5=Giner|first5=Francisco|last6=Navarro|first6=Samuel|last7=Ferrandez|first7=Antonio|last8=Llombart-Bosch|first8=Antonio|date=2020-04|title=Solitary fibrous tumor: a case series identifying pathological adverse factors-implications for risk stratification and classification|url=https://pubmed.ncbi.nlm.nih.gov/31529158|journal=Virchows Archiv: An International Journal of Pathology|volume=476|issue=4|pages=597–607|doi=10.1007/s00428-019-02660-3|issn=1432-2307|pmid=31529158}}</ref><ref name=":4" />
 +
|No
 +
|Single base pair substitution have been identified in exon 5 or exon 6 of TP53. <ref name=":3" /> Mutations of TP53 have been associated with malignant and dedifferentiated SFTs.<ref>{{Cite journal|last=Dagrada|first=Gian P.|last2=Spagnuolo|first2=Rosalin D.|last3=Mauro|first3=Valentina|last4=Tamborini|first4=Elena|last5=Cesana|first5=Luca|last6=Gronchi|first6=Alessandro|last7=Stacchiotti|first7=Silvia|last8=Pierotti|first8=Marco A.|last9=Negri|first9=Tiziana|date=2015-08|title=Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation|url=https://pubmed.ncbi.nlm.nih.gov/26022454|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=28|issue=8|pages=1074–1083|doi=10.1038/modpathol.2015.70|issn=1530-0285|pmid=26022454}}</ref><ref>{{Cite journal|last=Kurisaki-Arakawa|first=Aiko|last2=Akaike|first2=Keisuke|last3=Hara|first3=Kieko|last4=Arakawa|first4=Atsushi|last5=Takahashi|first5=Michiko|last6=Mitani|first6=Keiko|last7=Yao|first7=Takashi|last8=Saito|first8=Tsuyoshi|date=2014-11|title=A case of dedifferentiated solitary fibrous tumor in the pelvis with TP53 mutation|url=https://pubmed.ncbi.nlm.nih.gov/25015562|journal=Virchows Archiv: An International Journal of Pathology|volume=465|issue=5|pages=615–621|doi=10.1007/s00428-014-1625-3|issn=1432-2307|pmid=25015562}}</ref><ref>{{Cite journal|last=Nonaka|first=Haruna|last2=Kandori|first2=Shuya|last3=Nitta|first3=Satoshi|last4=Shiga|first4=Masanobu|last5=Nagumo|first5=Yoshiyuki|last6=Kimura|first6=Tomokazu|last7=Kawahara|first7=Takashi|last8=Negoro|first8=Hiromitsu|last9=Hoshi|first9=Akio|date=2021|title=Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study|url=https://pubmed.ncbi.nlm.nih.gov/35004271|journal=Frontiers in Oncology|volume=11|pages=736969|doi=10.3389/fonc.2021.736969|issn=2234-943X|pmc=8727594|pmid=35004271}}</ref>
 +
|-
 +
|APAF1
 +
|Other
 +
|66.7%
 +
|
 +
|
 +
|No
 +
|Yes<ref name=":1" />
 +
|No
 +
|Alteration of APAF1 results in gain of a stop codon. The gene is inactivated by DNA methylation of the promoter region. Decreased APAF1 is considered to lead to inhibition of apoptosis.  This alteration and decreased APAF1 mRNA expression was observed in metastatic SFT.
 +
|}
 
==Epigenomic Alterations==
 
==Epigenomic Alterations==
−
Put your text here
+
Not Applicable
 
==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
−
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>
 
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
+
|NAB2::STAT6; Activating mutation
−
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
+
|EGR Pathway
−
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
+
|Increased activation of EGR1
−
|-
 
−
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
 
−
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
 
−
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 
−
|-
 
−
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
 
−
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
 
−
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
 
 
|}
 
|}
 
==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
−
Put your text here
+
Ancillary studies such as immunohistochemistry and molecular tests are useful in differentiating soft tissue tumors. SFTs have historically been diagnosed by morphology and strong diffuse CD34 positivity. Additional immunohistochemical phenotype previously used for identification included expression of Bcl2, CD99, and vimentin and absence of expression of epithelial, muscle, and neural markers. However, the introduction of STAT6 (signal transducer and activator of transcription 6) immunostain now dominates due to its high sensitivity and specificity. STAT6 expression is demonstrated by nuclear staining. Next generation sequencing (NGS) using mRNA is also highly useful in detecting the NAB2::STAT6 fusion. Breakapart fluorescence in situ hybridization (FISH) probe for STAT6 can detect rearrangement of this gene.  In the context of SFT, the rearrangement of the ''STAT6'' gene is highly suggestive for the presence of ''NAB2-STAT6'' fusion. [https://pubmed.ncbi.nlm.nih.gov/27802414/ A dual color dual fusion probe targeting both genes would be a direct confirmation for ''NAB2-STAT6'' fusion.]
 
==Familial Forms==
 
==Familial Forms==
−
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
+
Not Applicable
 
==Additional Information==
 
==Additional Information==
 
Put your text here
 
Put your text here
Line 189: Line 199:
 
==Notes==
 
==Notes==
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 +
<references />

Latest revision as of 17:48, 2 May 2024

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click nearby within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

Reba Daniel and Shashi Shetty

WHO Classification of Disease

Structure Disease
Book WHO Classification of Soft Tissue and Bone Tumours (5th Edition)
Category Soft tissue tumours
Family Fibroblastic and myofibroblastic tumours
Type Solitary fibrous tumour
Subtype(s) None

Definition / Description of Disease

Solitary fibrous tumor (SFT) is a mesenchymal spindle cell neoplasm that can develop at any site in the body, including soft tissue, visceral organs, bone, etc.  It was first described by Klemperer and Rabin[1] in 1992 as a tumor of the pleura. However, since then this entity has been increasingly described from extrapleural sites. A morphologic clue to the diagnosis is the distinctive branching “staghorn” vessels. SFT is characterized by NAB2::STAT6 fusion resulting from a small paracentric inversion at chromosome 12q13.

Synonyms / Terminology

Formerly SFTs were categorized as hemangiopericytomas.

Epidemiology / Prevalence

SFT occurs most commonly in adults with no gender predilection. Incidence of the tumor is highest in the age group of 40-70 years.

Clinical Features


Signs and Symptoms SFTs present as slow-growing, painless neoplasms. Clinical symptoms can be due to mass effect in the site of involvement.

e.g. Abdomen/Pelvis: abdominal distention, constipation, urinary retention

Head/Neck: Dysphonia, nasal obstruction, dysphagia

Laboratory Findings

Sites of Involvement

SFTs may occur at any site of the body. Involvement of head and neck, deep soft tissues, abdominal cavity, retroperitoneum, pelvis, bone, and visceral organs have been reported.

Morphologic Features

Morphologically, biopsy or resection specimens will show a bland spindle cell proliferation arranged haphazardly in a background of collagenous stroma. Cells contain ovoid nuclei within eosinophilic cytoplasm with indistinct cell borders. Tumors can vary in cellularity and stromal collagen. On low power, branching, “staghorn” shaped vessels can often be appreciated. Mitotic counts are usually low. Myxoid and lipomatous change have been described. SFT with adipocytic component are referred to as fat-forming (lipomatous) SFTs. There is also a variant known as giant cell rich SFT, which has the classic patternless spindle cell proliferation admixed with multinucleated giant cells. Dedifferentiated SFTs will show conventional SFT transitioning to a high-grade pleomorphic variant. Heterologous elements may be present. Standard immunophenotypic expression of CD34 and STAT6 is often lost in the dedifferentiated component.

Immunophenotype[2]

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)

Finding Marker
Positive CD34
Positive STAT6 (nuclear)
Positive BCL2 (30%)
Positive CD99 (70%)
Positive EMA (30%)
Positive Actin (20%)
Negative S100
Negative Desmin
Negative Cytokeratins

Chromosomal Rearrangements (Gene Fusions)

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
inv(12)(q13q13) 3'STAT6 / 5'NAB2[3][4][5][6][7][8] NA 55-100% Yes Unknown No Many different breakpoints in the exons and introns are associated with this fusion. Ex: NAB2ex4-STAT6ex2; NAB2ex6-STAT6ex16/17

Individual Region Genomic Gain / Loss / LOH

Not Applicable

Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes

Characteristic Chromosomal Patterns

Not Applicable

Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes

Gene Mutations (SNV / INDEL)

There are multiple genes with single nucleotide variations that have been reported only in metastatic solitary fibrous tumor tissues including TP53 and APAF1.[9]

Gene; Genetic Alteration Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) Prevalence (COSMIC / TCGA / Other) Concomitant Mutations Mutually Exclusive Mutations Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
TERT Oncogene 13-29% [10][11][12][13][14] No Yes[8][10][14][15][16] No
TP53 TSG 6.3-41%[17][9] No Yes[18][17] No Single base pair substitution have been identified in exon 5 or exon 6 of TP53. [10] Mutations of TP53 have been associated with malignant and dedifferentiated SFTs.[19][20][21]
APAF1 Other 66.7% No Yes[9] No Alteration of APAF1 results in gain of a stop codon. The gene is inactivated by DNA methylation of the promoter region. Decreased APAF1 is considered to lead to inhibition of apoptosis. This alteration and decreased APAF1 mRNA expression was observed in metastatic SFT.

Epigenomic Alterations

Not Applicable

Genes and Main Pathways Involved

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
NAB2::STAT6; Activating mutation EGR Pathway Increased activation of EGR1

Genetic Diagnostic Testing Methods

Ancillary studies such as immunohistochemistry and molecular tests are useful in differentiating soft tissue tumors. SFTs have historically been diagnosed by morphology and strong diffuse CD34 positivity. Additional immunohistochemical phenotype previously used for identification included expression of Bcl2, CD99, and vimentin and absence of expression of epithelial, muscle, and neural markers. However, the introduction of STAT6 (signal transducer and activator of transcription 6) immunostain now dominates due to its high sensitivity and specificity. STAT6 expression is demonstrated by nuclear staining. Next generation sequencing (NGS) using mRNA is also highly useful in detecting the NAB2::STAT6 fusion. Breakapart fluorescence in situ hybridization (FISH) probe for STAT6 can detect rearrangement of this gene.  In the context of SFT, the rearrangement of the STAT6 gene is highly suggestive for the presence of NAB2-STAT6 fusion. A dual color dual fusion probe targeting both genes would be a direct confirmation for NAB2-STAT6 fusion.

Familial Forms

Not Applicable

Additional Information

Put your text here

Links

(use the "Link" icon that looks like two overlapping circles at the top of the page) (Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "http://www." portion.)

References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)

Notes

*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

  1. ↑ Klemperer, Paul; et al. (1992-01). "Primary Neoplasms of the pleura. A report of five cases". American Journal of Industrial Medicine. 22 (1): 4–31. doi:10.1002/ajim.4700220103. ISSN 0271-3586. Check date values in: |date= (help)
  2. ↑ Goldblum, John R, et al. Enzinger & Weiss’s Soft Tissue Tumors. 7th ed., Philadelphia, PA, Elsevier, 2020, pp. 1133–1147.
  3. ↑ Huang, Shih‐Chiang; et al. (2016-02). "The clinicopathological significance of NAB 2‐ STAT 6 gene fusions in 52 cases of intrathoracic solitary fibrous tumors". Cancer Medicine. 5 (2): 159–168. doi:10.1002/cam4.572. ISSN 2045-7634. Check date values in: |date= (help)
  4. ↑ Chmielecki, Juliann; et al. (2013-02). "Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors". Nature Genetics. 45 (2): 131–132. doi:10.1038/ng.2522. ISSN 1061-4036. Check date values in: |date= (help)
  5. ↑ Robinson, Dan R; et al. (2013-02). "Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing". Nature Genetics. 45 (2): 180–185. doi:10.1038/ng.2509. ISSN 1061-4036. Check date values in: |date= (help)
  6. ↑ Mohajeri, Arezoo; et al. (2013-10). "Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor". Genes, Chromosomes and Cancer. 52 (10): 873–886. doi:10.1002/gcc.22083. ISSN 1045-2257. Check date values in: |date= (help)
  7. ↑ Vogels, Rob JC; et al. (2014-12). "Solitary fibrous tumor – clinicopathologic, immunohistochemical and molecular analysis of 28 cases". Diagnostic Pathology. 9 (1). doi:10.1186/s13000-014-0224-6. ISSN 1746-1596. Check date values in: |date= (help)
  8. ↑ 8.0 8.1 Akaike, Keisuke; et al. (2015-03). "Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential". Human Pathology. 46 (3): 347–356. doi:10.1016/j.humpath.2014.11.018. Check date values in: |date= (help)
  9. ↑ 9.0 9.1 9.2 Park, Hyung Kyu; et al. (2019). "Molecular changes in solitary fibrous tumor progression". Journal of Molecular Medicine (Berlin, Germany). 97 (10): 1413–1425. doi:10.1007/s00109-019-01815-8. ISSN 0946-2716. PMC 6746689. PMID 31321477.
  10. ↑ 10.0 10.1 10.2 Bahrami, Armita; et al. (2016-12). "TERT promoter mutations and prognosis in solitary fibrous tumor". Modern Pathology. 29 (12): 1511–1522. doi:10.1038/modpathol.2016.126. Check date values in: |date= (help)
  11. ↑ Liu, Xiaoli; et al. (2013-08). "Highly prevalent TERT promoter mutations in aggressive thyroid cancers". Endocrine-Related Cancer. 20 (4): 603–610. doi:10.1530/ERC-13-0210. ISSN 1351-0088. PMC 3782569. PMID 23766237. Check date values in: |date= (help)CS1 maint: PMC format (link)
  12. ↑ Killela, Patrick J.; et al. (2013-04-09). "TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal". Proceedings of the National Academy of Sciences. 110 (15): 6021–6026. doi:10.1073/pnas.1303607110. ISSN 0027-8424. PMC 3625331. PMID 23530248.CS1 maint: PMC format (link)
  13. ↑ Koelsche, Christian; et al. (2014-12). "TERT promoter hotspot mutations are recurrent in myxoid liposarcomas but rare in other soft tissue sarcoma entities". Journal of Experimental & Clinical Cancer Research. 33 (1). doi:10.1186/1756-9966-33-33. ISSN 1756-9966. Check date values in: |date= (help)
  14. ↑ 14.0 14.1 Demicco, Elizabeth G.; et al. (2018-11). "TERT promoter mutations in solitary fibrous tumour". Histopathology. 73 (5): 843–851. doi:10.1111/his.13703. ISSN 1365-2559. PMID 29985536. Check date values in: |date= (help)
  15. ↑ Park, Hyung Kyu; et al. (2019-10). "Molecular changes in solitary fibrous tumor progression". Journal of Molecular Medicine (Berlin, Germany). 97 (10): 1413–1425. doi:10.1007/s00109-019-01815-8. ISSN 1432-1440. PMC 6746689. PMID 31321477. Check date values in: |date= (help)
  16. ↑ Bahrami, Armita; et al. (2016-12). "TERT promoter mutations and prognosis in solitary fibrous tumor". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 29 (12): 1511–1522. doi:10.1038/modpathol.2016.126. ISSN 1530-0285. PMC 5731237. PMID 27562490. Check date values in: |date= (help)
  17. ↑ 17.0 17.1 Yao, Chen-Chen; et al. (2023). "Prognostic analysis of extrameningeal solitary fibrous tumor using the modified Demicco model: a clinicopathologic study of 111 Chinese cases". Frontiers in Oncology. 13: 1272090. doi:10.3389/fonc.2023.1272090. ISSN 2234-943X. PMC PMC10796168 Check |pmc= value (help). PMID 38239634 Check |pmid= value (help).CS1 maint: PMC format (link)
  18. ↑ Machado, Isidro; et al. (2020-04). "Solitary fibrous tumor: a case series identifying pathological adverse factors-implications for risk stratification and classification". Virchows Archiv: An International Journal of Pathology. 476 (4): 597–607. doi:10.1007/s00428-019-02660-3. ISSN 1432-2307. PMID 31529158. Check date values in: |date= (help)
  19. ↑ Dagrada, Gian P.; et al. (2015-08). "Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 28 (8): 1074–1083. doi:10.1038/modpathol.2015.70. ISSN 1530-0285. PMID 26022454. Check date values in: |date= (help)
  20. ↑ Kurisaki-Arakawa, Aiko; et al. (2014-11). "A case of dedifferentiated solitary fibrous tumor in the pelvis with TP53 mutation". Virchows Archiv: An International Journal of Pathology. 465 (5): 615–621. doi:10.1007/s00428-014-1625-3. ISSN 1432-2307. PMID 25015562. Check date values in: |date= (help)
  21. ↑ Nonaka, Haruna; et al. (2021). "Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study". Frontiers in Oncology. 11: 736969. doi:10.3389/fonc.2021.736969. ISSN 2234-943X. PMC 8727594 Check |pmc= value (help). PMID 35004271 Check |pmid= value (help).
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