Compendium of Cancer Genome Aberrations

STBT5:Solitary fibrous tumour

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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 paracentric inversion at chromosome 12q13q13.

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]

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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)

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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. Molecular testing by next generation sequencing 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

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Links

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References

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Notes

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  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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