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 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 | EXAMPLE: Cytopenias
EXAMPLE: Lymphocytosis (low level) |
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
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| Finding | Marker |
|---|---|
| Positive (universal) | CD34 |
| Positive (universal) | STAT6 (nuclear) |
| Negative (universal) | |
| Negative (subset) |
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 | 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 |
|---|---|---|---|---|---|---|---|
| EXAMPLE:
7 |
EXAMPLE: Loss | EXAMPLE:
chr7:1-159,335,973 [hg38] |
EXAMPLE:
chr7 |
EXAMPLE: Yes | EXAMPLE: Yes | EXAMPLE: No | EXAMPLE:
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). |
| EXAMPLE:
8 |
EXAMPLE: Gain | EXAMPLE:
chr8:1-145,138,636 [hg38] |
EXAMPLE:
chr8 |
EXAMPLE: No | EXAMPLE: No | EXAMPLE: No | EXAMPLE:
Common recurrent secondary finding for t(8;21) (add reference). |
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 |
|---|---|---|---|---|
| EXAMPLE:
Co-deletion of 1p and 18q |
EXAMPLE: Yes | EXAMPLE: No | EXAMPLE: No | EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). |
Gene Mutations (SNV / INDEL)
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| 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 |
|---|---|---|---|---|---|---|---|---|
| EXAMPLE: TSG | EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add Reference) |
EXAMPLE: IDH1 R123H | EXAMPLE: EGFR amplification | EXAMPLE: Yes | EXAMPLE: No | EXAMPLE: No | EXAMPLE: 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.
Epigenomic Alterations
Not Applicable
Genes and Main Pathways Involved
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| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| NAB2::STAT6; Activating mutation | EGR Pathway | Increased activation of EGR1 |
| EXAMPLE: CDKN2A; Inactivating mutations | EXAMPLE: Cell cycle regulation | EXAMPLE: Unregulated cell division |
| EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
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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