Fibrosarcoma is a malignant fibroblastic mesenchymal neoplasm that can arise in soft tissue or bone. Contemporary evidence is strongest for the congenital/infantile fibrosarcoma subset, which commonly carries an ETV6-NTRK3 fusion and can respond to TRK inhibitors. Classic adult-type fibrosarcoma remains less directly covered by the currently cached evidence.
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name: Fibrosarcoma
creation_date: "2026-05-07T18:59:55Z"
updated_date: "2026-05-07T20:18:00Z"
category: Cancer
categories:
- Sarcoma
- Soft Tissue Sarcoma
- Rare Cancer
parents:
- fibroblastic neoplasm
- soft tissue sarcoma
disease_term:
preferred_term: fibrosarcoma
term:
id: MONDO:0005164
label: fibrosarcoma
description: >-
Fibrosarcoma is a malignant fibroblastic mesenchymal neoplasm that can arise
in soft tissue or bone. Contemporary evidence is strongest for the
congenital/infantile fibrosarcoma subset, which commonly carries an
ETV6-NTRK3 fusion and can respond to TRK inhibitors. Classic adult-type
fibrosarcoma remains less directly covered by the currently cached evidence.
synonyms:
- fibrocytic tumor
- malignant fibromatous neoplasm
- infantile fibrosarcoma
- congenital fibrosarcoma
has_subtypes:
- name: Infantile Fibrosarcoma
subtype_term:
preferred_term: infantile fibrosarcoma
term:
id: MONDO:0004557
label: congenital fibrosarcoma
description: >-
A pediatric fibrosarcoma subset, often congenital or presenting during
infancy, characterized by rapidly growing localized masses and frequent
ETV6-NTRK3 fusion.
evidence:
- reference: PMID:37576877
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Infantile fibrosarcoma (IFS) is a rare tumor in childhood characterized
by a single, localized, painless mass that grows rapidly but has a
relatively indolent biological behavior and a favorable prognosis.
explanation: >-
The abstract directly defines the infantile fibrosarcoma subtype and its
typical clinical presentation.
- name: Adult-Type Fibrosarcoma
description: >-
A fibrosarcoma pattern occurring outside infancy. Direct evidence in this
curation is limited, but recent kinase-fusion spindle-cell tumor literature
includes adult fibrosarcoma-like high-grade sarcomas within the broader
differential diagnosis.
evidence:
- reference: PMID:37782551
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
Notably, all four tumors presenting in the elderly were high-grade spindle
cell sarcomas, with adult fibrosarcoma (FS)-like, malignant peripheral
nerve sheath tumor (MPNST)-like and MPNST phenotypes.
explanation: >-
This supports the existence of adult fibrosarcoma-like morphology in a
kinase-fusion spindle-cell tumor series, but it does not by itself define
all classic adult fibrosarcoma biology.
pathophysiology:
- name: Fibroblastic Malignant Proliferation
description: >-
Fibrosarcoma originates from fibroblast-lineage cells and behaves as a
malignant neoplasm with proliferative spindle-cell growth.
cell_types:
- preferred_term: fibroblast
term:
id: CL:0000057
label: fibroblast
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
evidence:
- reference: PMID:37920823
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Fibrosarcoma, originating from fibroblast cells, represents a malignant
neoplasm that can manifest across all genders and age groups.
explanation: >-
The review abstract supports fibroblast-cell origin and malignant neoplasm
classification for fibrosarcoma.
downstream:
- target: Fusion-Driven Oncogenic Signaling
description: Recurrent fusion genes can drive tumorigenesis in fibrosarcoma subtypes
- name: Fusion-Driven Oncogenic Signaling
description: >-
Recurrent fusion genes, especially ETV6-NTRK3 in infantile fibrosarcoma,
create oncogenic kinase signaling that supports tumor growth and provides a
therapeutic target.
molecular_functions:
- preferred_term: protein tyrosine kinase activity
modifier: INCREASED
term:
id: GO:0004713
label: protein tyrosine kinase activity
evidence:
- reference: PMID:37576877
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Eighty-five percent of infantile fibrosarcomas are associated with t
(12;15) (p13;25) chromosomal translocation resulting in ETV6-NTRK3 gene
fusion, which provides the target for targeted therapy.
explanation: >-
The abstract directly links most infantile fibrosarcoma cases to the
ETV6-NTRK3 fusion and its therapeutic relevance.
- reference: PMID:37920823
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Many fusion genes underlie the pathogenic mechanisms triggering the onset
of this disease.
explanation: >-
The review abstract supports fusion genes as pathogenic drivers across
fibrosarcoma subtypes.
downstream:
- target: TRK-Inhibitor-Sensitive Tumor Maintenance
description: NTRK fusion signaling creates a targetable dependency in fusion-positive tumors
- name: TRK-Inhibitor-Sensitive Tumor Maintenance
description: >-
NTRK-fusion infantile fibrosarcoma can remain dependent on constitutive TRK
kinase signaling for tumor maintenance, making the tumor susceptible to TRK
inhibitor pharmacotherapy.
molecular_functions:
- preferred_term: protein tyrosine kinase activity
modifier: INCREASED
term:
id: GO:0004713
label: protein tyrosine kinase activity
evidence:
- reference: PMID:32784118
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Targeted neurotrophic tropomyosin receptor kinase (TRK) inhibitors offer
a highly specific therapeutic option for patients with infantile
fibrosarcoma (IFS) carrying the NTRK gene translocation.
explanation: >-
This consensus review supports a targetable TRK-dependent state in
NTRK-translocated infantile fibrosarcoma.
- reference: PMID:32784118
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
TRKI have demonstrated very rapid responses in the vast majority of
children with IFS with limited acute toxicity.
explanation: >-
Rapid clinical responses to TRK inhibitors support tumor maintenance by a
drug-sensitive TRK kinase dependency.
- name: Infantile Fibrosarcoma Tumor Microenvironment
description: >-
Single-cell RNA sequencing of infantile fibrosarcoma tumors identifies
malignant cell subtypes and tumor microenvironment interactions involving
endothelial cells and macrophages.
cell_types:
- preferred_term: endothelial cell
term:
id: CL:0000115
label: endothelial cell
- preferred_term: macrophage
term:
id: CL:0000235
label: macrophage
biological_processes:
- preferred_term: angiogenesis
modifier: ABNORMAL
term:
id: GO:0001525
label: angiogenesis
- preferred_term: inflammatory response
modifier: ABNORMAL
term:
id: GO:0006954
label: inflammatory response
evidence:
- reference: PMID:38715675
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Endothelial cells and macrophages were found to dominate the cell-cell
communication landscape within the microenvironment, promoting
tumorigenesis via multiple receptor-ligand interactions.
explanation: >-
This single-cell study directly supports endothelial and macrophage
involvement in the infantile fibrosarcoma microenvironment.
histopathology:
- name: Spindle Cell Sarcoma
finding_term:
preferred_term: spindle cell pattern
term:
id: NCIT:C53643
label: Spindle Cell Pattern
diagnostic: true
description: >-
Fibrosarcoma and fibrosarcoma-like kinase-fusion tumors show spindle-cell
sarcoma morphology.
evidence:
- reference: PMID:37782551
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Mesenchymal spindle cell tumors with kinase fusions, often presenting in
superficial or deep soft tissue locations, may rarely occur in bone.
explanation: >-
Supports spindle-cell morphology and soft-tissue presentation in the
kinase-fusion tumor spectrum overlapping fibrosarcoma-like phenotypes.
phenotypes:
- category: Musculoskeletal
name: Localized Painless Mass
frequency: FREQUENT
description: >-
Infantile fibrosarcoma often presents as a localized painless mass that
grows rapidly.
phenotype_term:
preferred_term: Localized painless soft tissue mass
term:
id: HP:0031459
label: Soft tissue neoplasm
onset:
onset_category: INFANTILE
notes: Infantile fibrosarcoma can present during infancy, including in newborns.
evidence:
- reference: PMID:37576877
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Infantile fibrosarcoma (IFS) is a rare tumor in childhood characterized
by a single, localized, painless mass that grows rapidly but has a
relatively indolent biological behavior and a favorable prognosis.
explanation: >-
The abstract directly supports localized painless rapidly growing mass as
a common infantile fibrosarcoma presentation.
- reference: PMID:37576877
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here, we report a case of IFS in a newborn with a mass in the left lower
extremity confirmed by imaging, histopathological examination, tissue FISH
testing, and high-throughput sequencing to detect gene rearrangement.
explanation: >-
The case report abstract supports newborn presentation of the localized
mass phenotype.
genetic:
- name: ETV6-NTRK3 Fusion
gene_term:
preferred_term: NTRK3
term:
id: hgnc:8033
label: NTRK3
relationship_type: SOMATIC_DRIVER
variant_origin: SOMATIC
frequency: VERY_FREQUENT
notes: >-
ETV6-NTRK3 is a recurrent somatic fusion in infantile fibrosarcoma; this
entry represents the therapeutically relevant NTRK3 side of the fusion with
ETV6 recorded in the mechanism node.
evidence:
- reference: PMID:37576877
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Eighty-five percent of infantile fibrosarcomas are associated with t
(12;15) (p13;25) chromosomal translocation resulting in ETV6-NTRK3 gene
fusion, which provides the target for targeted therapy.
explanation: >-
Directly supports the recurrent ETV6-NTRK3 fusion and approximate
frequency in infantile fibrosarcoma.
- name: ETV6-NTRK3 Fusion - ETV6 Partner
gene_term:
preferred_term: ETV6
term:
id: hgnc:3495
label: ETV6
relationship_type: SOMATIC_DRIVER
variant_origin: SOMATIC
frequency: VERY_FREQUENT
notes: >-
Dedicated representation of the ETV6 fusion partner in the recurrent
ETV6-NTRK3 translocation in infantile fibrosarcoma.
evidence:
- reference: PMID:37576877
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Eighty-five percent of infantile fibrosarcomas are associated with t
(12;15) (p13;25) chromosomal translocation resulting in ETV6-NTRK3 gene
fusion, which provides the target for targeted therapy.
explanation: >-
Directly supports ETV6 as the recurrent fusion partner in the
ETV6-NTRK3 driver fusion in infantile fibrosarcoma.
- name: Broader Kinase Fusion Spectrum
gene_term:
preferred_term: NTRK1
term:
id: hgnc:8031
label: NTRK1
relationship_type: SOMATIC_DRIVER
variant_origin: SOMATIC
notes: >-
NTRK1, NTRK3, RET, BRAF, and RAF1 fusions occur in a broader
fibrosarcoma-like spindle-cell tumor spectrum; only NTRK1 is mapped here to
avoid unsupported multi-gene encoding in a single gene descriptor.
evidence:
- reference: PMID:37782551
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The fusions spanned a large spectrum of kinase genes, including in
descending order NTRK3 (n = 6), NTRK1 (n = 4), RET (n = 2), BRAF (n = 2),
and RAF1 (n = 1).
explanation: >-
Supports NTRK1 and other kinase fusions in fibrosarcoma-like spindle-cell
tumor biology.
treatments:
- name: Surgical Resection
description: >-
Complete or conservative tumor resection is a historical standard component
of infantile fibrosarcoma management, with attention to avoiding mutilating
surgery when possible.
treatment_term:
preferred_term: surgical excision
term:
id: MAXO:0000447
label: surgical excision
evidence:
- reference: PMID:37533946
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Primary therapy involves complete surgical resection with or without
chemotherapy.
explanation: >-
The abstract states the standard role of surgery, with chemotherapy as an
optional component.
- reference: PMID:32784118
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Therapies consisted of tumour resection and/or perioperative chemotherapy
for extensive tumours.
explanation: >-
The consensus review abstract supports tumor resection and perioperative
chemotherapy as conventional treatment approaches.
- name: Chemotherapy
description: >-
Perioperative or non-surgical chemotherapy has been used for extensive
infantile fibrosarcoma, although TRK inhibitors are now an important option
in NTRK fusion-positive disease.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
evidence:
- reference: PMID:32784118
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Sixty-five patients (40% of all survivors) were treated with surgery
alone and 64 patients (39%) with surgery combined with chemotherapy.
explanation: >-
Supports chemotherapy as a common historical component of infantile
fibrosarcoma treatment.
- name: Larotrectinib
description: >-
Selective TRK-inhibitor pharmacotherapy for NTRK fusion-positive infantile
fibrosarcoma and other NTRK-fused pediatric tumors.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: Larotrectinib
term:
id: NCIT:C115977
label: Larotrectinib
target_mechanisms:
- target: TRK-Inhibitor-Sensitive Tumor Maintenance
treatment_effect: INHIBITS
description: Larotrectinib inhibits TRK kinase signaling driven by NTRK fusions.
evidence:
- reference: PMID:37576877
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Based on gene fusion targeted drug testing results, the patient was
treated with standard doses of larotrectinib, resulting in significant
mass shrinkage with no adverse effects, demonstrating the treatment effect
of targeted therapy.
explanation: >-
Case-level evidence supports larotrectinib activity in a newborn with
fusion-positive infantile fibrosarcoma.
- reference: PMID:38810175
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Radiologic review revealed objective tumor responses (OR) in 11 of 14
patients: Complete responses: two; partial responses: nine; and stable
disease: three cases.
explanation: >-
Real-world pediatric oncology data support larotrectinib responses in
NTRK-fused tumors, including soft-tissue sarcomas.
- name: Entrectinib
description: >-
TRK-inhibitor pharmacotherapy option for NTRK fusion-positive tumors,
including the NTRK-translocated infantile fibrosarcoma context.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: Entrectinib
term:
id: NCIT:C114984
label: Entrectinib
target_mechanisms:
- target: TRK-Inhibitor-Sensitive Tumor Maintenance
treatment_effect: INHIBITS
description: Entrectinib inhibits TRK kinase signaling in NTRK fusion-positive tumors.
evidence:
- reference: PMID:33258061
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
If NTRK gene fusions are detected, TRK inhibitors such as entrectinib and
larotrectinib can be used regardless of the tumor entity.
explanation: >-
This review supports entrectinib as a TRK inhibitor option when NTRK
fusions are detected.
- reference: PMID:32784118
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Targeted neurotrophic tropomyosin receptor kinase (TRK) inhibitors offer
a highly specific therapeutic option for patients with infantile
fibrosarcoma (IFS) carrying the NTRK gene translocation.
explanation: >-
This links the TRK-inhibitor class to NTRK-translocated infantile
fibrosarcoma, while the companion evidence identifies entrectinib as a
TRK inhibitor.
clinical_trials:
- name: NCT03834961
phase: PHASE_II
status: RECRUITING
description: >-
Children's Oncology Group trial of larotrectinib for previously untreated
TRK fusion pediatric solid tumors and relapsed TRK fusion leukemia.
evidence:
- reference: clinicaltrials:NCT03834961
supports: SUPPORT
snippet: >-
This phase II trial studies the side effects and how well larotrectinib
works in treating patients with previously untreated TRK fusion solid
tumors and TRK fusion acute leukemia that has come back.
explanation: >-
ClinicalTrials.gov summary supports an active larotrectinib trial for TRK
fusion pediatric solid tumors relevant to NTRK fusion-positive
fibrosarcoma.
- name: NCT05236257
phase: NOT_APPLICABLE
status: RECRUITING
description: >-
Observational comparison of larotrectinib-treated infantile fibrosarcoma
patients from SCOUT with external historical cohorts.
evidence:
- reference: clinicaltrials:NCT05236257
supports: SUPPORT
snippet: >-
This is an observational study in which data from the past of children
and young people with a specific cancer, called NTRK gene fusion positive
infantile fibrosarcoma (IFS) is studied.
explanation: >-
ClinicalTrials.gov summary directly names NTRK fusion-positive infantile
fibrosarcoma as the study population.
diagnosis:
- name: Molecular Fusion Testing
description: >-
Imaging and histopathology define the mass and spindle-cell tumor, while
FISH and high-throughput sequencing can confirm ETV6-NTRK3 rearrangement in
infantile fibrosarcoma.
evidence:
- reference: PMID:37576877
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here, we report a case of IFS in a newborn with a mass in the left lower
extremity confirmed by imaging, histopathological examination, tissue FISH
testing, and high-throughput sequencing to detect gene rearrangement.
explanation: >-
Supports a diagnostic workflow combining imaging, pathology, FISH, and
sequencing for fusion confirmation.
notes: >-
This initial curation emphasizes infantile/congenital fibrosarcoma and
NTRK-fusion-positive fibrosarcoma because those were the strongest supported
areas in the Falcon report and cached abstracts. Classic adult-type
fibrosarcoma may need additional targeted curation.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on Fibrosarcoma covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.
For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.
Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed
Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
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Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC
For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities
For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype
Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser
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Search first: PubMed, Gene Ontology, Reactome
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Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types
Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Search first: OMIM, Orphanet, HPO, PubMed
Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.
Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
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Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease
This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details
Fibrosarcoma is a malignant mesenchymal (fibroblastic) tumor diagnosis that, in contemporary practice, is best understood as a family of entities and mimics spanning classic “adult-type” fibrosarcoma patterns, congenital/infantile fibrosarcoma (CFS/IFS), and related fusion-defined fibroblastic/spindle-cell neoplasms (including sclerosing epithelioid fibrosarcoma and low-grade fibromyxoid sarcoma). A major recent trend is the use of fusion genes (notably NTRK fusions) to improve classification, diagnostics, and targeted therapy selection—particularly in IFS, where TRK inhibitors have shown high response rates and are now implemented in real-world pediatric oncology. (tang2023progressiveinsightsinto pages 3-6, tang2023progressiveinsightsinto pages 12-13)
Note: Direct retrieval of MeSH, ICD-10/ICD-11, Orphanet, and OMIM identifiers for fibrosarcoma was not available in the current tool context/evidence set; these should be populated from ontology sources (e.g., MeSH Browser, ICD-11, Orphanet, OMIM) during downstream curation.
The information in this report is derived from aggregated disease-level resources and peer-reviewed literature (reviews, clinical studies/case series, and clinical trial registry entries) rather than individual EHR records, except where case reports are explicitly discussed. (wang2023larotrectinibtreatmentfor pages 1-2, sahni2023limbsalvageof pages 5-7, NCT03834961 chunk 1)
Molecular (fusion-driven) oncogenesis is central in many fibrosarcoma-related entities: * In IFS, t(12;15)(p13;q25) leading to ETV6::NTRK3 is strongly associated with tumorigenesis and provides a direct drug target. (wang2023larotrectinibtreatmentfor pages 1-2) * Reviews emphasize that fusion genes are prevalent drivers across fibrosarcoma subtypes and are increasingly leveraged for subcategorization and targeted treatment. (tang2023progressiveinsightsinto pages 3-6)
Robust, population-level risk factor data specific to fibrosarcoma was not captured in the current evidence set. For IFS specifically, disease onset is predominantly in infancy (often congenital presentation), implying developmental/embryonal rather than lifestyle-driven risk in many cases. (wang2023larotrectinibtreatmentfor pages 1-2)
No high-confidence protective factors or gene–environment interaction evidence specific to fibrosarcoma was retrieved in the current evidence set.
Suggested HPO terms (mapping for KB curation; not all were explicitly coded in the evidence text): * Localized mass: HP:0002664 (Tumor) / HP:0100242 (Soft tissue mass) * Pain absent: HP:0030199 (Painless) (conceptual) * Rapid growth: HP:0003676 (Rapidly progressive) (conceptual)
IFS lacks a unique IHC marker; reported IHC patterns include: * Frequent vimentin positivity and often desmin/S100 negativity, with lack of a specific immunohistochemical tumor marker overall. (li2024characterizationofthe pages 1-2)
Key genes strongly implicated via recurrent fusions: * NTRK3 (ETV6::NTRK3) in IFS/CFS; a central oncogenic driver and therapeutic target. (wang2023larotrectinibtreatmentfor pages 1-2, OpenTargets Search: Fibrosarcoma,Infantile fibrosarcoma-NTRK3,NTRK1,NTRK2) * Broader kinase-fusion spectra include NTRK1, NTRK3, RET, BRAF, RAF1 across spindle-cell tumors with fibrosarcoma-like morphologies (including IFS-like and adult FS-like). (suurmeijer2024kinasefusionpositive pages 1-3)
Hallmark fusion summary (including DFSP, LGFMS/SEF context from a 2023 review): | Entity/subtype | Key fusion/alteration | Evidence/frequency | Typical age group | Clinical utility (diagnostic/therapeutic) | Key source (DOI URL) and year | |---|---|---|---|---|---| | Congenital/infantile fibrosarcoma (CFS/IFS) | ETV6::NTRK3 from t(12;15)(p13;q25) | Reported in ~85% of IFS cases; canonical defining lesion (wang2023larotrectinibtreatmentfor pages 1-2, li2024characterizationofthe pages 1-2) | Predominantly infants; most common soft-tissue sarcoma in children <1 year (wang2023larotrectinibtreatmentfor pages 1-2, li2024characterizationofthe pages 1-2) | Strong diagnostic marker; supports TRK inhibitor use such as larotrectinib in fusion-positive disease (wang2023larotrectinibtreatmentfor pages 1-2, sahni2023limbsalvageof pages 5-7) | Wang et al., Front Oncol, 2023, https://doi.org/10.3389/fonc.2023.1206833 | | Congenital/infantile fibrosarcoma (variant fusions) | EML4::NTRK3, LMNA::NTRK1, PHIP::BRAF | Reported as additional/non-canonical fusions in CFS/IFS; Tang 2023 cites case-level responses including near-complete response to crizotinib in LMNA::NTRK1 and proposed trametinib relevance for PHIP::BRAF (tang2023progressiveinsightsinto pages 3-6, tang2023progressiveinsightsinto pages 12-13) | Infants/young children (tang2023progressiveinsightsinto pages 3-6) | Helps refine diagnosis in ETV6-negative cases; suggests targeted therapy options matched to kinase alteration (tang2023progressiveinsightsinto pages 3-6, tang2023progressiveinsightsinto pages 12-13) | Tang et al., Front Cell Dev Biol, 2023, https://doi.org/10.3389/fcell.2023.1284428 | | Dermatofibrosarcoma protuberans (DFSP) | COL1A1::PDGFB | Identified in 172 cases (91.4%); described as recurrent/classic DFSP fusion (tang2023progressiveinsightsinto pages 3-6) | Not specified in provided snippet | High-value diagnostic marker; PDGFB-axis relevance for molecular classification and targeted approaches (tang2023progressiveinsightsinto pages 3-6) | Tang et al., Front Cell Dev Biol, 2023, https://doi.org/10.3389/fcell.2023.1284428 | | DFSP (alternative fusions) | COL1A2::PDGFB, COL6A3::PDGFD, EMILIN2::PDGFD, SLC2A5::BTBD7 | RNA-seq has uncovered alternative fusions beyond COL1A1::PDGFB (tang2023progressiveinsightsinto pages 3-6) | Not specified in provided snippet | Expands molecular diagnosis, especially for atypical/classic-fusion-negative DFSP (tang2023progressiveinsightsinto pages 3-6) | Tang et al., Front Cell Dev Biol, 2023, https://doi.org/10.3389/fcell.2023.1284428 | | Kinase fusion–positive spindle cell tumors (bone/soft tissue spectrum; IFS-like, adult FS-like, MPNST-like, LPFNT-like, myxoma-like) | NTRK3, NTRK1, RET, BRAF, RAF1 fusions | Combined literature series: NTRK3 n=6, NTRK1 n=4, RET n=2, BRAF n=2, RAF1 n=1; 73% occurred in patients <30 years; NTRK3 associated with high-grade morphology in 5/6 and NTRK1 with lower grade in 3/4 (suurmeijer2024kinasefusionpositive pages 1-3) | Mostly children and young adults; some older adults reported (suurmeijer2024kinasefusionpositive pages 1-3) | Fusion status aids classification, supports pan-TRK IHC/RNA sequencing workup, and identifies actionable kinase targets (suurmeijer2024kinasefusionpositive pages 1-3) | Suurmeijer et al., Genes Chromosomes Cancer, 2024, https://doi.org/10.1002/gcc.23205 | | Low-grade fibromyxoid sarcoma (LGFMS) | FUS::BBF2H7 (as reported in Tang 2023) | Listed by Tang 2023 as a key recurrent fusion in LGFMS (tang2023progressiveinsightsinto pages 12-13, tang2023progressiveinsightsinto media b1dcbf19) | Not specified in provided snippet | Important diagnostic fusion for subtype assignment (tang2023progressiveinsightsinto pages 12-13) | Tang et al., Front Cell Dev Biol, 2023, https://doi.org/10.3389/fcell.2023.1284428 | | Sclerosing epithelioid fibrosarcoma (SEF) | FUS rearrangements rare in pure SEF | Tang 2023 notes FUS rearrangements are rare in pure SEF; SEF also described as aggressive (tang2023progressiveinsightsinto pages 12-13) | Not specified in provided snippet | Molecular findings may help with differential diagnosis, but rarity limits routine fusion-based definition from provided evidence (tang2023progressiveinsightsinto pages 12-13) | Tang et al., Front Cell Dev Biol, 2023, https://doi.org/10.3389/fcell.2023.1284428 | | Fibrosarcoma-related entities overview table | Multiple subtype-defining fusions summarized in a single review table | Tang 2023 Table 1 summarizes DFSP, CFS/IFS, LGFMS and associated hallmark fusions (tang2023progressiveinsightsinto media b1dcbf19) | Mixed by subtype | Useful as a compact classification/knowledge-base curation reference (tang2023progressiveinsightsinto media b1dcbf19) | Tang et al., Front Cell Dev Biol, 2023, https://doi.org/10.3389/fcell.2023.1284428 |
Table: This table summarizes fibrosarcoma-related entities and their hallmark molecular alterations using only the supported evidence snippets. It highlights which fusions are most diagnostically informative and which currently have therapeutic implications, especially for NTRK-driven infantile fibrosarcoma.
A 2024 scRNA-seq study profiled four IFS tumors and reported: * A cellular atlas comprising 14 cell populations. * Potential novel diagnostic markers: POSTN, IGFBP2, CTHRC1. * Tumor microenvironment interactions dominated by endothelial cells and macrophages, supporting a mechanistic role for tumor–stroma/immune crosstalk. (li2024characterizationofthe pages 1-2)
No specific environmental toxin/lifestyle/infectious causal agents were retrieved in the current evidence set for fibrosarcoma.
Suggested ontology terms: * GO biological processes (suggested): GO:0001525 (angiogenesis); GO:0006954 (inflammatory response); GO:0008283 (cell population proliferation). * CL cell types (suggested): CL:0000115 (endothelial cell); CL:0000235 (macrophage).
Fibrosarcoma/IFS are soft tissue tumors; IFS often occurs in extremities and other soft tissue sites in infancy (case reports include lower extremity masses). (wang2023larotrectinibtreatmentfor pages 1-2)
Suggested UBERON terms (for KB curation): * Soft tissue: UBERON:0000479 * Lower limb: UBERON:0002101 (when extremity presentation)
No evidence in the retrieved set supports a germline inheritance pattern for fibrosarcoma/IFS; the key drivers described are tumor (somatic) fusions. (wang2023larotrectinibtreatmentfor pages 1-2)
Disease-specific population incidence/prevalence for fibrosarcoma was not directly retrieved.
However, for the broader biomarker epidemiology of NTRK fusion–positive tumors (relevant because many IFS are NTRK-fusion driven), one large series summarized in a 2025 review reported 0.30% NTRK-positive tumors overall (889/295,676), with higher frequency in children (1.34%) than adults (0.28%). (kubota2025currentmanagementof pages 1-2)
A contemporary IFS diagnostic workup described in a 2023 newborn case report included: * Imaging (MRI/CT) to define mass extent and vascular involvement. * Biopsy (e.g., ultrasound-guided fine-needle biopsy) with histopathology showing spindle-cell tumor. * Immunohistochemistry (e.g., vimentin positivity; variable results for other markers; lack of a specific marker). * Molecular confirmation with FISH demonstrating ETV6 breakage and sequencing confirming ETV6::NTRK3. (wang2023larotrectinibtreatmentfor pages 1-2)
Real-world pediatric oncology practice shows NTRK fusion testing is commonly performed via DNA/RNA NGS panels, often triggered by tumor behavior (poor response/progression/aggressiveness) or tumor type suggestive of NTRK fusions, and is required to justify TRK inhibitor use. (vince2024beyondclinicaltrials pages 1-2)
For IFS, standard care historically emphasizes surgical resection (with or without chemotherapy), with attention to avoiding mutilating surgery when possible. (orbach2020spotlightonthe pages 5-6, kubota2025currentmanagementof pages 8-9)
Suggested MAXO terms: * Surgical tumor resection: MAXO:0000468 (surgical excision) (suggested) * Chemotherapy: MAXO:0000647 (suggested)
Larotrectinib * Mechanism: TRK inhibitor targeting NTRK fusion proteins; used orally including liquid formulations for infants. (orbach2020spotlightonthe pages 5-6) * Implementation examples: * Newborn IFS treated at 20 days with oral larotrectinib showed significant tumor shrinkage without adverse effects in a case report. (wang2023larotrectinibtreatmentfor pages 1-2) * Limb-salvage case achieved complete response at 8 months. (sahni2023limbsalvageof pages 5-7)
Entrectinib * Discussed as an orally available selective inhibitor targeting NTRK/ROS1/ALK; clinical trial analyses show activity in NTRK fusion–positive tumors. (orbach2020spotlightonthe pages 9-9)
Suggested MAXO terms: * Targeted therapy: MAXO:0000749 (targeted molecular therapy) (suggested)
No primary prevention or population screening strategies specific to fibrosarcoma/IFS were retrieved. Given the rarity and early-life onset of IFS, prevention is largely not established; secondary prevention is focused on timely diagnosis, molecular testing, and referral for appropriate multimodal therapy. (vince2024beyondclinicaltrials pages 1-2, NCT03834961 chunk 1)
Comparative oncology evidence in the retrieved set includes canine fibrosarcoma proteomic work indicating that fibrosarcoma/soft tissue sarcoma biology can be studied in companion animals, but detailed cross-species natural history for “fibrosarcoma” per se was not extracted in the current evidence snippets. (tang2023progressiveinsightsinto pages 3-6)
No dedicated in vivo genetic model organism data for fibrosarcoma was retrieved in the current evidence set.
A review table summarizing fibrosarcoma-related entities and hallmark fusion genes is available (Table 1 from Tang et al., 2023). (tang2023progressiveinsightsinto media b1dcbf19)
References
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