Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive fibroblastic tumor of the dermis and subcutaneous tissue characterized by the COL1A1-PDGFB fusion gene. This translocation, typically t(17;22)(q22;q13), results in constitutive PDGF-BB expression driving autocrine PDGFR-beta signaling. DFSP exemplifies the success of targeted therapy in fusion-driven cancers, as the PDGFR inhibitor imatinib is highly effective for unresectable or metastatic disease. While locally aggressive with high recurrence rates after incomplete excision, DFSP rarely metastasizes. Wide local excision with Mohs micrographic surgery achieves the best local control. DFSP occurs in adults of all ages, most commonly on the trunk.
Ask a research question about Dermatofibrosarcoma Protuberans. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Dermatofibrosarcoma Protuberans
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-05-08T20:47:43Z'
description: >-
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive fibroblastic
tumor of the dermis and subcutaneous tissue characterized by the COL1A1-PDGFB
fusion gene. This translocation, typically t(17;22)(q22;q13), results in
constitutive PDGF-BB expression driving autocrine PDGFR-beta signaling. DFSP
exemplifies the success of targeted therapy in fusion-driven cancers, as the
PDGFR inhibitor imatinib is highly effective for unresectable or metastatic
disease. While locally aggressive with high recurrence rates after incomplete
excision, DFSP rarely metastasizes. Wide local excision with Mohs micrographic
surgery achieves the best local control. DFSP occurs in adults of all ages,
most commonly on the trunk.
categories:
- Sarcoma
- Skin Cancer
- Rare Cancer
parents:
- skin neoplasm
has_subtypes:
- name: Classic DFSP
description: >-
The typical form presenting as a slow-growing, indurated plaque that
progressively develops a multinodular or protuberant appearance. Low
metastatic potential.
- name: Fibrosarcomatous DFSP
description: >-
A higher-grade variant with fibrosarcomatous transformation in approximately
10-15% of cases. Associated with increased local recurrence and metastatic
potential. May lose imatinib sensitivity.
evidence:
- reference: PMID:38841035
reference_title: "Metastatic Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans With Lung Metastasis: A Case Report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In this study, we report a case of DFSP with fibrosarcomatous
transformation, a rare but well-known phenomenon encountered in DFSP
that is correlated with an increased risk of adverse outcomes in
patients with DFSP.
explanation: >-
Directly supports fibrosarcomatous transformation as a recognized
adverse-prognosis variant of DFSP.
- name: Pigmented DFSP (Bednar Tumor)
description: >-
A variant containing melanin-producing dendritic cells, giving the tumor
a pigmented appearance. Shares the same COL1A1-PDGFB fusion and clinical
behavior as classic DFSP.
pathophysiology:
- name: COL1A1-PDGFB Fusion Oncogene
description: >-
The t(17;22)(q22;q13) translocation or supernumerary ring chromosomes
containing material from chromosomes 17 and 22 fuse the COL1A1 gene to
PDGFB. This places PDGFB under control of the highly active COL1A1 promoter,
resulting in constitutive expression of a functional PDGF-BB growth factor.
evidence:
- reference: PMID:17397592
reference_title: "[Dermatofibrosarcoma protuberans]."
supports: SUPPORT
snippet: "The demonstration of the oncogenic power of the translocation COL1A1-PDGFB in DFSP has allowed the successful introduction of drug therapy with antagonists of the PDGFB receptor for metastatic or locally advanced cases."
explanation: "Supports the COL1A1-PDGFB translocation as a driver in DFSP."
biological_processes:
- preferred_term: positive regulation of transcription by RNA polymerase II
modifier: ABNORMAL
term:
id: GO:0045944
label: positive regulation of transcription by RNA polymerase II
locations:
- preferred_term: skin of body
term:
id: UBERON:0002097
label: skin of body
downstream:
- target: Autocrine PDGFR Signaling
description: PDGF-BB secretion activates PDGFR-beta on tumor cells
- name: Autocrine PDGFR Signaling
description: >-
Tumor cells secrete mature PDGF-BB which binds to PDGFR-beta on the same
or neighboring tumor cells, creating an autocrine/paracrine growth loop.
PDGFR-beta activation drives proliferation through the MAPK and PI3K
pathways. This signaling can be blocked by imatinib.
evidence:
- reference: PMID:17397592
reference_title: "[Dermatofibrosarcoma protuberans]."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The demonstration of the oncogenic power of the translocation
COL1A1-PDGFB in DFSP has allowed the successful introduction of
drug therapy with antagonists of the PDGFB receptor for metastatic
or locally advanced cases.
explanation: >-
Directly supports PDGFB receptor signaling as the actionable
oncogenic pathway downstream of the COL1A1-PDGFB fusion in DFSP.
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
downstream:
- target: Sustained Proliferation
description: PDGFR activation drives continuous cell division
- name: Sustained Proliferation
description: >-
Constitutive PDGFR-beta signaling drives sustained proliferation of dermal
fibroblasts. The infiltrative growth pattern with finger-like projections
into subcutaneous fat explains the high local recurrence rate after
incomplete excision.
biological_processes:
- preferred_term: MAPK cascade
modifier: INCREASED
term:
id: GO:0000165
label: MAPK cascade
histopathology:
- name: Dermal Soft Tissue Sarcoma
finding_term:
preferred_term: Dermatofibrosarcoma Protuberans
term:
id: NCIT:C4683
label: Dermatofibrosarcoma Protuberans
frequency: VERY_FREQUENT
description: Dermatofibrosarcoma protuberans is a low- to intermediate-grade dermal soft tissue malignant tumor.
evidence:
- reference: PMID:38841035
reference_title: "Metastatic Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans With Lung Metastasis: A Case Report."
supports: SUPPORT
snippet: "Dermatofibrosarcoma protuberans (DFSP) is a low- to intermediate-grade dermal"
explanation: Abstract describes DFSP as a low- to intermediate-grade dermal soft tissue malignancy.
phenotypes:
- category: Dermatologic
name: Skin Nodule
frequency: VERY_FREQUENT
diagnostic: true
description: >-
A slow-growing dermal plaque or nodule that progressively enlarges over
months to years. The tumor often has a protuberant or multinodular surface
and may be skin-colored, red-brown, or violaceous.
phenotype_term:
preferred_term: Skin nodule
term:
id: HP:0200036
label: Skin nodule
evidence:
- reference: PMID:17397592
reference_title: "[Dermatofibrosarcoma protuberans]."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
Dermatofibrosarcoma protuberans (DFSP) is a soft tissue neoplasm of
intermediate malignancy that is initially localized to the skin from
where it can invade deep structures (fat, fascia, muscle and bone).
explanation: >-
Supports the cutaneous origin of DFSP; the snippet does not directly
specify nodule morphology.
- category: Dermatologic
name: Soft Tissue Mass
frequency: FREQUENT
description: >-
As the tumor grows, it may form a larger soft tissue mass extending into
subcutaneous tissues. The tumor has an infiltrative growth pattern.
phenotype_term:
preferred_term: Soft tissue neoplasm
term:
id: HP:0031459
label: Soft tissue neoplasm
evidence:
- reference: PMID:38841035
reference_title: "Metastatic Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans With Lung Metastasis: A Case Report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
On gross examination, DFSP usually manifests as a white or yellow
soft tissue mass with a smooth outer surface and poor circumscription.
explanation: >-
Directly supports presentation as a soft tissue mass with poor
circumscription, consistent with its infiltrative dermal/subcutaneous
growth pattern.
- category: Systemic
name: Local Recurrence
frequency: FREQUENT
description: >-
High rates of local recurrence (20-50%) occur after inadequate excision
due to the infiltrative growth pattern with subclinical extension beyond
visible tumor margins.
evidence:
- reference: PMID:38841035
reference_title: "Metastatic Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans With Lung Metastasis: A Case Report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Dermatofibrosarcoma protuberans (DFSP) is a low- to intermediate-grade
dermal soft tissue malignant tumor (sarcoma) with a high local
recurrence rate but low metastatic potential.
explanation: >-
Directly identifies high local recurrence as a characteristic
clinical feature of DFSP.
biochemical:
- name: COL1A1-PDGFB Fusion Detection
notes: >-
FISH or RT-PCR detection of the COL1A1-PDGFB fusion is diagnostic.
Cytogenetic analysis may show ring chromosomes containing the fusion.
evidence:
- reference: PMID:38841035
reference_title: "Metastatic Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans With Lung Metastasis: A Case Report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Molecularly, DFSP is defined by a COL1A1-PDGFB fusion transcript
that is targetable with imatinib therapy.
explanation: >-
Directly supports COL1A1-PDGFB fusion transcript detection as the
defining molecular diagnostic feature of DFSP.
- name: CD34 Expression
notes: >-
CD34 immunohistochemistry is diffusely positive in classic DFSP and
helps distinguish from dermatofibroma (CD34 negative). CD34 may be
lost in fibrosarcomatous areas.
evidence:
- reference: PMID:38841035
reference_title: "Metastatic Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans With Lung Metastasis: A Case Report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
DFSP is characterized by uniform spindle cell fascicles arranged
classically in a storiform pattern and by CD34 immunoreactivity.
explanation: >-
Directly supports diffuse CD34 immunoreactivity as a characteristic
immunohistochemical feature of DFSP.
genetic:
- name: COL1A1-PDGFB Fusion
association: Somatic Fusion Oncogene
notes: >-
The t(17;22)(q22;q13) translocation or ring chromosomes create the
COL1A1-PDGFB fusion in >90% of cases. This fusion is both diagnostic
and represents the primary therapeutic target for imatinib.
evidence:
- reference: PMID:17950782
reference_title: "Dermatofibrosarcoma protuberans COL1A1-PDGFB fusion is identified in virtually all dermatofibrosarcoma protuberans cases when investigated by newly developed multiplex reverse transcription polymerase chain reaction and fluorescence in situ hybridization assays."
supports: SUPPORT
snippet: "fusion of exon 2 of PDGFB to various exons of the COL1A1 gene."
explanation: "Abstract describes the COL1A1-PDGFB fusion underlying DFSP."
treatments:
- name: Wide Local Excision
description: >-
Surgery with wide margins (2-4 cm) or Mohs micrographic surgery is the
primary treatment. Mohs technique provides margin control and is associated
with the lowest recurrence rates.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
evidence:
- reference: PMID:17397592
reference_title: "[Dermatofibrosarcoma protuberans]."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Treatment of localized disease consists in complete surgical excision
of the lesion by conventional surgery with wide margins (>3 cm) or
by micrographic Mohs surgery.
explanation: >-
Directly supports wide-margin surgical excision (or Mohs micrographic
surgery) as the standard primary treatment of localized DFSP.
- name: Imatinib Targeted Therapy
description: >-
Imatinib mesylate, a PDGFR inhibitor, is highly effective for unresectable
or metastatic DFSP. Response rates exceed 50%. Imatinib may also be used
as neoadjuvant therapy to shrink tumors before surgery. Fibrosarcomatous
transformation may confer imatinib resistance.
treatment_term:
preferred_term: targeted therapy
term:
id: NCIT:C93352
label: Targeted Therapy
therapeutic_agent:
- preferred_term: imatinib
term:
id: CHEBI:45783
label: imatinib
evidence:
- reference: PMID:17397592
reference_title: "[Dermatofibrosarcoma protuberans]."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The demonstration of the oncogenic power of the translocation
COL1A1-PDGFB in DFSP has allowed the successful introduction of
drug therapy with antagonists of the PDGFB receptor for metastatic
or locally advanced cases.
explanation: >-
Directly supports PDGFB receptor antagonism, including imatinib
targeted therapy, for metastatic or locally advanced DFSP.
- name: Radiation Therapy
description: >-
Adjuvant radiation may be considered for positive margins when re-excision
is not feasible. Primary radiation is an option for unresectable cases
not amenable to imatinib.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
evidence:
- reference: PMID:38841035
reference_title: "Metastatic Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans With Lung Metastasis: A Case Report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Treatment involves wide surgical resection, with adjuvant radiation
therapy in select cases. Radiation therapy may be employed in cases
with close or positive margins, while conventional chemotherapy has
limited utility.
explanation: >-
Directly supports adjuvant radiation therapy as an option for DFSP
with close or positive surgical margins.
disease_term:
preferred_term: dermatofibrosarcoma protuberans
term:
id: MONDO:0011934
label: dermatofibrosarcoma protuberans
classifications:
icdo_morphology:
classification_value: Sarcoma
harrisons_chapter:
- classification_value: cancer
- classification_value: solid tumor
references:
- reference: DOI:10.3389/fonc.2024.1399486
title: Hotspots and future trends of dermatofibrosarcoma protuberans
found_in:
- Dermatofibrosarcoma_Protuberans-deep-research-falcon.md
findings:
- statement: Dermatofibrosarcoma protuberans (DFSP) is a moderately malignant soft tissue sarcoma with localized infiltrative growth.
supporting_text: Dermatofibrosarcoma protuberans (DFSP) is a moderately malignant soft tissue sarcoma with localized infiltrative growth.
evidence:
- reference: DOI:10.3389/fonc.2024.1399486
reference_title: Hotspots and future trends of dermatofibrosarcoma protuberans
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Dermatofibrosarcoma protuberans (DFSP) is a moderately malignant soft tissue sarcoma with localized infiltrative growth.
explanation: Deep research cited this publication as relevant literature for Dermatofibrosarcoma Protuberans.
- reference: DOI:10.3390/cancers16183124
title: 'Dermatofibrosarcoma Protuberans: An Updated Review of the Literature'
found_in:
- Dermatofibrosarcoma_Protuberans-deep-research-falcon.md
findings:
- statement: Dermatofibrosarcoma protuberans (DFSP) is a rare proliferative condition representing skin sarcomas which is known to locally recur yet very rarely metastasizes.
supporting_text: Dermatofibrosarcoma protuberans (DFSP) is a rare proliferative condition representing skin sarcomas which is known to locally recur yet very rarely metastasizes.
evidence:
- reference: DOI:10.3390/cancers16183124
reference_title: 'Dermatofibrosarcoma Protuberans: An Updated Review of the Literature'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Dermatofibrosarcoma protuberans (DFSP) is a rare proliferative condition representing skin sarcomas which is known to locally recur yet very rarely metastasizes.
explanation: Deep research cited this publication as relevant literature for Dermatofibrosarcoma Protuberans.
- reference: DOI:10.3390/dermatopathology10010008
title: 'Rare Variants of Dermatofibrosarcoma Protuberans: Clinical, Histologic, and Molecular Features and Diagnostic Pitfalls'
found_in:
- Dermatofibrosarcoma_Protuberans-deep-research-falcon.md
findings:
- statement: Dermatofibrosarcoma protuberans (DFSP) is a dermal malignant mesenchymal tumor.
supporting_text: Dermatofibrosarcoma protuberans (DFSP) is a dermal malignant mesenchymal tumor.
evidence:
- reference: DOI:10.3390/dermatopathology10010008
reference_title: 'Rare Variants of Dermatofibrosarcoma Protuberans: Clinical, Histologic, and Molecular Features and Diagnostic Pitfalls'
supports: SUPPORT
evidence_source: OTHER
snippet: Dermatofibrosarcoma protuberans (DFSP) is a dermal malignant mesenchymal tumor.
explanation: Deep research cited this publication as relevant literature for Dermatofibrosarcoma Protuberans.
- reference: DOI:10.3390/jcm13061798
title: 'The Role of Postoperative Radiotherapy in the Management of Dermatofibrosarcoma Protuberans: A Multidisciplinary Systematic Review'
found_in:
- Dermatofibrosarcoma_Protuberans-deep-research-falcon.md
findings:
- statement: Dermatofibrosarcoma protuberans (DFSP) is a superficial soft tissue sarcoma, and surgical excision is the first-line treatment.
supporting_text: Dermatofibrosarcoma protuberans (DFSP) is a superficial soft tissue sarcoma, and surgical excision is the first-line treatment.
evidence:
- reference: DOI:10.3390/jcm13061798
reference_title: 'The Role of Postoperative Radiotherapy in the Management of Dermatofibrosarcoma Protuberans: A Multidisciplinary Systematic Review'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Dermatofibrosarcoma protuberans (DFSP) is a superficial soft tissue sarcoma, and surgical excision is the first-line treatment.
explanation: Deep research cited this publication as relevant literature for Dermatofibrosarcoma Protuberans.
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 Dermatofibrosarcoma Protuberans 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
Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Search first: CTD, PubMed, PheGenI, GxE databases
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
Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Search first: CDC databases, WHO, PubMed, NHANES
Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON
Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Search first: PubMed, Gene Ontology, Reactome
Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
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
Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Search first: NSGC resources, ACMG guidelines, GeneReviews
Search first: Clinical guidelines, FDA approvals, PubMed
Search first: NCBI Taxonomy
Search first: VBO (Vertebrate Breed Ontology)
Search first: NCBI Gene
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
Dermatofibrosarcoma protuberans is a rare, locally aggressive dermal/superficial soft tissue sarcoma characterized by infiltrative growth in the dermis and subcutaneous fat, frequent local recurrence, and typically low metastatic potential (fionda2024theroleof pages 1-2, trinidad2023rarevariantsof pages 1-3, algarin2024cutaneousmalignanciesin pages 2-4). DFSP is molecularly defined in most cases by a COL1A1::PDGFB fusion (often arising from t(17;22)) that drives PDGF/PDGFRβ (PDGFRB) signaling (trinidad2023rarevariantsof pages 1-3, ono2024establishmentandcharacterization pages 1-5, NCT00122473 chunk 2).
Recent (2023–2024) synthesis papers emphasize: (i) improved fusion detection (including NGS for atypical/cryptic fusions), (ii) more precise surgery (Mohs/slow Mohs and image-guided approaches) to reduce recurrence, and (iii) continued clinical use of imatinib for unresectable/metastatic disease, with ongoing focus on mechanisms of resistance and alternative targeted strategies (meng2024hotspotsandfuture pages 10-12, ono2024establishmentandcharacterization pages 1-5, NCT00243191 chunk 1).
DFSP is a superficial sarcoma involving dermis and subcutaneous fat and rarely muscle/fascia (fionda2024theroleof pages 1-2). It tends to present as a slow-growing plaque or firm nodule that may become protuberant over time (algarin2024cutaneousmalignanciesin pages 2-4, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4).
Direct abstract quote (primary pathology review, 2023): - “Dermatofibrosarcoma protuberans (DFSP) is a dermal malignant mesenchymal tumor. Most variants are associated with a high risk of local recurrence and a low risk of metastasis.” (Trinidad et al., Dermatopathology, 2023-01-29; DOI: 10.3390/dermatopathology10010008; URL: https://doi.org/10.3390/dermatopathology10010008) (trinidad2023rarevariantsof pages 1-3)
Evidence retrieved in this run supports: - MONDO: MONDO:0011934 (OpenTargets Search: Dermatofibrosarcoma protuberans) - MeSH concept used by ClinicalTrials.gov browsing: “Dermatofibrosarcoma” (MeSH term) (NCT00243191 chunk 1, NCT00122473 chunk 2)
Not available in the retrieved evidence set (therefore not asserted here): OMIM, Orphanet, ICD-10/ICD-11 codes, MeSH tree identifiers.
The information in this report is derived from: - Aggregated disease-level resources and analyses (e.g., SEER population-based registry) (kreicher2016incidenceandsurvival pages 4-6) - Systematic reviews and narrative reviews (2023–2024 prioritized) (meng2024hotspotsandfuture pages 10-12, fionda2024theroleof pages 1-2, trinidad2023rarevariantsof pages 1-3) - ClinicalTrials.gov trial records (interventional trials of imatinib) (NCT00243191 chunk 1, NCT00084630 chunk 1) - Preclinical model development (patient-derived DFSP cell line) (ono2024establishmentandcharacterization pages 1-5)
The dominant etiologic driver is a tumor-specific rearrangement that places PDGFB under control of the COL1A1 promoter, generating COL1A1::PDGFB, producing functional PDGF ligand and enabling autocrine signaling (trinidad2023rarevariantsof pages 1-3, NCT00122473 chunk 2, ono2024establishmentandcharacterization pages 1-5). This supports PDGFR pathway dependence and explains sensitivity to PDGFR inhibition in fusion-positive disease (ono2024establishmentandcharacterization pages 1-5, meng2024hotspotsandfuture pages 10-12).
Direct abstract quote (clinical trial background citation in record): - “The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB.” (Shimizu et al., Cancer Research, 1999; cited within the ClinicalTrials.gov record) (NCT00122473 chunk 2)
High-quality, exposure-based risk factors (environmental/occupational) were not identified in the retrieved evidence set. Population patterns (sex/race/age) are addressed in Epidemiology below.
No protective factors or gene–environment interactions were identified in the retrieved evidence set.
Suggested phenotype mappings are provided in the injected artifact below.
| Feature | Description (include age of onset/course/frequency when available) | Suggested HPO term(s) | Suggested UBERON term(s) for anatomical site | Notes | Citation (pqac IDs) |
|---|---|---|---|---|---|
| Slow-growing plaque or firm nodule | Typical presentation is a slow-growing, firm, flesh-colored to red plaque or multilobular nodule; most often diagnosed in young to middle-aged adults, especially ages 20–59 years, with peak incidence between the 2nd and 5th decades | Slow-growing cutaneous nodule; Skin plaque; HP:0001482 Nodular skin lesion; best-effort: Slow progression | UBERON:0002097 skin of trunk; UBERON:0000974 integumental system | Common first clinical manifestation; often initially asymptomatic | (fionda2024theroleof pages 1-2, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4, algarin2024cutaneousmalignanciesin pages 2-4, ono2024establishmentandcharacterization pages 1-5) |
| Protuberant tumor mass | Classic DFSP presents as an indurated tumor nodule that protrudes above the skin surface; lesions may evolve from plaque-like to bulky protuberant masses over years | HP:0001482 Nodular skin lesion; best-effort: Protruding skin mass | UBERON:0001003 skin | “Protuberans” refers to the raised/exophytic morphology | (trinidad2023rarevariantsof pages 1-3, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
| Preprotuberant non-bulging plaque stage | Some cases remain nonprotuberant plaques for a mean of ~7 years before becoming nodular/protuberant | Skin plaque; best-effort: Insidious onset; best-effort: Delayed progression | UBERON:0001003 skin | Important source of delayed diagnosis/misdiagnosis | (jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
| Pain and ulceration in progressive lesions | Although often asymptomatic initially, progression can lead to pain and ulceration | HP:0012531 Pain; HP:0001070 Skin ulcer | UBERON:0001003 skin | Pain is more typical of advanced/progressive lesions rather than early disease | (algarin2024cutaneousmalignanciesin pages 2-4) |
| Local recurrence | DFSP is locally aggressive and recurrence is a hallmark; reported overall recurrence ranges from 0–60% depending on treatment modality; local recurrence common after incomplete margin control, median time reported as 34 months in one review/model paper | HP:0033677 Neoplasm recurrence; best-effort: Local recurrence | UBERON:0001003 skin; UBERON:0001474 dermis; UBERON:0003568 subcutaneous tissue | Core disease-course phenotype; long-term follow-up needed | (algarin2024cutaneousmalignanciesin pages 2-4, fionda2024theroleof pages 1-2, ono2024establishmentandcharacterization pages 1-5) |
| Low metastatic potential | Distant spread is uncommon; reviews cite metastatic potential as low, often <1–5%, but risk rises with fibrosarcomatous transformation | best-effort: Rare metastasis; best-effort: Low metastatic potential | UBERON:0001003 skin | Distinguishes classic DFSP from FS-DFSP | (algarin2024cutaneousmalignanciesin pages 2-4, trinidad2023rarevariantsof pages 1-3, fionda2024theroleof pages 1-2) |
| Fibrosarcomatous transformation with worse behavior | FS-DFSP shows higher local recurrence and greater metastatic potential than classic DFSP; associated with progression and increased proliferation | best-effort: Sarcoma progression; best-effort: Increased metastatic risk | UBERON:0001474 dermis; UBERON:0003568 subcutaneous tissue | Aggressive histologic subtype; adverse prognostic factor | (trinidad2023rarevariantsof pages 1-3, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4, ono2024establishmentandcharacterization pages 1-5) |
| Honeycomb subcutaneous fat infiltration | Pathology classically shows infiltration of subcutis in a diffuse “honeycomb” pattern, reflecting tentacle-like spread through fat lobules/septa | best-effort: Subcutaneous tissue infiltration | UBERON:0003568 subcutaneous tissue; UBERON:0001474 dermis | Useful diagnostic microscopic clue and reason margins are difficult to assess | (trinidad2023rarevariantsof pages 1-3, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
| Storiform spindle-cell neoplasm | Histology shows uniform spindle-shaped cells arranged in storiform/cartwheel pattern with low atypia and low mitotic activity in classic DFSP | best-effort: Spindle cell neoplasm; best-effort: Storiform histology | UBERON:0001474 dermis | Foundational pathology phenotype for diagnosis | (trinidad2023rarevariantsof pages 1-3, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4, fionda2024theroleof pages 1-2) |
| Diffuse CD34 positivity | Classic DFSP usually demonstrates strong diffuse CD34 immunopositivity on IHC | best-effort: Abnormal CD34 expression positive | UBERON:0001474 dermis | Key diagnostic pathology finding; helps distinguish from dermatofibroma | (trinidad2023rarevariantsof pages 1-3, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4, fionda2024theroleof pages 1-2) |
| Reduced or absent CD34 in fibrosarcomatous areas | CD34 expression may be lost in FS-DFSP; one review notes only ~50% positivity in fibrosarcomatous component in one study and as low as 45% in another; CD34-negative DFSP overall reported in 9.1%, especially FS-DFSP | best-effort: Loss of CD34 expression | UBERON:0001474 dermis; UBERON:0003568 subcutaneous tissue | Important pitfall in diagnosis of high-grade transformation | (jozwik2024dermatofibrosarcomaprotuberansan pages 2-4, meng2024hotspotsandfuture pages 10-12) |
| Trunk predominance | Most common primary site is trunk; examples include ~41.7% in SEER and ~50% in review literature | best-effort: Neoplasm of trunk skin | UBERON:0002097 skin of trunk | Principal anatomic predilection | (kreicher2016incidenceandsurvival pages 1-2, fionda2024theroleof pages 1-2, ono2024establishmentandcharacterization pages 1-5) |
| Extremity involvement | Upper and lower extremities are common sites after trunk; SEER and review data place extremities collectively in roughly one-third or more of cases | best-effort: Neoplasm of limb skin | UBERON:0002101 forelimb; UBERON:0002102 hindlimb | Common anatomic distribution pattern | (kreicher2016incidenceandsurvival pages 1-2, fionda2024theroleof pages 1-2, ono2024establishmentandcharacterization pages 1-5) |
| Head and neck involvement | Head/neck tumors are less common than trunk/extremities but clinically important because margins are harder to obtain; reported around 10–16% in several series | best-effort: Neoplasm of head skin; best-effort: Neoplasm of neck skin | UBERON:0000033 head; UBERON:0000974 neck | Higher recurrence risk in anatomically constrained areas | (fionda2024theroleof pages 1-2, ono2024establishmentandcharacterization pages 1-5, kreicher2016incidenceandsurvival pages 4-6) |
| Pediatric/congenital occurrence | Most cases occur in adults, but 10–15% may arise in children/adolescents; pediatric DFSP estimated at ~6% of cases in one source; giant-cell fibroblastoma is considered a juvenile form | best-effort: Childhood onset; best-effort: Adolescent onset | UBERON:0001003 skin | Pediatric disease is uncommon but recognized | (fionda2024theroleof pages 1-2, ono2024establishmentandcharacterization pages 1-5, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
| Long interval to recurrence / chronic course | Very delayed local recurrence can occur; longest interval from excision to local recurrence reported as 16 years | HP:0033677 Neoplasm recurrence; best-effort: Chronic relapsing course | UBERON:0001003 skin | Supports prolonged surveillance after treatment | (jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
| Black patients present with larger tumors more often | Review of disparities literature notes Black patients often present with larger tumors (>3 cm) and more advanced stage at diagnosis | best-effort: Large skin neoplasm | UBERON:0001003 skin | Likely reflects delayed diagnosis/access differences rather than a distinct biologic phenotype alone | (algarin2024cutaneousmalignanciesin pages 2-4) |
| Female predominance in some registry datasets | SEER 2000–2010 showed 53.1% female and incidence 1.14 times higher than men, though some other series report slight male predominance | best-effort: Female predominance | not applicable | Population characteristic rather than patient phenotype, but useful for disease knowledge base | (kreicher2016incidenceandsurvival pages 1-2, kreicher2016incidenceandsurvival pages 4-6) |
Table: This table maps common clinical, pathologic, and disease-course features of dermatofibrosarcoma protuberans to suggested HPO and UBERON terms using recent reviews and key epidemiologic sources. It is intended as a knowledge-base ready artifact for phenotype annotation and structured curation.
While formal QoL instruments were not extracted from the retrieved texts, DFSP management has functional and cosmetic implications due to wide excision requirements and need for complex reconstruction, particularly in anatomically constrained sites (e.g., head/neck) (meng2024hotspotsandfuture pages 10-12).
A 2024 review highlights that ~4%–10% of DFSP cases may not show detectable COL1A1–PDGFB by standard methods; among these, some may have cryptic COL1A1–PDGFB and others may be associated with PDGFD (meng2024hotspotsandfuture pages 10-12). The same review discusses newer fusions discovered via sequencing approaches (e.g., COL6A3–PDGFD, MAP3K7CL–ERG, SLC2A5–BTBD7) (meng2024hotspotsandfuture pages 10-12), motivating use of RNA-seq/NGS in diagnostically difficult cases.
Causal chain (simplified): 1. Structural rearrangement → COL1A1 promoter drives PDGFB expression (trinidad2023rarevariantsof pages 1-3). 2. PDGFB ligand production → autocrine/paracrine PDGFRβ (PDGFRB) activation (NCT00243191 chunk 1, ono2024establishmentandcharacterization pages 1-5). 3. Sustained growth signaling → locally infiltrative spindle-cell tumor with “finger-like” extensions into subcutis (honeycomb infiltration), producing high local recurrence risk if margins are incomplete (meng2024hotspotsandfuture pages 10-12, trinidad2023rarevariantsof pages 1-3).
OpenTargets disease–target associations include PDGFRB and PDGFB among top associated targets for DFSP (supporting centrality of PDGF axis in disease biology and therapeutics) (OpenTargets Search: Dermatofibrosarcoma protuberans).
No validated environmental, lifestyle, or infectious causal factors were identified in the retrieved evidence set.
DFSP is characterized by a storiform spindle-cell proliferation with subclinical tentacle-like infiltration into subcutaneous fat yielding a honeycomb pattern (trinidad2023rarevariantsof pages 1-3, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4). This invasive growth pattern is the pathologic basis for: - difficulty in defining true tumor boundaries (meng2024hotspotsandfuture pages 10-12) - frequent local recurrence without complete margin control (meng2024hotspotsandfuture pages 10-12, algarin2024cutaneousmalignanciesin pages 2-4)
Immune-specific mechanistic data were not extracted from the currently retrieved evidence set.
Direct GO/CL annotations were not contained in the retrieved texts. Based on described biology, plausible candidates include: - GO (best-effort): “platelet-derived growth factor receptor signaling pathway”; “positive regulation of cell proliferation”; “extracellular matrix organization”. - CL (best-effort): “fibroblast” / “myofibroblast” lineage (supported by fibroblastic/myofibroblastic differentiation statements) (trinidad2023rarevariantsof pages 1-3).
DFSP primarily involves: - Dermis and subcutaneous fat, and rarely muscle/fascia (fionda2024theroleof pages 1-2).
Common locations in SEER (2000–2010): trunk most common, followed by upper and lower limbs; head/neck less frequent but clinically significant (kreicher2016incidenceandsurvival pages 4-6).
From SEER-18 (2000–2010): trunk 33.6%, upper limb 28.1%, lower limb 28.9%, head 8.6% in one excerpted breakdown (kreicher2016incidenceandsurvival pages 4-6).
DFSP is not described as a germline inherited disorder in the retrieved evidence; the defining COL1A1::PDGFB alteration is a somatic rearrangement in tumor tissue (trinidad2023rarevariantsof pages 1-3).
A population-based U.S. SEER-18 analysis (2000–2010) reported: - “Overall annual incidence rate of DFSP from 2000 to 2010 was 4.1 persons per million person-years.” (Kreicher et al., Dermatologic Surgery, 2016-01; DOI: 10.1097/DSS.0000000000000300; URL: https://doi.org/10.1097/dss.0000000000000300) (kreicher2016incidenceandsurvival pages 4-6) - Time trend: “Age-adjusted annual incidence of primary DFSP dropped from 4.1 in 2000 to 3.1 in 2010, but time-trend analysis showed that there was no significant change in incidence over the decade.” (kreicher2016incidenceandsurvival pages 4-6)
A 2024 systematic review of postoperative radiotherapy provides a broader range estimate: “The incidence is 0.8–4.5 cases per one million persons” (Fionda et al., Journal of Clinical Medicine, 2024-03-21; DOI: 10.3390/jcm13061798; URL: https://doi.org/10.3390/jcm13061798) (fionda2024theroleof pages 1-2).
Kreicher et al. (SEER-18, 2000–2010) reported: - “Incidence among women from 2000 to 2010 was 1.14 times higher than men” (kreicher2016incidenceandsurvival pages 4-6). - “Overall incidence rates were 3.6 for all whites … and 7.1 for all blacks …” (kreicher2016incidenceandsurvival pages 4-6). - Age-specific peak: peak incidence 7.0 per million ages 35–44 overall; among Black individuals, peak 10.4 ages 45–49 (kreicher2016incidenceandsurvival pages 4-6).
Kreicher et al. reported: - “Five-year observed survival was 96.2%… Ten-year relative survival rate was 99.1%” (kreicher2016incidenceandsurvival pages 4-6). - DFSP-attributed deaths in SEER cause-specific analysis: 92 deaths (kreicher2016incidenceandsurvival pages 4-6).
A definitive diagnosis requires skin biopsy and histology/IHC showing spindle-cell storiform tumor with CD34 positivity (fionda2024theroleof pages 1-2, trinidad2023rarevariantsof pages 1-3). Trinidad et al. (2023) explicitly summarize diagnostic hallmarks and variant spectrum in the abstract (quote shown above) (trinidad2023rarevariantsof pages 1-3).
Molecular assays used/mentioned in reviews include: - FISH and multiplex RT-PCR for COL1A1::PDGFB/PDGFB rearrangements (trinidad2023rarevariantsof pages 1-3, NCT00084630 chunk 1). - NGS/RNA sequencing for unusual or fusion-negative cases; 2024 review notes fusion-negative fraction and new fusions found via WGS/RNA-seq approaches (meng2024hotspotsandfuture pages 10-12).
Immunophenotypic pitfalls include that CD34 is not fully specific and can be negative in a subset (particularly FS-DFSP): one review notes “9.1% of DFSP patients were CD34 negative, especially FS-DFSP” (meng2024hotspotsandfuture pages 10-12). This motivates confirmatory molecular testing where morphology/IHC is ambiguous (meng2024hotspotsandfuture pages 10-12, trinidad2023rarevariantsof pages 1-3).
Surgery is first-line treatment (fionda2024theroleof pages 1-2). Two major strategies are wide local excision (WLE) and Mohs micrographic surgery (MMS).
A 2024 review synthesizing recurrence data reports: - Overall: “local recurrence after tumor resection ranges from 26% to 60%. WLE can reduce this to 0%-41%, while MMS can control it to 0%-8.3%.” (Meng et al., Frontiers in Oncology, 2024-11; DOI: 10.3389/fonc.2024.1399486; URL: https://doi.org/10.3389/fonc.2024.1399486) (meng2024hotspotsandfuture pages 10-12) - Meta-analysis (684 patients): “recurrence rates of 9.10% after WLE and 2.72% after MMS” (meng2024hotspotsandfuture pages 10-12).
A 2024 review focused on people of color also summarizes comparative recurrence: “Mohs micrographic surgery in DFSP shows a recurrence rate of only 1%, compared to 6.3–8.8% with wide local excision.” (Algarin et al., Current Dermatology Reports, 2024-06; DOI: 10.1007/s13671-024-00432-0; URL: https://doi.org/10.1007/s13671-024-00432-0) (algarin2024cutaneousmalignanciesin pages 2-4).
A 2024 multidisciplinary systematic review (papers 1989–2023) reports typical dosing and control: - “most authors reported using standard fractionation (2 Gy/die) with a wide total dose ranging from 50 to 70 Gy. The local control after postoperative radiotherapy was excellent (75–100%), with a median follow-up time of 69 months.” (Fionda et al., 2024-03-21; URL: https://doi.org/10.3390/jcm13061798) (fionda2024theroleof pages 1-2)
It concludes postoperative radiotherapy may be considered adjuvantly for risk factors (close margins, recurrence, aggressive histology) or as salvage for positive margins in multidisciplinary context (fionda2024theroleof pages 1-2).
A 2024 patient-derived DFSP cell line study summarizes real-world clinical positioning and a quantitative resistance/progression statistic: - “Although PDGF receptor inhibitor imatinib mesylate was approved for the treating patients with unresectable or metastatic DFSP, disease progression was shown in 9.2% of the patients.” (Ono et al., Human Cell, 2024-02-19 online; DOI: 10.1007/s13577-024-01030-9; URL: https://doi.org/10.1007/s13577-024-01030-9) (ono2024establishmentandcharacterization pages 1-5).
ClinicalTrials.gov records support practical implementation and biomarker integration in DFSP trials: - Neoadjuvant imatinib trial (Phase 2): NCT00243191 (completed; started 2006-05). Primary outcome included comparing phosphorylated PDGFRB pre/post short imatinib exposure (ClinicalTrials.gov; URL in record: http://www.sarctrials.org) (NCT00243191 chunk 1). - Advanced/recurrent/metastatic DFSP imatinib Phase 2 trial: NCT00084630 (completed; started 2004-05) includes objectives to measure response rate, 1-year PFS, toxicity, and correlation with PDGFB rearrangement by RT-PCR/FISH (NCT00084630 chunk 1).
A 2024 review emphasizes a key clinical caveat: “cases without fusion genes may not respond to imatinib,” motivating genetic confirmation before therapy (meng2024hotspotsandfuture pages 10-12).
A 2024 review discusses resistance and alternative targets/agents, including pazopanib and sunitinib as potential options in selected contexts, but high-quality comparative outcome evidence was not extracted in the retrieved text set (meng2024hotspotsandfuture pages 10-12, felix2024dermatofibrosarcomaprotuberansthe pages 3-4).
MAXO IDs were not present in the retrieved texts. Best-effort action labels: - Surgical excision of tumor (WLE) - Mohs micrographic surgery - Adjuvant radiotherapy - Tyrosine kinase inhibitor therapy (imatinib) - Molecular diagnostic testing (FISH/RT-PCR/NGS)
A structured summary of treatments/outcomes is provided below.
| Domain | Modality | Key details/outcomes | Evidence type | Citation |
|---|---|---|---|---|
| Diagnosis | Histology + immunohistochemistry | Definitive diagnosis is based on biopsy showing uniform spindle cells in a storiform/cartwheel pattern with diffuse dermal and subcutaneous infiltration in a honeycomb pattern; tumor cells are typically strongly CD34-positive and usually negative for factor XIIIa, desmin, D2-40, and CD163. CD34 loss is more common in fibrosarcomatous DFSP. | Review, pathology review | (trinidad2023rarevariantsof pages 1-3, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4, fionda2024theroleof pages 1-2) |
| Diagnosis | Molecular fusion testing: FISH, multiplex RT-PCR, RNA in situ hybridization | COL1A1::PDGFB rearrangement is the canonical molecular lesion; FISH and multiplex RT-PCR are established assays, and PDGFB RNA chromogenic in situ hybridization can serve as a surrogate marker. Fusion-gene detection is diagnostically useful because ~4%–10% of DFSP lack detectable canonical COL1A1::PDGFB by routine testing; some have cryptic COL1A1::PDGFB or PDGFD-associated fusions. | Review, molecular pathology | (trinidad2023rarevariantsof pages 1-3, meng2024hotspotsandfuture pages 10-12) |
| Diagnosis | NGS / RNA-seq / genomic profiling | Recent molecular work identified additional rare fusions including COL6A3-PDGFD, MAP3K7CL-ERG, and SLC2A5-BTBD7, supporting NGS/RNA-seq in diagnostically challenging or fusion-negative cases. | Review | (meng2024hotspotsandfuture pages 10-12) |
| Diagnosis | Imaging | MRI is used to define extent, especially for larger or recurrent lesions; case/model reports describe homogeneously low T2 signal with heterogeneous enhancement. Imaging is supportive rather than diagnostic. | Review, case/preclinical model report | (acosta2017dermatofibrosarcomaprotuberans pages 1-3, ono2024establishmentandcharacterization pages 1-5) |
| Treatment | Wide local excision (WLE) | Standard surgical option for localized DFSP; commonly recommended margins are 2–3 cm. Reported post-resection recurrence after WLE ranges from 0%–41%; 2023 NCCN-cited range ~1.7%–30.8%. One meta-analysis cited in review reported 9.10% recurrence after WLE. | Review, meta-analytic summary | (meng2024hotspotsandfuture pages 10-12, acosta2017dermatofibrosarcomaprotuberans pages 1-3, felix2024dermatofibrosarcomaprotuberansthe pages 3-4) |
| Treatment | Mohs micrographic surgery (MMS) | Margin-controlled surgery that examines essentially the full peripheral/deep margin and preserves tissue; recurrence is consistently lower than WLE. Reported recurrence ranges 0%–8.3%, with 2023 NCCN-cited range ~0%–6.6%; meta-analysis reported 2.72% recurrence after MMS. | Review, meta-analytic summary | (meng2024hotspotsandfuture pages 10-12, algarin2024cutaneousmalignanciesin pages 2-4, acosta2017dermatofibrosarcomaprotuberans pages 1-3) |
| Treatment | Surgery choice by site | Head/neck tumors have higher recurrence risk because adequate margins are harder to achieve; MMS or modified slow MMS is often favored in anatomically constrained areas, including face/neck and pediatric cases. | Review | (felix2024dermatofibrosarcomaprotuberansthe pages 3-4, meng2024hotspotsandfuture pages 10-12) |
| Treatment | Postoperative radiotherapy | Used adjuvantly for close margins, recurrent tumors, or aggressive histology, and as salvage for positive margins. Most reports used standard fractionation of 2 Gy/day to total 50–70 Gy; local control after postoperative RT was 75%–100% with median follow-up 69 months. | Systematic review | (fionda2024theroleof pages 1-2) |
| Treatment | Imatinib (PDGFR inhibitor) | Approved for unresectable or metastatic DFSP and rationally targeted to PDGFR signaling driven by COL1A1::PDGFB. Clinical activity is best in fusion-positive tumors; fusion-negative tumors may not respond. Across nine studies totaling 152 patients, disease progression occurred in 9.2% (14/152). Neoadjuvant and advanced-disease phase II trials are completed. | Clinical trials, review, preclinical rationale | (ono2024establishmentandcharacterization pages 1-5, NCT00243191 chunk 1, NCT00084630 chunk 1, NCT00122473 chunk 2) |
| Treatment | Other TKIs / salvage targeted therapy | Sunitinib and pazopanib are discussed as potential options in imatinib-resistant or advanced DFSP; evidence is limited and largely non-randomized or review-based. Pazopanib has antiangiogenic and PDGFR-targeting activity; sunitinib is mentioned as salvage in refractory cases. | Review, limited clinical evidence | (meng2024hotspotsandfuture pages 10-12, felix2024dermatofibrosarcomaprotuberansthe pages 3-4) |
| Treatment | Preclinical drug discovery models | New DFSP cell line NCC-DFSP5-C1 retains COL1A1::PDGFB, forms spheroids, is invasive, and enabled drug-library screening to identify anti-cancer agents inhibiting DFSP proliferation, expanding preclinical testing capacity. | Preclinical model study | (ono2024establishmentandcharacterization pages 1-5) |
| Prognosis | Local recurrence | DFSP is locally aggressive with recurrence strongly influenced by margin status and treatment modality. Reviews cite overall local recurrence after tumor resection from 26%–60%, while treatment-specific recurrence falls substantially with WLE or MMS. Fibrosarcomatous transformation increases recurrence risk. | Review, pathology review | (meng2024hotspotsandfuture pages 10-12, trinidad2023rarevariantsof pages 1-3, algarin2024cutaneousmalignanciesin pages 2-4) |
| Prognosis | Metastatic risk | Metastatic potential is low, generally reported as <1%–5% overall, but is higher in fibrosarcomatous DFSP. | Review | (algarin2024cutaneousmalignanciesin pages 2-4, trinidad2023rarevariantsof pages 1-3) |
| Prognosis | SEER survival | In SEER-18 (2000–2010), 5-year observed survival was 96.2%, 5-year relative survival 99.8%, 10-year observed survival 91.1%, and 10-year relative survival 99.1%. DFSP-specific deaths identified in SEER were 92 cases. | Registry study | (kreicher2016incidenceandsurvival pages 4-6) |
| Prognosis | Adverse prognostic factors | Worse outcomes are associated with increasing age, male sex, black race in some registry analyses, larger tumor size, limb/head location, positive or narrow margins, and fibrosarcomatous transformation. | Registry study, review | (kreicher2016incidenceandsurvival pages 4-6, criscito2016prognosticfactorstreatment pages 1-2, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
| Prognosis | Surveillance / follow-up | Long preprotuberant phases and very late local recurrence are documented; reviews note nonprotuberant plaques may persist for a mean of 7 years before becoming nodular, and recurrence has been reported up to 16 years after excision, supporting long-term surveillance. | Review | (jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
Table: This table summarizes key diagnostic approaches, treatments, and prognostic data for dermatofibrosarcoma protuberans, emphasizing quantitative outcomes such as recurrence, radiotherapy local control, and survival. It is useful as a compact evidence map linking practical management choices to the underlying literature.
Primary prevention strategies are not established in the retrieved evidence. Secondary prevention is effectively early recognition and complete excision with margin control to prevent repeated recurrences and morbidity (meng2024hotspotsandfuture pages 10-12, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4). No population screening programs were identified in the retrieved evidence.
No naturally occurring DFSP-equivalent veterinary disease was established from the retrieved evidence set in this run.
A major 2024 development is expansion of DFSP preclinical resources: - Ono et al. report establishment of a patient-derived DFSP cell line (NCC-DFSP5-C1) retaining COL1A1::PDGFB and enabling drug screening (published 2024-02; DOI: 10.1007/s13577-024-01030-9; URL: https://doi.org/10.1007/s13577-024-01030-9) (ono2024establishmentandcharacterization pages 1-5).
Direct abstract quote: “Here, we successfully established a novel DFSP cell line (NCC-DFSP5-C1) using surgically resected tumor tissue from a patient with DFSP. NCC-DFSP5-C1 cells were confirmed to carry the COL1A1-PDGFB translocation…” (ono2024establishmentandcharacterization pages 1-5).
| Item | Value | Evidence/Citation |
|---|---|---|
| Disease name | Dermatofibrosarcoma protuberans (DFSP) | (trinidad2023rarevariantsof pages 1-3, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
| MONDO ID | MONDO:0011934 | (OpenTargets Search: Dermatofibrosarcoma protuberans) |
| Disease class / brief nomenclature note | Rare dermal/superficial soft-tissue sarcoma; described as the most common dermal sarcoma and about 1% of soft-tissue sarcomas | (fionda2024theroleof pages 1-2, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
| Canonical molecularly defined form | COL1A1::PDGFB fusion-positive DFSP is the classic molecular form | (acosta2017dermatofibrosarcomaprotuberans pages 1-3, trinidad2023rarevariantsof pages 1-3) |
| Variant / synonym | Bednar tumor (pigmented DFSP variant) | (felix2024dermatofibrosarcomaprotuberansthe pages 3-4, fionda2024theroleof pages 1-2) |
| Variant / synonym | Fibrosarcomatous DFSP (FS-DFSP), an aggressive histologic variant with higher recurrence/metastatic risk | (trinidad2023rarevariantsof pages 1-3, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
| Related juvenile form | Giant-cell fibroblastoma, described as a juvenile form occurring predominantly in the first decade of life | (jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
| Other named variants | Myxoid, myoid, granular cell, sclerosing, and atrophic DFSP variants | (trinidad2023rarevariantsof pages 1-3) |
| US incidence estimate | 4.1 per million person-years overall in SEER-18 (2000-2010) | (kreicher2016incidenceandsurvival pages 4-6, kreicher2016incidenceandsurvival pages 1-2) |
| Broader reported incidence range | Approximately 0.8-4.5 cases per million across reviews/population datasets | (fionda2024theroleof pages 1-2, jozwik2024dermatofibrosarcomaprotuberansan pages 1-2) |
| Higher-incidence registry examples | Alberta Cancer Registry 9.3 per million; Denmark 5.3 per million; Sweden about 4.4 in men vs 4.0 in women per million/year | (jozwik2024dermatofibrosarcomaprotuberansan pages 1-2, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
| Sex disparity | Slight female excess in SEER-18: 53.1% female; incidence 1.14 times that of males in one large US study, though some other series report slight male predominance | (kreicher2016incidenceandsurvival pages 1-2, kreicher2016incidenceandsurvival pages 4-6, jozwik2024dermatofibrosarcomaprotuberansan pages 2-4) |
| Race disparity | Black individuals have roughly twice the incidence of White individuals in US SEER analyses; example rates 7.1 vs 3.6 per million and 6.5 vs 3.9 per million in cited datasets | (kreicher2016incidenceandsurvival pages 4-6, jozwik2024dermatofibrosarcomaprotuberansan pages 1-2) |
| Age distribution | Can occur at any age, but peaks in young to middle-aged adults; largest SEER age group 20-39 years, with peak incidence around the 4th-5th decades | (kreicher2016incidenceandsurvival pages 2-4, jozwik2024dermatofibrosarcomaprotuberansan pages 1-2) |
Table: This table summarizes the currently available standardized identifier, key names and variants, and the main epidemiologic patterns for dermatofibrosarcoma protuberans using only evidence already gathered. It is useful as a compact knowledge-base ready reference for nomenclature and population context.
References
(OpenTargets Search: Dermatofibrosarcoma protuberans): Open Targets Query (Dermatofibrosarcoma protuberans, 8 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(fionda2024theroleof pages 1-2): Bruno Fionda, Antonella Loperfido, Alessandro Di Stefani, Valentina Lancellotta, Andrea Paradisi, Martina De Angeli, Simone Cappilli, Ernesto Rossi, Anna Amelia Caretto, Tiziano Zinicola, Giovanni Schinzari, Stefano Gentileschi, Alessio Giuseppe Morganti, Agata Rembielak, Ketty Peris, and Luca Tagliaferri. The role of postoperative radiotherapy in the management of dermatofibrosarcoma protuberans: a multidisciplinary systematic review. Journal of Clinical Medicine, 13:1798, Mar 2024. URL: https://doi.org/10.3390/jcm13061798, doi:10.3390/jcm13061798. This article has 29 citations.
(jozwik2024dermatofibrosarcomaprotuberansan pages 2-4): Marcin Jozwik, Katarzyna Bednarczuk, and Zofia Osierda. Dermatofibrosarcoma protuberans: an updated review of the literature. Cancers, 16:3124, Sep 2024. URL: https://doi.org/10.3390/cancers16183124, doi:10.3390/cancers16183124. This article has 31 citations.
(trinidad2023rarevariantsof pages 1-3): Celestine M. Trinidad, Sintawat Wangsiricharoen, Victor G. Prieto, and Phyu P. Aung. Rare variants of dermatofibrosarcoma protuberans: clinical, histologic, and molecular features and diagnostic pitfalls. Dermatopathology, 10:54-62, Jan 2023. URL: https://doi.org/10.3390/dermatopathology10010008, doi:10.3390/dermatopathology10010008. This article has 37 citations.
(algarin2024cutaneousmalignanciesin pages 2-4): Yanci A. Algarin, Anika Pulumati, Jiali Tan, and Nathalie C. Zeitouni. Cutaneous malignancies in people of color: a review of dermatofibrosarcoma protuberans and kaposi sarcoma. Current Dermatology Reports, 13:217-225, Jun 2024. URL: https://doi.org/10.1007/s13671-024-00432-0, doi:10.1007/s13671-024-00432-0. This article has 1 citations.
(ono2024establishmentandcharacterization pages 1-5): Takuya Ono, Rei Noguchi, Julia Osaki, Taro Akiyama, Yuki Adachi, Naoki Kojima, Yu Toda, Suguru Fukushima, Yuki Yoshimatsu, Akihiko Yoshida, Akira Kawai, and Tadashi Kondo. Establishment and characterization of ncc-dfsp5-c1: a novel patient-derived dermatofibrosarcoma protuberans cell line. Human cell, 37:854-864, Feb 2024. URL: https://doi.org/10.1007/s13577-024-01030-9, doi:10.1007/s13577-024-01030-9. This article has 2 citations and is from a peer-reviewed journal.
(NCT00122473 chunk 2): Imatinib in Dermatofibrosarcoma Protuberans (DFSP). Dermatologic Cooperative Oncology Group. 2004. ClinicalTrials.gov Identifier: NCT00122473
(meng2024hotspotsandfuture pages 10-12): Zhen Meng, Rui Zhang, Zhihong Sun, Cong Fu, Zhiyu Li, Luying Wang, Ran Huo, and Feng Xue. Hotspots and future trends of dermatofibrosarcoma protuberans. Frontiers in Oncology, Nov 2024. URL: https://doi.org/10.3389/fonc.2024.1399486, doi:10.3389/fonc.2024.1399486. This article has 3 citations.
(NCT00243191 chunk 1): Neoadjuvant Imatinib in Dermatofibrosarcoma Protuberans. Sarcoma Alliance for Research through Collaboration. 2006. ClinicalTrials.gov Identifier: NCT00243191
(felix2024dermatofibrosarcomaprotuberansthe pages 3-4): Bryan Felix and Suma Kaza. Dermatofibrosarcoma protuberans: the impact of the surgical incision site in relation to tumor recurrence. Cureus, Dec 2024. URL: https://doi.org/10.7759/cureus.75591, doi:10.7759/cureus.75591. This article has 5 citations.
(kreicher2016incidenceandsurvival pages 4-6): Kathryn L. Kreicher, David E. Kurlander, Haley R. Gittleman, Jill S. Barnholtz-Sloan, and Jeremy S. Bordeaux. Incidence and survival of primary dermatofibrosarcoma protuberans in the united states. Dermatologic Surgery, 42:S24–S31, Jan 2016. URL: https://doi.org/10.1097/dss.0000000000000300, doi:10.1097/dss.0000000000000300. This article has 260 citations and is from a peer-reviewed journal.
(NCT00084630 chunk 1): Imatinib Mesylate in Treating Patients With Locally Recurrent or Metastatic Dermatofibrosarcoma Protuberans. National Cancer Institute (NCI). 2004. ClinicalTrials.gov Identifier: NCT00084630
(kreicher2016incidenceandsurvival pages 1-2): Kathryn L. Kreicher, David E. Kurlander, Haley R. Gittleman, Jill S. Barnholtz-Sloan, and Jeremy S. Bordeaux. Incidence and survival of primary dermatofibrosarcoma protuberans in the united states. Dermatologic Surgery, 42:S24–S31, Jan 2016. URL: https://doi.org/10.1097/dss.0000000000000300, doi:10.1097/dss.0000000000000300. This article has 260 citations and is from a peer-reviewed journal.
(acosta2017dermatofibrosarcomaprotuberans pages 1-3): Alvaro E. Acosta and Catalina Santa Vélez. Dermatofibrosarcoma protuberans. Current Treatment Options in Oncology, 18:1-14, Aug 2017. URL: https://doi.org/10.1007/s11864-017-0498-5, doi:10.1007/s11864-017-0498-5. This article has 119 citations and is from a peer-reviewed journal.
(criscito2016prognosticfactorstreatment pages 1-2): Maressa C. Criscito, Kathryn J. Martires, and Jennifer A. Stein. Prognostic factors, treatment, and survival in dermatofibrosarcoma protuberans. JAMA Dermatology, 152:1365, Dec 2016. URL: https://doi.org/10.1001/jamadermatol.2016.1886, doi:10.1001/jamadermatol.2016.1886. This article has 104 citations and is from a domain leading peer-reviewed journal.
(jozwik2024dermatofibrosarcomaprotuberansan pages 1-2): Marcin Jozwik, Katarzyna Bednarczuk, and Zofia Osierda. Dermatofibrosarcoma protuberans: an updated review of the literature. Cancers, 16:3124, Sep 2024. URL: https://doi.org/10.3390/cancers16183124, doi:10.3390/cancers16183124. This article has 31 citations.
(kreicher2016incidenceandsurvival pages 2-4): Kathryn L. Kreicher, David E. Kurlander, Haley R. Gittleman, Jill S. Barnholtz-Sloan, and Jeremy S. Bordeaux. Incidence and survival of primary dermatofibrosarcoma protuberans in the united states. Dermatologic Surgery, 42:S24–S31, Jan 2016. URL: https://doi.org/10.1097/dss.0000000000000300, doi:10.1097/dss.0000000000000300. This article has 260 citations and is from a peer-reviewed journal.