Embryonal Rhabdomyosarcoma

MONDO:0009993 Pathograph 2 rhabdomyosarcoma

Embryonal rhabdomyosarcoma (ERMS) is the most common subtype of rhabdomyosarcoma, accounting for approximately 60-70% of cases. It typically affects children under 10 years of age with favorable primary sites including orbit, head and neck, and genitourinary tract. ERMS is characterized by loss of heterozygosity at 11p15, the locus containing IGF2 and other imprinted genes. Unlike alveolar rhabdomyosarcoma, ERMS lacks characteristic fusion genes and instead harbors a variety of mutations in RAS pathway genes. ERMS generally has a better prognosis than fusion-positive alveolar rhabdomyosarcoma, with 5-year survival rates exceeding 70% for localized disease.

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0
Mappings
0
Definitions
0
Inheritance
3
Pathophysiology
1
Histopathology
4
Phenotypes
2
Pathograph
3
Genes
3
Treatments
3
Subtypes
0
Differentials
0
Datasets
0
Trials
0
Models
8
References
1
Deep Research
🏷

Classifications

Harrison's Chapter
cancer solid tumor
ICD-O Morphology
Sarcoma
◆

Subtypes

3
Botryoid Embryonal Rhabdomyosarcoma
A variant that grows as grape-like polypoid masses in mucosal-lined hollow organs such as the bladder, vagina, and nasopharynx. Has the best prognosis among ERMS variants.
Spindle Cell Embryonal Rhabdomyosarcoma
A variant with elongated spindle-shaped cells. When arising in paratesticular region, has excellent prognosis. Some cases harbor MYOD1 mutations.
Anaplastic Embryonal Rhabdomyosarcoma
A variant with marked nuclear pleomorphism and anaplasia. Associated with TP53 mutations and carries a worse prognosis.
⚙

Pathophysiology

3
Loss of Heterozygosity at 11p15
Loss of heterozygosity (LOH) at chromosome 11p15.5 is the hallmark genetic event in ERMS, occurring in approximately 80% of cases. This region contains the imprinted IGF2 gene, and LOH results in loss of the maternal allele with duplication of the paternal allele, leading to biallelic IGF2 expression and growth factor pathway activation.
skeletal muscle myoblast link
cell population proliferation link ↑ INCREASED
Downstream
IGF2 Overexpression Loss of imprinting leads to biallelic IGF2 expression
Show evidence (1 reference)
PMID:10095436 PARTIAL
"Allelic losses of 11p15.5 are characteristic of embryonal RMS (eRMS), whereas an increase in the expression of the Igf2 gene located on 11p15.5 has regularly been observed in eRMS and alveolar RMS (aRMS)."
Supports characteristic 11p15.5 LOH and IGF2 dysregulation in ERMS, but not all detailed mechanistic/frequency specifics in this descriptor.
IGF2 Overexpression
Loss of imprinting at 11p15 results in biallelic expression of IGF2, leading to autocrine and paracrine growth stimulation through IGF1R signaling. This promotes cell proliferation and survival in ERMS cells.
regulation of cell population proliferation link ⚠ ABNORMAL
Show evidence (1 reference)
PMID:10095436 SUPPORT Human Clinical
"Allelic losses of 11p15.5 are characteristic of embryonal RMS (eRMS), whereas an increase in the expression of the Igf2 gene located on 11p15.5 has regularly been observed in eRMS and alveolar RMS (aRMS)."
Directly supports IGF2 overexpression as a characteristic consequence of 11p15.5 allelic loss in ERMS.
RAS Pathway Activation
Activating mutations in RAS pathway genes (NRAS, KRAS, HRAS) occur in approximately 27% of ERMS cases. FGFR4 mutations occur in 7-10% of cases. These mutations drive proliferation through MAPK and PI3K pathway activation.
MAPK cascade link ↑ INCREASED
Show evidence (1 reference)
PMID:34755412 SUPPORT Human Clinical
"In conclusion, RAS mutations occur in 27% of ERMS, with NRAS mutations encompassing half of the cases."
Directly supports activating RAS-family mutations (with NRAS predominating) as a common oncogenic driver subset in ERMS.
✶

Histopathology

1
Rhabdomyosarcoma VERY_FREQUENT
Rhabdomyosarcoma is a malignant tumor of mesenchymal origin.
Show evidence (1 reference)
PMID:10337369 SUPPORT
"Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin thought to"
Abstract describes rhabdomyosarcoma as a malignant tumor of mesenchymal origin.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Embryonal Rhabdomyosarcoma Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

4
Eye 1
Proptosis FREQUENT Proptosis (HP:0000520)
Show evidence (1 reference)
PMID:34755412 PARTIAL Human Clinical
"Tumor sites varied with H&N and GU sites accounting for 62% of cases."
Indirectly supports head and neck site enrichment in ERMS; it does not directly document proptosis as a presenting symptom.
Genitourinary 1
Hematuria OCCASIONAL Hematuria (HP:0000790)
Show evidence (1 reference)
PMID:34755412 PARTIAL Human Clinical
"Tumor sites varied with H&N and GU sites accounting for 62% of cases."
Indirectly supports genitourinary site enrichment in ERMS; it does not directly document hematuria as a presenting symptom.
Growth 1
Weight Loss OCCASIONAL Weight loss (HP:0001824)
Neoplasm 1
Soft Tissue Mass VERY_FREQUENT Soft tissue neoplasm (HP:0031459)
Show evidence (1 reference)
PMID:29939543 SUPPORT Human Clinical
"Rhabdomyosarcoma (RMS) is a malignant soft tissue sarcoma that is believed to originate from primitive mesenchymal cells that typically differentiate into skeletal tissue."
Supports presentation as a malignant soft tissue neoplasm for rhabdomyosarcoma, including ERMS.
🧬

Genetic Associations

3
Loss of Heterozygosity at 11p15 (Characteristic Genetic Event)
Show evidence (1 reference)
PMID:10095436 SUPPORT Human Clinical
"Allelic losses of 11p15.5 are characteristic of embryonal RMS (eRMS), whereas an increase in the expression of the Igf2 gene located on 11p15.5 has regularly been observed in eRMS and alveolar RMS (aRMS)."
Supports 11p15.5 LOH as the characteristic genetic lesion in ERMS with associated IGF2 deregulation.
RAS Pathway Mutations (Oncogenic Driver Mutations)
Show evidence (1 reference)
PMID:34755412 SUPPORT Human Clinical
"Fourteen (54%) cases had NRAS mutations, 6 (23%) had KRAS mutations, 5 (19%) had HRAS mutations, and 1 case (4%) had BRAF mutation."
Directly supports NRAS/KRAS/HRAS mutations as the dominant RAS-pathway alterations in the RAS-mutated ERMS subset.
TP53 Mutations (Tumor Suppressor Loss)
💊

Treatments

3
Multi-Agent Chemotherapy
Action: chemotherapy MAXO:0000647
Agent: vincristine ↗ actinomycin D ↗ cyclophosphamide ↗
Standard chemotherapy includes vincristine, actinomycin D, and cyclophosphamide (VAC). Treatment intensity is risk-stratified based on stage, site, and resectability. Low-risk patients may receive less intensive therapy.
Show evidence (1 reference)
PMID:32630642 SUPPORT Human Clinical
"The standard chemotherapy regimen for patients with rhabdomyosarcoma is the combination of vincristine, actinomycin, and cyclophosphamide/ifosfamide."
Directly supports the VAC (vincristine, actinomycin, cyclophosphamide) regimen as the standard multi-agent chemotherapy backbone in RMS.
Surgical Resection
Action: surgical procedure MAXO:0000004
Complete surgical resection when feasible without significant morbidity. For favorable sites like orbit, chemotherapy may allow for organ preservation.
Show evidence (1 reference)
PMID:29939543 SUPPORT Human Clinical
"treatment is multimodal, combining surgery, when feasible, to completely remove the primary tumor and chemotherapy to control disease spread"
Supports complete surgical resection as a core component of RMS multimodality therapy whenever feasible.
Radiation Therapy
Action: radiation therapy MAXO:0000014
Radiation is used for local control in patients with residual disease or unfavorable features. May be omitted in selected low-risk patients.
Show evidence (1 reference)
PMID:29939543 SUPPORT Human Clinical
"Radiotherapy is used to treat most high and intermediate-risk patients as well."
Directly supports use of radiation therapy in RMS risk-stratified management, especially for high- and intermediate-risk patients.
🔬

Biochemical Markers

1
Myogenic Markers
{ }

Source YAML

click to show 
name: Embryonal Rhabdomyosarcoma
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-05-08T23:53:01Z'
description: >-
  Embryonal rhabdomyosarcoma (ERMS) is the most common subtype of rhabdomyosarcoma,
  accounting for approximately 60-70% of cases. It typically affects children under
  10 years of age with favorable primary sites including orbit, head and neck, and
  genitourinary tract. ERMS is characterized by loss of heterozygosity at 11p15,
  the locus containing IGF2 and other imprinted genes. Unlike alveolar rhabdomyosarcoma,
  ERMS lacks characteristic fusion genes and instead harbors a variety of mutations
  in RAS pathway genes. ERMS generally has a better prognosis than fusion-positive
  alveolar rhabdomyosarcoma, with 5-year survival rates exceeding 70% for localized
  disease.
categories:
- Pediatric Cancer
- Soft Tissue Sarcoma
- Sarcoma
parents:
- rhabdomyosarcoma
has_subtypes:
- name: Botryoid Embryonal Rhabdomyosarcoma
  description: >-
    A variant that grows as grape-like polypoid masses in mucosal-lined hollow
    organs such as the bladder, vagina, and nasopharynx. Has the best prognosis
    among ERMS variants.
- name: Spindle Cell Embryonal Rhabdomyosarcoma
  description: >-
    A variant with elongated spindle-shaped cells. When arising in paratesticular
    region, has excellent prognosis. Some cases harbor MYOD1 mutations.
- name: Anaplastic Embryonal Rhabdomyosarcoma
  description: >-
    A variant with marked nuclear pleomorphism and anaplasia. Associated with
    TP53 mutations and carries a worse prognosis.
pathophysiology:
- name: Loss of Heterozygosity at 11p15
  description: >-
    Loss of heterozygosity (LOH) at chromosome 11p15.5 is the hallmark genetic
    event in ERMS, occurring in approximately 80% of cases. This region contains
    the imprinted IGF2 gene, and LOH results in loss of the maternal allele with
    duplication of the paternal allele, leading to biallelic IGF2 expression
    and growth factor pathway activation.
  evidence:
  - reference: PMID:10095436
    reference_title: "[Evidence of genetic alterations in chromosome 11 in embryonal and alveolar rhabdomyosarcoma]."
    supports: PARTIAL
    snippet: "Allelic losses of 11p15.5 are characteristic of embryonal RMS (eRMS), whereas an increase in the expression of the Igf2 gene located on 11p15.5 has regularly been observed in eRMS and alveolar RMS (aRMS)."
    explanation: "Supports characteristic 11p15.5 LOH and IGF2 dysregulation in ERMS, but not all detailed mechanistic/frequency specifics in this descriptor."
  cell_types:
  - preferred_term: skeletal muscle myoblast
    term:
      id: CL:0000515
      label: skeletal muscle myoblast
  biological_processes:
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  downstream:
  - target: IGF2 Overexpression
    description: Loss of imprinting leads to biallelic IGF2 expression
- name: IGF2 Overexpression
  description: >-
    Loss of imprinting at 11p15 results in biallelic expression of IGF2, leading
    to autocrine and paracrine growth stimulation through IGF1R signaling. This
    promotes cell proliferation and survival in ERMS cells.
  evidence:
  - reference: PMID:10095436
    reference_title: "[Evidence of genetic alterations in chromosome 11 in embryonal and alveolar rhabdomyosarcoma]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Allelic losses of 11p15.5 are characteristic of embryonal RMS (eRMS),
      whereas an increase in the expression of the Igf2 gene located on
      11p15.5 has regularly been observed in eRMS and alveolar RMS (aRMS).
    explanation: >-
      Directly supports IGF2 overexpression as a characteristic consequence
      of 11p15.5 allelic loss in ERMS.
  biological_processes:
  - preferred_term: regulation of cell population proliferation
    modifier: ABNORMAL
    term:
      id: GO:0042127
      label: regulation of cell population proliferation
- name: RAS Pathway Activation
  description: >-
    Activating mutations in RAS pathway genes (NRAS, KRAS, HRAS) occur in
    approximately 27% of ERMS cases. FGFR4 mutations occur in 7-10% of cases.
    These mutations drive proliferation through MAPK and PI3K pathway activation.
  evidence:
  - reference: PMID:34755412
    reference_title: >-
      Clinicopathologic and survival correlates of embryonal rhabdomyosarcoma
      driven by RAS/RAF mutations.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In conclusion, RAS mutations occur in 27% of ERMS, with NRAS mutations
      encompassing half of the cases.
    explanation: >-
      Directly supports activating RAS-family mutations (with NRAS
      predominating) as a common oncogenic driver subset in ERMS.
  biological_processes:
  - preferred_term: MAPK cascade
    modifier: INCREASED
    term:
      id: GO:0000165
      label: MAPK cascade
histopathology:
- name: Rhabdomyosarcoma
  finding_term:
    preferred_term: Rhabdomyosarcoma
    term:
      id: NCIT:C3359
      label: Rhabdomyosarcoma
  frequency: VERY_FREQUENT
  description: Rhabdomyosarcoma is a malignant tumor of mesenchymal origin.
  evidence:
  - reference: PMID:10337369
    reference_title: "Rhabdomyosarcoma: an overview."
    supports: SUPPORT
    snippet: "Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin thought to"
    explanation: Abstract describes rhabdomyosarcoma as a malignant tumor of mesenchymal origin.

phenotypes:
- category: Musculoskeletal
  name: Soft Tissue Mass
  frequency: VERY_FREQUENT
  diagnostic: true
  description: >-
    A soft tissue mass is the most common presentation. Location varies by
    age and subtype, with head and neck common in younger children and
    genitourinary sites in adolescents.
  phenotype_term:
    preferred_term: Soft tissue neoplasm
    term:
      id: HP:0031459
      label: Soft tissue neoplasm
  evidence:
  - reference: PMID:29939543
    reference_title: Rhabdomyosarcoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Rhabdomyosarcoma (RMS) is a malignant soft tissue sarcoma that is
      believed to originate from primitive mesenchymal cells that typically
      differentiate into skeletal tissue.
    explanation: >-
      Supports presentation as a malignant soft tissue neoplasm for
      rhabdomyosarcoma, including ERMS.
- category: Ophthalmologic
  name: Proptosis
  frequency: FREQUENT
  description: >-
    Orbital ERMS commonly presents with proptosis and is associated with
    excellent prognosis. The orbit is a favorable primary site.
  phenotype_term:
    preferred_term: Proptosis
    term:
      id: HP:0000520
      label: Proptosis
  evidence:
  - reference: PMID:34755412
    reference_title: >-
      Clinicopathologic and survival correlates of embryonal rhabdomyosarcoma
      driven by RAS/RAF mutations.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Tumor sites varied with H&N and GU sites accounting for 62% of cases.
    explanation: >-
      Indirectly supports head and neck site enrichment in ERMS; it does
      not directly document proptosis as a presenting symptom.
- category: Genitourinary
  name: Hematuria
  frequency: OCCASIONAL
  description: >-
    Bladder or prostate ERMS may present with hematuria or urinary obstruction.
  phenotype_term:
    preferred_term: Hematuria
    term:
      id: HP:0000790
      label: Hematuria
  evidence:
  - reference: PMID:34755412
    reference_title: >-
      Clinicopathologic and survival correlates of embryonal rhabdomyosarcoma
      driven by RAS/RAF mutations.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Tumor sites varied with H&N and GU sites accounting for 62% of cases.
    explanation: >-
      Indirectly supports genitourinary site enrichment in ERMS; it does
      not directly document hematuria as a presenting symptom.
- category: Constitutional
  name: Weight Loss
  frequency: OCCASIONAL
  description: >-
    Weight loss and failure to thrive may occur with advanced disease.
  phenotype_term:
    preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
biochemical:
- name: Myogenic Markers
  notes: >-
    Immunohistochemistry demonstrates myogenic markers including desmin,
    myogenin, and MyoD1. Myogenin expression is typically focal and less
    intense than in alveolar rhabdomyosarcoma.
genetic:
- name: Loss of Heterozygosity at 11p15
  association: Characteristic Genetic Event
  notes: >-
    LOH at 11p15.5 with loss of the maternal allele occurs in approximately
    80% of ERMS cases. This leads to biallelic IGF2 expression.
  evidence:
  - reference: PMID:10095436
    reference_title: "[Evidence of genetic alterations in chromosome 11 in embryonal and alveolar rhabdomyosarcoma]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Allelic losses of 11p15.5 are characteristic of embryonal RMS (eRMS),
      whereas an increase in the expression of the Igf2 gene located on
      11p15.5 has regularly been observed in eRMS and alveolar RMS (aRMS).
    explanation: >-
      Supports 11p15.5 LOH as the characteristic genetic lesion in ERMS with
      associated IGF2 deregulation.
- name: RAS Pathway Mutations
  association: Oncogenic Driver Mutations
  notes: >-
    NRAS, KRAS, and HRAS mutations occur in approximately 27% of ERMS cases
    and are mutually exclusive. These represent therapeutic targets.
  evidence:
  - reference: PMID:34755412
    reference_title: >-
      Clinicopathologic and survival correlates of embryonal rhabdomyosarcoma
      driven by RAS/RAF mutations.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Fourteen (54%) cases had NRAS mutations, 6 (23%) had KRAS mutations, 5
      (19%) had HRAS mutations, and 1 case (4%) had BRAF mutation.
    explanation: >-
      Directly supports NRAS/KRAS/HRAS mutations as the dominant RAS-pathway
      alterations in the RAS-mutated ERMS subset.
- name: TP53 Mutations
  association: Tumor Suppressor Loss
  notes: >-
    TP53 mutations occur in a subset of ERMS, particularly the anaplastic
    variant, and are associated with worse prognosis.
treatments:
- name: Multi-Agent Chemotherapy
  description: >-
    Standard chemotherapy includes vincristine, actinomycin D, and cyclophosphamide
    (VAC). Treatment intensity is risk-stratified based on stage, site, and
    resectability. Low-risk patients may receive less intensive therapy.
  treatment_term:
    preferred_term: chemotherapy
    term:
      id: MAXO:0000647
      label: chemotherapy
    therapeutic_agent:
    - preferred_term: vincristine
      term:
        id: CHEBI:28445
        label: vincristine
    - preferred_term: actinomycin D
      term:
        id: CHEBI:27666
        label: actinomycin D
    - preferred_term: cyclophosphamide
      term:
        id: CHEBI:4027
        label: cyclophosphamide
  evidence:
  - reference: PMID:32630642
    reference_title: Recent Advances and Challenges in the Treatment of Rhabdomyosarcoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The standard chemotherapy regimen for patients with rhabdomyosarcoma
      is the combination of vincristine, actinomycin, and
      cyclophosphamide/ifosfamide.
    explanation: >-
      Directly supports the VAC (vincristine, actinomycin, cyclophosphamide)
      regimen as the standard multi-agent chemotherapy backbone in RMS.
- name: Surgical Resection
  description: >-
    Complete surgical resection when feasible without significant morbidity.
    For favorable sites like orbit, chemotherapy may allow for organ preservation.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
  evidence:
  - reference: PMID:29939543
    reference_title: Rhabdomyosarcoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      treatment is multimodal, combining surgery, when feasible, to
      completely remove the primary tumor and chemotherapy to control
      disease spread
    explanation: >-
      Supports complete surgical resection as a core component of RMS
      multimodality therapy whenever feasible.
- name: Radiation Therapy
  description: >-
    Radiation is used for local control in patients with residual disease
    or unfavorable features. May be omitted in selected low-risk patients.
  treatment_term:
    preferred_term: radiation therapy
    term:
      id: MAXO:0000014
      label: radiation therapy
  evidence:
  - reference: PMID:29939543
    reference_title: Rhabdomyosarcoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Radiotherapy is used to treat most high and intermediate-risk patients
      as well.
    explanation: >-
      Directly supports use of radiation therapy in RMS risk-stratified
      management, especially for high- and intermediate-risk patients.
disease_term:
  preferred_term: embryonal rhabdomyosarcoma
  term:
    id: MONDO:0009993
    label: embryonal rhabdomyosarcoma

classifications:
  icdo_morphology:
    classification_value: Sarcoma
  harrisons_chapter:
  - classification_value: cancer
  - classification_value: solid tumor
references:
- reference: DOI:10.1002/pbc.30556
  title: "Children's Oncology Group's 2023 blueprint for research: Soft tissue sarcomas"
  found_in:
  - Embryonal_Rhabdomyosarcoma-deep-research-falcon.md
  findings:
  - statement: In the United States, approximately 850–900 children and adolescents each year are diagnosed with soft tissue sarcomas (STS).
    supporting_text: In the United States, approximately 850–900 children and adolescents each year are diagnosed with soft tissue sarcomas (STS).
    evidence:
    - reference: DOI:10.1002/pbc.30556
      reference_title: "Children's Oncology Group's 2023 blueprint for research: Soft tissue sarcomas"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: In the United States, approximately 850–900 children and adolescents each year are diagnosed with soft tissue sarcomas (STS).
      explanation: Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
- reference: DOI:10.1007/s00247-023-05596-8
  title: 'Imaging in rhabdomyosarcoma: a patient journey'
  found_in:
  - Embryonal_Rhabdomyosarcoma-deep-research-falcon.md
  findings:
  - statement: Rhabdomyosarcoma, although rare, is the most frequent soft tissue sarcoma in children and adolescents.
    supporting_text: Rhabdomyosarcoma, although rare, is the most frequent soft tissue sarcoma in children and adolescents.
    evidence:
    - reference: DOI:10.1007/s00247-023-05596-8
      reference_title: 'Imaging in rhabdomyosarcoma: a patient journey'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Rhabdomyosarcoma, although rare, is the most frequent soft tissue sarcoma in children and adolescents.
      explanation: Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
- reference: DOI:10.1200/jco.22.00409
  title: "Circulating Tumor DNA Is Prognostic in Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group"
  found_in:
  - Embryonal_Rhabdomyosarcoma-deep-research-falcon.md
  findings:
  - statement: Novel biomarkers are needed to differentiate outcomes in intermediate-risk rhabdomyosarcoma (IR RMS).
    supporting_text: Novel biomarkers are needed to differentiate outcomes in intermediate-risk rhabdomyosarcoma (IR RMS).
    evidence:
    - reference: DOI:10.1200/jco.22.00409
      reference_title: "Circulating Tumor DNA Is Prognostic in Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Novel biomarkers are needed to differentiate outcomes in intermediate-risk rhabdomyosarcoma (IR RMS).
      explanation: Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
- reference: DOI:10.20944/preprints202309.0846.v1
  title: 'Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies'
  found_in:
  - Embryonal_Rhabdomyosarcoma-deep-research-falcon.md
  findings:
  - statement: Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults.
    supporting_text: Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults.
    evidence:
    - reference: DOI:10.20944/preprints202309.0846.v1
      reference_title: 'Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults.
      explanation: Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
- reference: DOI:10.3389/fonc.2025.1546607
  title: Clinicopathological analysis of 13 patients with embryonal rhabdomyosarcoma of the female reproductive system in the Chinese population
  found_in:
  - Embryonal_Rhabdomyosarcoma-deep-research-falcon.md
  findings:
  - statement: Clinicopathological analysis of 13 patients with embryonal rhabdomyosarcoma of the female reproductive system in the Chinese population
    supporting_text: Examine clinicopathological traits and differential diagnosis of ERMS in female reproductive system.MethodsRetrospectively assess 13 patients’ data (Jan 2018 - Jun 2024, West China Second Univsity Hospital), covering clinical, histological, immunohistochemical aspects and literature review.ResultsAge 2 months - 67 years (median 21), sites in cervix (5), ovaries (3), uterus (2).
    evidence:
    - reference: DOI:10.3389/fonc.2025.1546607
      reference_title: Clinicopathological analysis of 13 patients with embryonal rhabdomyosarcoma of the female reproductive system in the Chinese population
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Examine clinicopathological traits and differential diagnosis of ERMS in female reproductive system.MethodsRetrospectively assess 13 patients’ data (Jan 2018 - Jun 2024, West China Second Univsity Hospital), covering clinical, histological, immunohistochemical aspects and literature review.ResultsAge 2 months - 67 years (median 21), sites in cervix (5), ovaries (3), uterus (2).
      explanation: Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
- reference: DOI:10.3390/cancers17193100
  title: Childhood, Adolescent and Young Adult Poor-Prognosis Rhabdomyosarcoma
  found_in:
  - Embryonal_Rhabdomyosarcoma-deep-research-falcon.md
  findings:
  - statement: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and young people.
    supporting_text: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and young people.
    evidence:
    - reference: DOI:10.3390/cancers17193100
      reference_title: Childhood, Adolescent and Young Adult Poor-Prognosis Rhabdomyosarcoma
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and young people.
      explanation: Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
- reference: DOI:10.3390/cancers18040690
  title: The Development of Novel Treatment Strategies for Rhabdomyosarcoma
  found_in:
  - Embryonal_Rhabdomyosarcoma-deep-research-falcon.md
  findings:
  - statement: Rhabdomyosarcoma is a small round-cell soft tissue tumor that occurs mainly in pediatric and adolescent/young adult (AYA) patients but also rarely in adults.
    supporting_text: Rhabdomyosarcoma is a small round-cell soft tissue tumor that occurs mainly in pediatric and adolescent/young adult (AYA) patients but also rarely in adults.
    evidence:
    - reference: DOI:10.3390/cancers18040690
      reference_title: The Development of Novel Treatment Strategies for Rhabdomyosarcoma
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Rhabdomyosarcoma is a small round-cell soft tissue tumor that occurs mainly in pediatric and adolescent/young adult (AYA) patients but also rarely in adults.
      explanation: Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
- reference: DOI:10.3390/cancers18060888
  title: Biological Advances and Current Challenges for Pediatric Rhabdomyosarcoma
  found_in:
  - Embryonal_Rhabdomyosarcoma-deep-research-falcon.md
  findings:
  - statement: Despite comprehensive and multi-modal therapy, outcomes for children and adolescents with rhabdomyosarcoma (RMS) have plateaued over the past four decades.
    supporting_text: Despite comprehensive and multi-modal therapy, outcomes for children and adolescents with rhabdomyosarcoma (RMS) have plateaued over the past four decades.
    evidence:
    - reference: DOI:10.3390/cancers18060888
      reference_title: Biological Advances and Current Challenges for Pediatric Rhabdomyosarcoma
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Despite comprehensive and multi-modal therapy, outcomes for children and adolescents with rhabdomyosarcoma (RMS) have plateaued over the past four decades.
      explanation: Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
📚

References & Deep Research

References

8
DOI:10.1002/pbc.30556
Children's Oncology Group's 2023 blueprint for research: Soft tissue sarcomas
1 finding
In the United States, approximately 850–900 children and adolescents each year are diagnosed with soft tissue sarcomas (STS).
"In the United States, approximately 850–900 children and adolescents each year are diagnosed with soft tissue sarcomas (STS)."
Show evidence (1 reference)
DOI:10.1002/pbc.30556 SUPPORT Human Clinical
"In the United States, approximately 850–900 children and adolescents each year are diagnosed with soft tissue sarcomas (STS)."
Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
DOI:10.1007/s00247-023-05596-8
Imaging in rhabdomyosarcoma: a patient journey
1 finding
Rhabdomyosarcoma, although rare, is the most frequent soft tissue sarcoma in children and adolescents.
"Rhabdomyosarcoma, although rare, is the most frequent soft tissue sarcoma in children and adolescents."
Show evidence (1 reference)
DOI:10.1007/s00247-023-05596-8 SUPPORT Human Clinical
"Rhabdomyosarcoma, although rare, is the most frequent soft tissue sarcoma in children and adolescents."
Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
DOI:10.1200/jco.22.00409
Circulating Tumor DNA Is Prognostic in Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group
1 finding
Novel biomarkers are needed to differentiate outcomes in intermediate-risk rhabdomyosarcoma (IR RMS).
"Novel biomarkers are needed to differentiate outcomes in intermediate-risk rhabdomyosarcoma (IR RMS)."
Show evidence (1 reference)
DOI:10.1200/jco.22.00409 SUPPORT Human Clinical
"Novel biomarkers are needed to differentiate outcomes in intermediate-risk rhabdomyosarcoma (IR RMS)."
Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
DOI:10.20944/preprints202309.0846.v1
Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies
1 finding
Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults.
"Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults."
Show evidence (1 reference)
DOI:10.20944/preprints202309.0846.v1 SUPPORT Human Clinical
"Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults."
Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
DOI:10.3389/fonc.2025.1546607
Clinicopathological analysis of 13 patients with embryonal rhabdomyosarcoma of the female reproductive system in the Chinese population
1 finding
Clinicopathological analysis of 13 patients with embryonal rhabdomyosarcoma of the female reproductive system in the Chinese population
"Examine clinicopathological traits and differential diagnosis of ERMS in female reproductive system.MethodsRetrospectively assess 13 patients’ data (Jan 2018 - Jun 2024, West China Second Univsity Hospital), covering clinical, histological, immunohistochemical aspects and literature..."
Show evidence (1 reference)
DOI:10.3389/fonc.2025.1546607 SUPPORT Human Clinical
"Examine clinicopathological traits and differential diagnosis of ERMS in female reproductive system.MethodsRetrospectively assess 13 patients’ data (Jan 2018 - Jun 2024, West China Second Univsity Hospital), covering clinical, histological, immunohistochemical aspects and literature..."
Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
DOI:10.3390/cancers17193100
Childhood, Adolescent and Young Adult Poor-Prognosis Rhabdomyosarcoma
1 finding
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and young people.
"Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and young people."
Show evidence (1 reference)
DOI:10.3390/cancers17193100 SUPPORT Human Clinical
"Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and young people."
Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
DOI:10.3390/cancers18040690
The Development of Novel Treatment Strategies for Rhabdomyosarcoma
1 finding
Rhabdomyosarcoma is a small round-cell soft tissue tumor that occurs mainly in pediatric and adolescent/young adult (AYA) patients but also rarely in adults.
"Rhabdomyosarcoma is a small round-cell soft tissue tumor that occurs mainly in pediatric and adolescent/young adult (AYA) patients but also rarely in adults."
Show evidence (1 reference)
DOI:10.3390/cancers18040690 SUPPORT Human Clinical
"Rhabdomyosarcoma is a small round-cell soft tissue tumor that occurs mainly in pediatric and adolescent/young adult (AYA) patients but also rarely in adults."
Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.
DOI:10.3390/cancers18060888
Biological Advances and Current Challenges for Pediatric Rhabdomyosarcoma
1 finding
Despite comprehensive and multi-modal therapy, outcomes for children and adolescents with rhabdomyosarcoma (RMS) have plateaued over the past four decades.
"Despite comprehensive and multi-modal therapy, outcomes for children and adolescents with rhabdomyosarcoma (RMS) have plateaued over the past four decades."
Show evidence (1 reference)
DOI:10.3390/cancers18060888 SUPPORT Human Clinical
"Despite comprehensive and multi-modal therapy, outcomes for children and adolescents with rhabdomyosarcoma (RMS) have plateaued over the past four decades."
Deep research cited this publication as relevant literature for Embryonal Rhabdomyosarcoma.

Deep Research

1
Falcon ▸
Embryonal Rhabdomyosarcoma (ERMS): Disease Characteristics Research Report
Edison Scientific Literature 28 citations 2026-05-08T15:25:56.050868

Embryonal Rhabdomyosarcoma (ERMS): Disease Characteristics Research Report

Target Disease

  • Disease name: Embryonal rhabdomyosarcoma (ERMS)
  • Category: Malignant pediatric soft-tissue sarcoma (skeletal muscle differentiation)
  • MONDO ID: Not identified in the retrieved evidence (see “Limitations”)

Executive summary (current understanding)

Embryonal rhabdomyosarcoma (ERMS) is the most common pediatric rhabdomyosarcoma subtype and largely overlaps with FOXO1 fusion–negative rhabdomyosarcoma (FN‑RMS) in modern molecular classification, which is increasingly used for risk stratification and treatment selection. Clinically, RMS frequently presents as a mass in the head/neck, genitourinary tract, or extremities. ERMS/FN‑RMS is characterized by recurrent chromosomal gains, 11p15 allelic loss/LOH (IGF2 region), and frequent RAS‑pathway alterations; poor‑prognosis subsets include TP53 and MYOD1 (L122R) altered tumors. Standard-of-care remains multimodal therapy (chemotherapy plus surgery and/or radiotherapy), while contemporary trials incorporate molecular risk markers and emerging biomarkers such as circulating tumor DNA (ctDNA). (vries2023imaginginrhabdomyosarcoma pages 1-3, oberoi2023childrensoncologygroups pages 1-3, oberoi2023childrensoncologygroups pages 3-5)

A compact, evidence-backed fact table is provided below.

Domain Item Summary Quantitative detail Citation-year Primary citation context id
Identifier/classification Disease name Embryonal rhabdomyosarcoma (ERMS) is the embryonal subtype of rhabdomyosarcoma and is a fusion-negative RMS category in most cases ERMS constitutes 70–80% of RMS in one clinicopathologic review; another review lists ERMS as 57% of RMS 2025; 2025 pqac-00000006
Identifier/classification Synonyms ERMS; embryonal RMS; fusion-negative RMS (FN-RMS) often used as molecular proxy because most ERMS are FOXO1 fusion-negative Not quantified 2025; 2025 pqac-00000003
Identifier/classification WHO classification WHO/2020-era classification lists four RMS subtypes: embryonal, alveolar, pleomorphic, spindle cell/sclerosing 4 major subtypes 2025; 2026 pqac-00000008
Identifier/classification MeSH / ICD / MONDO / Orphanet Specific MeSH, ICD-10/11, MONDO, and Orphanet identifiers were not provided in the retrieved evidence; Open Targets lists disease term “embryonal rhabdomyosarcoma” as EFO_0000437 Not available in provided evidence 2023–2025 evidence set pqac-00000000
Epidemiology Pediatric cancer burden RMS is the most common pediatric soft tissue sarcoma and accounts for about 3% of pediatric cancers ~3% of pediatric cancers 2023 pqac-00000010
Epidemiology Annual U.S. cases Approximate number of U.S. pediatric RMS diagnoses per year ~350 cases/year 2023 pqac-00000010
Epidemiology Incidence Pediatric RMS annual incidence 4.6 per million children (COG blueprint); ~4 per million age 0–19 in European registry summary 2023; 2023 pqac-00000010
Epidemiology Age/sex distribution RMS median age at diagnosis is early childhood and males are more often affected Median age 5 years; 72–81% diagnosed before age 10; male:female ratio ~1.4 2023 pqac-00000001
Prognosis Overall localized vs metastatic RMS Outcomes vary strongly by risk group and metastatic status 5-year OS ~80% for localized disease; ~35% for metastatic disease 2023 pqac-00000001
Prognosis COG low/intermediate/high risk Long-term survival ranges by risk group in COG framework ~90% / 50–70% / ~20% 5-year survival for low / intermediate / high risk STS/RMS frameworks 2023 pqac-00000010
Prognosis Favorable fusion-negative groups Excellent survival for selected favorable FN-RMS groups 5-year EFS/OS 92%/99% for FN Stage 1, Clinical Group I; 87%/97% for FN Stage 1 CG II / Stage 2 CG I-II / orbit CG III 2023 pqac-00000010
Prognosis ctDNA prognostic value in FN-RMS Detectable baseline ctDNA identifies worse-outcome intermediate-risk FN-RMS ctDNA detectable in 13/75 FN-RMS sera (17%); EFS 33.3% vs 68.9%, OS 33.3% vs 83.2%, P=.0028 and P<.0001 2023 pqac-00000014
Prognosis Poor-risk biomarkers MYOD1 and TP53 mutations worsen prognosis in FN-RMS MYOD1 L122R associated survival 0–30%; TP53 mutations in ~13% FN-RMS and worse outcomes 2023 pqac-00000012
Molecular feature FOXO1 status Fusion status has replaced histologic subtype in risk stratification; FOXO1 fusion-negative disease has better prognosis than fusion-positive disease Qualitative prognostic effect; no single percentage for ERMS itself 2023 pqac-00000010
Molecular feature 11p15 loss ERMS frequently shows 11p15 loss of heterozygosity involving IGF2 region ~80% have 11p15 LOH 2023 pqac-00000007
Molecular feature RAS-pathway mutations Fusion-negative/embryonal RMS is characterized by recurrent RAS-pathway alterations Frequent, but no single pooled percentage given in retrieved evidence 2023 pqac-00000012
Molecular feature TP53 TP53 is a recurrent poor-risk alteration in FN-RMS/ERMS ~13% of FN-RMS 2023 pqac-00000012
Molecular feature MYOD1 MYOD1 L122R marks biologically aggressive RMS subset and is integrated into modern risk frameworks Survival 0–30% in MYOD1-mutant disease 2023 pqac-00000012
Molecular feature DICER1 in gynecologic ERMS DICER1 alterations are enriched in cervical and uterine ERMS and may aid diagnosis Almost all cervical ERMS and nearly 67% of uterine corpus ERMS carry DICER1 mutations; 4/5 tested gynecologic ERMS in one cohort were DICER1-mutant 2025 pqac-00000006
Molecular feature Chromosomal/copy-number pattern FN-RMS/ERMS shows whole-chromosome gains; one transcriptomic/genomic analysis highlighted chromosome 8 cytoband amplification/gain in FN-RMS chr8-related amplification highlighted; exact ERMS frequency not provided in compact evidence set 2023 pqac-00000012
Diagnostics Histology/IHC ERMS diagnosis relies on morphology plus skeletal muscle markers Common markers: desmin, myogenin, MyoD1; in one gynecologic ERMS series Myogenin 11/13, Desmin 13/13, MyoD1 12/13, Myoglobin 5/9 2025 pqac-00000006

Table: This table condenses the most actionable evidence from the retrieved sources for embryonal rhabdomyosarcoma, covering classification, epidemiology, prognosis, and molecular features. It is useful as a compact reference for knowledge-base population using only facts directly supported by the available context IDs.

1. Disease information

1.1 Definition/overview

Rhabdomyosarcoma (RMS) is described as the most frequent pediatric soft tissue sarcoma, with major subtypes including embryonal and alveolar; ERMS is typically fusion-negative and is described as being driven by oncogenic driver mutations such as RAS and TP53 in the imaging-focused review by de Vries et al. (Pediatric Radiology, 2023‑02, URL: https://doi.org/10.1007/s00247-023-05596-8). (vries2023imaginginrhabdomyosarcoma pages 1-3)

1.2 Key identifiers and classifications

  • WHO classification: Reviews in the retrieved set summarize the WHO approach as including four main RMS subtypes (embryonal, alveolar, pleomorphic, spindle cell/sclerosing). (nakano2026thedevelopmentof pages 1-2)
  • Fusion status classification: COG and other cooperative groups increasingly classify RMS into FOXO1 fusion‑positive vs FOXO1 fusion‑negative, with fusion status replacing histology as a key risk classifier. (oberoi2023childrensoncologygroups pages 1-3)
  • Open Targets disease concept: “Embryonal rhabdomyosarcoma” appears as EFO_0000437 in Open Targets outputs. (OpenTargets Search: embryonal rhabdomyosarcoma)

Not found in the retrieved evidence: ICD‑10/ICD‑11, MeSH identifier, Orphanet (ORPHA) code, MONDO ID.

1.3 Synonyms and alternative names

  • Embryonal rhabdomyosarcoma (ERMS)
  • Embryonal RMS
  • Fusion‑negative rhabdomyosarcoma (FN‑RMS) (used as a molecular proxy in many contemporary sources because most ERMS are FOXO1 fusion‑negative) (wasti2025childhoodadolescentand pages 2-4, oberoi2023childrensoncologygroups pages 1-3)

1.4 Evidence provenance

This report is derived from aggregated disease-level resources (COG blueprint review; imaging guideline review; multi-institutional clinical study; trial registry) and selected clinicopathologic series. (vries2023imaginginrhabdomyosarcoma pages 1-3, oberoi2023childrensoncologygroups pages 1-3, abbou2023circulatingtumordna pages 1-2)

2. Etiology

2.1 Primary causal factors (molecular/genetic)

ERMS/FN‑RMS is characterized by: - Chromosomal alterations: Whole-chromosome gains and 11p15.5 allelic loss are described as characteristic genomic features in the COG blueprint review. (oberoi2023childrensoncologygroups pages 3-5) - 11p15 loss of heterozygosity (LOH): A 2023 review reports that ~80% of ERMS have LOH at 11p15 involving the IGF‑2/IGF2 region. (zarrabi2023rhabdomyosarcomacurrenttherapy pages 3-5) - RAS pathway alterations: The COG blueprint describes frequent RAS‑pathway and point mutations (e.g., NRAS, KRAS, HRAS) in fusion-negative disease. (oberoi2023childrensoncologygroups pages 3-5)

2.2 Risk factors

2.2.1 Genetic predisposition syndromes

Multiple cancer predisposition syndromes are reported as increasing RMS risk in a 2023 imaging guideline review, including: - Neurofibromatosis type 1 (NF1) - Li–Fraumeni syndrome (TP53 germline) - DICER1 syndrome - Noonan syndrome - Beckwith–Wiedemann syndrome - Costello syndrome (vries2023imaginginrhabdomyosarcoma pages 1-3)

2.2.2 Environmental/lifestyle risk factors

No specific environmental or lifestyle risk factors were identified in the retrieved evidence.

2.3 Protective factors

No protective genetic or environmental factors were identified in the retrieved evidence.

2.4 Gene–environment interactions

No ERMS-specific gene–environment interaction evidence was identified in the retrieved set.

3. Phenotypes (clinical presentation)

3.1 Typical phenotypes and presentation

RMS “can present as a mass at nearly any site in the body,” with most common presentations in head and neck, genitourinary tract, and extremities. (vries2023imaginginrhabdomyosarcoma pages 1-3)

3.2 Age of onset and sex ratio

European registry–summarized epidemiology in the imaging review reports: - Median age at diagnosis: ~5 years - Proportion <10 years: ~72–81% - Male:female ratio: ~1.4 (95% CI 1.2–1.6) (vries2023imaginginrhabdomyosarcoma pages 1-3)

3.3 Suggested HPO terms (examples)

Evidence in the retrieved set is not granular enough to assign frequencies per phenotype; the following HPO terms are consistent with common presentations noted (mass lesion by site): - Mass of head and neck (e.g., HP:0000235 Abnormality of head or neck [broad parent]; site-specific “mass” terms may be used in implementation) - Pelvic mass (HP:0002681) / Abdominal mass (HP:0003270) for genitourinary presentations - Soft tissue mass (HP:0030832 [soft-tissue abnormality/mass terms])

Note: HPO IDs above are provided as ontology suggestions; confirm exact term mapping during curation.

4. Genetic / molecular information

4.1 Causal genes and recurrent somatic alterations (ERMS/FN‑RMS)

From the COG blueprint review, fusion‑negative disease is described as having frequent point mutations including NRAS, KRAS, HRAS, TP53, MYOD1, PIK3CA, FGFR4 and characteristic chromosomal events including 11p15.5 allelic loss. (oberoi2023childrensoncologygroups pages 3-5)

4.2 Clinically important poor-risk biomarkers

  • MYOD1 L122R: Reported to predict very poor survival (0–30%) in the COG blueprint summary. (oberoi2023childrensoncologygroups pages 3-5)
  • TP53: TP53 mutations are reported in ~13% of FN‑RMS and are associated with worse outcomes. (oberoi2023childrensoncologygroups pages 3-5)

4.3 DICER1 (site-associated enrichment)

A clinicopathological series of female reproductive system ERMS highlights enrichment for DICER1 alterations, stating: “Almost all cervical ERMS and nearly 67% of uterine corpus ERMS carry DICER1 mutations,” and in their cohort 4/5 tested cases had DICER1 mutations. (Frontiers in Oncology, 2025‑03, URL: https://doi.org/10.3389/fonc.2025.1546607) (bai2025clinicopathologicalanalysisof pages 1-2)

4.4 Epigenetics and omics

The retrieved evidence set did not provide ERMS-specific quantitative epigenetic signatures; however, the COG blueprint emphasizes that molecular profiling (including fusion status and specific mutations) is increasingly incorporated into risk stratification and prospective trials. (oberoi2023childrensoncologygroups pages 1-3)

4.5 Suggested GO and CL terms (mechanism-relevant)

Based on evidence-supported biology (RAS pathway activation; differentiation blockade implied by MYOD1 axis and RMS myogenic markers): - GO (Biological Process) suggestions: - Ras protein signal transduction (e.g., GO:0007265) - Regulation of cell proliferation (GO:0042127) - Myoblast differentiation / skeletal muscle cell differentiation (myogenic program dysregulation; use appropriate child terms during curation) - CL (Cell Ontology) suggestions: - Skeletal muscle cell / myoblast lineages (tumor shows skeletal muscle differentiation markers)

5. Environmental information

No ERMS-specific environmental, lifestyle, or infectious causal contributors were identified in the retrieved evidence.

6. Mechanism / pathophysiology (causal chain)

6.1 Upstream initiating events

In ERMS/FN‑RMS, recurrent genomic alterations include 11p15.5 allelic loss/LOH (IGF2 locus region) and frequent RAS pathway mutations (NRAS/KRAS/HRAS), with subsets harboring TP53 or MYOD1 alterations that confer poor prognosis. (zarrabi2023rhabdomyosarcomacurrenttherapy pages 3-5, oberoi2023childrensoncologygroups pages 3-5)

6.2 Downstream cellular consequences and clinical manifestation

A mechanistic chain supported by the retrieved evidence: 1. Genetic alterations (e.g., 11p15 LOH; RAS-pathway mutations; TP53/MYOD1 in poor-risk subsets) (zarrabi2023rhabdomyosarcomacurrenttherapy pages 3-5, oberoi2023childrensoncologygroups pages 3-5) 2. Promote oncogenic signaling and tumor growth in mesenchymal lineage cells with skeletal muscle differentiation, producing a soft-tissue mass presentation at diverse sites (head/neck, GU tract, extremity) (vries2023imaginginrhabdomyosarcoma pages 1-3) 3. Disease aggressiveness and treatment resistance are increased in molecularly defined high-risk subsets (TP53, MYOD1), reflected in poorer survival outcomes. (oberoi2023childrensoncologygroups pages 3-5)

7. Anatomical structures affected

7.1 Organ/system level (common sites)

Most common presentations: head and neck, genitourinary tract, extremities. (vries2023imaginginrhabdomyosarcoma pages 1-3)

7.2 Suggested UBERON terms (examples)

  • Head and neck region (e.g., UBERON:0000033 [head])
  • Urinary bladder (UBERON:0001255)
  • Prostate gland (UBERON:0002367)
  • Skeletal muscle of limb/extremity (use appropriate limb muscle terms)

8. Temporal development

  • Onset: Predominantly pediatric with early childhood peak (median ~5 years; most diagnosed before age 10). (vries2023imaginginrhabdomyosarcoma pages 1-3)
  • Course/progression: Variable; outcomes depend strongly on risk group and metastatic status. (vries2023imaginginrhabdomyosarcoma pages 1-3, oberoi2023childrensoncologygroups pages 1-3)

9. Inheritance and population

9.1 Epidemiology

  • Incidence (children): 4.6 per million children (COG blueprint). (oberoi2023childrensoncologygroups pages 1-3)
  • Annual U.S. cases: ~350 children diagnosed with RMS per year (COG blueprint). (oberoi2023childrensoncologygroups pages 1-3)
  • European registry summary: ~4 per million (age 0–19), ~400 new patients per year (age 0–19) (as summarized in the imaging review). (vries2023imaginginrhabdomyosarcoma pages 1-3)

9.2 Sex ratio and age distribution

  • Male predominance: male:female ratio ~1.4. (vries2023imaginginrhabdomyosarcoma pages 1-3)

9.3 Inheritance pattern

Most ERMS appears sporadic; however, multiple germline cancer predisposition syndromes increase risk (NF1, Li–Fraumeni/TP53, DICER1, Noonan, Beckwith–Wiedemann, Costello). (vries2023imaginginrhabdomyosarcoma pages 1-3)

10. Diagnostics

10.1 Pathology and immunohistochemistry (IHC)

A 2023 RMS review notes use of IHC muscle markers including alpha-actin, MyoD1, myogenin, and desmin to distinguish RMS from other small round blue cell tumors. (zarrabi2023rhabdomyosarcomacurrenttherapy pages 3-5)

In a 13‑patient gynecologic ERMS series, IHC positivity rates were: - Desmin: 13/13 - MyoD1: 12/13 - Myogenin: 11/13 - Myoglobin: 5/9 (bai2025clinicopathologicalanalysisof pages 1-2)

10.2 Molecular testing and risk stratification

COG emphasizes fusion status as central: FOXO1 fusion status has replaced histologic subtype in risk stratification, with FOXO1 fusion-positive conferring worse prognosis than fusion-negative. (oberoi2023childrensoncologygroups pages 1-3)

10.3 Imaging and staging (real-world implementation)

The imaging guideline review highlights multidisciplinary management and notes European collaborative imaging guidance (EpSSG/CWS/ESPR collaboration) spanning clinical suspicion, biopsy, staging, response assessment, and follow-up. (vries2023imaginginrhabdomyosarcoma pages 1-3)

10.4 Liquid biopsy / ctDNA (emerging diagnostic/prognostic tool)

In intermediate-risk RMS, baseline ctDNA detection is feasible and prognostic. - Cohort: 124 intermediate-risk RMS patients (75 FN‑RMS; 49 FP‑RMS) - FN‑RMS ctDNA detection at diagnosis: 13/75 (17%) - FN‑RMS outcomes with detectable ctDNA vs not detectable: - EFS: 33.3% vs 68.9% (P = .0028) - OS: 33.3% vs 83.2% (P < .0001) - Similar adverse associations were reported for FP‑RMS. (Journal of Clinical Oncology, 2023‑05, URL: https://doi.org/10.1200/JCO.22.00409) (abbou2023circulatingtumordna pages 1-2)

Additional quantitative details from the same study (alternate excerpt) include: CNAs in tumors 71%, translocations in tumors 93%, and overall ctDNA detection 57% using combined approaches. (abbou2023circulatingtumordna pages 6-7)

11. Outcome / prognosis

11.1 Risk-group outcome ranges

In the imaging-focused review, 5-year overall survival is summarized as: - Localized disease: ~80% - Metastatic disease: ~35% - Broad risk-group range: ~50.6% (very high-risk) to 100% (low-risk) (vries2023imaginginrhabdomyosarcoma pages 1-3)

COG blueprint examples for favorable fusion-negative groups include: - FN Stage 1, Clinical Group I: 5‑year EFS/OS 92% / 99% - Other favorable groups: EFS/OS 87% / 97% (oberoi2023childrensoncologygroups pages 1-3)

11.2 Prognostic biomarkers

Poorer prognosis is associated with FOXO1 fusion positivity, and within FN‑RMS, MYOD1 and TP53 mutations are noted as adverse factors. (oberoi2023childrensoncologygroups pages 1-3, oberoi2023childrensoncologygroups pages 3-5)

12. Treatment

12.1 Standard multimodal therapy

The imaging review describes standard management as multimodal: systemic chemotherapy plus local therapy (surgery and/or radiotherapy). (vries2023imaginginrhabdomyosarcoma pages 1-3)

COG blueprint specifies typical chemotherapy backbones: - VA (vincristine + dactinomycin) ± cyclophosphamide (VAC) - VAC/VI (VAC with irinotecan-containing components) (oberoi2023childrensoncologygroups pages 1-3)

COG-reported comparative outcomes in intermediate-risk trials: - ARST0531: 4-year EFS 63% vs 59% and OS 73% vs 72% for VAC vs VAC/VI strategies (with different cumulative cyclophosphamide exposure). (oberoi2023childrensoncologygroups pages 1-3)

12.2 Current applications: molecularly informed treatment intensification

COG notes that patients meeting very-low/low-risk clinical criteria but with TP53 or MYOD1 mutations are treated with 42 weeks VAC (cumulative cyclophosphamide 16.6 g/m²) and not considered very-low/low risk. (oberoi2023childrensoncologygroups pages 19-20)

12.3 Ongoing / recent clinical trials (selected)

COG ARST2032: very low/low-risk FN-RMS (real-world implementation: enrolling)

  • Trial: NCT05304585 (ClinicalTrials.gov)
  • Title: “Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma”
  • Sponsor/Group: Children’s Oncology Group
  • Status: Recruiting (per retrieved registry snippet)
  • Key regimens: Regimen VA (very low-risk), VAC/VA (low-risk), and a regimen for mutation-positive patients (“Regimen M”) that includes radiotherapy; uses vincristine, dactinomycin, cyclophosphamide (and imaging/staging procedures).
  • Primary endpoint: 3‑year failure‑free survival (Kaplan–Meier)
  • Feasibility endpoint: central molecular risk stratification feasible if ≥80% results returned by 6 weeks. (NCT05304585 chunk 2)

12.4 Suggested MAXO terms (examples)

  • Multiagent chemotherapy (MAXO term for antineoplastic chemotherapy)
  • Tumor resection / surgical excision
  • Radiotherapy
  • Molecular diagnostic procedure (for fusion testing)

13. Prevention

No primary prevention strategies specific to ERMS were identified in the retrieved evidence. Secondary prevention in practice centers on timely recognition, imaging workup, and standardized staging/risk stratification within multidisciplinary pediatric oncology pathways. (vries2023imaginginrhabdomyosarcoma pages 1-3)

14. Other species / natural disease

The retrieved evidence did not provide specific naturally occurring veterinary ERMS epidemiology.

15. Model organisms

A 2023 RMS review notes that in vivo mouse and zebrafish models are used to screen future therapeutic approaches and study mechanisms. (zarrabi2023rhabdomyosarcomacurrenttherapy pages 3-5)

A 2026 review emphasizes that advances in animal models and tissue acquisition have improved understanding of RMS biology, though the provided excerpt does not enumerate specific engineered ERMS models. (hebron2026biologicaladvancesand pages 22-23)

Visual evidence: COG RMS prognostic groups

The COG rhabdomyosarcoma prognostic group table (risk stratification schema with associated long-term EFS ranges) is provided in the retrieved cropped table image. (oberoi2023childrensoncologygroups media 44b370af)

Limitations of the current evidence set

  • Ontology identifiers (MONDO, Orphanet/ORPHA, ICD‑10/11, MeSH) were not present in the retrieved texts; additional targeted retrieval (Orphanet/MONDO/MeSH/ICD sources) would be required for a fully populated identifier section.
  • Several topics requested in the template (environmental modifiers, epigenomic signatures, metabolomics, detailed differential diagnosis lists, and cross-species natural disease frequency) were not covered with ERMS-specific primary data in the retrieved evidence.

Key sources (with publication dates and URLs)

  • de Vries ISA et al. Imaging in rhabdomyosarcoma: a patient journey. Pediatric Radiology. 2023‑02. https://doi.org/10.1007/s00247-023-05596-8 (vries2023imaginginrhabdomyosarcoma pages 1-3)
  • Oberoi S et al. Children’s Oncology Group’s 2023 blueprint for research: Soft tissue sarcomas. Pediatric Blood & Cancer. 2023‑07. https://doi.org/10.1002/pbc.30556 (oberoi2023childrensoncologygroups pages 1-3, oberoi2023childrensoncologygroups pages 3-5)
  • Abbou S et al. Circulating tumor DNA is prognostic in intermediate-risk rhabdomyosarcoma. Journal of Clinical Oncology. 2023‑05. https://doi.org/10.1200/JCO.22.00409 (abbou2023circulatingtumordna pages 1-2)
  • Zarrabi A et al. Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies. Cancers (preprint version listed). 2023‑11. https://doi.org/10.20944/preprints202309.0846.v1 (zarrabi2023rhabdomyosarcomacurrenttherapy pages 3-5)
  • ClinicalTrials.gov. NCT05304585 / COG ARST2032. First posted year shown in excerpt: 2022. https://clinicaltrials.gov/study/NCT05304585 (NCT05304585 chunk 2)

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