Definition/General
Introduction:
Rhabdomyosarcoma is a malignant tumor showing skeletal muscle differentiation
It is the most common soft tissue sarcoma in children
Represents 40-50% of pediatric sarcomas
FNAC shows primitive round to spindle cells.
Origin:
Arises from primitive mesenchymal cells with myogenic potential
Can occur anywhere in the body
Head/neck and genitourinary regions common in children
Extremities more common in adolescents/adults.
Classification:
WHO classification includes: Embryonal rhabdomyosarcoma (most common)
Alveolar rhabdomyosarcoma (aggressive)
Pleomorphic rhabdomyosarcoma (adults)
Spindle cell/sclerosing rhabdomyosarcoma (rare).
Epidemiology:
Bimodal age distribution: Peak in <1 year and 15-19 years
Male predominance (1.4:1)
Accounts for 3-4% of childhood cancers
Most common sarcoma in children <15 years
Li-Fraumeni syndrome association.
Clinical Features
Presentation:
Rapidly enlarging mass
Painless initially
Soft tissue swelling
Variable consistency
Location-specific symptoms
Systemic symptoms (advanced disease).
Symptoms:
Mass effect symptoms
Pain (late symptom)
Proptosis (orbital)
Nasal obstruction (parameningeal)
Urinary symptoms (genitourinary)
Dysphagia (head/neck).
Risk Factors:
Li-Fraumeni syndrome (TP53 mutations)
Neurofibromatosis type 1
Beckwith-Wiedemann syndrome
Costello syndrome
Previous radiation exposure
Congenital anomalies.
Screening:
Clinical examination for masses
Imaging studies (MRI/CT)
FNAC/Biopsy for diagnosis
Bone marrow evaluation
CSF examination (parameningeal)
Genetic counseling if syndrome suspected.
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Gross Description
Appearance:
Fleshy, gray-white mass
Soft consistency
Areas of necrosis and hemorrhage
Poorly circumscribed
Infiltrative growth
Variable size.
Characteristics:
Heterogeneous appearance
Necrosis (especially alveolar type)
Hemorrhage and cystic change
Myxoid areas
Firm to soft consistency
Gray-pink color.
Size Location:
Head/neck (35-40%)
Genitourinary (25%)
Extremities (20%)
Trunk (10%)
Other sites (10%)
Size: Variable 2-20 cm.
Multifocality:
Usually solitary
Multifocal disease rare
Regional spread common
Lymph node involvement
Distant metastases (lung, bone)
CSF dissemination (parameningeal).
Microscopic Description
Histological Features:
FNAC shows primitive round to oval cells
High nuclear-cytoplasmic ratio
Hyperchromatic nuclei
Scanty cytoplasm
Rhabdomyoblasts (variable)
High mitotic activity.
Cellular Characteristics:
Small blue round cells (embryonal)
Oval to elongated cells (alveolar)
Pleomorphic cells (pleomorphic type)
Rhabdomyoblasts with eosinophilic cytoplasm
Multinucleated giant cells.
Architectural Patterns:
Loose cellular cohesion
Individual cells predominant
Alveolar pattern (alveolar type)
Syncytial arrangement
Necrotic background
Hemorrhagic background.
Grading Criteria:
Risk stratification based on subtype
Embryonal: Intermediate risk
Alveolar: High risk
Pleomorphic: High risk
Age and site important factors
Stage determines treatment.
Immunohistochemistry
Positive Markers:
MyoD1 - positive (nuclear, sensitive)
Myogenin - positive (nuclear, specific)
Desmin - positive (variable)
Muscle-specific actin - positive
Vimentin - positive
MYOD1 - positive.
Negative Markers:
CD99 - negative (vs Ewing sarcoma)
FLI1 - negative
Cytokeratin - negative
S-100 - negative
CD45 - negative
Synaptophysin - negative.
Diagnostic Utility:
MyoD1 and myogenin essential for diagnosis
Myogenin more specific than MyoD1
Differentiates from other small round cell tumors
Ki-67 high (>20%)
p53 variable.
Molecular Subtypes:
Embryonal: MyoD1+, myogenin+ (focal)
Alveolar: MyoD1+, myogenin+ (diffuse)
Pleomorphic: MyoD1+, myogenin+ (variable)
PAX-FOXO1 fusion in alveolar type.
Molecular/Genetic
Genetic Mutations:
PAX3-FOXO1 fusion t(2;13) - alveolar
PAX7-FOXO1 fusion t(1;13) - alveolar
TP53 mutations
RAS pathway alterations
PIK3CA mutations
Complex karyotype (pleomorphic).
Molecular Markers:
FOXO1 rearrangement (alveolar)
Myogenic transcription factors
High proliferation markers
p53 pathway alterations
IGF2 overexpression
MDM2 amplification (some cases).
Prognostic Significance:
Subtype determines prognosis
Embryonal: Better prognosis
Alveolar: Poor prognosis
PAX3-FOXO1: Worse than PAX7-FOXO1
Age <10 years: Better outcome
Site and stage important.
Therapeutic Targets:
Multi-agent chemotherapy (vincristine, dactinomycin, cyclophosphamide)
Radiation therapy
IGF-1R inhibitors
mTOR inhibitors
Immunotherapy (investigational)
Targeted therapy for fusion-positive.
Differential Diagnosis
Similar Entities:
Ewing sarcoma
Lymphoma
Neuroblastoma
Synovial sarcoma
Desmoplastic small round cell tumor
Primitive neuroectodermal tumor.
Distinguishing Features:
Rhabdomyosarcoma: MyoD1+, myogenin+
Ewing sarcoma: CD99+, FLI1+, t(11;22)
Lymphoma: CD45+, B/T cell markers
Neuroblastoma: Synaptophysin+, catecholamine metabolites
Synovial sarcoma: TLE1+, t(X;18)
DSRCT: Desmin+, cytokeratin+.
Diagnostic Challenges:
Distinguishing from other small round cell tumors
Subtype classification requires molecular studies
Poorly differentiated cases challenging
Limited tissue in FNAC
Immunostaining interpretation.
Rare Variants:
Spindle cell rhabdomyosarcoma
Sclerosing rhabdomyosarcoma
Mixed type
Anaplastic variant
Epithelioid variant.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Fine needle aspiration from [site], [size] cm soft tissue mass
Clinical History
[age]/[sex] with [duration] history of rapidly growing mass at [site]
Microscopic Examination
Highly cellular smears showing primitive small round to oval cells with high N:C ratio, hyperchromatic nuclei, and scanty cytoplasm. Occasional rhabdomyoblasts with eosinophilic cytoplasm noted.
Immunocytochemistry
MyoD1: Positive (nuclear), Myogenin: Positive (nuclear), Desmin: [result], CD99: Negative
Cytological Diagnosis
Cytological features consistent with RHABDOMYOSARCOMA, [subtype]
Comments
Histopathological examination and molecular studies recommended for subtyping. Multidisciplinary pediatric oncology evaluation required.