Definition/General
Introduction:
Endometrial rhabdomyosarcoma is an extremely rare malignant tumor showing skeletal muscle differentiation
It represents less than 1% of all uterine sarcomas
It can occur as primary endometrial tumor or as part of carcinosarcoma
It demonstrates rhabdomyoblastic differentiation with cross-striations.
Origin:
Arises from endometrial mesenchymal cells with skeletal muscle differentiation
May develop from primitive mesenchymal cells
Can arise in the context of adenosarcoma with heterologous elements
Rarely occurs as pure rhabdomyosarcoma
Most commonly seen as component of carcinosarcoma.
Classification:
Classified as heterologous sarcoma by WHO classification
Embryonal type most common in adults
Pleomorphic type in older patients
May be part of mixed heterologous sarcoma
Alveolar type extremely rare in uterus.
Epidemiology:
Extremely rare tumor
Peak incidence in 5th-6th decades
Postmenopausal women predominantly affected
Associated with previous pelvic radiation
May be linked to tamoxifen therapy
Family history of sarcomas may be relevant.
Clinical Features
Presentation:
Abnormal uterine bleeding (most common)
Rapidly enlarging pelvic mass
Postmenopausal bleeding
Pelvic pressure symptoms
Passage of tissue per vaginum
Abdominal distension
Weight loss and fatigue.
Symptoms:
Heavy menstrual bleeding
Intermenstrual bleeding
Pelvic pain
Urinary frequency
Constipation
Abdominal bloating
Systemic symptoms in advanced cases
Rapid symptom progression.
Risk Factors:
Previous pelvic radiation
Tamoxifen therapy
Age >50 years
Genetic predisposition (Li-Fraumeni syndrome)
Family history of sarcomas
Previous chemotherapy
Immunosuppression.
Screening:
No specific screening recommendations
High index of suspicion for rapidly growing masses
Imaging studies for evaluation
Tissue sampling essential for diagnosis
Genetic counseling for familial cases.
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Gross Description
Appearance:
Polypoid or sessile mass in uterine cavity
Gray-white to tan cut surface
Soft, fleshy consistency
Areas of hemorrhage and necrosis
May show gelatinous appearance
Surface ulceration common.
Characteristics:
Size varies from 3-15 cm
Heterogeneous cut surface
Cystic and solid areas
Myxoid appearance in some cases
Hemorrhagic foci
Necrotic areas common
Infiltrative margins.
Size Location:
Usually large at presentation
Mean size 7-10 cm
Involves endometrial cavity
May extend to myometrium
Cervical extension possible
Extrauterine spread in advanced cases.
Multifocality:
Usually unifocal presentation
Deep myometrial invasion common
May show lymphovascular invasion
Parametrial extension in advanced cases
Multiple satellite nodules possible.
Microscopic Description
Histological Features:
Malignant cells with rhabdomyoblastic differentiation
Cross-striations in cytoplasm (pathognomonic)
Strap cells and tadpole cells
High mitotic activity
Pleomorphic nuclei
Abundant eosinophilic cytoplasm
Necrosis common.
Cellular Characteristics:
Large polygonal cells with abundant cytoplasm
Eccentric nuclei
Prominent nucleoli
Cross-striations (diagnostic feature)
Multinucleated giant cells
Bizarre cell forms
High nuclear-to-cytoplasmic ratio.
Architectural Patterns:
Sheets and fascicles of malignant cells
Myxoid stroma in some areas
Alveolar pattern (rare)
Storiform pattern possible
Solid growth predominant
Areas of necrosis and hemorrhage.
Grading Criteria:
All cases considered high-grade by definition
Mitotic count >10/10 HPF
Marked nuclear pleomorphism
Necrosis present
FNCLCC grading may be applied
Cross-striations confirm diagnosis.
Immunohistochemistry
Positive Markers:
Desmin (positive, specific pattern)
MyoD1 (nuclear staining)
Myogenin (nuclear staining, highly specific)
Muscle-specific actin
Vimentin
MSA (muscle-specific actin)
Myosin (may be positive).
Negative Markers:
Cytokeratins (negative)
S-100 (negative)
CD34 (negative)
Smooth muscle actin (usually negative)
Caldesmon (negative)
CD117 (negative)
EMA (negative).
Diagnostic Utility:
MyoD1 and Myogenin confirm skeletal muscle differentiation
Desmin shows specific sarcomeric pattern
Negative cytokeratins exclude carcinoma
Myogenin more specific than MyoD1
Cross-striations with positive muscle markers diagnostic.
Molecular Subtypes:
FOXO1 rearrangements rare in uterine location
PAX3/7-FOXO1 fusions typical of alveolar type
TP53 mutations in pleomorphic type
RAS pathway alterations
PIK3CA mutations possible.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (common in pleomorphic type)
RB1 pathway alterations
CDKN2A/p16 deletions
PIK3CA mutations
PTEN loss
MYC amplification
MDM2 amplification (some cases).
Molecular Markers:
p53 overexpression (pleomorphic type)
Loss of RB expression
p16 loss
High Ki-67 index (>30%)
PTEN loss
Chromosomal instability.
Prognostic Significance:
TP53 mutations indicate poor prognosis
FOXO1 rearrangements associated with aggressive behavior
High grade correlates with poor outcome
Pleomorphic type has worst prognosis
Size >5 cm indicates poor prognosis.
Therapeutic Targets:
IGF-1R inhibitors (investigational)
mTOR pathway inhibitors
Multi-kinase inhibitors
Immunotherapy (checkpoint inhibitors)
Combination chemotherapy (standard treatment)
Anti-angiogenic agents.
Differential Diagnosis
Similar Entities:
Leiomyosarcoma (smooth muscle differentiation)
Endometrial stromal sarcoma (stromal features)
Carcinosarcoma (epithelial component)
Adenosarcoma with heterologous elements
Metastatic rhabdomyosarcoma.
Distinguishing Features:
Leiomyosarcoma: Smooth muscle actin positive
Leiomyosarcoma: Caldesmon positive
ESS: CD10 positive, low-grade
Carcinosarcoma: Cytokeratin positive component
Rhabdomyosarcoma: MyoD1/Myogenin positive
Rhabdomyosarcoma: Cross-striations present.
Diagnostic Challenges:
Identifying cross-striations may be difficult
Distinguishing from poorly differentiated carcinoma
Separating from other sarcomas
Recognizing in mixed tumors
Immunohistochemistry essential for diagnosis.
Rare Variants:
Embryonal rhabdomyosarcoma (most common adult type)
Pleomorphic rhabdomyosarcoma (older patients)
Alveolar rhabdomyosarcoma (extremely rare)
Spindle cell rhabdomyosarcoma
Mixed rhabdomyosarcoma.
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
[specimen type], measuring [size] cm in greatest dimension
Diagnosis
Rhabdomyosarcoma of the endometrium
Classification
WHO Classification: [Embryonal/Pleomorphic/Alveolar] rhabdomyosarcoma
Histological Features
Malignant tumor with rhabdomyoblastic differentiation, cross-striations [present/absent], mitoses: [count]/10 HPF
Grade
Grade: High-grade sarcoma
Size and Extent
Size: [X] cm, myometrial invasion: [depth/percentage]
Necrosis
Necrosis: [present/absent], [percentage if present]%
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Immunohistochemistry
Muscle markers: MyoD1 [+/-], Myogenin [+/-], Desmin [+/-]
Negative: Cytokeratins, S-100, SMA
Ki-67: [percentage]%
Final Diagnosis
[Type] rhabdomyosarcoma of endometrium, high-grade