Definition/General
Introduction:
Endometrial alveolar soft part sarcoma (ASPS) is an extremely rare malignant soft tissue tumor occurring in the uterus
It is characterized by distinctive alveolar architecture and PAS-positive crystalline inclusions
It represents less than 0.1% of all uterine sarcomas
It has a characteristic molecular signature.
Origin:
Arises from uncertain cellular origin
Possibly from mesenchymal stem cells
May develop from endometrial stroma
Myogenic origin proposed but disputed
Occurs as primary uterine tumor.
Classification:
Classified as soft tissue sarcoma with distinctive features
Intermediate to high-grade malignancy
Defined by ASPSCR1-TFE3 gene fusion
Unique molecular signature
Indolent but ultimately fatal behavior.
Epidemiology:
Extremely rare in uterine location
Peak incidence in 2nd-4th decades (younger than other uterine sarcomas)
Young adult women predominantly affected
No clear ethnic predilection
Associated with t(X;17)(p11;q25) translocation.
Clinical Features
Presentation:
Abnormal uterine bleeding (most common)
Pelvic mass
Abdominal pain
Slow-growing tumor
May be asymptomatic initially
Metastases may be presenting feature.
Symptoms:
Heavy menstrual bleeding
Pelvic pressure
Abdominal distension
Constitutional symptoms rare initially
Pulmonary symptoms (lung metastases)
Bone pain (skeletal metastases).
Risk Factors:
Young age (15-35 years)
No established environmental risk factors
Genetic predisposition unclear
Sporadic occurrence
No association with radiation exposure.
Screening:
No specific screening recommendations
High index of suspicion in young women with soft tissue masses
Imaging studies for staging
Molecular testing essential for diagnosis.
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Gross Description
Appearance:
Well-circumscribed mass with pseudocapsule
Tan-yellow cut surface
Soft, fleshy consistency
Rich vascular network visible
Areas of hemorrhage and necrosis variable.
Characteristics:
Size ranges from 4-12 cm
Lobulated external surface
Cut surface shows distinctive yellow color
Prominent vasculature
Homogeneous appearance.
Size Location:
Usually large at presentation
Mean size 7-10 cm
Involves uterine corpus
May extend to parametrium
Well-demarcated from surrounding tissue.
Multifocality:
Usually unifocal presentation
Indolent local growth
Late metastases common
Lung metastases characteristic
Bone and liver metastases possible.
Microscopic Description
Histological Features:
Alveolar or organoid pattern
Large polygonal cells with abundant cytoplasm
Vesicular nuclei with prominent nucleoli
PAS-positive crystalline inclusions
Rich sinusoidal vasculature
Low mitotic activity.
Cellular Characteristics:
Large epithelioid cells
Abundant granular cytoplasm
Vesicular nuclei
Prominent single nucleoli
Intracytoplasmic crystals (PAS-positive)
Minimal pleomorphism.
Architectural Patterns:
Alveolar pattern with fibrous septa
Organoid arrangement
Sinusoidal blood vessels
Pseudoalveolar spaces
Nested growth pattern
Loss of cellular cohesion centrally.
Grading Criteria:
Deceptively benign appearance
Low mitotic rate (<2/10 HPF)
Minimal nuclear atypia
No conventional grading applicable
Behavior does not correlate with morphology.
Immunohistochemistry
Positive Markers:
TFE3 (nuclear, strong and diffuse)
Cathepsin K
CD68 (variable)
Vimentin
MyoD1 (nuclear, may be positive)
Myogenin (may be focally positive).
Negative Markers:
Cytokeratins (negative)
Desmin (negative)
S-100 (negative)
Melanoma markers (negative)
CD34 (negative)
EMA (negative).
Diagnostic Utility:
TFE3 nuclear positivity highly specific and sensitive
Cathepsin K supports diagnosis
MyoD1 positivity does not indicate muscle differentiation
ASPSCR1-TFE3 fusion confirmatory
Negative epithelial markers.
Molecular Subtypes:
ASPSCR1-TFE3 fusion (unbalanced translocation)
TFE3 overexpression
MET pathway activation
mTOR pathway activation.
Molecular/Genetic
Genetic Mutations:
t(X;17)(p11;q25) unbalanced translocation
ASPSCR1-TFE3 fusion gene
TFE3 gene rearrangement
Chromosomal imbalances
Complex karyotype in some cases.
Molecular Markers:
TFE3 overexpression
ASPSCR1-TFE3 fusion protein
MET upregulation
mTOR pathway activation
VEGF expression.
Prognostic Significance:
Indolent but ultimately fatal behavior
Late metastases (5-20 years)
Young age may have better prognosis
Size >5 cm may indicate worse outcome
Lung metastases eventually fatal.
Therapeutic Targets:
Anti-angiogenic agents (sunitinib, pazopanib)
mTOR inhibitors (temsirolimus)
MET inhibitors (crizotinib)
TFE3-targeted therapy (investigational)
Immunotherapy (limited efficacy).
Differential Diagnosis
Similar Entities:
Paraganglioma
Granular cell tumor
Epithelioid smooth muscle tumor
Renal cell carcinoma metastasis
Melanoma.
Distinguishing Features:
Paraganglioma: Chromogranin positive
Granular cell: S-100 positive
Smooth muscle: Desmin positive
ASPS: TFE3 positive
ASPS: PAS-positive crystals
RCC: RCC markers positive.
Diagnostic Challenges:
Recognizing characteristic alveolar pattern
Identifying PAS-positive crystals
Confirming TFE3 expression
Excluding metastatic renal cell carcinoma
Molecular confirmation preferred.
Rare Variants:
Classic alveolar pattern
Solid variant
Myxoid variant
Microalveolar pattern.
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, well-circumscribed mass
Diagnosis
Alveolar soft part sarcoma of the endometrium
Classification
Soft tissue sarcoma with ASPSCR1-TFE3 fusion
Histological Features
Alveolar pattern with large epithelioid cells, PAS-positive crystals [present/absent]
Mitotic Activity
Mitoses: [count]/10 HPF (typically <2/10 HPF)
Special Stains
PAS: [positive/negative] crystalline inclusions
Immunohistochemistry
TFE3: [+/-] (nuclear), Cathepsin K: [+/-]
MyoD1: [+/-], Myogenin: [+/-]
Negative: Cytokeratins, Desmin, S-100
Molecular Studies
ASPSCR1-TFE3 fusion: [detected/not detected/pending]
Final Diagnosis
Alveolar soft part sarcoma with ASPSCR1-TFE3 rearrangement