Definition/General
Introduction:
Phyllodes tumor with alveolar soft part sarcoma (ASPS) is an extraordinarily rare malignant phyllodes tumor where the stromal component shows characteristic alveolar soft part sarcoma differentiation
This represents one of the rarest forms of heterologous phyllodes tumor.
Origin:
Develops from intralobular breast stroma with acquisition of ASPS-like morphology and molecular features
Likely represents transdifferentiation or dedifferentiation of mesenchymal stromal cells.
Classification:
WHO Classification categorizes this as malignant phyllodes tumor with heterologous sarcomatous differentiation
ASPS component shows characteristic features with ASPSCR1-TFE3 fusion.
Epidemiology:
Extremely rare with fewer than 10 cases reported in medical literature
Peak age 30-50 years
Female predominance
Associated with poor prognosis and high metastatic potential.
Clinical Features
Presentation:
Large, rapidly growing breast mass
Usually painless initially
May become painful with rapid growth
Skin involvement possible in advanced cases.
Symptoms:
Progressive breast enlargement
Breast asymmetry
Skin changes over large tumors
Rarely nipple discharge
Constitutional symptoms in metastatic disease.
Risk Factors:
Previous history of phyllodes tumor
Young age
Possible genetic predisposition
No established environmental risk factors.
Screening:
No specific screening guidelines
Clinical breast examination
Imaging with mammography and MRI
Tissue sampling mandatory for diagnosis.
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Gross Description
Appearance:
Large, well-circumscribed to partially infiltrative mass
Cut surface shows variegated appearance with solid and cystic areas
Rich vascular network visible.
Characteristics:
Size typically >5 cm (range 4-15 cm)
Soft to firm consistency
Tan to pink cut surface
Prominent vascularity
Focal hemorrhage possible.
Size Location:
Can occur in any breast quadrant
Usually involves significant breast volume
Unilateral presentation
May extend to chest wall.
Multifocality:
Typically unifocal large lesion
Multifocal disease extremely rare
Local extension possible
Skin ulceration in advanced cases.
Microscopic Description
Histological Features:
Biphasic tumor with epithelial and mesenchymal components
Stromal areas show alveolar pattern with large polygonal cells
Rich sinusoidal vascular network.
Cellular Characteristics:
Large cells with abundant eosinophilic cytoplasm
Vesicular nuclei with prominent nucleoli
Low mitotic activity despite malignant behavior
PAS-positive diastase-resistant crystals.
Architectural Patterns:
Alveolar or nest-like arrangement separated by thin-walled vessels
Solid areas possible
Pseudo-alveolar spaces
Organoid pattern focally.
Grading Criteria:
Malignant phyllodes tumor criteria met
Paradoxically low mitotic rate despite aggressive behavior
Large cell size and nuclear atypia present.
Immunohistochemistry
Positive Markers:
TFE3 positive (nuclear - strong)
Melanoma markers (Melan-A, HMB-45) positive
MyoD1 positive
Epithelial component: CK7+, EMA+.
Negative Markers:
Desmin negative
SMA negative
S-100 negative
CD68 negative
Cytokeratins negative in stromal component.
Diagnostic Utility:
TFE3 nuclear positivity pathognomonic with molecular confirmation
Melanoma markers help support diagnosis
MyoD1 positivity characteristic.
Molecular Subtypes:
ASPSCR1-TFE3 fusion characteristic
TFE3 gene rearrangement
Different from renal cell carcinoma TFE3 fusions.
Molecular/Genetic
Genetic Mutations:
ASPSCR1-TFE3 fusion (pathognomonic)
TFE3 gene rearrangement at Xp11.2
Rare alternative fusion partners possible.
Molecular Markers:
TFE3 gene rearrangement by FISH
ASPSCR1 break-apart FISH
TFE3 protein overexpression
Low proliferation index.
Prognostic Significance:
ASPSCR1-TFE3 fusion confirms diagnosis
Slow growth but high metastatic potential
Late metastases characteristic.
Therapeutic Targets:
mTOR pathway inhibitors
Anti-angiogenic agents (sunitinib, pazopanib)
MET inhibitors under investigation
Immunotherapy trials ongoing.
Differential Diagnosis
Similar Entities:
Primary breast alveolar soft part sarcoma
Metastatic alveolar soft part sarcoma
Renal cell carcinoma metastasis
Granular cell tumor.
Distinguishing Features:
Phyllodes with ASPS: Leaf-like areas, ASPSCR1-TFE3 fusion
Primary ASPS: No epithelial component
RCC: Different TFE3 fusion, cytokeratin positive.
Diagnostic Challenges:
Recognition of ASPS features
Molecular confirmation essential
Distinction from other clear cell tumors
Assessment of phyllodes components.
Rare Variants:
Solid variant without alveolar pattern
Mixed with other sarcomatous elements
Dedifferentiated areas
Metastatic deposits to breast.
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
[diagnosis name]
Classification
Classification: [classification system] [grade/type]
Histological Features
Shows [architectural pattern] with [nuclear features] and [mitotic activity]
Size and Extent
Size: [X] cm, extent: [local/regional/metastatic]
Margins
Margins are [involved/uninvolved] with closest margin [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Lymph Node Status
Lymph nodes: [X] positive out of [X] examined
Special Studies
IHC: [marker]: [result]
Molecular: [test]: [result]
[other study]: [result]
Prognostic Factors
Prognostic factors: [list factors]
Final Diagnosis
Final diagnosis: [complete diagnosis]