Definition/General
Introduction:
Phyllodes tumor with metaplastic carcinoma is an extremely rare malignant phyllodes tumor where the stromal component contains metaplastic carcinoma characterized by squamous differentiation, spindle cell features, and/or heterologous elements.
Origin:
Develops from intralobular breast stroma with differentiation toward metaplastic carcinoma
May arise through epithelial-mesenchymal transition and loss of epithelial characteristics.
Classification:
WHO Classification categorizes this as malignant phyllodes tumor with heterologous elements
Metaplastic carcinoma component may show squamous, spindle cell, or sarcomatoid differentiation.
Epidemiology:
Exceptionally rare with fewer than 15 cases reported worldwide
Peak age 45-65 years
Female predominance
Generally associated with aggressive behavior and poor prognosis.
Clinical Features
Presentation:
Large, rapidly growing breast mass
Usually presents as irregular, poorly circumscribed mass
May show rapid enlargement over weeks to months
Often clinically suspicious.
Symptoms:
Progressive rapid breast enlargement
May be painful due to rapid growth
Skin changes possible with large tumors
Breast asymmetry
Constitutional symptoms rare.
Risk Factors:
Previous phyllodes tumor history
Prior radiation exposure
BRCA1/2 mutations possible
Family history of breast cancer
Older age.
Screening:
No specific screening available
Clinical examination for rapidly growing masses
Imaging with mammography and MRI
Core needle biopsy may be challenging.
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Gross Description
Appearance:
Large, irregular mass with firm to hard consistency
Cut surface shows gray-white areas with possible hemorrhage and necrosis
Heterogeneous appearance typical.
Characteristics:
Size typically >5 cm (range 3-20 cm)
Firm to hard consistency
Irregular borders
Heterogeneous cut surface
Hemorrhage and necrosis common.
Size Location:
Can occur in any breast region
Usually involves significant breast tissue
Unilateral presentation
May infiltrate surrounding structures.
Multifocality:
Typically unifocal mass
Metaplastic areas may be multifocal within tumor
Infiltrative borders
Local extension possible.
Microscopic Description
Histological Features:
Biphasic tumor with epithelial and mesenchymal components
Metaplastic carcinoma areas show squamous differentiation, spindle cell features, or heterologous elements like chondrosarcoma or osteosarcoma.
Cellular Characteristics:
Pleomorphic cells with variable morphology
Squamous cells with keratinization
Spindle cells resembling sarcoma
High nuclear grade
High mitotic activity.
Architectural Patterns:
Loss of glandular architecture
Squamous nests with keratinization
Spindle cell fascicles
Sarcomatoid areas
Infiltrative growth pattern.
Grading Criteria:
High nuclear grade (Grade 3)
High mitotic rate (>20 per 10 HPF)
Marked pleomorphism
Necrosis common
Poor differentiation.
Immunohistochemistry
Positive Markers:
Cytokeratins may be focal or negative
p63 positive in squamous areas
Vimentin positive in spindle areas
SMA may be positive
Epithelial component variable.
Negative Markers:
Estrogen receptor negative
Progesterone receptor negative
HER2 negative (triple-negative)
E-cadherin often lost.
Diagnostic Utility:
Triple-negative phenotype characteristic
p63 highlights squamous differentiation
Vimentin confirms mesenchymal features
CK cocktail may be focal.
Molecular Subtypes:
Triple-negative metaplastic carcinoma
Basal-like molecular subtype
Claudin-low subtype possible
Sarcomatoid type.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (>80%)
PIK3CA mutations
PTEN loss
Wnt pathway alterations
EMT-related gene expression changes.
Molecular Markers:
Basal-like gene expression profile
EMT signature activation
High proliferation markers
DNA damage response alterations.
Prognostic Significance:
Poor prognosis due to triple-negative status and high grade
Metaplastic features predict chemotherapy resistance
High recurrence rate.
Therapeutic Targets:
Limited therapeutic options
Platinum-based chemotherapy
Immune checkpoint inhibitors
PI3K/mTOR inhibitors
Anti-angiogenic therapy.
Differential Diagnosis
Similar Entities:
Primary metaplastic carcinoma of breast
Sarcoma of breast
Phyllodes tumor with sarcomatous overgrowth
Spindle cell carcinoma
Carcinosarcoma.
Distinguishing Features:
Phyllodes with metaplastic: Leaf-like areas, biphasic tumor
Primary metaplastic: No phyllodes component
Sarcoma: Negative cytokeratins.
Diagnostic Challenges:
Recognition of metaplastic features
Distinction from sarcoma
Assessment of epithelial vs mesenchymal components
Immunohistochemical interpretation.
Rare Variants:
Squamous cell carcinoma
Spindle cell carcinoma
Carcinosarcoma with heterologous elements
Matrix-producing carcinoma.
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]