Definition/General
Introduction:
Phyllodes tumor with malignant peripheral nerve sheath tumor (MPNST) is an extremely rare malignant phyllodes tumor where the stromal component shows neural differentiation consistent with MPNST
This represents one of the most aggressive forms of heterologous phyllodes tumor.
Origin:
Develops from intralobular breast stroma with acquisition of neural features and Schwann cell differentiation
May arise through transdifferentiation of mesenchymal stromal elements.
Classification:
WHO Classification categorizes this as malignant phyllodes tumor with heterologous sarcomatous elements
MPNST component shows characteristic neural markers and possible NF1 alterations.
Epidemiology:
Exceptionally rare with fewer than 15 cases reported in medical literature
Peak age 30-60 years
May be associated with neurofibromatosis type 1 (NF1) in some cases.
Clinical Features
Presentation:
Large, rapidly growing breast mass
Often painful
May be associated with neurological symptoms if large
Skin involvement possible.
Symptoms:
Progressive breast enlargement over months
Breast pain and tenderness
Possible nerve-related symptoms
Skin changes in advanced cases.
Risk Factors:
Neurofibromatosis type 1 (NF1)
Previous phyllodes tumor
Radiation exposure
Genetic predisposition to neural tumors
Family history of sarcomas.
Screening:
NF1 patients require regular surveillance
Clinical examination for masses
Imaging with MRI preferred for neural tumors
Genetic counseling if indicated.
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Gross Description
Appearance:
Large, lobulated mass with firm to hard consistency
Cut surface shows gray-white areas with possible yellow foci
Focal necrosis and hemorrhage.
Characteristics:
Size typically >6 cm (range 4-20 cm)
Irregular borders
Firm consistency
May have whorled appearance
Areas of myxoid change possible.
Size Location:
Can occur in any breast region
Usually involves significant breast volume
Unilateral presentation
May extend to chest wall.
Multifocality:
Typically unifocal large lesion
Multiple nodules rare
Local extension possible
Skin involvement in large tumors.
Microscopic Description
Histological Features:
Biphasic tumor with epithelial and mesenchymal components
MPNST areas show fascicular pattern with spindle cells
Neural differentiation with Schwann cell features.
Cellular Characteristics:
Spindle-shaped cells with wavy nuclei
Moderate to marked nuclear atypia
High mitotic activity (>4 per 10 HPF)
Perivascular accentuation.
Architectural Patterns:
Fascicular arrangement in intersecting bundles
Herringbone pattern
Storiform areas possible
Perivascular hypercellularity
Myxoid change focally.
Grading Criteria:
High-grade malignant phyllodes tumor
MPNST requires high-grade features
Mitotic rate >4 per 10 HPF
Marked nuclear atypia.
Immunohistochemistry
Positive Markers:
S-100 protein focally positive (weak, <50%)
SOX10 focally positive
p53 overexpression common
Epithelial component: CK7+, EMA+.
Negative Markers:
Desmin negative
SMA negative
CD34 negative
Neurofilament negative
Synaptophysin negative.
Diagnostic Utility:
S-100 focal positivity supports neural differentiation
SOX10 helps confirm Schwann cell origin
p53 overexpression common in MPNST.
Molecular Subtypes:
NF1-associated MPNST
Sporadic MPNST
Radiation-induced MPNST
Epithelioid MPNST variant rare.
Molecular/Genetic
Genetic Mutations:
NF1 gene inactivation (in NF1-associated cases)
TP53 mutations (70-80%)
CDKN2A/B deletions
SUZ12 or EED mutations.
Molecular Markers:
Loss of NF1 protein expression
p53 overexpression
Loss of H3K27me3 (EED/SUZ12 mutations)
High Ki-67 index.
Prognostic Significance:
NF1 status affects prognosis
Large size (>5 cm) predicts poor outcome
High-grade features indicate aggressive behavior.
Therapeutic Targets:
MEK inhibitors for NF1-deficient tumors
mTOR pathway inhibitors
HDAC inhibitors under study
Immune checkpoint inhibitors in trials.
Differential Diagnosis
Similar Entities:
Primary breast MPNST
Metastatic MPNST
Malignant phyllodes tumor with fibrosarcoma
Spindle cell carcinoma
Synovial sarcoma.
Distinguishing Features:
Phyllodes with MPNST: Leaf-like areas, focal S-100
Primary MPNST: No epithelial component
Synovial sarcoma: TLE1+, SS18 fusion.
Diagnostic Challenges:
Recognition of neural features
Focal S-100 positivity
Distinction from other spindle cell sarcomas
Assessment of NF1 status.
Rare Variants:
Epithelioid MPNST
Glandular MPNST
MPNST with rhabdomyoblastic differentiation
Combined patterns.
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]