Definition/General
Introduction:
Phyllodes tumor with medullary carcinoma is an extremely rare malignant phyllodes tumor where the stromal component contains medullary carcinoma characterized by syncytial growth pattern, lymphoplasmacytic infiltrate, and pushing borders.
Origin:
Develops from intralobular breast stroma with differentiation toward medullary carcinoma
May arise through specific genetic alterations leading to medullary-type carcinoma features.
Classification:
WHO Classification categorizes this as malignant phyllodes tumor with heterologous elements
Medullary carcinoma component shows characteristic syncytial growth and lymphoid infiltrate.
Epidemiology:
Exceptionally rare with fewer than 10 cases reported worldwide
Peak age 45-65 years
Female predominance
May be associated with BRCA1 mutations.
Clinical Features
Presentation:
Large, rapidly growing breast mass
Usually presents as well-circumscribed mass
May show rapid enlargement over months
Often clinically suspicious.
Symptoms:
Progressive breast enlargement
Usually painless initially
May become symptomatic with rapid growth
Breast asymmetry
Constitutional symptoms rare.
Risk Factors:
Previous phyllodes tumor history
BRCA1 mutations possible
Ashkenazi Jewish ancestry
Family history of breast/ovarian cancer
Young age.
Screening:
No specific screening available
Clinical examination for rapidly growing masses
BRCA testing if family history
Imaging with mammography and MRI.
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Gross Description
Appearance:
Large, well-circumscribed mass with soft to firm consistency
Cut surface shows gray-white areas with possible hemorrhage
Fleshy appearance typical.
Characteristics:
Size typically >4 cm (range 3-15 cm)
Soft to firm consistency
Well-circumscribed borders
Fleshy, brain-like appearance
Hemorrhage and necrosis possible.
Size Location:
Can occur in any breast region
Usually involves significant breast tissue
Unilateral presentation
Well-demarcated from surrounding tissue.
Multifocality:
Typically unifocal mass
Medullary areas may be multifocal within tumor
Pushing borders characteristic
Local extension uncommon.
Microscopic Description
Histological Features:
Biphasic tumor with epithelial and mesenchymal components
Medullary carcinoma areas show syncytial growth pattern with sheets of cells and dense lymphoplasmacytic infiltrate.
Cellular Characteristics:
Large pleomorphic cells with high nuclear grade
Vesicular nuclei with prominent nucleoli
High mitotic rate
Syncytial growth without glandular differentiation.
Architectural Patterns:
Syncytial sheets of tumor cells
Pushing borders with surrounding tissue
Dense lymphoplasmacytic infiltrate at periphery
Minimal stromal desmoplasia.
Grading Criteria:
High nuclear grade (Grade 3)
High mitotic rate
Syncytial growth pattern
Dense lymphoid infiltrate
Pushing borders required for diagnosis.
Immunohistochemistry
Positive Markers:
Cytokeratins positive (usually CK5/6 positive)
p53 overexpression common
High Ki-67 index
EGFR positive
Epithelial component: CK7+, EMA+.
Negative Markers:
Estrogen receptor negative
Progesterone receptor negative
HER2 negative (triple-negative)
E-cadherin may be decreased.
Diagnostic Utility:
Triple-negative phenotype characteristic
CK5/6 positivity supports medullary features
p53 overexpression common
High proliferation index.
Molecular Subtypes:
Triple-negative medullary carcinoma
BRCA1-associated type
Basal-like molecular subtype
Medullary-like carcinoma.
Molecular/Genetic
Genetic Mutations:
BRCA1 mutations (up to 15% of medullary carcinomas)
TP53 mutations (>80%)
PIK3CA mutations
High tumor mutational burden.
Molecular Markers:
Basal-like gene expression profile
High proliferation signature
DNA damage response pathway alterations
Homologous recombination deficiency.
Prognostic Significance:
BRCA1 mutations predict better response to platinum therapy
High tumor mutational burden may predict immunotherapy response
Triple-negative status affects treatment.
Therapeutic Targets:
PARP inhibitors (if BRCA1 mutated)
Immune checkpoint inhibitors
Platinum-based chemotherapy
Anti-EGFR therapy.
Differential Diagnosis
Similar Entities:
Primary medullary carcinoma of breast
Atypical medullary carcinoma
Invasive ductal carcinoma with medullary features
Large cell lymphoma.
Distinguishing Features:
Phyllodes with medullary: Leaf-like areas, triple-negative
Primary medullary: No phyllodes component
Lymphoma: LCA positive, cytokeratin negative.
Diagnostic Challenges:
Recognition of medullary features
Distinction from high-grade ductal carcinoma
Assessment of phyllodes components
Lymphoid infiltrate evaluation.
Rare Variants:
Medullary carcinoma with squamous differentiation
Atypical medullary carcinoma
Mixed medullary and ductal 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]