Definition/General
Introduction:
Phyllodes tumor with large cell carcinoma is an extremely rare malignant phyllodes tumor where the stromal component contains large cell carcinoma, typically showing neuroendocrine or undifferentiated features
This represents one of the most aggressive forms of heterologous phyllodes tumor.
Origin:
Develops from intralobular breast stroma with dedifferentiation toward large cell carcinoma
May arise through transformation of stromal cells with loss of epithelial differentiation.
Classification:
WHO Classification categorizes this as malignant phyllodes tumor with heterologous elements
Large cell carcinoma component may show neuroendocrine or undifferentiated features.
Epidemiology:
Exceptionally rare with fewer than 10 cases reported in medical literature
Peak age 50-70 years
Female predominance
Associated with aggressive behavior and poor prognosis.
Clinical Features
Presentation:
Large, rapidly growing breast mass
Often presents with advanced local disease
May be associated with constitutional symptoms
Aggressive clinical course.
Symptoms:
Rapid breast enlargement over weeks to months
Constitutional symptoms (weight loss, fatigue, fever)
Breast pain and tenderness
Skin changes possible.
Risk Factors:
Previous phyllodes tumor history
Smoking history
Radiation exposure
Advanced age
Genetic predisposition to sarcomas.
Screening:
No specific screening available
Clinical examination for rapidly growing masses
Imaging with CT/PET for staging if diagnosed
Tissue diagnosis essential.
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Gross Description
Appearance:
Large, lobulated mass with firm to hard consistency
Cut surface shows gray-white to tan areas with necrosis and hemorrhage
Friable areas common.
Characteristics:
Size typically >5 cm (range 3-15 cm)
Irregular borders
Firm to hard consistency
Central necrosis common
Areas of hemorrhage and cystic degeneration.
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 necrotic areas within tumor
Local invasion possible
Extensive parenchymal involvement.
Microscopic Description
Histological Features:
Biphasic tumor with epithelial and mesenchymal components
Large cell carcinoma areas show sheets of large cells with high nuclear-cytoplasmic ratio
Prominent nucleoli and pleomorphism.
Cellular Characteristics:
Large cells with abundant cytoplasm
Pleomorphic nuclei with coarse chromatin
Prominent nucleoli
High mitotic rate
Multinucleated giant cells possible.
Architectural Patterns:
Sheets of large cells with minimal stroma
Solid growth pattern predominant
Geographic necrosis common
Vascular invasion frequent.
Grading Criteria:
High-grade carcinoma by definition
Marked nuclear pleomorphism
High mitotic rate (>10 per 10 HPF)
Necrosis commonly present.
Immunohistochemistry
Positive Markers:
Pancytokeratin focally positive
EMA focally positive
Vimentin positive
P53 overexpression common
Epithelial component: CK7+, EMA+.
Negative Markers:
Organ-specific markers negative (TTF-1, CDX2, PSA, PAX8)
Melanoma markers negative
Lymphoid markers negative.
Diagnostic Utility:
Broad-spectrum cytokeratins help confirm epithelial differentiation
Vimentin positivity supports mesenchymal component
P53 overexpression common.
Molecular Subtypes:
Large cell carcinoma with neuroendocrine features
Undifferentiated large cell carcinoma
Large cell carcinoma with squamous features.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (>80%)
RB1 alterations possible
KRAS mutations
Complex chromosomal alterations
High tumor mutational burden.
Molecular Markers:
p53 overexpression by immunohistochemistry
High Ki-67 proliferation index (>30%)
Loss of tumor suppressor genes common.
Prognostic Significance:
TP53 mutation associated with poor prognosis
High Ki-67 indicates aggressive behavior
Large size predicts worse outcome.
Therapeutic Targets:
Platinum-based chemotherapy
Immune checkpoint inhibitors
PARP inhibitors in select cases
Targeted therapy based on molecular profile.
Differential Diagnosis
Similar Entities:
Primary breast large cell carcinoma
Metastatic large cell carcinoma to breast
Anaplastic carcinoma
High-grade sarcoma
Undifferentiated pleomorphic sarcoma.
Distinguishing Features:
Phyllodes with large cell: Leaf-like areas, cytokeratin+
Primary large cell: No phyllodes component
Sarcoma: Cytokeratin negative.
Diagnostic Challenges:
Recognition of large cell features
Distinction from undifferentiated sarcoma
Assessment of phyllodes components
Differentiation from metastatic disease.
Rare Variants:
Large cell neuroendocrine carcinoma
Pleomorphic large cell carcinoma
Combined large cell and small cell 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]