Definition/General

Introduction:
-Phyllodes tumor with epithelioid sarcoma is an extremely rare malignant phyllodes tumor where the stromal component shows epithelioid sarcoma differentiation
-This represents one of the most aggressive forms of heterologous phyllodes tumor with poor prognosis.
Origin:
-Develops from intralobular breast stroma with acquisition of epithelioid sarcoma features
-May arise through dedifferentiation of stromal elements with loss of INI1/SMARCB1 expression.
Classification:
-WHO Classification categorizes this as malignant phyllodes tumor with heterologous sarcomatous elements
-Epithelioid sarcoma component shows characteristic INI1/SMARCB1 loss.
Epidemiology:
-Exceptionally rare with fewer than 10 cases described in literature
-Peak age 30-50 years
-Female predominance
-Associated with high local recurrence and metastatic rates.

Clinical Features

Presentation:
-Rapidly growing, often painful breast mass
-Large size at presentation
-May present with skin involvement or ulceration in advanced cases.
Symptoms:
-Progressive breast enlargement
-Breast pain and tenderness
-Skin changes over tumor
-Nipple retraction possible
-Constitutional symptoms rare.
Risk Factors:
-Previous phyllodes tumor history
-Young to middle age
-Genetic predisposition to sarcomas possible
-No established environmental factors.
Screening:
-No specific screening available
-Clinical examination for rapidly growing masses
-Imaging with ultrasound, mammography, and MRI essential.

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Gross Description

Appearance:
-Large, multinodular mass with firm to hard consistency
-Cut surface shows gray-white to tan areas with possible central necrosis
-Hemorrhage may be present.
Characteristics:
-Size typically >5 cm (range 3-15 cm)
-Irregular borders
-Firm consistency
-Focal cystic degeneration possible
-Areas of necrosis common.
Size Location:
-Can occur in any breast quadrant
-Usually involves significant breast tissue
-Unilateral presentation
-May extend to pectoral fascia.
Multifocality:
-Typically unifocal large mass
-Satellite nodules possible
-Local invasion in advanced cases
-Skin involvement in large tumors.

Microscopic Description

Histological Features:
-Biphasic tumor with epithelial and mesenchymal components
-Epithelioid sarcoma areas show nodular growth with epithelioid cells
-Central necrosis with peripheral viable rim.
Cellular Characteristics:
-Large epithelioid cells with abundant eosinophilic cytoplasm
-Vesicular nuclei with prominent nucleoli
-Moderate to high mitotic activity
-Occasional multinucleated cells.
Architectural Patterns:
-Nodular growth pattern with central necrosis
-Granuloma-like appearance
-Fascicular areas possible
-Hemorrhage and inflammation.
Grading Criteria:
-High-grade malignant phyllodes tumor
-Marked stromal overgrowth
-High mitotic rate
-Significant nuclear atypia
-Geographic necrosis.

Immunohistochemistry

Positive Markers:
-EMA positive (strong)
-Cytokeratins focally positive
-CD34 positive
-FLI-1 positive
-Epithelial component: CK7+, EMA+.
Negative Markers:
-INI1/SMARCB1 negative (loss of expression - diagnostic)
-Desmin negative
-S-100 negative
-Melanoma markers negative.
Diagnostic Utility:
-Loss of INI1/SMARCB1 pathognomonic for epithelioid sarcoma
-EMA and cytokeratin positivity supportive
-CD34 positivity characteristic.
Molecular Subtypes:
-Classical epithelioid sarcoma (distal type)
-Proximal epithelioid sarcoma (large cell type)
-Loss of SMARCB1 gene function.

Molecular/Genetic

Genetic Mutations:
-SMARCB1 gene inactivation (22q11.23)
-Homozygous deletion or mutation
-Rarely SMARCA4 alterations
-Complex karyotype.
Molecular Markers:
-INI1/SMARCB1 protein loss by immunohistochemistry
-SMARCB1 gene deletion by FISH
-High Ki-67 proliferation index.
Prognostic Significance:
-SMARCB1 loss confirms diagnosis
-Large size (>5 cm) predicts poor prognosis
-Proximal location associated with worse outcome.
Therapeutic Targets:
-EZH2 inhibitors (tazemetostat approved)
-HDAC inhibitors under study
-mTOR pathway inhibitors
-Immunotherapy trials.

Differential Diagnosis

Similar Entities:
-Primary epithelioid sarcoma of breast
-Metastatic epithelioid sarcoma
-Poorly differentiated carcinoma
-Anaplastic large cell lymphoma.
Distinguishing Features:
-Phyllodes with epithelioid sarcoma: Leaf-like areas, SMARCB1 loss
-Primary epithelioid sarcoma: No phyllodes component
-Carcinoma: SMARCB1 retained.
Diagnostic Challenges:
-Recognition of epithelioid features
-INI1 staining essential
-Distinction from carcinoma
-Assessment of phyllodes components.
Rare Variants:
-Proximal type (large cell)
-Classical distal type
-Rhabdoid features
-Combined with other sarcomas.

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]