Definition/General

Introduction:
-Phyllodes tumor with clear cell sarcoma is an extremely rare malignant phyllodes tumor where the stromal component shows clear cell sarcoma (melanoma of soft parts) differentiation
-This represents one of the most unusual forms of heterologous phyllodes tumor.
Origin:
-Arises from intralobular breast stroma with development of clear cell sarcoma features
-Clear cell sarcoma typically arises from tendons and aponeuroses, making breast location highly unusual.
Classification:
-WHO Classification categorizes this as malignant phyllodes tumor with heterologous sarcomatous elements
-Clear cell sarcoma component shows characteristic EWSR1-ATF1 or EWSR1-CREB1 fusions.
Epidemiology:
-Exceptionally rare with fewer than 5 cases reported worldwide
-Peak age 40-60 years
-Female predominance
-Associated with aggressive behavior and poor prognosis.

Clinical Features

Presentation:
-Large, rapidly growing breast mass
-May be initially painless but becomes symptomatic
-Potential for skin involvement in advanced cases.
Symptoms:
-Progressive breast enlargement over weeks to months
-Breast asymmetry
-Skin changes possible
-Constitutional symptoms rare unless metastatic.
Risk Factors:
-Previous phyllodes tumor history
-Young to middle age
-No established genetic predisposition
-Possible association with trauma.
Screening:
-No specific screening available
-Clinical examination for masses
-Imaging with ultrasound and MRI
-Biopsy essential for diagnosis.

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Gross Description

Appearance:
-Large, lobulated mass with variable consistency
-Cut surface shows gray-white to tan areas
-May have darker pigmented foci
-Focal necrosis possible.
Characteristics:
-Size typically >4 cm (range 3-12 cm)
-Firm to hard consistency
-Partially circumscribed borders
-Focal leaf-like clefts may be present.
Size Location:
-Can occur in any breast region
-Usually unilateral
-May involve significant breast volume
-Extension to chest wall possible.
Multifocality:
-Typically unifocal mass
-Multifocal disease not reported
-Satellite nodules rare
-Local invasion in advanced cases.

Microscopic Description

Histological Features:
-Biphasic tumor with epithelial and mesenchymal components
-Clear cell sarcoma areas show nested pattern with clear to lightly eosinophilic cytoplasm
-Melanin pigment may be present.
Cellular Characteristics:
-Cells with clear to pale eosinophilic cytoplasm
-Vesicular nuclei with prominent nucleoli
-Moderate mitotic activity
-Occasional multinucleated giant cells.
Architectural Patterns:
-Nested to fascicular growth pattern
-Prominent vascular network
-Alveolar arrangement focally
-Storiform pattern in some areas.
Grading Criteria:
-Malignant phyllodes tumor criteria
-High-grade stromal component
-Moderate to high mitotic rate
-Nuclear pleomorphism present.

Immunohistochemistry

Positive Markers:
-S-100 protein strongly positive
-Melanoma markers (Melan-A, HMB-45) positive
-SOX10 positive
-Epithelial component: CK7+, EMA+.
Negative Markers:
-Desmin negative
-SMA negative
-CD68 negative
-Cytokeratins negative in stromal component
-CD34 negative.
Diagnostic Utility:
-S-100 strong positivity characteristic
-Melanoma markers support diagnosis
-SOX10 positivity helpful
-Combined with molecular studies confirmatory.
Molecular Subtypes:
-EWSR1-ATF1 fusion (most common)
-EWSR1-CREB1 fusion (less common)
-EWSR1 gene rearrangement pathognomonic.

Molecular/Genetic

Genetic Mutations:
-EWSR1-ATF1 fusion (90% of clear cell sarcomas)
-EWSR1-CREB1 fusion (5-10%)
-Rare other EWSR1 fusion partners.
Molecular Markers:
-EWSR1 gene rearrangement by FISH
-ATF1 or CREB1 break-apart studies
-Strong S-100 expression
-Moderate Ki-67 index.
Prognostic Significance:
-EWSR1-ATF1 fusion confirms diagnosis
-High propensity for local recurrence
-Metastatic potential significant
-Late metastases possible.
Therapeutic Targets:
-Limited targeted options
-mTOR inhibitors under study
-Anti-angiogenic agents
-Immunotherapy in clinical trials.

Differential Diagnosis

Similar Entities:
-Primary clear cell sarcoma of breast
-Metastatic clear cell sarcoma
-Metastatic melanoma
-Clear cell renal cell carcinoma metastasis.
Distinguishing Features:
-Phyllodes with clear cell sarcoma: Leaf-like areas, EWSR1-ATF1 fusion
-Melanoma: Different genetics, clinical history
-RCC: Cytokeratin positive.
Diagnostic Challenges:
-Recognition of clear cell sarcoma features
-Molecular confirmation essential
-Distinction from melanoma
-Assessment of phyllodes component.
Rare Variants:
-Amelanotic variant
-Pigmented variant
-Mixed with other sarcomatous elements
-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]