Definition/General

Introduction:
-Phyllodes tumor with melanoma is an extraordinarily rare malignant phyllodes tumor where the stromal component shows melanocytic differentiation consistent with melanoma
-This represents one of the most unusual forms of heterologous phyllodes tumor.
Origin:
-Develops from intralobular breast stroma with acquisition of melanocytic features
-May arise through neural crest cell migration during development or transdifferentiation of stromal cells.
Classification:
-WHO Classification categorizes this as malignant phyllodes tumor with heterologous elements
-Melanoma component shows characteristic melanocytic markers and possible BRAF/NRAS mutations.
Epidemiology:
-Exceptionally rare with fewer than 10 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 show surface pigmentation
-Usually painless initially but becomes symptomatic with growth.
Symptoms:
-Progressive breast enlargement
-Visible pigmentation possible
-Breast asymmetry
-Skin changes over tumor
-Constitutional symptoms rare.
Risk Factors:
-Previous phyllodes tumor history
-UV exposure history
-Family history of melanoma
-Dysplastic nevus syndrome
-Fair skin type.
Screening:
-No specific screening guidelines
-Clinical examination for pigmented lesions
-Dermoscopy if surface pigmentation
-Full skin examination recommended.

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Gross Description

Appearance:
-Large, lobulated mass with variable consistency
-Cut surface may show dark pigmented areas
-Gray-white to black coloration possible
-Focal necrosis.
Characteristics:
-Size typically >4 cm (range 3-12 cm)
-Firm to hard consistency
-Irregular borders
-Pigmented areas variably present
-Hemorrhage possible.
Size Location:
-Can occur in any breast quadrant
-Usually involves significant breast tissue
-Unilateral presentation
-May extend to skin.
Multifocality:
-Typically unifocal mass
-Satellite lesions rare
-Pigmented skin involvement possible
-Local extension in advanced cases.

Microscopic Description

Histological Features:
-Biphasic tumor with epithelial and mesenchymal components
-Melanoma areas show epithelioid to spindled cells
-Melanin pigment variably present
-Junctional activity absent.
Cellular Characteristics:
-Epithelioid to spindle-shaped melanocytes
-Large vesicular nuclei with prominent nucleoli
-Moderate to high mitotic activity
-Melanin pigment variable.
Architectural Patterns:
-Nested to sheet-like growth pattern
-Alveolar arrangement possible
-Spindle cell areas
-No surface junctional component.
Grading Criteria:
-High-grade malignant phyllodes tumor
-Melanoma requires high-grade cytologic features
-Mitotic rate variable
-Nuclear pleomorphism present.

Immunohistochemistry

Positive Markers:
-S-100 protein strongly positive
-Melanoma markers (Melan-A, HMB-45) positive
-SOX10 positive
-MITF positive
-Epithelial component: CK7+, EMA+.
Negative Markers:
-Cytokeratins negative in melanoma component
-Desmin negative
-SMA negative
-CD68 negative
-TTF-1 negative.
Diagnostic Utility:
-S-100 strong positivity characteristic
-Melanoma cocktail (Melan-A, HMB-45) confirmatory
-SOX10 and MITF support melanocytic differentiation.
Molecular Subtypes:
-BRAF-mutated melanoma
-NRAS-mutated melanoma
-Triple wild-type melanoma
-KIT-mutated (rare)
-Different from cutaneous melanoma.

Molecular/Genetic

Genetic Mutations:
-BRAF mutations (40-50%)
-NRAS mutations (20-30%)
-KIT mutations (rare)
-CDKN2A deletions
-TP53 mutations possible.
Molecular Markers:
-BRAF V600E mutation (if present)
-NRAS mutations
-High Ki-67 proliferation index
-Melanoma-associated copy number alterations.
Prognostic Significance:
-BRAF mutation status affects targeted therapy options
-Large size predicts poor prognosis
-High mitotic rate adverse factor.
Therapeutic Targets:
-BRAF inhibitors (vemurafenib, dabrafenib) if BRAF-mutated
-MEK inhibitors
-Immune checkpoint inhibitors (pembrolizumab, nivolumab).

Differential Diagnosis

Similar Entities:
-Primary breast melanoma
-Metastatic melanoma to breast
-Melanoma metastatic to phyllodes tumor
-Pigmented sarcoma
-Clear cell sarcoma.
Distinguishing Features:
-Phyllodes with melanoma: Leaf-like areas, melanoma markers
-Primary melanoma: No phyllodes component
-Metastatic: Clinical history, imaging.
Diagnostic Challenges:
-Recognition of melanocytic features
-Distinction from metastatic melanoma
-Assessment of phyllodes components
-Molecular confirmation helpful.
Rare Variants:
-Amelanotic variant
-Spindle cell melanoma
-Desmoplastic melanoma
-Combined nevus-melanoma features.

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]