Definition/General

Introduction:
-Phyllodes tumor with clear cell carcinoma is an extremely rare malignant phyllodes tumor where the stromal component contains clear cell carcinoma characterized by cells with clear cytoplasm due to glycogen accumulation
-This represents a unique form of heterologous phyllodes tumor.
Origin:
-Develops from intralobular breast stroma with differentiation toward clear cell carcinoma
-May arise through metabolic alterations in stromal cells leading to glycogen accumulation and clear cell morphology.
Classification:
-WHO Classification categorizes this as malignant phyllodes tumor with heterologous elements
-Clear cell carcinoma component shows characteristic clear cytoplasm and specific immunoprofile.
Epidemiology:
-Exceptionally rare with fewer than 10 cases reported in medical literature
-Peak age 40-65 years
-Female predominance
-Clinical behavior depends on grade and size.

Clinical Features

Presentation:
-Large, slowly to rapidly growing breast mass
-Usually presents as painless mass
-May show progressive enlargement over months to years.
Symptoms:
-Progressive breast enlargement
-Breast asymmetry
-Usually painless initially
-May become symptomatic with large size
-Skin changes in advanced cases.
Risk Factors:
-Previous phyllodes tumor history
-Middle to older age
-Diabetes mellitus possible association
-No specific genetic predisposition identified.
Screening:
-No specific screening available
-Clinical examination for masses
-Imaging with mammography, ultrasound, and MRI
-Tissue diagnosis essential.

Master Phyllodes Tumor with Clear Cell Carcinoma Pathology with RxDx

Access 100+ pathology videos and expert guidance with the RxDx app

Gross Description

Appearance:
-Large, well-circumscribed to partially circumscribed mass
-Cut surface shows gray-white areas with possible clear or translucent appearance
-Variable consistency.
Characteristics:
-Size typically >3 cm (range 2-10 cm)
-Soft to firm consistency
-May have characteristic clear or glassy areas
-Focal cystic change possible.
Size Location:
-Can occur in any breast region
-Usually involves moderate to significant breast tissue
-Unilateral presentation typical.
Multifocality:
-Typically unifocal mass
-Multifocal clear cell areas within tumor
-Satellite lesions rare
-Local extension uncommon.

Microscopic Description

Histological Features:
-Biphasic tumor with epithelial and mesenchymal components
-Clear cell carcinoma areas show cells with clear, glycogen-rich cytoplasm
-Well-defined cell borders.
Cellular Characteristics:
-Cells with clear, optically empty cytoplasm
-Small to moderate-sized nuclei
-Glycogen-rich cytoplasm (PAS positive)
-Low to moderate mitotic activity.
Architectural Patterns:
-Solid nests and sheets of clear cells
-Trabecular pattern possible
-Rich vascular network
-Minimal stromal component in clear cell areas.
Grading Criteria:
-Variable grade depending on nuclear features and mitotic activity
-Low-grade: minimal atypia, <5 mitoses/10 HPF
-High-grade: marked atypia, >10 mitoses/10 HPF.

Immunohistochemistry

Positive Markers:
-Cytokeratins positive (broad spectrum)
-EMA positive
-Periodic acid-Schiff (PAS) positive (diastase sensitive)
-CEA may be positive
-Epithelial component: CK7+, EMA+.
Negative Markers:
-Renal cell carcinoma markers negative (CD10, RCC marker)
-Hepatocyte markers negative
-S-100 negative
-Melanoma markers negative.
Diagnostic Utility:
-PAS positivity (diastase sensitive) confirms glycogen
-Cytokeratin positivity confirms epithelial nature
-Negative RCC markers exclude metastatic renal cell carcinoma.
Molecular Subtypes:
-Glycogen-rich clear cell carcinoma
-Lipid-rich clear cell carcinoma
-Mixed clear cell and conventional carcinoma.

Molecular/Genetic

Genetic Mutations:
-PIK3CA mutations possible
-mTOR pathway alterations
-TP53 mutations in high-grade tumors
-Metabolic pathway gene alterations.
Molecular Markers:
-Altered glucose metabolism
-High glycogen content
-Variable Ki-67 index depending on grade
-mTOR pathway activation.
Prognostic Significance:
-Grade most important prognostic factor
-Low-grade tumors have better prognosis
-Size and mitotic rate important
-Complete excision crucial.
Therapeutic Targets:
-mTOR inhibitors (everolimus)
-PI3K pathway inhibitors
-Metabolic targeting approaches
-Conventional chemotherapy for high-grade tumors.

Differential Diagnosis

Similar Entities:
-Metastatic renal cell carcinoma
-Glycogen-rich carcinoma of breast
-Lipid-rich carcinoma
-Secretory carcinoma
-Metastatic adrenal cortical carcinoma.
Distinguishing Features:
-Phyllodes with clear cell: Leaf-like areas, PAS+ (diastase sensitive)
-RCC metastasis: CD10+, RCC marker+
-Secretory carcinoma: S-100+.
Diagnostic Challenges:
-Recognition of clear cell features
-Distinction from metastatic clear cell tumors
-Assessment of phyllodes components
-PAS staining interpretation.
Rare Variants:
-Clear cell carcinoma with squamous differentiation
-Mixed clear cell and mucinous carcinoma
-Clear cell with neuroendocrine 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]