Definition/General
Introduction:
Clear cell carcinoma of the breast is a rare subtype of invasive breast cancer characterized by a predominance of cells with clear cytoplasm due to the accumulation of glycogen
It is a diagnosis of exclusion, and metastasis from other sites (e.g., kidney, ovary) must be ruled out.
Origin:
It is thought to be a variant of adenocarcinoma with extensive clear cell change
The clear cell appearance is due to intracytoplasmic glycogen.
Classification:
It is classified as a rare subtype of invasive breast carcinoma
It is also known as glycogen-rich clear cell carcinoma.
Epidemiology:
Extremely rare, accounting for 1-3% of all breast cancers
It primarily affects postmenopausal women.
Clinical Features
Presentation:
Presents as a palpable breast mass
The clinical and radiological features are non-specific.
Symptoms:
A painless breast lump is the most common symptom.
Risk Factors:
The risk factors are similar to those for conventional breast cancer.
Screening:
Usually diagnosed after investigation of a palpable mass
Mammographic and ultrasound findings are non-specific.
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Gross Description
Appearance:
A well-circumscribed or infiltrative, firm, gray-white mass.
Characteristics:
Size is variable
The cut surface is typically solid.
Size Location:
Can occur anywhere in the breast.
Multifocality:
Rare.
Microscopic Description
Histological Features:
The tumor is composed of sheets and nests of polygonal cells with abundant clear cytoplasm and distinct cell borders
The cytoplasm is clear due to glycogen, which is positive with PAS stain and sensitive to diastase.
Cellular Characteristics:
The nuclei are typically pleomorphic with prominent nucleoli
Mitotic activity is variable.
Architectural Patterns:
The growth pattern is usually solid or nested.
Grading Criteria:
These tumors are often high-grade.
Immunohistochemistry
Positive Markers:
The tumor cells are positive for cytokeratins (e.g., CK7)
They are often ER and PR positive.
Negative Markers:
HER2 is usually negative
It is important to use a panel to exclude metastasis, including markers like PAX8 and RCC (for renal cell carcinoma) and WT1 (for ovarian serous carcinoma).
Diagnostic Utility:
IHC is crucial to confirm the epithelial nature of the tumor and to exclude metastasis from other sites.
Molecular Subtypes:
Most are of the Luminal A or B molecular subtype.
Molecular/Genetic
Genetic Mutations:
The molecular genetics are not well characterized but may involve pathways similar to luminal breast cancers.
Molecular Markers:
No specific molecular markers are routinely used for diagnosis.
Prognostic Significance:
The prognosis is thought to be similar to or slightly worse than that of adenocarcinoma NST of similar grade and stage.
Therapeutic Targets:
Treatment is similar to that of conventional breast cancer, based on ER, PR, and HER2 status.
Differential Diagnosis
Similar Entities:
Metastatic clear cell carcinoma (kidney, ovary, lung)
Lipid-rich carcinoma
Secretory carcinoma.
Distinguishing Features:
Metastatic renal cell carcinoma is positive for PAX8 and RCC
Lipid-rich carcinoma has lipid vacuoles instead of glycogen
Secretory carcinoma has eosinophilic secretions and the ETV6-NTRK3 fusion.
Diagnostic Challenges:
The main challenge is excluding a metastasis, which is much more common than primary clear cell carcinoma of the breast.
Rare Variants:
The entire entity is a rare variant.
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]
Final Diagnosis
Final diagnosis: [complete diagnosis]