Definition/General
Introduction:
Metaplastic carcinoma of the breast is a rare and aggressive subtype of invasive breast cancer, accounting for less than 1% of all cases
It is characterized by the presence of both glandular (carcinomatous) and non-glandular (sarcomatous) components
The non-glandular component can be squamous, spindle cell, osseous, or chondroid.
Origin:
The exact origin is debated, but it is thought to arise from the metaplastic transformation of mammary epithelial cells or myoepithelial cells
This transformation leads to a tumor with a mixture of epithelial and mesenchymal elements.
Classification:
Classified based on the type of mesenchymal differentiation
Subtypes include: Squamous cell carcinoma
Spindle cell carcinoma
Carcinoma with osseous metaplasia
Carcinoma with chondroid metaplasia
Mixed metaplastic carcinoma.
Epidemiology:
Typically affects women in their 50s and 60s
It is more common in African American women
It often presents as a large, rapidly growing mass
It is less likely to have axillary lymph node involvement at diagnosis compared to IDC.
Clinical Features
Presentation:
Presents as a large, palpable, well-circumscribed mass
Skin changes such as ulceration or fixation can occur due to the large size
Nipple discharge is uncommon.
Symptoms:
A rapidly growing, often painless breast mass
Skin redness or ulceration may be present
Axillary lymphadenopathy is less common than in IDC of similar size.
Risk Factors:
Risk factors are not well-defined but are generally similar to other breast cancers
No specific genetic predispositions have been strongly linked, although some association with BRCA1 mutations has been suggested.
Screening:
Often presents as a palpable mass rather than being detected by screening mammography
On mammography, it typically appears as a well-circumscribed, high-density mass, which can mimic a benign lesion.
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Gross Description
Appearance:
Usually a large, well-circumscribed, firm to hard mass
The cut surface is often variegated, with fleshy, gray-white areas mixed with areas of hemorrhage, necrosis, or cystic change
Osseous or chondroid components may be grossly apparent.
Characteristics:
The tumor size is typically larger than that of IDC at diagnosis, often exceeding 2 cm
The consistency can be variable depending on the components, from soft and fleshy to hard and gritty.
Size Location:
Can occur anywhere in the breast but does not show a predilection for a specific quadrant
Size can range from 1 cm to over 10 cm.
Multifocality:
Multifocality and multicentricity are rare.
Microscopic Description
Histological Features:
A mixture of carcinomatous and sarcomatous elements
The carcinomatous component is usually a high-grade invasive ductal carcinoma or squamous cell carcinoma
The sarcomatous component can be spindle cells, chondroid, osseous, or rhabdomyoid differentiation.
Cellular Characteristics:
The epithelial cells are pleomorphic with high-grade nuclei
The mesenchymal cells vary depending on the type of differentiation (e.g., spindle cells with elongated nuclei, chondrocytes in a cartilaginous matrix).
Architectural Patterns:
The tumor shows a biphasic pattern with intimate mixing of epithelial and mesenchymal components
The growth pattern is often solid and pushing.
Grading Criteria:
These tumors are almost always high-grade (Grade 3) due to their high nuclear pleomorphism and mitotic activity.
Immunohistochemistry
Positive Markers:
The carcinomatous component is positive for cytokeratins (e.g., AE1/AE3, CAM5.2)
The sarcomatous component may be positive for vimentin and other mesenchymal markers depending on the differentiation (e.g., S100 for chondroid, desmin for rhabdomyoid)
p63 is often positive in the spindle cell and squamous components.
Negative Markers:
Most metaplastic carcinomas are triple-negative (ER negative, PR negative, HER2 negative)
This is a key feature and contributes to their aggressive behavior.
Diagnostic Utility:
IHC is essential to confirm the biphasic nature of the tumor and to classify the subtype of metaplastic carcinoma
It is also crucial for determining the hormone receptor and HER2 status for therapy.
Molecular Subtypes:
The vast majority are classified as triple-negative/basal-like breast cancer.
Molecular/Genetic
Genetic Mutations:
High frequency of TP53 mutations
PIK3CA mutations are also common
Wnt pathway alterations and EMT (epithelial-mesenchymal transition) pathway activation are frequently observed.
Molecular Markers:
Often show EGFR overexpression
High levels of Ki-67 proliferation index
Loss of E-cadherin expression can be seen.
Prognostic Significance:
Generally has a poorer prognosis than IDC of similar stage
Higher rates of local and distant recurrence
Hematogenous spread (to lungs, bone) is more common than lymphatic spread.
Therapeutic Targets:
As most are triple-negative, they do not respond to hormonal therapy or HER2-targeted therapy
Chemotherapy is the mainstay of systemic treatment
Research into targeted therapies for the Wnt and EMT pathways is ongoing.
Differential Diagnosis
Similar Entities:
Phyllodes tumor (malignant)
Primary breast sarcoma
Invasive ductal carcinoma with squamous or spindle cell features
Adenomyoepithelioma.
Distinguishing Features:
Malignant phyllodes tumors have a benign epithelial component and a sarcomatous stromal component, but the epithelial component is not malignant
Primary breast sarcomas lack an epithelial component
IHC for cytokeratins is key to identify the carcinomatous element in metaplastic carcinoma.
Diagnostic Challenges:
Distinguishing from other spindle cell lesions of the breast
A wide panel of IHC markers is often necessary
Sampling error on core biopsy can be an issue, as the biopsy may only show one component.
Rare Variants:
The entire entity is rare, but variants like carcinosarcoma (a specific type of metaplastic carcinoma) are recognized.
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]