Definition/General

Introduction:
-Carcinosarcoma of the breast is a rare type of metaplastic carcinoma, characterized by a mixture of malignant epithelial (carcinomatous) and malignant mesenchymal (sarcomatous) elements
-It is a highly aggressive tumor with a poor prognosis.
Origin:
-It is believed to arise from the metaplastic transformation of a single epithelial stem cell that differentiates along both epithelial and mesenchymal pathways
-This is supported by the frequent finding of a gradual transition between the two components.
Classification:
-It is classified as a subtype of metaplastic breast carcinoma
-The sarcomatous component can be homologous (e.g., fibrosarcoma, osteosarcoma) or heterologous (e.g., rhabdomyosarcoma).
Epidemiology:
-Carcinosarcoma is very rare, accounting for less than 0.1% of all breast cancers
-It typically affects postmenopausal women.

Clinical Features

Presentation:
-Presents as a large, rapidly growing, palpable breast mass
-The mass is often firm and may be fixed to the skin or chest wall.
Symptoms:
-A painless, large breast lump is the most common symptom
-Skin changes like ulceration can occur.
Risk Factors:
-The risk factors are not well-defined but are thought to be similar to other breast cancers
-A history of radiation therapy may be a predisposing factor.
Screening:
-Usually presents as a palpable mass
-Mammographic and ultrasound findings are non-specific and can mimic other benign or malignant lesions.

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Gross Description

Appearance:
-A large, well-circumscribed or infiltrative mass
-The cut surface is often variegated, with fleshy, gray-white areas (sarcomatous) and firm, white areas (carcinomatous)
-Areas of necrosis and hemorrhage are common.
Characteristics:
-The tumor is typically large, often exceeding 5 cm
-The consistency is variable, depending on the components.
Size Location: Can occur anywhere in the breast.
Multifocality: Rare.

Microscopic Description

Histological Features:
-A biphasic tumor with an intimate mixture of malignant epithelial and mesenchymal components
-The carcinomatous component is usually a high-grade ductal or squamous carcinoma
-The sarcomatous component can be fibrosarcoma, osteosarcoma, chondrosarcoma, or other types.
Cellular Characteristics:
-Both components show high-grade malignant features, including pleomorphism, hyperchromasia, and high mitotic activity.
Architectural Patterns:
-The two components are typically intermingled
-A transition zone between the carcinoma and sarcoma may be seen.
Grading Criteria: These are considered high-grade tumors by definition.

Immunohistochemistry

Positive Markers:
-The carcinomatous component is positive for cytokeratins (e.g., AE1/AE3)
-The sarcomatous component is positive for mesenchymal markers like vimentin and other markers depending on the differentiation (e.g., desmin for rhabdomyosarcoma).
Negative Markers:
-Both components are typically negative for hormone receptors (ER, PR) and HER2, making it a type of triple-negative breast cancer.
Diagnostic Utility: IHC is essential to confirm the biphasic nature of the tumor and to differentiate it from other spindle cell lesions.
Molecular Subtypes: Most are classified as triple-negative/basal-like breast cancer.

Molecular/Genetic

Genetic Mutations:
-High frequency of TP53 mutations
-Alterations in the PI3K/AKT/mTOR pathway are also common
-Clonal analysis often shows a common origin for both components.
Molecular Markers: Activation of the epithelial-mesenchymal transition (EMT) pathway is thought to play a key role.
Prognostic Significance:
-Carcinosarcoma has a poor prognosis with a high rate of local and distant recurrence
-Hematogenous spread is common.
Therapeutic Targets:
-Treatment is primarily surgical
-Due to its triple-negative status, it does not respond to hormonal or HER2-targeted therapy
-Platinum-based chemotherapy is often used.

Differential Diagnosis

Similar Entities:
-Malignant phyllodes tumor
-Primary breast sarcoma
-Metaplastic carcinoma with a single mesenchymal component.
Distinguishing Features:
-Malignant phyllodes tumors have a benign epithelial component
-Primary breast sarcomas lack an epithelial component
-The distinction from other metaplastic carcinomas is based on the presence of both carcinomatous and sarcomatous malignant elements.
Diagnostic Challenges:
-Distinguishing from other high-grade breast tumors on small biopsies can be difficult
-A wide IHC panel is crucial.
Rare Variants: The entire entity is a rare variant of metaplastic carcinoma.

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]