Definition/General

Introduction:
-Primary breast sarcomas are a heterogeneous group of malignant mesenchymal tumors that arise from the connective tissue of the breast
-They are extremely rare, accounting for less than 0.1% of all breast malignancies
-They are distinct from phyllodes tumors and angiosarcomas.
Origin:
-These tumors arise from the non-epithelial, stromal tissues of the breast, such as fibrous tissue, fat, and blood vessels
-Unlike carcinomas, they do not originate from the ducts or lobules.
Classification:
-Breast sarcomas are classified based on their line of differentiation, similar to soft tissue sarcomas elsewhere in the body
-Common subtypes include fibrosarcoma, liposarcoma, and leiomyosarcoma
-Angiosarcoma is a specific type of breast sarcoma but is often considered a separate entity.
Epidemiology:
-Breast sarcomas can occur at any age, but they are most common in middle-aged and older women
-A history of prior radiation therapy to the chest wall is a known risk factor.

Clinical Features

Presentation:
-Typically presents as a large, rapidly growing, palpable breast mass
-The mass is usually painless and firm
-Skin changes such as ulceration can occur with large tumors.
Symptoms:
-A painless, enlarging breast lump is the most common symptom
-The rapid growth can cause a sensation of pressure or discomfort.
Risk Factors:
-Prior radiation therapy is the most well-established risk factor
-Lymphedema (Stewart-Treves syndrome) is a risk factor for lymphangiosarcoma
-Genetic syndromes like Li-Fraumeni syndrome can also predispose to sarcomas.
Screening:
-They are usually diagnosed after a palpable mass is investigated
-On mammography, they appear as large, non-calcified masses with indistinct or circumscribed margins.

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Gross Description

Appearance:
-A large, fleshy, gray-white mass
-The borders can be well-circumscribed or infiltrative
-Areas of necrosis and hemorrhage are common.
Characteristics:
-The size is typically large at diagnosis
-The consistency is often firm, but can be soft or myxoid depending on the subtype.
Size Location:
-Can occur anywhere in the breast
-Size is highly variable.
Multifocality: Multifocality is rare.

Microscopic Description

Histological Features:
-The histology is that of a sarcoma, with a monotonous proliferation of spindle or pleomorphic cells
-The features depend on the subtype (e.g., herringbone pattern in fibrosarcoma, lipoblasts in liposarcoma)
-An epithelial component is absent.
Cellular Characteristics:
-The tumor cells are mesenchymal in appearance, ranging from uniform spindle cells to highly pleomorphic cells with bizarre nuclei
-Mitotic activity is often high.
Architectural Patterns:
-The growth pattern is typically diffuse and infiltrative
-The tumor cells are arranged in fascicles or sheets.
Grading Criteria:
-Grading is based on the French Federation of Cancer Centers Sarcoma Group (FNCLCC) system, which assesses tumor differentiation, mitotic count, and necrosis.

Immunohistochemistry

Positive Markers:
-The IHC profile depends on the line of differentiation
-For example, desmin and smooth muscle actin in leiomyosarcoma, S100 in liposarcoma
-Vimentin is generally positive.
Negative Markers:
-Crucially, breast sarcomas are negative for cytokeratins, which rules out metaplastic carcinoma
-They are also negative for hormone receptors (ER, PR) and HER2.
Diagnostic Utility:
-IHC is essential for diagnosis and subtyping
-The main role is to differentiate sarcoma from sarcomatoid (metaplastic) carcinoma.
Molecular Subtypes: Not applicable in the same way as for breast carcinomas.

Molecular/Genetic

Genetic Mutations:
-The genetic alterations are specific to the sarcoma subtype and are similar to those of soft tissue sarcomas elsewhere (e.g., MDM2 amplification in well-differentiated liposarcoma).
Molecular Markers:
-Specific translocations can be seen in certain subtypes (e.g., synovial sarcoma).
Prognostic Significance:
-The prognosis is generally poor and depends on tumor size, grade, and margin status
-Hematogenous metastasis (especially to the lungs) is more common than lymphatic spread
-Axillary lymph node metastasis is rare.
Therapeutic Targets:
-Treatment is primarily wide surgical excision
-The role of adjuvant chemotherapy and radiation is determined by the tumor grade and size, similar to soft tissue sarcomas.

Differential Diagnosis

Similar Entities:
-Metaplastic carcinoma
-Malignant phyllodes tumor
-Cellular fibroadenoma.
Distinguishing Features:
-Metaplastic carcinoma has a malignant epithelial component that is positive for cytokeratins
-Malignant phyllodes tumor is a biphasic tumor with a benign epithelial component
-Cellular fibroadenoma is benign and lacks the atypia and high mitotic rate of sarcoma.
Diagnostic Challenges:
-The main challenge is distinguishing breast sarcoma from metaplastic carcinoma, which has significant therapeutic implications
-A wide IHC panel is often necessary.
Rare Variants: Many different subtypes of sarcoma can occur in the breast, all of which are rare.

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]