Definition/General

Introduction:
-Angiosarcoma of the breast is a rare malignant tumor of vascular endothelial cells
-It can be primary (arising de novo in the breast) or secondary (most commonly arising as a complication of radiation therapy for breast cancer).
Origin: It arises from the endothelial cells lining blood vessels within the breast parenchyma or skin.
Classification:
-Angiosarcomas are graded as low, intermediate, or high grade based on the degree of atypia, mitotic activity, and solid/spindle cell areas
-Secondary angiosarcomas are almost always high-grade.
Epidemiology:
-Primary angiosarcoma is very rare and typically affects younger women (30s-40s)
-Secondary angiosarcoma occurs in older women (60s-70s), typically 5-10 years after radiation therapy for breast cancer.

Clinical Features

Presentation:
-Primary angiosarcoma often presents as a painless, palpable mass
-Secondary angiosarcoma typically presents as a skin lesion, such as a bruise-like macule, papule, or nodule in the irradiated skin.
Symptoms:
-The clinical presentation can be subtle, especially for secondary angiosarcoma, which may be mistaken for a benign skin condition
-The lesions can be multifocal and grow rapidly.
Risk Factors:
-The main risk factor for secondary angiosarcoma is prior radiation therapy to the breast
-Chronic lymphedema (Stewart-Treves syndrome) is another risk factor
-Risk factors for primary angiosarcoma are not well understood.
Screening:
-There is no specific screening
-A high index of suspicion is needed for any new skin lesion or mass in a previously irradiated breast.

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Gross Description

Appearance:
-The gross appearance is variable
-It can be a poorly defined, hemorrhagic mass
-The tissue is often soft and spongy
-In secondary cases, the skin shows violaceous, ecchymotic lesions.
Characteristics:
-The tumor can be infiltrative and difficult to delineate grossly
-Hemorrhage and necrosis are common.
Size Location:
-Size is variable
-Primary angiosarcomas are in the breast parenchyma, while secondary ones are in the skin and subcutaneous tissue.
Multifocality:
-Multifocality is common, especially in secondary angiosarcoma.

Microscopic Description

Histological Features:
-The tumor is composed of anastomosing vascular channels that dissect through the breast stroma and fat
-The channels are lined by atypical endothelial cells
-The degree of atypia and architectural complexity determines the grade.
Cellular Characteristics:
-The endothelial cells can range from bland and flat (low-grade) to highly pleomorphic and epithelioid with prominent nucleoli and frequent mitoses (high-grade)
-Papillary tufts and solid sheets of cells can be seen in high-grade tumors.
Architectural Patterns:
-Low-grade tumors show well-formed vascular channels
-High-grade tumors show solid and spindle cell areas, necrosis, and hemorrhage.
Grading Criteria:
-Grading is based on features like cellularity, atypia, mitotic rate, and presence of solid/spindle cell areas
-A common system is the three-tiered system (low, intermediate, high grade).

Immunohistochemistry

Positive Markers:
-The tumor cells are positive for vascular endothelial markers such as CD31, CD34, and ERG
-FLI1 is another useful marker.
Negative Markers:
-Negative for cytokeratins, which helps distinguish it from carcinoma
-Also negative for S100 and melanocytic markers.
Diagnostic Utility:
-IHC is essential for confirming the endothelial nature of the tumor and distinguishing it from other malignancies, especially poorly differentiated carcinomas or melanoma.
Molecular Subtypes: Not applicable in the same way as for breast carcinomas.

Molecular/Genetic

Genetic Mutations:
-Secondary angiosarcomas often have amplification of the MYC gene, which is a key diagnostic and pathogenetic feature
-Primary angiosarcomas are typically MYC-negative.
Molecular Markers: FISH for MYC amplification is a useful ancillary test to confirm the diagnosis of secondary angiosarcoma.
Prognostic Significance:
-The prognosis is generally poor, especially for high-grade and secondary angiosarcomas
-The 5-year survival rate is low
-They have a high rate of local recurrence and distant metastasis, primarily to the lungs.
Therapeutic Targets:
-Treatment is primarily surgical, with wide excision or mastectomy
-The role of chemotherapy and radiation is not well-defined but may be used for advanced or recurrent disease
-There are no established targeted therapies, but research is ongoing.

Differential Diagnosis

Similar Entities:
-Hemangioma (benign)
-Atypical vascular lesion (AVL)
-Angiolipoma
-Metaplastic carcinoma with angiosarcomatous features
-Melanoma.
Distinguishing Features:
-Hemangiomas are well-circumscribed and lack atypia and infiltrative growth
-AVL is a precursor lesion to secondary angiosarcoma and shows milder atypia
-Carcinomas are positive for cytokeratins
-Melanoma is positive for S100 and melanocytic markers.
Diagnostic Challenges:
-Distinguishing low-grade angiosarcoma from benign vascular lesions can be difficult on small biopsies
-The presence of infiltrative growth and dissection through stroma are key features of angiosarcoma
-MYC IHC and FISH are very helpful in the post-radiation setting.
Rare Variants: Epithelioid angiosarcoma is a high-grade variant with large, epithelioid cells that can mimic 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]