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]