Definition/General
Introduction:
Angiosarcoma is a malignant vascular tumor
It shows endothelial differentiation with aggressive behavior
Represents 1-2% of all soft tissue sarcomas
FNAC reveals atypical endothelial cells.
Origin:
Arises from vascular endothelium
Can develop from blood or lymphatic vessels
Primary or secondary (radiation-induced)
Multifocal origin possible
Shows rapid proliferation and dissemination.
Classification:
WHO classification: Malignant vascular tumor
Types: Cutaneous angiosarcoma
Soft tissue angiosarcoma
Breast angiosarcoma
Radiation-associated angiosarcoma
Epithelioid angiosarcoma.
Epidemiology:
Peak incidence 6th-7th decades
Slight male predominance
Radiation-associated: 8-10 year latency
Chronic lymphedema association (Stewart-Treves syndrome)
Poor prognosis overall.
Clinical Features
Presentation:
Rapidly enlarging mass
Bruise-like appearance
Purple-red discoloration
Ulceration common
Bleeding tendency
Ill-defined margins
Multifocal lesions.
Symptoms:
Pain (variable)
Bleeding from lesion
Ulceration and infection
Rapid growth
Functional impairment
Systemic symptoms (advanced disease).
Risk Factors:
Previous radiation therapy (5-15 year latency)
Chronic lymphedema
Li-Fraumeni syndrome
Neurofibromatosis
Klippel-Trenaunay syndrome
Vinyl chloride exposure.
Screening:
Clinical examination
Imaging studies (MRI/CT)
FNAC/Biopsy for diagnosis
Staging workup
PET scan
Multidisciplinary evaluation.
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Gross Description
Appearance:
Hemorrhagic, friable mass
Purple-red color
Soft consistency
Ill-defined margins
Areas of necrosis
Cystic spaces filled with blood.
Characteristics:
Highly vascular
Hemorrhagic cut surface
Friable tissue
Necrosis and ulceration
Infiltrative growth
Multifocal lesions.
Size Location:
Scalp (elderly)
Face and neck
Extremities
Breast (post-radiation)
Deep soft tissues
Size: Variable 2-15 cm
Multifocal presentation.
Multifocality:
Multifocal in 50% cases
Satellite lesions
Skip metastases
Lymphatic spread
Distant metastases early
Lung metastases common.
Microscopic Description
Histological Features:
FNAC shows atypical endothelial cells
Nuclear pleomorphism
Prominent nucleoli
Mitotic activity
Vascular channel formation
Hemorrhagic background.
Cellular Characteristics:
Pleomorphic endothelial cells
Enlarged, hyperchromatic nuclei
Prominent nucleoli
Moderate to abundant cytoplasm
Mitotic figures
Multinucleated cells.
Architectural Patterns:
Loose cohesion
Individual cells predominant
Rudimentary vascular spaces
Hemorrhagic background
Necrotic debris
Papillary-like clusters.
Grading Criteria:
High-grade by definition
Nuclear atypia
Mitotic count >5/10 HPF
Endothelial differentiation
Infiltrative growth
Necrosis common.
Immunohistochemistry
Positive Markers:
CD31 - positive (endothelial)
CD34 - positive (variable)
ERG - positive (nuclear)
FLI1 - positive (nuclear)
Factor VIII - variable
Prox1 - positive (lymphatic).
Negative Markers:
Cytokeratin - negative (usually)
EMA - negative
S-100 - negative
Desmin - negative
CD68 - negative
GLUT1 - negative.
Diagnostic Utility:
Endothelial markers confirm vascular differentiation
ERG and FLI1 most reliable
CD31 often positive
Ki-67 high (>20%)
p53 may be overexpressed.
Molecular Subtypes:
Conventional angiosarcoma: CD31+, ERG+, FLI1+
Epithelioid angiosarcoma: Same markers
Lymphangiosarcoma: Prox1+, D2-40+
All types show endothelial markers.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (common)
RB1 alterations
MYC amplification
FLT4 mutations
PIK3CA mutations
Complex karyotype
VEGFR2 alterations.
Molecular Markers:
p53 pathway disruption
PI3K/AKT pathway activation
Angiogenesis pathways dysregulated
High mutational burden
Chromosomal instability
VEGF overexpression.
Prognostic Significance:
Poor prognosis overall
5-year survival: 20-35%
Size >5 cm: Worse outcome
Deep location: Poor prognosis
Multifocal disease: Very poor
Early metastases common.
Therapeutic Targets:
Anthracycline-based chemotherapy
Paclitaxel effective
Anti-angiogenic therapy (bevacizumab)
Immunotherapy (pembrolizumab)
Targeted therapy (investigational)
Combination regimens.
Differential Diagnosis
Similar Entities:
Hemangioma
Hemangioendothelioma
Kaposi sarcoma
Carcinoma with vascular differentiation
Melanoma
Poorly differentiated carcinoma.
Distinguishing Features:
Angiosarcoma: Atypical endothelium, infiltrative, ERG+, high Ki-67
Hemangioma: Benign endothelium, well-circumscribed
Hemangioendothelioma: Intermediate grade
Kaposi: Spindle cells, HHV8+
Carcinoma: Cytokeratin+
Melanoma: S-100+, melanoma markers.
Diagnostic Challenges:
Distinguishing from poorly differentiated carcinoma
Epithelioid variant mimics carcinoma
Hemangioendothelioma vs angiosarcoma
Metastatic melanoma
Sampling adequacy.
Rare Variants:
Epithelioid variant
Lymphangiosarcoma
Hemangiosarcoma
Post-radiation type
Primary cardiac.
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
Fine needle aspiration from [site], [size] cm hemorrhagic lesion
Clinical History
[age]/[sex] with [duration] history of rapidly enlarging, hemorrhagic lesion at [site]. [Previous radiation/lymphedema history].
Microscopic Examination
Smears show highly atypical endothelial cells with marked nuclear pleomorphism, prominent nucleoli, and high mitotic activity. Rudimentary vascular channel formation noted. Hemorrhagic background.
Immunocytochemistry
CD31: Positive, ERG: Positive, FLI1: Positive, Cytokeratin: Negative, Ki-67: High (>20%)
Cytological Diagnosis
Cytological features consistent with ANGIOSARCOMA
Comments
High-grade malignant vascular tumor. Urgent histopathological confirmation recommended. Multidisciplinary oncology evaluation required. Poor prognosis.