ANGIOSARCOMA
Rare Aggressive Vascular Malignancy | Poor Prognosis | Multimodal Treatment Required
CLINICAL SUBTYPES
Critical Must-Knows
- Extremely rare and highly aggressive - under 1% of sarcomas with 20-35% 5-year survival
- Three major associations: chronic lymphedema (Stewart-Treves), radiation therapy, and foreign bodies
- Multifocal disease common - 50% have multiple sites at presentation or develop additional lesions
- Early metastases - lung most common, occur early and frequently (50% of patients)
- Wide excision with negative margins mandatory - intralesional surgery leads to rapid recurrence
Examiner's Pearls
- "Stewart-Treves syndrome: angiosarcoma arising in chronic lymphedema (classically post-mastectomy)
- "Radiation-induced angiosarcoma has 5-10 year latency after breast cancer treatment
- "CD31 and CD34 positive on immunohistochemistry - confirms endothelial origin
- "Scalp angiosarcoma in elderly has worst prognosis - multifocal, infiltrative, high recurrence
Classification
AJCC 8th Edition (Soft Tissue Sarcoma)
Angiosarcoma is staged using the AJCC soft tissue sarcoma staging system. However, most angiosarcomas are high-grade and present at advanced stage due to multifocal disease and early metastases.
| Stage | T | Grade | Metastases | 5-Year Survival |
|---|---|---|---|---|
| IIIA | T1 (under 5cm) | High (G3) | M0 | 40-50% |
| IIIB | T2-4 (over 5cm or deep) | High (G3) | M0 | 30-40% |
| IV | Any T | Any G | M1 (metastatic) | Under 10% |
Most angiosarcomas present as Stage III or IV due to high grade and extent of disease.
Clinical Presentation
Cutaneous Angiosarcoma (Head and Neck)
Classic presentation in elderly patients:
- Scalp lesion (most common site)
- Bruise-like appearance: Purple or red discoloration
- Rapid enlargement: Over weeks to months
- Multifocal: Multiple areas of involvement
- No trauma history: Unlike hematoma
Do Not Mistake for Bruise
Elderly patient with persistent scalp bruising without trauma should raise suspicion for cutaneous angiosarcoma. Biopsy is mandatory. Delay in diagnosis is common because lesion resembles benign ecchymosis.
Radiation-Induced Angiosarcoma
Post-breast cancer radiation:
- Latency: 5-10 years after radiotherapy
- Presentation: Skin changes on irradiated breast (redness, ecchymosis, palpable nodules)
- Location: Within radiation field
- Differential: Radiation dermatitis, inflammatory breast cancer
Stewart-Treves Syndrome
Post-mastectomy lymphedema:
- Latency: Usually greater than 10 years
- Presentation: Purple nodules or plaques in chronically edematous arm
- Rapidly progressive
- Often multifocal
Deep Soft Tissue Angiosarcoma
- Large mass in extremity or trunk
- Often painless until late
- Rapid growth
- May present with pathological fracture if bone involvement
Investigations and Staging
Diagnostic Imaging and Biopsy Protocol
Gold standard for local staging. Features: Heterogeneous signal, prominent enhancement (vascular tumor), infiltrative margins, multifocal areas.
Essential for metastatic workup. Lung metastases present in 30-40% at diagnosis. Also check liver, bone.
Mandatory for diagnosis. Request immunohistochemistry (CD31, CD34, Factor VIII, ERG). MYC amplification testing if radiation-associated.
Consider for extent of disease. Angiosarcoma is typically FDG-avid. Useful for detecting occult metastases and multifocal disease.
Histopathology
Morphology:
- Vasoformative: Blood-filled vascular channels
- Solid areas: Sheets of atypical endothelial cells
- High mitotic rate, nuclear atypia
- Variable differentiation (well-differentiated can appear bland)
Immunohistochemistry is essential:
- CD31: 90% positive (most sensitive)
- CD34: 80% positive
- Factor VIII: 60% positive
- ERG, FLI1: Positive nuclear staining
Differential diagnosis:
- Epithelioid hemangioma (benign)
- Kaposi sarcoma (HHV8 positive)
- Poorly differentiated carcinoma (cytokeratin positive)
Management
Treatment Algorithm
Wide Excision with Negative Margins Mandatory
Surgery is the cornerstone of curative treatment. Wide excision with negative margins (R0 resection) is essential. However, achieving negative margins is challenging due to multifocal nature and infiltrative growth. Positive margins dramatically increase local recurrence (50-80% vs 20-30% with negative margins).
Surgical Resection Principles
Goals:
- Wide excision with 2-3cm margins (if feasible)
- En bloc resection of all involved areas
- Reconstruction as needed
Site-Specific Surgery:
| Site | Surgical Approach | Challenges |
|---|---|---|
| Scalp angiosarcoma | Wide local excision, often requires skin grafting | Multifocal disease makes complete excision difficult |
| Radiation-induced breast | Mastectomy + chest wall resection | Extensive resection needed, often positive margins |
| Stewart-Treves (arm) | Amputation (often required) | Limb salvage rarely achievable due to extent |
| Deep soft tissue | Wide excision + reconstruction | Best chance of negative margins |
Amputation indications:
- Stewart-Treves syndrome with extensive involvement
- Neurovascular encasement precluding limb salvage
- Recurrent disease after prior limb-sparing surgery
- Patient choice for local control
Amputation is often necessary for Stewart-Treves syndrome to achieve local control.
Multimodal Treatment by Subtype
| Subtype | Surgery | Radiation | Chemotherapy |
|---|---|---|---|
| Cutaneous head/neck | Wide excision (often incomplete) | Adjuvant 60-66 Gy | Paclitaxel neoadjuvant or adjuvant |
| Radiation-induced breast | Mastectomy + chest wall | Consider (in previously irradiated field) | Adjuvant paclitaxel |
| Stewart-Treves | Amputation | Adjuvant if residual limb | Palliative if metastatic |
| Deep soft tissue | Wide excision | Adjuvant 60-66 Gy | Consider neoadjuvant + adjuvant |
Prognosis and Outcomes
Prognostic Factors
| Factor | Favorable | Unfavorable |
|---|---|---|
| Location | Deep soft tissue | Head/neck, radiation-induced, lymphedema |
| Size | Under 5cm | Over 10cm |
| Margin status | Negative (R0) | Positive (R1/R2) |
| Metastases | Localized (M0) | Metastatic (M1) |
| Multifocality | Unifocal | Multifocal |
Worst Prognosis Subtype
Cutaneous angiosarcoma of the scalp has the worst prognosis of all angiosarcoma subtypes (10-20% 5-year survival). Reasons: multifocal disease at presentation, infiltrative growth pattern, difficulty achieving negative margins, and elderly patient population. Even with aggressive multimodal therapy, outcomes remain poor.
Survival by Subtype
5-Year Survival by Subtype
| Subtype | 5-Year Survival | Key Factors |
|---|---|---|
| Deep soft tissue | 30-40% | Best prognosis, margins achievable |
| Radiation-induced breast | 20-30% | Aggressive disease, prior radiation limits re-irradiation |
| Cutaneous head/neck | 10-20% | Worst prognosis, multifocal, elderly |
| Stewart-Treves | 15-25% | Extensive disease, requires amputation |
Complications
Disease-Related Complications
| Complication | Incidence | Management |
|---|---|---|
| Local recurrence | 30-60% | Re-excision, radiation, systemic therapy |
| Distant metastases (lung) | 50% | Chemotherapy (paclitaxel), consider metastasectomy if oligometastatic |
| Hemorrhage from tumor | 10-20% (vascular tumor) | Embolization, surgical hemostasis |
| Lymphedema (post-resection) | Variable | Compression, physiotherapy |
Treatment-Related Complications
- Wound complications (15-25%): Infection, dehiscence, flap necrosis
- Radiation toxicity: Fibrosis, chronic pain (especially if re-irradiating)
- Chemotherapy toxicity: Neuropathy (paclitaxel), myelosuppression
Postoperative Care and Surveillance
Follow-Up Protocol
- Clinical examination
- CT chest every 3-4 months (high metastatic rate)
- MRI primary site every 4-6 months
- Clinical examination
- CT chest every 6 months
- MRI primary site every 6-12 months
- Clinical examination
- Imaging as clinically indicated
- Late recurrences and metastases possible
Surveillance continues indefinitely due to risk of late recurrence.
Evidence Base and Key Studies
Angiosarcoma of the Scalp: A Systematic Review
- 155 patients with scalp angiosarcoma analyzed
- 5-year survival: 15% (extremely poor prognosis)
- Multifocal disease in 50% at presentation
- Local recurrence 50-70% despite aggressive treatment
Paclitaxel in Angiosarcoma: ANGIOTAX Study
- Weekly paclitaxel (80 mg/m²) in 30 angiosarcoma patients
- Overall response rate 40%
- Median progression-free survival 4 months
- Superior to historical doxorubicin-based regimens
Radiation-Induced Angiosarcoma After Breast Cancer
- Incidence 0.1-0.2% of irradiated breast cancer patients
- Median latency 7 years (range 2-20 years)
- 5-year survival 20-30% despite aggressive treatment
- Mastectomy with chest wall resection required
Stewart-Treves Syndrome: Systematic Review
- Angiosarcoma in chronic lymphedema (typically post-mastectomy)
- Median latency greater than 10 years after initial surgery
- 5-year survival 10-20% despite aggressive treatment
- Amputation often required for local control (limb salvage rarely achievable)
Exam Viva Scenarios
Practice these scenarios to excel in your viva examination
Scenario 1: Elderly Patient with Scalp Bruise
"A 75-year-old man presents with a persistent purple discoloration on his scalp that has enlarged over 3 months. He denies trauma. On examination, there is a 5cm bruise-like lesion on the vertex. What is your differential diagnosis and management?"
Scenario 2: Breast Mass After Radiation
"A 58-year-old woman treated with lumpectomy and radiation for breast cancer 8 years ago presents with skin changes on her treated breast - ecchymosis and a palpable 3cm mass. What is your assessment and management?"
Scenario 3: Stewart-Treves Syndrome
"A 65-year-old woman with history of left mastectomy and axillary dissection 15 years ago presents with violaceous nodules on her chronically swollen left arm. Biopsy shows angiosarcoma. How do you manage this?"
MCQ Practice Points
Epidemiology Question
Q: What is the most common site for cutaneous angiosarcoma? A: Scalp - Cutaneous angiosarcoma has predilection for the scalp in elderly patients, presenting as bruise-like lesions without trauma. This subtype has the worst prognosis (10-20% 5-year survival) due to multifocal nature and infiltrative growth.
Association Question
Q: What is Stewart-Treves syndrome? A: Angiosarcoma arising in chronic lymphedema, classically in the arm after mastectomy with axillary dissection. Latency is usually over 10 years. Presentation: violaceous nodules in lymphedematous limb. Prognosis extremely poor (15-25% 5-year survival). Treatment often requires amputation.
Immunohistochemistry Question
Q: What immunohistochemical markers confirm vascular origin in angiosarcoma? A: CD31 (90% positive - most sensitive), CD34 (80% positive), and Factor VIII/von Willebrand factor (60% positive). ERG and FLI1 show nuclear positivity. CD31 is the most sensitive endothelial marker.
Treatment Question
Q: What is the preferred first-line chemotherapy for angiosarcoma? A: Paclitaxel (weekly dosing 80 mg/m²) has superior response rates (40-50%) compared to traditional doxorubicin-based regimens. The ANGIOTAX study established paclitaxel as preferred first-line therapy.
Prognosis Question
Q: What is the 5-year survival for angiosarcoma overall? A: 20-35% for all sites combined. Prognosis varies by subtype: deep soft tissue (30-40%), radiation-induced (20-30%), scalp (10-20%), Stewart-Treves (15-25%). Poor prognosis due to early metastases, multifocal disease, and high local recurrence rates.
Australian Context
Sarcoma Service Referral
Australian sarcoma centers:
- Peter MacCallum Cancer Centre (VIC)
- Royal Prince Alfred Hospital (NSW)
- Princess Alexandra Hospital (QLD)
- Royal Perth Hospital (WA)
All suspected angiosarcomas should be referred to sarcoma MDT before biopsy and treatment.
Treatment Access
PBS/Medicare:
- Paclitaxel: PBS-listed for soft tissue sarcomas
- Doxorubicin: PBS-listed
- Imaging: MRI and CT staging rebated
- Radiation therapy: Public hospital access
Clinical trials may be available through sarcoma centers.
Medicolegal Considerations
Key documentation:
- Biopsy any persistent scalp bruising in elderly (delay common)
- Radiation-induced angiosarcoma: counsel breast cancer patients about late risk
- Stewart-Treves: document discussion of amputation vs palliative options
- Informed consent: include poor prognosis, high recurrence, multimodal treatment needs
- Surveillance protocol documented (intensive due to metastatic risk)
ANGIOSARCOMA
High-Yield Exam Summary
Key Epidemiology
- •Extremely rare: under 1% of soft tissue sarcomas
- •Bimodal age: young adults (deep) and elderly (cutaneous)
- •Scalp most common site for cutaneous type (40% of cases)
- •Highly aggressive with poor prognosis (20-35% 5-year survival)
Classic Associations (RALF Mnemonic)
- •Radiation therapy (5-10 year latency, 0.1-0.2% of irradiated patients)
- •Arsenal chemicals (vinyl chloride, arsenic, thorotrast)
- •Lymphedema chronic (Stewart-Treves syndrome)
- •Foreign bodies (synthetic grafts, surgical materials)
Clinical Features (VAMP Mnemonic)
- •Vascular markers positive (CD31 90%, CD34 80%, Factor VIII 60%)
- •Aggressive behavior (early metastases, multifocal, rapid growth)
- •Multifocal disease (50% at presentation or develop multiple lesions)
- •Poor prognosis (20-35% overall, 10-20% scalp, 15-25% Stewart-Treves)
Diagnostic Workup
- •Biopsy: Core needle with immunohistochemistry (CD31, CD34, Factor VIII)
- •MRI primary site: Assess extent and multifocality
- •CT chest/abdomen/pelvis: Metastases in 30-40% at diagnosis (lung most common)
- •PET-CT: Consider for extent and occult disease (angiosarcoma FDG-avid)
Treatment Principles
- •Surgery: Wide excision 2-3cm margins, R0 resection critical
- •Radiation: Adjuvant 60-66 Gy (all high-grade cases)
- •Chemotherapy: Paclitaxel first-line (40-50% response rate)
- •Scalp: Often unresectable, multimodal therapy
- •Stewart-Treves: Amputation often required for local control
Prognosis by Subtype
- •Deep soft tissue: 30-40% 5-year survival (best of poor options)
- •Radiation-induced breast: 20-30% 5-year survival
- •Cutaneous scalp: 10-20% 5-year survival (worst prognosis)
- •Stewart-Treves: 15-25% 5-year survival
- •Metastatic disease: under 10% 5-year survival
Complications and Surveillance
- •Local recurrence: 30-60% despite multimodal therapy
- •Distant metastases: 50% (lung most common)
- •Follow-up: Q2-3mo years 1-2, Q4-6mo years 3-5, then Q6-12mo
- •CT chest Q3-4mo first 2 years (high metastatic rate)
- •Late recurrences possible - indefinite surveillance