Angiosarcoma
Epidemiology and Etiology:
- Older
adults peak incidence (7th decade)
- All
ages are affected
- Extremely
rare in deep soft tissue of children
- 60-80
years for breast angiosarcoma following
radiation & mastectomy
- carcinogens
in liver angiosarcoma:
- arsenic
- Thorotrast
- Polyvinyl
chloride (PVC) – a widely used plastic
- Arise
in the setting of lymphedema (lymphangiosarcoma) (10%)
- Typically
10 years post radical mastectomy
- Tumour syndromes
- Neurofibromatosis
- Mafucci syndrome
- Other
risk factors:
- Radiation
– avg 5-6y post (30-156 months post
radiotherapy following mastectomy, median 84-120 months)
- usually
high-grade with poor prognosis
- a
few reported have been low-grade or borderline with no metasases
- Foreign
material or synthetic graft
- Vicinity
of arteriovenous fistulas in patients who have undergone renal
transplant
- Occur
within other tumours rarely
Common sites:
- Skin
(35%)
- Head
and neck (50% of skin AS)
- Skin
of chest wall, subsequent to radiotherapy following mastectomy (most
commonly in skin in this setting)
- Skin after
lumpectomy and radiotherapy for breast carcinoma
- Soft
tissue (25%)
- Deep
muscles of the lower extremities
- Retroperitoneum
- Mediastinum
- mesentery
- Breast
- Chest
wall, subsequent to radiotherapy following mastectomy
- After
lumpectomy and radiotherapy for breast carcinoma
- lymphedema-associated
(Stewart-Treves syndrome)
- 4-27y
(usually <10y) post-surgery
-
- Liver
- Bone
- Spleen
- Mets
to:
- Lung
- Skin
- Bone
- Liver
- Spleen
- Lymph
nodes (ex. Cervical) (only rarely to axillary lymph nodes for breast angiosarcoma)
-
Gross features:
- Early:
- Small
- Poorly-defined
- Red
plaque resembling a bruise
- Multifocal
often
- Red
nodules
- Late:
- Large
- Fleshy
mass
- Pale,
gray-white
- Imperceptible
margins
- Often
more extensive than grossly appreciated
- Areas
of necrosis and hemorrhage frequently
Histologic features:
- Borders
may extend for several centimeters beyond what is visible to the naked
eye
- Often
very poorly demarcated
- usually
do not form well-organized vessels
- jagged-edged
vessels
- insinuate
themselves between collagen bundles of the reticular dermis
- unlike
KS, there is no tendency of spindled cells to first appear in increased
number around pre-existent vessels and or adnexa
- CD31
or CD34 may highlight single-cell invasion
- Enlarged,
hyperchromatic nuclei
- Often
pile up along the lumina, creating papillations typical of angiosarcomas
(but may also be seen in reactive vascular proliferations such as
papillary endothelila hyperplasia
- Extensive
haemorrhage commonly
- Well-differentiated:
- Plump,
anaplastic endothelial cells producing vascular channels
- Vascular
channels are of irregular size and shape
- Vascular
channels appear to dissect through collagen, creating their own tissue
planes
- Tendency
of channels to anastomose with one another
- May
see intraluminal buds, projections, or papillae (vasoformative
areas)
- Undifferentiated:
- No
definite blood vessels
- Markedly
atypical
- Solid
spindle cell arrangement
- Cytoplasmic
vacuoles may be a clue
- Epithelioid
(such areas common in soft tissue angiosarcomas):
- Sheets,
nests and clusters, or rudimentary vascular channels of round cells
- Large
rounded cells
- High
nuclear grade
- Epithelioid
angiosarcoma is 100% epithelioid pattern
Immunophenotype:
|
Marker:
|
Sensitivity:
|
Specificity:
|
|
CD31*
|
|
Good
|
|
CD34*
|
|
Not as good
|
|
VWF (factor
VIII)*
|
Some, not
all
|
|
|
FLI-1
(nuclear)*
|
|
|
|
CK
(epithelioid)
|
|
|
|
EMA
(epithelioid)
|
|
|
|
HHV-8 (neg)
|
consistently
|
|
|
ERG
|
|
|
|
D2-40
|
occasionally
|
|
- *Poorly
differentiated tumours can lose one or more of these antigens
Molecular features:
- Vascular-specific
receptor tyrosine kinases (upregulation)
- vascular
endothelial growth factor (VEGF) and its receptors
- TIE1
- KDR
(VEGFR)
- Mutation
(10% of soft tissue)
- Strong
expression of KDR
- Location
in the breast, irrespective of exposure to radiation
- TEK
- FLT1
- MYC amplication (8q24) (consistent hallmark of
radiation-induced and lymphedema-associated angiosarcoma)
- FLT4
(VEGFR3) coamplification (5q35) (25% of
secondary angiosarcomas)
- Neither
of these amplifications have been reported in primary deep-seated soft
tissue angiosarcoma or radiation-associated
atypical vascular lesions as of 2013
Other features:
- poor
prognosis
- >
50% mortality in 1 year for soft tissue angiosarcoma
- Breast
angiosarcoma:
- <
3 y recurrence-free survival
- <
6 years median OS
- locally
aggressive
- distant
metastasis
- prognostic
factors:
- greatest
prognostic factor is success of obtaining wide surgical margins (not
validated in soft tissue angiosarcoma)
- older
age
- retroperitoneal
location (poor)
- size
is a prognostic factor:
- <5cm
survival advantage
- >10cm
worst survival
- High
Ki-67
- Painful
mass maybe
- predilection
for metastasis to nodes
- treatment:
- wide
excision with postoperative radiotherapy to primary site and regional
lymphatics
- but
most lesions are too extensive at diagnosis for complete excision
- chemotherapy
for palliation (no data to support adjuvant chemotherapy)
- high
risk of both local-regional and distant relapse
References:
- Robbins
2005
- WHO
book 2002, 2013
- Enzinger
2001
- Am J
Clin Onc 2006; 29(5): 524.
- Am J
Otolaryngology 1999; 20(4): 223.