Proc (Bayl Univ Med Cent) 2012;25(1):70–72
Primary angiosarcoma of the breast is a rare malignant tumor. We report
a case of breast primary cutaneous angiosarcoma in a patient with a
strong family history of malignancy. For definitive diagnosis, a tissue
biopsy is needed, with immunostaining for the presence of blood vessel
endothelial markers CD31 and CD34. Total mastectomy is the preferred
method of surgical treatment. Chemotherapy has not been shown to
increase overall survival, but in some instances it may improve local
control and disease-free survival. Surgery combined with radiation may
increase local control, but patients at high risk of recurrence may benefit
from adjuvant treatment as well. We discuss the potential benefits from
various treatments for primary cutaneous breast angiosarcoma.
nancy (2–4). True primary angiosarcomas account for <0.04%
of malignant breast neoplasms (5), and primary angiosarcomas
of the breast have a reported incidence of 17 new cases per
million women (6). We describe a case of primary cutaneous
angiosarcoma of the breast in a patient with a family history
ngiosarcoma of the breast is a very rare malignant tu-
mor, with few patients surviving long term (1). It may
occur as a primary tumor, as a complication of radia-
tion therapy after breast conservation, or during preg-
A 54-year-old Caucasian woman visited her dermatologist
with complaints of a “rash” on her breast present for approxi-
mately 3 months. She was referred for biopsy, which revealed
cutaneous angiosarcoma. She presented to our offi ce with com-
plaints of thickened, purple discoloration located around the
4:00 position on the right breast (Figure 1). Th e patient’s his-
tory was unremarkable except for a history of breast implants
along with a record of several breast surgeries, most recently in
2006, for correction of fi brotic capsulation around the implant.
She also had trauma to her right breast following a skiing ac-
cident about 4 to 5 months before presentation. A punch bi-
opsy showed fi ndings suggestive of chronic infl ammation and
malignancy. Magnetic resonance imaging (MRI) of the breast
revealed hematoma associated with skin thickening. A second
punch biopsy of the lesion revealed an atypical intradermal
vascular proliferation suspicious for malignancy.
From the Departments of Oncology (Cao, Panos, Mennel) and Pathology (Graham),
Baylor Charles A. Sammons Cancer Center and Baylor University Medical Center
at Dallas; and Skin Cancer Consultants, Dallas, Texas (Parker).
Corresponding author: Ying Cao, MD, Fellow, Department of Oncology, Baylor
Sammons Cancer Center at Baylor University Medical Center at Dallas, 3410
Worth Street, Dallas, Texas 75246 (e-mail: Ying.Cao@BaylorHealth.edu).
A full-thickness skin biopsy was then performed. Histo-
logically, the tumor consisted of nodules of vascular prolif-
eration with atypical spindle cells in a cuff -like appearance
(Figure 2a). Th e neoplastic cells showed moderate to focally
marked pleomorphic nuclei, a high mitotic index, and an overall
infi ltrative pattern. Immunostaining indicated that these cells
strongly expressed CD34 (Figure 2b) and CD31 (not shown)
but did not express HHV8. Th ese fi ndings led to a diagnosis
Th e patient had a negative metastatic workup (complete
blood count, complete metabolic profi le and computed to-
mography scan). She then received a right mastectomy. Th e
pathology of the tumor revealed a grade 2 (7) tumor 4.5 cm in
diameter. Th e patient is currently undergoing adjuvant chemo-
therapy with single-agent paclitaxel every 3 weeks.
She has a strong family history of malignancy. Her father
died at the age of 64 of chronic leukemia, reportedly diagnosed
Primary cutaneous angiosarcoma of the breast after
Ying Cao, MD, PhD, Laura Panos, MS, CGC, Robbie L. Graham, MD, Thornwell H. Parker III, MD, and Robert Mennel, MD
Baylor Sammons Cancer Center at Dallas Site Tumor Conference
Figure 1. Angiosarcoma of the breast.
at 62 years of age. Her brother died as a result of glioblastoma di-
agnosed at age 56, and her sister died at age 43 of non-Hodgkin’s
lymphoma, initially diagnosed at the age of 43. In addition, her
paternal aunt was diagnosed with breast cancer in her 60s.
Angiosarcoma of the breast
Th e fi rst documented case of breast angiosarcoma was pre-
sented by Borrman in 1907 (8). Diff erent from breast carcino-
mas, primary angiosarcoma of the breast occurs sporadically in
young women, usually during the third and fourth decades of
life. Th e probability of developing angiosarcoma of the breast
has been attributed to multiple risk factors, including trauma,
radiation, lymphedema, and breast implants. In a retrospec-
tive study of almost 200,000 women with breast cancer, those
who received adjuvant radiotherapy were at a 16-fold increased
risk for development of angiosarcoma (9). Lymphedema as a
result of axillary lymph node dissection is considered a risk for
developing angiosarcoma; however, there are no defi nitive data
to support this claim. Th e same is true for trauma and breast
implants. Both have been observed to occur in cases of breast
angiosarcoma, but there are no defi nitive data to support these
claims. On the other hand, there are reports of cases of angi-
osarcoma of the breast and chest wall associated with implants
and fi brocystic breast disease (10, 11). Whether the combina-
tion of trauma and reaction to breast implants was the cause of
cutaneous angiosarcoma in our patient is an intriguing idea, but
one that needs evidence to support it. Due to the rarity of angi-
osarcoma, especially a primary cutaneous angiosarcoma of the
breast, it is diffi cult to make any conclusions as to causality.
Patients with primary breast angiosarcoma normally present
with a palpable mass. Bluish skin discoloration occurs in up to a
third of patients and is thought to be attributable to the vascular
nature of the tumor (5). In a study of a series of 24 breast angi-
osarcoma cases, the mean tumor size of the mass at presentation
was 5.9 cm (5). Mammographic fi ndings tend to be nonspecifi c
for angiosarcoma, while with ultrasound, angiosarcoma typically
presents as a heterogeneous, hyperechoic, hypervascular mass (5).
MRI is more likely to image an angiosarcoma; however, this was
not true in our case. An MRI of angiosarcoma shows a heterogene-
ous mass with low signal intensity on T1-weighted images, but sig-
nal intensity is high in images that are heavily T2-weighted (5, 12).
Although not defi nitive, MRI is useful in ascertaining the extent of
tumor and in planning surgery. Positron emission
tomography (PET) with 18F-fl uorodeoxyglucose
(FDG) may be used for staging of angiosarcoma
(13). One case report showed focal, intense accu-
mulation of FDG in angiosarcomas of the heart,
with a standard uptake value of 7.5 (14).
A defi nitive preoperative diagnosis may be
achieved with fi ne-needle aspiration cytology or
a core needle biopsy (15). Immunohistochemi-
cal stains for epithelial markers (pancytokera-
tin), endothelial markers (CD34 and CD31),
and other sarcoma markers are helpful in mak-
ing the correct diagnosis (16). Rosen’s method
for grading breast angiosarcoma correlates well
with the clinical outcome, as a low grade is associated with a
better outcome (7). His system is very similar to the French
soft tissue sarcoma grading system, where various histologic
aspects of the tumor are scored (tumor diff erentiation, mitotic
count, tumor necrosis) and added together to give a fi nal his-
tologic grade (17). Rosen’s study gave estimated probabilities of
disease-free survival of 5 years following initial treatment: stage
I, 76%; stage II, 70%; and stage III, 15%. Our patient had stage
II disease (7). Th us, prompt localization and identifi cation of
angiosarcoma is vital in the treatment of this disease.
Total mastectomy alone is the preferred method of surgical
treatment (18). Sarcomas are less likely to spread to the lymph
nodes, as Sher et al demonstrated (3). Sarcomas most com-
monly spread to the lung. In 31 cases of breast angiosarcoma,
only two had lymph node invasion (3). Studies examining the
effi cacy of adjuvant chemotherapy are lacking, due in part to
the low incidence of breast angiosarcomas. One retrospective
study revealed that 36% of patients with primary angiosarcoma
received chemotherapy in an adjuvant or neoadjuvant setting
(7). Sher et al reported that adjuvant chemotherapy using an
anthracycline and ifosfamide or gemcitabine and a taxane did
not signifi cantly improve recurrence-free survival compared
with patients who did not receive chemotherapy (38 vs. 31
patients; hazard ratio, 0.47; P = 0.11). However, administra-
tion of chemotherapy at the time of recurrence resulted in a
48% response rate (3). In the case of secondary angiosarcomas
induced by radiation treatment, docetaxel showed promise for
treating secondary breast angiosarcomas that were refractory
to anthracycline-based chemotherapy (19). Bevacizumab, the
anti–vascular endothelial growth factor antibody, has been used
as treatment for angiosarcomas to block blood vessel growth, but
the results have been variable. Currently two phase II clinical
trials are investigating the use of bevacizumab in cases of sar-
coma, including angiosarcoma. Th e goal of the fi rst trial, which
has completed accrual, is to determine the eff ect of treatment
with bevacizumab alone and to measure disease-free survival
in patients with angiosarcoma (20). Th e second trial, which is
still accruing patients, involves treatment with bevacizumab in
combination with gemcitabine and docetaxel in patients with
various sarcomas, including angiosarcoma (21). Once results of
these studies are available, we may better know the eff ect of this
adjuvant therapy in cases of primary breast angiosarcomas.
Figure 2. Histology of the grade II tumor. (a) Angiosarcoma stained with hematoxylin and eosin (original
magnification 400×). (b) Angiosarcoma stained with antibody to CD34 (original magnification 400×).
Primary cutaneous angiosarcoma of the breast after breast trauma January 2012
72 Download full-text
Baylor University Medical Center Proceedings Volume 25, Number 1
For patients with sarcomas of the breast, it has been sug-
gested that radiation therapy after surgical resection may have
a benefi cial eff ect on outcome, especially for patients with mi-
croscopically positive margins (18). Th ere was no statistical cor-
relation of adjuvant radiation therapy with survival in this study,
due to the small number of patients and the retrospective nature
of the study. But, patients at high risk of recurrence (with large,
high-grade tumors) may benefi t from adjuvant treatment with
improved local control and disease-free survival (18). Adjuvant
radiation therapy should be administered especially when the
margins of resection are microscopically involved after defi nitive
surgical treatment, such as in this case.
Li-Fraumeni syndrome (LFS) is a cancer predisposition
syndrome associated with soft tissue sarcoma, osteosarcoma,
premenopausal breast cancer, brain tumors, adrenocortical car-
cinoma, and a variety of other neoplasms (22). More than 70%
of individuals diagnosed clinically have an identifi ed disease-
causing germline mutation in TP53, the only gene known to
be associated with LFS (23).
Since our patient had a personal history of sarcoma, as well
as a family history of brain tumors, leukemia, and lymphoma,
she met with a genetic counselor to assess the possibility of LFS.
Using sequencing and deletion/duplication studies, no mutation
was found in her p53 gene. Based on the patient’s family history
of malignancy, there is likely a genetic predisposition to cancer.
At this time, it is not known what gene(s) are contributing to
this familial cancer risk.
Primary cutaneous angiosarcoma of the breast is a very
rare disease. PET–computed tomography is useful for staging
workup. Defi nitive diagnosis is based on pathology results. Total
mastectomy is the preferred treatment. Although no clinical
trial proves the benefi t of adjuvant chemotherapy or radiation
therapy, both therapies should be considered in patients at high
risk of recurrence.
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