“A 35 year-old Woman with a Lump in the Breast”
California Tumor Tissue Registry’s
Case of the Month
CTTR COTM www.cttr.org Vol 7(3), 2004
December, 2004
During a routine physical examination, a 35 year-old woman
was found to have a lump in her right breast. Following a
needle biopsy, a modified radical mastectomy was performed.
The 550 gram, 17.0 x 17.0 x 10.0 cm breast resection contained
a 4.5 x 3.5 x 3.5 cm poorly circumscribed indurated red-tan mass.
The tumor was microscopically composed of anastomosing vascular channels lined by
mildly atypical endothelial cells (Fig. 1). Focal areas showed more proliferative activity,
and increased cellularity (Fig. 2). Scattered regions demonstrated ‘tufting’ and focal
papillary growth (Fig 3). Mitotic figures were present, but rare (Fig. 4). Some lobularity
was retained, but these areas were scattered, and had an infiltrative perimeter. The tumor
periphery was infiltrative into the surrounding fat (Fig. 5).
Diagnosis: “Angiosarcoma of the breast, Intermediate-grade / type 2”
Sajjad P Syed, MD, and Donald R Chase, MD
Loma Linda University Medical Center
Loma Linda, California
Angiosarcoma (AS, aka hemangiosarcoma, hemangioendothelioma, hemangioblastoma,
angioblastoma and benign metastasizing hemangioma) is a rare, highly lethal neoplasm
accounting for < 0.05% of primary mammary cancers. It is exceptionally rare in males,
with only five reported cases, but in females, it has been described as occurring between
the ages of 14 and 82 years, at a rate of one for every 2000 – 3500 “traditional” breast
cancers 1. Patients diagnosed during pregnancy tend to have high-grade tumors, and
ultimately, an exceptionally bad prognosis3.
AS has an insidious clinical onset and usually presents as a painless, discrete mass that
grows rapidly and may, in rare incidences, acquire large proportions. Twelve percent of
patients present with diffuse enlargement of the breast. Although the breast surface
usually is unremarkable, a bluish red discoloration has been described. Nipple retraction,
discharge, or axillary node enlargement are generally absent. Bilateral tumors have been
reported 5 particularly in association to pregnancy and in postmenopausal women 6,7. On
mammography, the lesion is ill-defined and displays a ‘soap bubble’ appearance 8, with a
mean size of around 4 cm 9. False negative results however have been reported, and in a
series of 29 cases, 33% were missed on mammography (9). Sonography usually can
confirm a solid, well defined, lobulated mass with both hyperechoic and hypoechoic
signals, which generally show no acoustic shadowing 10. MRI shows the presence of
CTTR’s Case of the Month
December, 2004
1
vascular channels containing slow-flowing blood 9. Because patients with angiosarcoma
in one breast may develop asynchronous contralateral lesions, MRI of the opposite breast
should is suggested at the time of diagnosis, and periodically during follow-up 3.
Postmastectomy angiosarcoma of the chest wall has been described in patients who
received postoperative radiotherapy in this anatomic region 3, furthermore, virtually all
sarcomas that have occurred in the mammary gland after breast-conservative surgery and
irradiation for carcinoma have been angiosarcomas 11-17, and most occur within 6 years
after radiotherapy. Postradiation angiosarcoma of the breast has a variety of
presentations; thus diagnosis is often delayed 18. The estimated risk of cutaneous or
parenchymal angiosarcoma of the breast after breast conservation and radiation for
carcinoma is 0.3% to 0.4% 17,19 . The prognosis of postradiation angiosarcoma of the
breast parenchyma or skin of the breast is influenced by the tumor grade and is most
favorable in women with low-grade tumors 20. The 3 and 5 year overall survival rates
have been reported as 72% and 55% respectively 20. The Kasabach-Merritt syndrome,
characterized by consumptive thrombocytopenia, has occasionally been attributed to
angiosarcoma of the breast 21. Angiosarcoma of a chronically lymphedematous limb as a
complication of the treatment of mammary carcinoma has been referred to as the StewartTreves syndrome 22
In general, mammary AS ranges from 1 - 12 cm, has poorly defined margins, and a
spongy, friable consistency. Extension to the pectoral fascia is rare. Histologically, the
tumor proliferates around and into lobular stroma, and usually advances into surrounding
tissue with ill-defined margins and significant infiltration of adipose tissue, separating the
lobules and terminal-duct units. The tumor is composed of irregular, anastomosing
vascular channels lined by one or more layers of endothelial cells (in tufts, papillae,
and/or solid nests). Solid areas are composed of spindle cells, blood lakes, and necrosis;
features usually indicative of poor differentiation (high-grade angiosarcoma). To avoid
undercalling angiosarcomas, generous sampling of large lesions is crucial. Epithelioid
transformation has been reported to occur where the tumor cells show cytoplasmic
microlumina which can be easily be misinterpreted as infiltrating ductal carcinoma 23.
Coincidentally, however, angiosarcoma and infiltrating ductal carcinoma can occur in the
same breast 24.
Three histologic patterns of growth in the primary tumor have been described. These
reflect the degree of differentiation and have been proven to correlate with prognosis 25,26
(Table 1):
Table 1 Grades of Angiosarcoma
Key features
Lobular glandular units
Endothelial cells
Low-gr./Type 1
Distinct, open,
anastomosing vascular
channels, proliferate
diffusely in the glandular
tissue and fat
Separated and atrophic
Hyperchromatic, flat
single-cell layer around
CTTR’s Case of the Month
Intermediate gr./Type 2
Type1 + Scattered focal
areas of more cellular
proliferation +/hemorrhage
Atrophic
Hyperchromatic, small
buds or papillary fronds
December, 2004
High gr./Type 3
Type 1 & 2 areas +
conspicuous solid and
spindled areas with
sparse vascular
elements
Infiltrated
Hyperchromatic,
cytologically
2
vascular spaces
Papillary formations
Mitotic figures
Solid and spindle cells
‘Blood lakes’
Necrosis
Variants
Absent
Rare to absent
Absent
Absent
Absent
Capillary type;
resembling
pseudoangiomatous
hyperplasia; resembling
angiolipoma
of endothelial cells
project into vascular
lumens
Focally present
Seen in papillary areas
Minimal
Absent
Absent
May show numerous
nodules of spindled cells
with a swirling pattern
malignant, prominent
endothelial tufting
Prominent
Easily identified
>50%
Present
Present
Epithelioid
angiosarcoma
Adapted from Rosen’s Breast Pathology. 2nd Ed. Pg. 831
With few exceptions, angiosarcomas have infiltrative borders that feature well-formed or
low-grade vascular channels. The peripheral vascular component may be so orderly that
the neoplastic vascular channels may be structurally indistinguishable from existing
capillaries in the normal parenchyma. It is the infiltrativeness, however, that separates
AS from benign mammary vascular tumors (i.e. hemangioma).
In the setting of conservative breast surgery and postoperative radiation, benign atypical
vascular lesions (AVL) must be distinguished from cutaneous postradiation angiosarcoma
of the breast. AVLs typically develop 2 to 5 years after radiotherapy as single or multiple
pink papules in the skin, usually < 5 mm in diameter (Table 2).
Table 2 Atypical Vascular Lesion (AVL) vs Angiosarcoma (AS)
Characteristic
Infiltration of subcutis
‘Blood lakes’
Papillary endothelial hyperplasia
Prominent nucleoli
Mitotic figures
Marked cytologic atypia
Anastomotic vessels
Chronic inflammation
Hyperchromatic endothelial cells
Dissection of dermal collagen
Relative circumscription
Projection of stroma into lumen
AVL
++
+++
+++
+/+++
+++
AS
+++
+++
+++
+++
+++
+++
+++
+
++
+++
-
Rosen’s Breast Pathology. 2nd Ed. Pg. 844
Immunohistochemical staining for CD31, CD34, factor VIII, Ulex europaeus agglutinin-I
(UEA-I), in angiosarcomas is usually positive 23,27,28. These stains are especially useful
for distinguishing epithelioid forms of AS from carcinoma and other neoplasms.
Ultrastructurally, Weibel-Palade bodies have been described in neoplastic endothelial
cells, which may also contain pinocytotic vesicles at the luminal and basal surface 23,29.
Total mastectomy is the recommended surgical therapy. Because the tumor metastasizes
usually via hematogenous routes, regional lymph node dissection is generally not
indicated. Recurrences have been reported to be less frequent with adjuvant
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December, 2004
3
chemotherapy and postoperative radiotherapy 26. Survival rates in mammary AS are
quite poor, with 14% - 41% of the patients have been reported to be disease free at 3
years and with only 7% - 33% survival (disease free) after 5 years 25,30,31. Tumor grade is
the most important prognostic factor. Virtually all women with high-grade tumors die of
recurrent disease within 5 years. In a series of 87 patients, disease free survival 5 and 10
years after treatment has been reported as: low-grade: 76%; intermediate-grade: 70%; and
high-grade: 15%. Hence, the prognosis of angiosarcoma of the breast after radiotherapy
is determined by the degree of differentiation of the tumor, which does not appear to
differ substantially from that of spontaneous parenchymal angiosarcoma unassociated
with radiotherapy. The most frequent sites of metastases are bone, lungs, liver,
contralateral breast, and the skin 26. Rare metastasis has also been described in the ovary
and placenta 32.
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