Keywords
primary angiosarcoma - mammography - ultrasound - MRI
Introduction
Angiosarcoma of the breast is a rare tumor divided into primary and secondary. Primary
breast angiosarcoma occurs in young women and presents as a palpable mass, usually
in the third and fourth decades of life. Bluish skin discoloration can be seen in
one-third of the patients and is attributed to the vascular nature of the tumor. Secondary
angiosarcoma occurs most frequently after breast conservation therapy with radiation
therapy and the average latent period is 5 to 6 years. It is scarce to see primary
angiosarcoma (PAS) in old age.[1]
[2]
Case Report
We present a rare case of PAS in a 65-year-old woman who complained of a lump in the
left breast's lower inner aspect associated with bluish discoloration of the overlying
skin for 1 month. There was no history of pain, nipple discharge, hormonal therapy,
trauma, breast surgery, or radiation therapy. She did not have any family history
of breast cancer.
On examination, a mobile, firm consistency lump was palpated in the lower inner quadrant
of the left breast. It was associated with mild bluish discoloration of the overlying
skin. No axillary lymphadenopathy was noticed.
A diagnostic CR-mammogram performed on alpha-RT (GE-Wipro) showed heterogeneous dense
breast with an oval, high density lesion with microlobulated margins measuring ∼3 × 2.6
cm in lower inner quadrant left breast in third anterior depth ([Fig. 1]). No intralesional calcification, skin thickening, nipple retraction, or axillary
lymphadenopathy was appreciated. Breast imaging-reporting and data system 4 (BIRADS
4) category was assigned to the left breast mass on mammography.
Fig. 1 Mediolateral oblique (A) and craniocaudal (B) mammogram of the left breast, showing an oval, high density mass with microlobulated
margin in lower inner quadrant left breast in anterior third depth (white arrow).
A breast ultrasound (US) was performed on Samsung RS 80A, using a 4 to 18 MHz linear
probe with an elastography facility. The US revealed an irregular shape, parallel
orientation, microlobulated margin, heterogeneously hypoechoic lesion with posterior
acoustic enhancement in the left breast at 8 to 9 o'clock in zone two. The lesion
showed peripheral and center vascularity with an E-Strain of 3.6. Right breast parenchyma
was normal. Bilateral benign axillary lymph nodes were noticed ([Fig. 2]). BIRADS 4 lesion was suspected on US imaging.
Fig. 2 Ultrasonography demonstrates an irregular shape, parallel orientation, microlobulated
margins, heterogeneously hypoechoic mass with posterior enhancement in left breast
at 8 to 9 o'clock position in zone two with an area of increased vascularity (A). A biopsy needle is seen within the lesion (B).
Plain and contrast magnetic resonance imaging (MRI) of the breast were performed for
further assessment of the characteristics and extent of the lesion. MRI of the breast
was done on a 1.5 Tesla MR system (GE Signa Excite) using a dedicated eight-channel
breast coil. On MRI examination, bilateral breast tissue was heterogeneous fibroglandular
with minimal background parenchymal enhancement. An oval-shaped, irregular margin,
altered signal intensity lesion measuring 3 × 2.5 cm was seen in the lower inner quadrant
of the left breast at 8 o'clock. The lesion appears hypointense on T1-weighted (T1WI)
images ([Fig. 3A]), heterogeneous hyperintense on T2-weighted (T2WI), and T2 fat saturated images
([Fig. 3B]). Few areas showed diffusion-weighted imaging restriction with the hypointense signal
on the apparent diffusion coefficient (ADC) map (ADC value 1.12e-09). The lesion was isointense on precontrast images. On dynamic postcontrast evaluation,
heterogeneous enhancement of the mass with type II kinetic curve (early rapid uptake
of contrast with persistent delayed enhancement) was noticed. Dilated vessels were
seen within and on the periphery of the lesion. While early images showed peripheral
enhancement, delayed images showed contrast enhancement in the central portion of
the tumor ([Fig. 3C, D]). No invasion of underlying pectoral fascia, muscles, or the overlying skin was
seen. No enlarged axillary lymphadenopathy was identified. Above findings point toward
BIRADS 4 lesion in the left breast.
Fig. 3 The lesion appears hypointense on T1-weighted images (A), heterogeneous hyperintense on T2 fat-saturated images (B). On dynamic postcontrast evaluation, heterogeneous enhancement of the mass seen
with dilated vessel within as well as on the periphery of the lesion. Early (C) and delayed postcontrast images (D).
Based on bluish skin discoloration, dilated tubular structure within and in the periphery
of the lesion on mammography, US features of hypervascularity, absence of axillary
lymphadenopathy, MRI features of heterogenous enhancement with center contrast enhancement
in the delayed phase led to the possible diagnosis of PAS of the breast.
Consequently, a core biopsy was performed under US guidance with a sample taken from
multiple sites. Histopathological examination revealed a predominantly necrotic vascular
neoplasm compressing closely proliferating hyalinized blood vessels lined by neoplastic
endothelial cells expressing CD31 and CD34 with a Ki 67 index of 30 to 40%. These cells do not express pan CK. Mitotic rate was 5 to 6
per high power examination. Features were suggestive of angiosarcoma of the breast
([Fig. 4A–D]).
Fig. 4 Ectatic vascular spaces lined by atypical endothelial cells and surrounded by collagenous
stroma, low power (A), high power (B). Immunohistochemistry showing positive tumor cells for CD34 (B) and CD31 (C).
The patient underwent a modified radical mastectomy. There was blush discoloration
of skin in the medial, lower quadrant. On the cut section deep to the bluish skin
discoloration, a gray-brown area measuring 3.5 × 2 × 2 cm was noticed 1 cm below the
skin margin. The microscopic section studied shows varying sizes of the blood vessel.
Some of which were ecstatic and same have a slit-like appearance. These vascular spaces
were lined by round to oval spindle-shaped cells, with finely dispersed chromatin,
inconspicuous nucleoli, and moderate cytoplasm. The vascular channels were seen communicating
with each other, forming a network of sinusoids. These vascular channels were seen
dissecting through the subcutaneous fat and collagen. Few mitotic figures were seen,
along with the area of hemorrhage and necrosis. Nipple-areola and deep surgical margins
were free of tumor infiltration. No lymph node involvement was seen. On immunohistochemistry
(IHC), tumor cells were positive for CD34/CD31 and negative for pan CK with a Ki 67 index of 20 to 25%. A diagnosis of low-grade angiosarcoma of the left breast was
made.
Discussion
Angiosarcoma is a rare malignant tumor arising from vascular endothelial cells. PAS
is rare and constitutes 0.04% of all malignant breast tumors.[1] Angiosarcoma of the breast can have no known risk factors and often develops in
young women. Very few cases of PAS have been reported in postmenopausal women. Secondary
angiosarcoma develops mainly after breast conservative therapy accompanied by radiation
therapy. Angiosarcoma arising in the region of chronic lymphedema after conservative
breast therapy regardless of radiation exposure is known as Stewart Treves syndrome.[3]
[4]
[5]
PAS usually arises in younger women in their third and fourth decades of life and
is often associated with pregnancy. These patients typically present with a painless
discrete palpable mass that grows rapidly, and ∼2% of patients may present with diffuse
enlargement of the breast. Bluish discoloration of the overlying skin may be there
in one-third of patients and is attributed to the vascular nature of the tumor.[6]
[7]
PAS may be missed on mammography due to the high density of breasts in young women.
They may present focal asymmetry or masses with round, oval, or irregular shapes and
may exhibit circumscribed or indistinct margins. They lack speculation and microcalcification,
often seen in breast carcinomas. Sonography usually shows a mass with circumscribed
or indistinct margins, with hypo or heterogeneous echotexture. Acoustic enhancement
may be seen. Color Doppler may show hypervascularity.[8]
[9]
[10]
[11]
MRI of angiosarcoma shows a mass with a hypointense signal on T1WIs and a hyperintense
signal on T2WIs. The latter suggests the presence of a vascular channel containing
slow-flowing blood. Irregular area of high T1 signal may be seen in the high-grade
lesions; these represent the area of hemorrhage or venous lakes. Low-grade angiosarcoma
shows progressive enhancement. High-grade angiosarcoma shows rapid enhancement and
washout or persistent enhancement. MRI is useful in the presurgical evaluation of
the patient.[12]
[13] Three grades of PAS have been described, namely (a) low-grade (comprising of anastomosing
vascular channels that invade the surrounding breast tissue), (b) intermediate-grade
(solid neoplastic vascular growth and an increased mitotic rate, and (c) high-grade
(frankly sarcomatous areas with an area of necrosis, hemorrhage, and infarction).
Five years survival rate for low-grade angiosarcoma can be 76%, while 70% for intermediate
grade and ∼15% for high grade. Large-sized tumors of PAB can lead to thrombocytopenia
and hemorrhagic manifestations (Kasabach-Merritt syndrome).
IHC for specific biomarkers can differentiate angiosarcoma from invasive carcinomas
(ductal/lobular), absence of cytokeratin, and presence of endothelial markers such
as CD31 and CD34 confirm angiosarcoma. CD31 is more specific, and CD34 is a more sensitive
marker for endothelial differentiation.
Positron emission tomography with fluorodeoxyglucose (FDG) helps in tumor staging
by showing FDG uptake in regions with angiosarcoma spread.
PAS of the breast in a postmenopausal female is very rare. Very few cases have been
reported till now. Previous studies have reported cases of PAS of the breast in 60-year
and 70-year-old postmenopausal women, where only the US was done. It showed a cystic
lesion with an internal hypoechoic mural nodule associated with vascularity or a pure
cystic lesion.[14]
[15]
In our case, we have investigated the patient through mammography, US, and MRI. After
a core biopsy of angiosarcoma, a metastatic workup was done, which came out to be
negative. Mastectomy was performed, and the final diagnosis was low-grade PAS. Differential
diagnosis of this rare malignancy includes benign hemangioma, hamartoma, stromal sarcoma,
malignant phyllodes, metaplastic carcinoma, fibromatosis, fibrosarcoma, liposarcoma,
and reactive spindle cell proliferative lesions.[12]
The treatment is primarily surgical, either by mastectomy or wide excision. Axillary
clearance is unnecessary for all patients because angiosarcoma does not usually follow
a lymphatic way of dissemination. Chemotherapy and radiation therapy are needed in
patients with high-grade tumors and distant metastasis. Common sites of metastasis
of PAS of the breast are skin, lung, bone, liver, brain, and ovary.
Conclusion
Our case report of PAS in a postmenopausal woman is a rare case showing typical bluish
discoloration of overlying skin, dilated vessels on mammography, and MRI with the
increased center as well as peripheral vascularity on US. All these findings can help
in early diagnosis of Angiosarcoma so that timely management is possible.
