Mammary sarcomas are a heterogeneous group of malignant neoplasms that arise from the mammary stroma
]. Angiosarcomas, one of the most common forms of mammary sarcoma, are developed from the endothelial lining of the blood vessels
Breast angiosarcoma can be observed as a primary neoplasm or, more commonly, is described in upper limb lymphedema as a result of mastectomy and radiotherapy for breast carcinoma
]. Both primary and secondary breast angiosarcomas carry a prognosis worse than mammary carcinoma
]. Synchronous bilateral angiosarcoma has been reported
]. In the present paper, in accordance to the case reported, only primary angiosarcomas will be discussed.
Primary angiosarcoma of the breast is exceedingly rare, and represents around 0.04% of malignant breast neoplasms. Its incidence among breast sarcomas varies from 2.7% to 9.1%
]. Breast angiosarcoma is more frequent in young women (20 to 50 years) like in our case with no previous cancer history or other known risk factors
Between 6 and 12% of primary breast angiosarcomas are diagnosed during pregnancy or shortly after, suggesting hormones involvement. However, cases reported to display positive estrogen receptors are so rare that it is presently impossible to establish a link between angiosarcomas and hormonal dependency
]. In the case reported here, estrogen and progesterone receptors were both negatives. Therefore, the role of estrogen dependency in angiosarcoma has yet to be proven and could be subject to future research.
The right breast is more commonly involved than the left breast
In most published cases, breast angiosarcoma is presented as a palpable mass, without pain and with a fast growing rate
Radiographically, breast angiosarcomas exhibit no pathognomonic features. They often appear as ill-defined masses on mammograms. Calcifications can be seen but differ from those seen with breast carcinomas
]. In a review of radiologic findings with angiosarcomas, Liebermane and et al established that the echotexture of these lesions is highly variable. They conclude that Patients with higher-grade lesions at pathologic evaluation were significantly (P less than .05) more likely to have abnormal mammograms, like in our case
In most cases, tumor size at diagnosis is larger than 4 cm
]. Angiosarcomas larger than 5 cm are associated to a shorter disease-free survival than angiosarcomas smaller than 5 cm. Indeed, tumors smaller than 5 cm are usually associated to a better prognosis, even in the presence of worsening factors.
Diagnosis prior to surgery, either by FNA (Fine needle aspiration) or NCB, is always difficult
]. Chen and et al. reported a percutaneous biopsy false-negative rate of 37%
]. The final diagnosis in doubtful cases was made by excisionnal biopsy or was based on the patient's clinical course, which is characterized by episodes of tumor recurrence
In our case, Biopsy showed a benign hemangioma but at radiology the tumor was ill defined and seemed more aggressive than a simple hemangioma. So Large-core macrobiopsy was mandatory. But as the tumor was highly vascular at doppler sonography, even macrobiopsy was very difficult to perform, consequently the mastectomy was done.
After mastectomy, further review of biopsy showed a few and focal vascular structures lined by atypical cells without papillary or spindle areas. Those features were not sufficient to confirm the malignancy.
Pathologically, these tumors are subdivided into three groups according to the classification proposed by Donnel and et al
]. Grade I (well differentiated) contains open anastomosing vascular channels that proliferate within dermis, subcutaneous tissue or breast tissue. A single layer of endothelial cells lines these channels, which dissect through the stroma, causing distortion but little destruction of the preexisting lobules and ducts. The endothelial cells are usually flat; the nuclei may be hyperchromatic and contains small nucleoli. Solid and spindle cell foci, blood lakes, and necrosis are not present. Intermediate-grade angiosarcoma differs from low-grade by containing additional cellular foci of papillary formations and/or solid and spindle cell proliferation. The greater part of the tumor, however, is still composed of low-grade histology. Slightly increased mitotic activity is observed. In Rosen's study, intermediate-grade angiosarcomas behave more like low-grade sarcomas
]. In grade III endothelial tufting and papillary formations are prominent. Conspicuous solid and spindle cell areas, mostly devoid of vascular formations, are present as well. Mitoses may be brisk, especially in more cellular areas. Areas of hemorrhage, known as “blood lakes,” and necrosis are also seen.
High grade angiosarcoma may contain low or intermediate grade elements, especially at the periphery of the tumor. These elements have deceptively benign appearing and are well differentiated
]. This explains the fact that the majority of NCB biopsies are negative.
The endothelial cells show reactivity for several markers, including CD31, CD34 and von Willebrand factor (factor VIII). Among them, CD31 is considered the most sensitive and most specific endothelial cell marker.
Some papers have documented that epithelioid angiosarcoma can express cytokeratin and P63
Differential diagnosis of this rare tumor include: benign hemangioma, phyllodes sarcoma, stromal sarcoma, metaplastic carcinoma, fibrosarcoma, liposarcoma, squamous cell carcinoma with sarcomatoid features, myoepithelioma, fibromatosis, reactive spindle cell proliferative lesion
], and high-grade mammary carcinoma especially in small biopsy specimens containing only solid areas. Immunohistochemical stains for epithelial markers (pancytokeratin), endothelial markers (CD34 and CD31), and other sarcoma markers should help in making the correct diagnosis.
Surgery is the principal mode of treatment for primary angiosarcoma of the breast and generally consists of a total mastectomy. Hematogenous dissemination is the rule, making axillary lymph node dissection unnecessary. Chemotherapy is observed to be beneficial in high-grade lesions and in the metastatic setting. Preoperative radiotherapy is not indicated in the treatment of angiosarcoma
The degree of differentiation has a significant prognostic value, with regard to both local failure and metastases. Well-differentiated tumors (grade I) have a better prognosis and a higher survival with lower metastatic rate. The prognosis for cases of moderate differentiation is not clear due to the limited number of cases. Other characteristics of the tumor which are of lower prognostic value include: cellular appearance, infiltration of the border, number of mitoses and stromal atypia.