Angiosarcoma is a mesenchymal malignant tumor which may occur in any part of the body, most commonly in the skin of the head, neck, and scalp; however, angiosarcoma of the breast is rare [3]. Breast angiosarcoma is categorized into two groups: primary angiosarcoma and secondary angiosarcoma. Secondary angiosarcoma is identified as postradiation angiosarcoma in breast cancer treatment or angiosarcoma that develops in chronic lymphedema resulting from axillary dissection, which is the so-called Stewart-Treves syndrome [1, 4]. Primary angiosarcoma occurs in a young population whose age ranges from 30 to 50 years old. Secondary angiosarcoma occurs in an elderly population and is commonly observed 5 to 10 years after breast cancer treatment [1, 4,5,6]. In most cases, primary angiosarcoma presents with a palpable mass, whereas secondary angiosarcoma tends to present with a skin color change [4].
Primary angiosarcoma of the breast is associated with a poor prognosis. Its median disease-free survival and OS times are 2.26 years and 2.96 years, respectively; the 5-year OS rate of a localized primary breast angiosarcoma is 50–66% [1, 5]. In addition to patients presenting with metastatic disease on their first visit, the tumor size, histologic characteristics, and surgical margin are considered to be other possible markers of prognosis [4, 7]. Well-differentiated angiosarcoma of less than 5 cm in size, with a lower grade, and with a negative margin tends to have a better prognosis [4, 8].
As primary angiosarcoma is likely to develop local recurrence at a later time, complete resection of the tumor is the main treatment strategy. Total mastectomy with or without axillary dissection or lymphadenectomy is recommended as a surgical treatment, and a wide local excision is also acceptable when sufficient margins can be left around the tumor [4, 9]. An additional rescue mastectomy may also be performed in case of a positive margin [10]. In the present case, a wide local excision was performed as the initial treatment because the patient selected a partial resection. We considered the patient’s choice as acceptable because the tumor was well defined and less than 5 cm in size. At this point, we did not expect the possibility of discontinuous daughter lesions. The main tumor was considered to have been successfully resected with sufficient margins around the tumor macroscopically. However, several small discontinuous lesions of angiosarcoma were incidentally observed around the main tumor. Based on this unexpected pathological finding and the fact that local recurrences usually have a poor prognosis, we decided to additionally perform mastectomy. As the following mastectomy revealed two other small lesions of angiosarcoma in the remnant right breast, there was a question of whether total mastectomy should have been performed in the first place. However, as three of the small lesions were less than 10 mm in size, and the other two lesions were even smaller (< 2 mm), it was difficult to find the skipped disease before the initial operation by ultrasonography or any other radiological examinations.
A cohort of 103 breast sarcoma has been shown to have a strong correlation between the residual tumor (including close margins of < 10 mm) and a poor survival rate [7]. Although this previous study included all soft tissue sarcomas, the result cannot be ignored as 41% of the cohort was angiosarcoma. Thus, we believe that our decision to perform additional mastectomy was adequate to ensure no residual disease.
Compared with secondary angiosarcoma, where cutaneous postradiation angiosarcomas are likely to present with multifocal tumors [6], such multifocal tumors of primary angiosarcoma appear to be extremely rare. Although Zelek et al. have reported six multicentric tumors of primary breast sarcoma (7% of the cohort), the histologic types of the sarcoma could not be obtained because they were not specified [9]. Pandey et al. reported a case with multiple primary angiosarcoma; however, this case had undergone bilateral reduction mammoplasty 14 years before the presentation of angiosarcoma [11]. In this previous case, preoperative MRI revealed multiple cystic structures in the entire right breast, and simple mastectomy showed multiple sections of low-grade angiosarcoma from the lower outer quadrant and mid-portion of the specimen [11]. Although it has been reported that radiation induces multifocal secondary angiosarcoma [6], it is not clear whether reduction mammoplasty can trigger the multifocal tumorigenesis of angiosarcoma. We speculate that such possibility cannot be completely excluded. Apart from these two reports, we have found no other reports to this writing noting multifocal primary angiosarcoma in the breast.
Multifocal angiosarcoma in other organs
Multifocal angiosarcoma in other organs has also been reported. Multifocal intestinal angiosarcoma has been described by Navarro-Chagoya et al. and multifocal hepatic angiosarcoma has been reported by Horiguchi et al. These reports describe the specific conditions of the patients, namely, postradiation for pelvic tumor and underlying disease with dyskeratosis congenita, respectively [12, 13]. As for cutaneous angiosarcoma, a multifocal spread within the dermis is characteristic [14]. Aside from these specific underlying conditions or cutaneous angiosarcoma, primary multifocal angiosarcoma in any organs appears to be very rare. In a previous report on multiple primary pulmonary angiosarcoma, Tanaka et al. pointed out two possible multifocal growth patterns, namely multicentric tumorigenesis and spreading from one primary site with preferred proliferation in a periarterial microenvironment [15]. In the present case, as all five small angiosarcoma lesions were located near the main tumor, it can be hypothesized that the latter growth pattern proposed by Tanaka et al. may be the development pattern in our case.
Possibility of unrecognized multifocal angiosarcoma in the remnant breast
As breast angiosarcoma usually induces local recurrence, it is possible that there are many more unrecognized cases of multifocal growth than the few reported cases of multifocal breast angiosarcoma. In a series of primary breast sarcoma treated in Mayo Clinic, local recurrence was observed in 11 cases out of 25 cases (five out of six angiosarcomas) [8]. By classifying these 25 cases according to the surgical procedure (the surgical procedure of one case is unknown), local recurrence was observed in seven cases out of 19 cases in the mastectomy group (three out of four angiosarcomas), whereas an increased local recurrence was observed in four cases out of five cases in the wide local excision group (two out of two angiosarcomas) [8]. The higher rate of local recurrence in the wide local excision group may support the contention that there might be more cases of multifocal angiosarcoma outside the resected specimen. Therefore, total mastectomy may be the best surgical strategy for primary angiosarcoma.
Surgical approach to axillary lymph nodes
Although angiosarcoma metastasis is considered to occur via the hematogenous route, lymph node metastasis has also been reported [4, 9, 10]. The lung has been identified as the most common metastatic site [10]. Lymphadenectomy or axillary dissection is commonly performed together with mastectomy when lymph node metastasis is suspected. In the present case, a round lymph node was detected by ultrasonography and CT scan. As the fine needle aspiration cytology revealed no malignancy, additional surgical examination was not performed in the first operation. However, as additional mastectomy was carried out and an intradermal injection of a radioisotope on the surface of the tumor accumulated on the same lymph node detected by ultrasonography, sentinel lymph node biopsy was performed along with mastectomy to make sure that the lymph node was completely benign. The result showed no malignancy in the sentinel lymph node. Although the exact mechanism of lymphatic metastasis of primary breast angiosarcoma remains to be clarified, sentinel lymph node biopsy also appears to be an acceptable approach for establishing malignancy.
Because of the rarity of breast angiosarcoma, there are only limited reports on the effects of adjuvant therapy. Thus, randomized trials of adjuvant radiotherapy or chemotherapy are not yet available [1, 4]. As the efficacy of adjuvant therapy for breast angiosarcoma still lacks evidence, we did not perform any adjuvant therapy in this present case.
