Angiosarcoma arises in the breast more often than in any other organ, and it is also the most common soft-tissue sarcoma involving the breast (8). Angiosarcoma of the breast tends to occur in younger women at a median of 38 years. Because the disease affects younger women, an association with pregnancy has been observed; however, there is no evidence for a hormonal basis for breast angiosarcoma. A correlation has also been suggested between prior radiation therapy in the setting of breast conserving surgery and the development of angiosarcomas (11). The SEER program data compiled by the National Cancer Institute included more than 194,000 women who were treated for breast carcinoma. Among patients in the radiotherapy cohort, the relative risk of developing angiosarcoma was 15.9 (5). The median latency period between radiation for breast cancer and the diagnosis of angiosarcoma has been estimated to be about 6 years. One study failed to confirm the observation that prior radiation increased the risk of developing angiosarcoma (19). In that series, only nine cases of angiosarcoma were documented, which represents a prevalence of 5 per 10,000. Cutaneous angiosarcoma of the chest wall after mastectomy and radiation therapy may also occur (7).

Typically, patients present with a rapidly growing painless breast mass. The overlying skin may have blue or purple discoloration (20). In the largest series, containing 69 patients with breast angiosarcoma, tumor size varied between 1 and 14 cm with a median of 5.5 cm (21). In the majority of cases, the angiosarcoma forms a friable, firm, or spongy hemorrhagic tumor. In high-grade lesions, cystic hemorrhagic necrosis is usually present. Hemorrhagic discoloration in the surrounding breast tissue may indicate that the tumor extends beyond the evident mass. In some cases, the tumors have been described as poorly defined areas of thickening or induration. Microscopically, three distinct patterns of growth have been described; they reflect the degree of differentiation and were thought to correlate with prognosis although one report did not find a relationship between grade and patient outcome (9). Low-grade or type I tumors (Fig. 64-1A) are composed of open, anastomosing vascular channels that invade mammary glandular tissue and fat, producing atrophy of the terminal duct lobular units. Some prominent hyperchromatic endothelial nuclei may be found, but most often they have inconspicuous nuclei. The endothelial cells are distributed in a flat monolayer around the vascular spaces without papillary endothelial proliferation, and rare mitoses are seen. Intermediate-grade or type II angiosarcoma (Fig. 64-1B) shows scattered focal areas of more cellular proliferation consisting of well-developed papillary endothelial proliferation that may combine polygonal or spindle cells. Infrequent mitoses may be found in cellular or spindle areas. Type III or high-grade angiosarcoma (Fig. 64-1C) exhibits highly malignant features that comprise more than 50% of the tumor (22). These tumors consist of prominent epithelial tufting and solid papillary formations with cytologically malignant endothelial cells. Mitoses are readily found. Areas of necrosis and hemorrhage, so called “blood lakes,” are only found in high-grade angiosarcomas. The high-grade tumors have infiltrative borders that feature low-grade vascular channels, which may lead to the erroneous diagnosis of a low-grade lesion on a core biopsy. Immunohistochemically, angiosarcomas are positive for Factor VIII related antigen, thrombomodulin, B72.3, CD31, and CD34. These reagents are useful for distinguishing angiosarcomas from carcinoma and other neoplasms. It has been reported that the level of the cell cycle protein SKp2 and the Ki-67 index as a measure of proliferation can be used to distinguish benign vascular lesions such as hemangiomas from malignant low-grade angiosarcomas (23).

Extraskeletal osteosarcoma of the breast is an extremely rare tumor, accounting for 12.5% of mammary sarcomas (29). Primary breast osteosarcomas are considered highly aggressive tumors with early local recurrence and hematogenous spread (most commonly to the lungs). The most common presentation is a circumscribed and movable mass that on mammography may show osseous trabeculae or coarse calcifications. Silver et al. (30) reported a series of 50 patients with osteogenic sarcoma of the breast diagnosed at the Armed Forces Institute of Pathology (AFIP) between 1957 and 1995. The median patient age at presentation in that study was 63.2 years, and the tumor size varied from 1.4 to 13 cm at the time of diagnosis. The histological features are similar to other skeletal osteosarcomas. The most common variants observed are fibroblastic, osteoblastic, and osteoclastic. In the osteoblastic osteosarcoma, the osteoid is deposited in a fine, ramifying, lacelike, or coarsely trabecular pattern
and sometimes in sheaths of osteoid or bone. Atypical cartilage has been reported in 36% of primary breast osteosarcomas. Necrotic foci can be identified in 30% of the cases. Multinucleated osteoclastic giant cells are usually present in areas of bone formation. Immunohistochemistry is helpful in ruling out a metaplastic carcinoma with heterologous elements, which expresses CAM 5.2, pancytokeratin, and high molecular weight keratin (Fig. 64-2).

The relationship between prior breast or chest wall irradiation and breast osteosarcoma is not clear. One of the patients in the AFIP series had received radiotherapy for ipsilateral breast carcinoma 9 years before presentation, but none of the other patients had been exposed to radiation therapy (30). Like other sarcomas, spread to regional lymph nodes is uncommon with breast osteosarcoma. No axillary lymph node involvement was noted in 20 patients who underwent axillary lymph node dissection in the AFIP series. Of 39 patients with follow-up, locally recurrent (n = 11) or metastatic disease (n = 15) was documented at a mean of 10.5 and 14.5 months from diagnosis, respectively, in the same study. Adjuvant radiation therapy and chemotherapy are not recommended.