Mesenchymal Neoplasms of the Breast

Angiosarcoma

Angiosarcomas (AS) are the most common sarcomas encountered in the breast. They account for <1% of all breast malignancies. They are divided into two categories: primary AS (idiopathic) and secondary AS. Secondary AS most often occur following radiation therapy, but they can also be associated with chronic lymphedema (Stewart-Treves syndrome).

Primary AS typically occur in younger women aged 15 to 74 years (mean 41.5, median 40). All reported cases are located within the breast parenchyma. Rare bilateral cases have been reported. Primary AS presents as a fast-growing, painless mass. Tumors range from 2 to 20 cm with an average of 5 cm. On rare occasions primary AS has been reported following pregnancy. Macroscopically, the cut surface varies from hemorrhagic and spongy to firm, dull white, and occasionally necrotic. Microscopically, the blood vessels are increased in number and form anastomosing channels. The endothelial cells may show papillary tufts. Nuclei are usually enlarged and hyperchromatic. Pleomorphism can be present. Various numbers of mitotic figures can be seen. These tumors can show occasional or focal epithelioid features. The complex branching vascular spaces infiltrate around preexisting structures and often show infiltrating margins. The lesion can also contain blood lakes due to the presence of extravasation of red blood cells. Neoplastic cells express endothelial markers, including factor VIII, CD34, CD31, and ERG. ERG is probably the most sensitive and specific marker by immunohistochemistry (IHC). Surgical excision with wide margins, often requiring mastectomy, is the most effective treatment. Axillary dissection is not indicated, since in the majority of cases the lymph nodes are uninvolved. Most authorities suggest that additional chemotherapy and radiation therapy require a multidisciplinary approach. Some patients, especially those with metastatic lesions, respond to chemotherapy. This tumor can locally recur, with most recurrences occurring within the first 3 years. These tumors also metastasize to distant sites, including lung, liver, and bone. In one of the larger reported series, overall survival was 50% at 5 years, and disease-free survival (DFS) was 20% at 3 years and 0% at 5 years ( Fig. 24.1 ).

Secondary AS develop following radiation therapy or in patients with lymphedema. The radiation-induced angiosarcoma (RIAS) usually occurs in the skin of the chest wall or within the residual breast tissue. The incidence of RIAS differs in various studies, ranging from 0.14% to 0.5%. The median interval from the primary breast cancer surgery to the diagnosis of AS is reported as 59 months (range 24–132 months). Some authorities believe the absolute number of RIAS will increase due to increased use of radiation therapy ( Fig. 24.2 ).

Unlike primary angiosarcoma, RIAS is primarily a dermal/subcutaneous tumor. RIAS usually starts as painless blue-red patches on the skin, similar to a hematoma. Later, it progresses to violaceous or nonpigmented nodules, plaques, vesicles, and macules and eventually ulcerates.

Light microscopy reveals an ill-defined infiltrative neoplasm dissecting within dermal collagen and involving subcutaneous fat. Cells lining slit-like spaces show moderate nucleomegaly, hyperchromasia, and distinct nucleoli. Mitotic figures and papillary tufting are common.

Lymphedema-induced AS, known as Stewart and Treves angiosarcoma, are usually associated with chronic lymphedema. Although the majority of these AS occur in patients with lymphedema following mastectomy, they can occur anywhere in the body because of chronic lymphedema. This is known as Stewart-Treves syndrome. The range of time for the progression of chronic lymphedema to develop angiosarcoma is 4 years to more than 50 years.

RIAS and Stewart-Treves syndrome are associated with MYC gene amplification and MYC protein overexpression, while other radiation-associated vascular lesions, including atypical vascular lesions, are not associated with MYC overexpression. MYC is not overexpressed in primary angiosarcoma.

Regardless of the etiology, AS have a relatively poor prognosis. The odds of 5-year local control are higher if a greater than 5-cm margin was achieved at the time of resection. Secondary AS, but not primary AS, is associated with improved survival with chemotherapy. Radiation therapy did not improve DFS or OS.

Hemangioma

Mammary hemangiomas have been described in patients of all ages, ranging from infancy to the elderly. Hemangiomas may occur in the mammary parenchyma or subcutaneous tissue. Various subtypes include perilobular hemangioma, venous hemangioma, cavernous hemangioma, and capillary hemangioma. The most common type is perilobular hemangioma. These lesions most likely represent non-neoplastic vascular malformation. Macroscopically these lesions are circumscribed with red or dark brown and are spongy. Microscopically they show proliferation of blood vessels of different sizes. All hemangiomas lack anastomosing connections, endothelial tufting, and atypical mitoses, and they are often an incidental finding.

Angiomatosis

Angiomatosis (diffuse hemangioma) of the breast is a rare benign vascular proliferation. It affects patients from infancy to the sixth decade but typically occurs in young women. A diffuse network of sinusoidal small and large anastomosing vessels affects a large area of the breast. Vessels proliferate around but not into terminal duct lobular units. Incompletely excised angiomatosis has a high risk of recurrence, but malignant transformation has not been described.

Atypical Vascular Lesion

Atypical vascular lesions are strictly seen at the previously irradiated skin. They present as small brown to erythematous papules or plaques. They are frequently multiple. This entity is also covered in the chapter on disorders of the skin, chapter 26 .

Mimics of Vascular Lesions

Pseudoangiomatous Stromal Hyperplasia (PASH)

PASH is not a true vascular lesion but a proliferation of cytologically bland stromal cells, fibroblasts/myofibroblasts that create empty slit-like spaces mimicking a vascular lesion. These lesions can occur in both sexes. Approximately 53% of patients with PASH present with abnormalities on screening mammogram. On imaging studies, PASH appears similar to fibroadenomas. On occasion PASH can present as a large mass. Bilateral cases have been reported. On average, patients are diagnosed in the fourth decade of life, but a wide continuum exists. Tissue spaces formed by separation of densely hyalinized collagen fibers may or may not be lined by cells. This proliferation may create a concentric perilobular pattern. Fibroblasts lack cytologic atypia or mitoses, and necrosis and effacement of normal breast tissue are absent. These cells express CD34, muscle-specific actin, calponin, and PR. CD31 and cytokeratin stains are negative. Surgical resection is required only if the lesion enlarges ( Fig. 24.3 ).

Angiolipoma

Angiolipoma is a variant of lipoma. It occurs typically in the subcutaneous tissue and shows small capillary-sized vessels within a lipoma. Intraluminal thrombi are commonly seen ( Fig. 24.4 ).