Angiosarcoma as well as other sarcoma subtypes may arise within breast tissue and may clinically mimic both primary breast malignancy as well as reactive/reparative masses of the breast. In a study compiling data from multiple small series of primary angiosarcoma cases, the median patient age ranges from 38 to 49, and median tumor size ranges from 3 to 6.8 cm. There are no definitive risk factors for primary angiosarcoma of the breast. (1) Angiosarcoma may also arise as the sarcomatous component within a malignant phyllodes tumor.
Angiosarcoma of the breast may also present as a secondary phenomenon associated with prior radiation treatment and chronic lymphedema post lymphadenectomy (Stewart-Treves syndrome); typically these patients are older (median age of 73 in one US study) than those presenting with primary angiosarcoma, the lesions are often located superficially/adjacent to skin, and further the history of prior therapy aids in diagnosis. (2,3,4)
Aspirates from angiosarcoma are most commonly described as bloody. (4) Reported cytologic features of direct smears of angiosarcoma, regardless of body site, include abnormal mitoses, spindle cells, multiple prominent nucleoli, and bar-shaped nucleoli. It can be very helpful to identify vasoformative features such as hemophagocytosis, cytoplasmic lumina/vacuoles containing erythrocytes, and/or endothelial wrapping; however, vasoformative features are not specific for angiosarcoma and can also be identified in nonvascular neoplasms, and vasoformative features are not identified in all angiosarcomas. (5) In this particular case, vasoformative features were not seen; however, little has been published about liquid based cytologic features of angiosarcoma and the vasoformative features described in the literature are seen on direct smears.
Immunocytochemistry or immunohistochemistry is useful to aid in diagnosis: the majority of angiosarcomas are positive for vascular markers such as CD31, CD34, D2-40, and ERG. A panel is recommended as loss of one or more of these markers is possible, most common is loss of CD34. A combination of the nuclear staining of ERG, with the cytoplasmic/membranous staining of CD31 increases the sensitivity of diagnosing angiosarcoma. (6) Another possible vascular marker with nuclear staining is FLI-1. Although mostly used in the diagnosis of Ewing’s sarcoma and primitive neuroectodermal tumors, it is also highlights benign and malignant vascular neoplasms and like ERG will also highlight a subset of epithelioid sarocma. (7,8)
Differential diagnoses based on cytologic features include metaplastic carcinoma, melanoma, epithelioid sarcoma, and benign/borderline vascular neoplasm. Metaplastic carcinoma will often have p63 positivity, with variable keratin positivity. An epithelioid sarcoma is negative for CD31 and shows loss of INI-1. Melanoma may be confirmed by positivity for melanoma markers such as SOX-10, S100, Melan-A, etc., as well as by lack of expression of vascular markers. However, separating an angiosarcoma from a non-malignant vascular neoplasm often require histologic examination. (5,9)
While grading of angiosarcomas may be attempted, there is some evidence that tumor grade does not aid in prognosis and so it may be clinically irrelevant. (9)
Acknowledgment: The contribution of the core biopsy and follow-up on patients are appreciated, along with photomicrographs of the histology, from Kamaljeet Singh M.D.