Vascular proliferations may arise in the breast following radiation treatment for a primary breast adenocarcinoma. A post-radiation vascular proliferation can usually be classified as angiosarcoma or as an atypical vascular lesion (AVL). Angiosarcomas with a “low-grade” morphology, behave aggressively but exhibit substantial histomorphologic overlap with AVLs, which have a generally benign clinical course. We present a case of a post-radiation angiosarcoma of the breast with histologic features that mimic an atypical vascular lesion and discuss this challenging differential diagnosis. In addition to histologic mimicry, the lesion exhibited only patchy amplification of the a vian myelocytomatosis viral oncogene homolog (MYC) gene by present fluorescence in-situ hybridization (FISH), and patchy MYC overexpression by immunohistochemistry. These features further complicate the distinction between AVL and angiosarcoma, and would be particularly problematic on a small biopsy. We believe that the morphologic and immunohistochemical overlap between these entities is suggestive of a biologic spectrum, and thus that, at least in some instances, angiosarcoma may arise from a pre-existing AVL or AVL-like lesion.
There have long been reports of vascular neoplasia arising in the female breast following therapy for a primary breast carcinoma. The earliest of these reports focused on chronic lymphedema-associated angiosarcoma―the so-called Stewart-Treves syndrome [
A 73-year-old female presented with a new violaceous macular “rash” in the field of radiation treatment for a prior invasive ductal carcinoma of the left breast two years ago. The invasive ductal carcinoma was treated with breast conservative excision, sentinel lymph node biopsy, adjuvant chemotherapy and whole breast radiation. As a consequence of therapy she experienced mild lymphedema of the breast beginning shortly after radiation therapy, but was otherwise well. A punch biopsy of the lesion was obtained, and the initial diagnosis rendered at an outside institution was reported to be atypical vascular lesion. Subsequent MRI studies revealed skin thickening and enhancement adjacent to the location of the biopsy. She underwent an excision of the area surrounding the biopsy, which included both the visible rash and the area with abnormal MRI findings. On excision, the specimen was found to contain an atypical vascular proliferation involving the superficial and deep dermis with the same features as the biopsy, but also areas of multi-layered endothelium, mild to moderate nuclear atypia and increased mitotic activity. Due to the presence of these features, the tumor was diagnosed as angiosarcoma at the outside institution. Because of the incomplete excision, the patient was referred to our institution for a re-exci- sion, and elected to undergo bilateral mastectomy with wound coverage using autologous free flap.
The excised specimen contained a healing scar and mild erythema, but lacked clearly identifiable cutaneous lesions suggestive of residual angiosarcoma (
scattered poorly defined areas of thin walled vessels, some angulated and some anastomosing, both within the superficial and deep dermis. The vessels in the superficial dermis were ectatic, and lined by a single layer of minimally atypical endothelial cells with condensed chromatin and no evident nucleoli (
mitotic activity. An immunohistochemical stain for D240 was diffusely positive in the atypical vascular proliferation, and helped identify the extent of the dermal involvement (
There are a number of interesting and illustrative features of this case that warrant particular attention, and highlight the challenges posed in the identification and classification of low-grade vascular lesions, particularly in the post-radiation setting. The most critical distinction in this context is between a post-radiation atypical vascular lesion (AVL) and post-radiation angiosarcoma. Radiation-associated angiosarcomas occur with a median latency period of 5 - 6 years after breast radiation, and have a poor prognosis, with aggressive local behavior and substantial metastatic potential [
In the current case, the short interval between the original breast excision and the development of the lesion (~23 months) might lead one to favor AVL, which has a shorter median latency period. Nonetheless, there is wide variation and substantial overlap in the latency period between radiation and the development of either an AVL or an angiosarcoma. Thus, while AVL have a shorter median latency period, this is not a reliable discriminator between AVL and angiosarcoma.
The histologic findings of the current case warrant particular attention. These features highlight the overlap between AVL and angiosarcoma, and are suggestive of a biologic relationship between these entities. Both the original and the subsequent descriptions of AVL noted a number of features useful in the distinction between AVL and angiosarcoma [
In addition to infiltration, there was other evidence for a diagnosis of malignancy in the form of immunohistochemical and in-situ hybridization showing MYC amplification. In the past several years, MYC amplification has received considerable attention as a diagnostic marker of post-irradiation angiosarcoma [
Another immunohistochemical feature worth noting in the current case is the lymphatic immunophenotype of the atypical vascular proliferation. AVLs have been classified as lymphatic or vascular types principally on the basis of immunophenotype, with the lymphatic-type AVLs (ltAVL) representing the majority, and expressing D240 [
We have presented a case of angiosarcoma that we feel, based on histomorphology and the focal nature of MYC amplification, is suggestive of anangiosarcoma arising from an atypical vascular lesion. It also serves as an important illustration of the substantial morphologic overlap of histologically low-grade vascular lesions. It is important to bear this in mind, especially in the context of a large lesion that is only sparsely sampled in a core biopsy. In a lesion that is clinically large, or in which the microscopic features (e.g. diffuse growth pattern) suggest a larger lesion than that seen clinically, one should be extremely cautious with a diagnosis of AVL, even in the context of negative MYC IHC or FISH studies. In the current case, evidence for malignancy was subtle and focal, and only evident upon wider excision. Care must be taken to avoid a misdiagnosis of angiosarcoma as AVL since this could have major therapeutic and prognostic significance.