Angiosarcoma

Radiographically, angiosarcoma usually is a completely lytic, uni- or multilocular lesion, with medullar and cortical permeation. Less commonly, it may be sclerotic or mixed, lytic and sclerotic. It usually has infiltrative margins, but these can be well defined and with no peripheral sclerosis. Periosteal reaction is absent. Invasion of the neighboring soft parts may also be seen.
CT and MRI demonstrate more clearly the multifocal aspect of the bone or bones affected. Secondary aneurysmal bone cyst may be seen in a few cases. Reactive changes may be seen. MRI, characteristically, demonstrates low signal intensity on T1-weighted images and heterogeneously intermediate to high signal intensity on T2-weighted images.
The imaging finding of multiple lesions by itself should be sufficient to include angiosarcoma as a diagnostic possibility.

Metastatic carcinoma, multiple myeloma, and lymphoma may be difficult to differentiate by image methods alone. See also epithelioid hemangioendothelioma.

Pathology

It is useful to radiograph the specimen in order to locate possible multiple foci as well as resection margins related to the lesions before sectioning.
The cut surface shows a large or multiple hemorrhagic lesions, friable, with cortex permeation.

Angiosarcoma is histologically classified in three grades according to cytological atypia.
Microscopically, the tumor is composed of sheets of atypical epithelioid cells with eosinophilic cytoplasm where one or more vacuoles may be seen (“blister cells”). The occasional finding of erythrocytes or its fragments in these vacuoles is characteristic of the endothelial origin of the tumor cells. In a minority of cases, cells may be spindled. The nuclei are large, vesicular, and with prominent nucleoli. Atypical and numerous mitotic figures are common.
Another tissue pattern that may be found, especially in well-differentiated tumors, is vasoformative, with the atypical endothelial cells lining irregular vascular spaces.
Inflammatory infiltrate, hemorrhage, hemosiderin deposits, and necrotic areas are usually seen, and the tumoral infiltration by erythrocytes and neutrophils is considered suggestive of endothelial tumors.

Epithelioid hemangioendothelioma or epithelioid hemangioma – These tumors do not present the numerous atypical cells and atypical mitosis usually seen in an angiosarcoma.
Metastatic carcinoma – As angiosarcoma may stain with epithelial markers, this differential must be considered in a biopsy sample. Endothelial markers are needed to establish the correct diagnosis. Desmoplastic stromal reaction is more common in metastatic carcinoma than in angiosarcoma.
Metastatic melanoma – Negative for endothelial markers and positive for melan-A, HMB45, and S100.

Angiosarcomas express endothelial markers as CD31, CD34, von Willebrand factor, FLI1, and ERG. Epithelioid cells of epithelioid angiosarcoma usually express epithelial markers. A few cells may be positive for SMA. Lymphangiogenic marker D2-40 may be positive in a few cases.

Translocation t(1;14)(p21;q24) was described in one case.
In nearly 55 % of the angiosarcomas of the bone, the retinoblastoma (Rb) pathway was affected, suggesting that this pathway is involved in tumorigenesis of angiosarcoma. The loss of CDKN2A expression was associated with a significantly worse prognosis. No overexpression of TP53 or MDM2 was found. Angiosarcoma of the bone showed highly active TGF-β signaling with immunoreactivity for phospho-Smad2 and PAI-1. PIK3CA hotspot mutations were absent. The PI3K/Akt pathway is activated in both angiosarcomas of the bone and soft tissue, however, with a different cause; contrary to its soft tissue counterpart, PTEN expression is decreased in angiosarcoma of the bone.