Thyroid angiosarcoma: a comprehensive review

Thyroid angiosarcoma (TAS) is an aggressive vascular tumor, accounting for 20 % of thyroid mesenchymal neoplasms and affecting elderly patients with frequent extra-thyroidal local extension and distant spread. It usually arises in the context of a long-standing goiter with higher incidence in iodine-deficient Alpine districts of Italy, Austria and Switzerland. Nevertheless, a relevant proportion of cases have been documented in iodine sufficient areas, being unrelated to goitrogen etiology and possibly associated with other risk factors. Histological features consist of large epithelioid cells with severe pleomorphism, arranged in a solid growth pattern with formation of vascular spaces, and set in a fibrotic stroma admixed with hemosiderin deposits and necrosis. Immunohistochemistry reveals positive staining for CD31, ERG and factor VIII, frequently accompanied by cytokeratin expression. Such findings may raise concern for the diagnosis of angiomatoid anaplastic carcinoma, which can be ruled out by the absence of thyroidal differentiation markers (including PAX8 and TTF-1). Cytological findings are rather non-specific and fine needle aspiration frequently yields inconclusive results. The genetic background of angiosarcoma is dominated by the impairment of genes deeply involved in angiogenesis, proliferation and survival (including MYC, KDR, FLT4, PTPRB and PLCG1) along with the dysregulation of crucial pathways like PIK3CA/AKT/mTOR and MAP kinase, with a relevant impact on possible novel therapeutic strategies. However, little is known about the molecular features of TAS and more investigations are needed to improve the characterization of this entity.