Primary malignant vascular tumors of the liver in children: Angiosarcoma and epithelioid hemangioendothelioma

Abstract

Primary malignant vascular neoplasms of the liver, angiosarcoma and epithelioid hemangioendothelioma, are extremely rare entities in the pediatric population. International Society for the Study of Vascular Anomalies classification system is recommended for the pathologic diagnosis of hepatic vascular lesions in this age group. In this article, we highlight the clinicopathologic characteristics of hepatic angiosarcoma and epithelioid hemangioendothelioma in the pediatric population. Hepatic angiosarcoma in children shows a slight female predominance with an average age of 40 mo at diagnosis. The distinct histologic features include whorls of atypical spindled cells and eosinophilic globules, in addition to the general findings of angiosarcoma. Histologic diagnosis of pediatric hepatic angiosarcoma is not always straightforward, and the diagnostic challenges are discussed in the article. Hepatic epithelioid hemangioendothelioma also demonstrates a female predominance, but is more commonly identified in adolescents (median age at diagnosis: 12 years). Histologically, the lesion is characterized by epithelioid cells and occasional intracytoplasmic lumina with a background of fibromyxoid stroma. While WWTR1-CAMTA1 and YAP1-TFE3 fusions have been associated with epithelioid hemangioendothelioma, there are currently no known signature genetic alterations seen in pediatric hepatic angiosarcoma. Advancement in molecular pathology, particularly for pediatric hepatic angiosarcoma, is necessary for a better understanding of the disease biology, diagnosis, and development of targeted therapies.

Keywords: Pediatric, Hepatic angiosarcoma, Epithelioid hemangioendothelioma, Infantile hemangioma, Liver tumor, Molecular genetics

Core Tip: Malignant hepatic vascular neoplasms are rarely encountered in the pediatric population. This review highlights the clinicopathologic characteristics of pediatric hepatic angiosarcoma and epithelioid hemangioendothelioma. They have variable clinical and radiological findings; therefore, histologic examination is the gold standard for diagnosis. Hepatic angiosarcoma in children is characterized by whorls of spindled cells and eosinophilic globules histologically. Meanwhile, epithelioid hemangioendothelioma shows epithelioid cells with intracytoplasmic lumina and a fibromyxoid background. Diagnostic challenges and molecular alterations of these entities are discussed in the article.