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: Epithelioid hemangioendothelioma; Hepatic angiosarcoma; Infantile hemangioma; Liver tumor; Molecular genetics; Pediatric.

Figure 1

Histologic findings of pediatric hepatic angiosarcoma. A: Whorls of atypical spindled cells (Hematoxylin-eosin staining, 10 ×); B: Moderate power view of the lesional cells show moderate nuclear atypia (Hematoxylin-eosin staining, 20 ×); C: Perineural invasion is be noted in this infiltrative lesion; note the nerve bundle (N) in the center (hematoxylin-eosin staining, 10 ×); D: Periodic acid-Schiff-positive eosinophilic globules are focally identified in the lesion, usually seen in association with the whorls of atypical spindled cells/glomeruloid bodies (para-aminosailcylic acid, 10 ×); E: The lesional cells are immunoreactive for vascular markers such as CD31 (10 ×) (note the glomeruloid body in the center); F: Factor VIII (20 ×).

Figure 2

Pediatric hepatic epithelioid hemangioendothelioma. A: Hypocellular epithelioid cells embedded in fibrotic stroma (right); entrapped hepatocytes with cholestasis are noted on the left (hematoxylin-eosin staining, 4 ×); B: High power view of the lesion demonstrates scattered atypical cells (arrowhead) with occasional intracytoplasmic lumen formation (arrow) (Hematoxylin-eosin staining, 20 ×); C: The neoplastic cells are immunoreactive for CD31 (20 ×); D: The neoplastic cells are immunoreactive for CK7 (20 ×).