Retiform hemangioendothelioma is a locally aggressive vascular neoplasm that can rarely metastasize. It is characterized by slit-like vascular channels with mildly atypical, protuberant endothelial cells.

Retiform hemangioendothelioma is very rare, with approximately 50 reported cases in the literature. The tumor occurs most commonly in young adults, with a wide age range that includes pediatric and middle-aged patients. ^1,2

Retiform hemangioendothelioma usually involves the skin or subcutis, and it occurs most commonly in the distal extremities, especially in the lower limb.  

Retiform hemangioendothelioma characteristically exhibits slit-like and infiltrative growth of neoplastic vessels, resembling the architecture of the rete testis. The neoplastic endothelial cells have mildly hyperchromatic and atypical nuclei with characteristic "hobnail" projections into vascular lumina. Retiform hemangioendothelioma-like areas are frequently a component of composite hemangioendothelioma, which harbors overlapping genetic alterations but is distinguished from retiform hemangioendothelioma based on the presence of other morphologic patterns.

Retiform hemangioendothelioma is positive for vascular markers such as CD31, CD34, and ERG. D2-40 can be positive, although in small published series it seems to be negative in most tumors. ³ Immunohistochemistry demonstrates loss of expression of the YAP1 C-terminus in cases with YAP1::MAML2 gene fusions (Fig. 1). ⁴

Figure 1. YAP1 immunohistochemistry in retiform hemangioendothelioma. Immunohistochemistry demonstrates loss of YAP1 expression in about a third of cases. The background stromal and inflammatory cells serve as an internal positive control, and the neoplastic endothelial cells are negative in this case.

Retiform hemangioendothelioma is locally aggressive, and over half of patients have local recurrences that are often multiple. ¹One tumor in the initial series was reported to exhibit local lymph node metastasis;¹ however, this tumor had a spindle cell component and in retrospect was likely a composite hemangioendothelioma.

• A recent series demonstrated YAP1 gene rearrangements in five of 13 tumors, including two with YAP1::MAML2. ²

• Similar gene fusions are present in a subset of composite hemangioendothelioma, raising the possibility that retiform and composite hemangioendothelioma are on a biologic spectrum.²