Composite hemangioendothelioma (CHE) is a rare, locally aggressive vascular neoplasm that has metastatic potential. It definitionally contains multiple morphologic patterns, which can include regions resembling retiform hemangioendothelioma, epithelioid hemangioendothelioma, angiosarcoma, and/or benign vascular tumors. Examples that show regions of nested growth with neuroendocrine marker expression behave more aggressively (so-called "neuroendocrine composite hemangioendothelioma").

CHE is very rare. It occurs across a wide age range, including in pediatric patients, with a median age of around 40 years.^1,2There is a slight female predominance .²

CHE occurs most commonly in the distal extremities, especially the hands and feet. Some arise in association with arteriovenous malformations or lymphangiomas.¹

CHE definitionally contains at least two distinct morphologic patterns, including regions resembling retiform hemangioendothelioma, epithelioid hemangioendothelioma, spindle cell hemangioma, and/or benign vascular lesions; some tumors contain angiosarcoma-like regions. There are sometimes foci of prominently vacuolated endothelial cells. Neuroendocrine CHE additionally contains regions with nests of tumors cells that express neuroendocrine markers; this subtype has a more aggressive clinical course.³

Conventional CHE expresses vascular markers such as CD31 and ERG. Neuroendocrine CHE additionally expresses neuroendocrine markers in nested areas, especially synaptophysin.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 composite 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.

CHE frequently exhibits local recurrence and, less commonly, regional lymph node metastasis. Distant metastases are rare in conventional CHE but occur in about half of patients with neuroendocrine CHE.

• Single cases of neuroendocrine CHE have been shown to harbor PTBP1::MAML2 and EPC1::PHC2 gene fusions.^3,5

• In one recent series, YAP1::MAML2 was identified in three of 11 cases of conventional CHE. ⁵

• The genetic and morphologic overlap between CHE and retiform hemangioendothelioma support the notion that these two tumor types exist on a continuum.⁵