Composite Haemangioendothelioma

Not clinically relevant

PTBP1-MAML2 and EPC1-PCH2 gene fusions have been identified in single cases of neuroendocrine CHE.

CHE presents as an infiltrative, uninodular or multinodular mass (individual nodules measure 0.4–30 cm; median: 3.2 cm) or as an area of ill-defined swelling. Some of the lesions are associated with reddish-purple skin discoloration, suggestive of a vascular neoplasm.

CHE is a poorly circumscribed, infiltrative lesion that is typically centered in the dermis and subcutis, although occasional cases are deep-seated or involve viscera. It comprises a complex admixture of histologically benign and malignant vascular components that vary greatly in their relative proportions. These lesions are unified by a similar admixture of the different components, which include epithelioid haemangioendothelioma, retiform haemangioendothelioma, spindle cell haemangioma, angiosarcoma-like areas, and benign vascular lesions (lymphangioma, angiomatosis, vascular malformation, and cavernous haemangioma). Not all cases contain every component. Vacuolated, pseudolipoblastic endothelial cells are frequently present. The angiosarcoma-like areas are usually characterized by a low-grade angiosarcomatous appearance, composed of complex dissecting vascular channels with subtle endothelial atypia and relatively few mitotic figures. However, there is a single convincing reported case containing foci resembling high-grade epithelioid angiosarcoma. Neuroendocrine CHE is characterized by a distinctive admixture of retiform haemangioendothelioma–like areas, epithelioid haemangioendothelioma–like areas, and a component with a striking nested appearance, as well as by expression of neuroendocrine markers (most often synaptophysin). CHEs are more generally consistently positive for CD31, ERG, and FLI1. About half of cases are positive for CD34 and D2-40; they are negative for CAMTA1.

Not clinically relevant

The behavior of CHE in general appears to be much less aggressive than that of conventional angiosarcoma. Several lesions recurred locally between 4 months and 10 years after excision of the primary mass, often with multiple recurrences. There is potential for lymph node metastasis. Neuroendocrine CHE appears to be considerably more aggressive, with distant metastases to bone, lung, liver, or brain reported in half of patients.

Not clinically relevant

Essential: minimal criteria for CHE include the presence of at least two morphologically distinct vascular tumor elements, most often closely resembling retiform haemangioendothelioma and epithelioid haemangioendothelioma; cases arising in pre-existing (lymphatic) vascular malformations must show at least two additional, discrete endothelial tumor components; CHEs showing foci resembling high-grade angiosarcoma are exceptionally rare, and this diagnosis should be made only after conventional angiosarcoma is rigorously excluded on clinical and morphological grounds.