Epithelioid hemangioendothelioma

by Jason Wasserman MD PhD FRCPC
November 15, 2023

Epithelioid hemangioendothelioma (EHE) is a rare type of cancer made up of endothelial cells, the specialized cells normally found on the inside of blood vessels.

Where is this type of cancer typically found in the body?

Common locations for EHE include the lungs, liver, bone, and soft tissue.

What are the symptoms of epithelioid hemangioendothelioma?

The symptoms of EHE depend on the size and location of the tumour in the body. Symptoms associated with tumours in the lungs include cough, shortness of breath, and chest pain. Tumours in the bone may cause pain and swelling over the involved bone. If left untreated, large tumours can cause the bone to break. Tumours arising in the liver and soft tissue sites tend to not cause any symptoms and these tumours tend to be found incidentally when imaging is performed for another reason.

What causes an epithelioid hemangioendothelioma?

Most EHEs harbor a genetic alteration called a translocation resulting in the fusion of two genes, WWTR1 and CAMTR1. The abnormal WWTR1:CAMTR1 gene activates a molecular pathway that causes endothelial cells to transform into cancer cells. A minority of EHEs harbour an alternative translocation involving the genes YAP1 and TFE3. The abnormal YAP1:TFE3 gene also activates a pathway that causes endothelial cells to transform into cancer cells. At this time, doctors do not know why some people develop these genetic alterations.

How is this diagnosis made?

The diagnosis of EHE can only be made after tissue from the tumour is examined under a microscope by a pathologist.

What does epithelioid hemangioendothelioma look like under the microscope?

When examined under the microscope, EHE is made up of round to oval-shaped tumour cells arranged in groups called nests or nodules. The tumour cells in EHE are described as ‘epithelioid’ because they look less like normal endothelial cells and more like the epithelial cells found on the surface of most organs. The tumour cells often appear pink because the cytoplasm (body) of the cell contains a moderate amount of eosinophilic (pink) material. A unique feature of EHE is the presence of small holes in the cytoplasm of the cells. These holes are often described as intracytoplasmic vacuoles or lumina are resemble the inside of a blood vessel and some may even contain erythrocytes (red blood cells). Blood vessels including arterioles, venules, and capillaries are often found scattered throughout the tumour with tumour cells often clinging to the outside walls of the blood vessels.

What other tests may be performed to confirm the diagnosis?

Immunohistochemistry

Immunohistochemistry (IHC) is a test that allows pathologists to identify different types of cells based on the chemicals (typically proteins) the cells are making. Cells making the chemical of interest are called positive or reactive while those that do not produce the chemical are called negative or non-reactive.

The tumour cells in epithelioid hemangioendothelioma are typically positive for the following immunohistochemical markers:

• ERG
• CD31
• CD34
• CAMTA1 (tumours with WWTR1:CAMTR1 fusion)
• TFE3 (tumours with YAP1:TFE3 fusion)

Some epithelioid hemangioendothelioma may be positive for the following immunohistochemical markers:

• Low molecular weight cytokeratins (cytokeratin 7 and cytokeratin 8/18)

Next generation sequencing

Next-generation sequencing (NGS) is a molecular test that allows pathologists to quickly look for large numbers of genetic changes at the same time. Pathologists often perform NGS on EHE to confirm the presence of one of the two translocations known to be associated with this tumour – WWTR1:CAMTR1 and YAP1:TFE3.