Facts About EHE

Facts About EHE

What is EHE?

Haemangioendothelioma (HE) is the name for a group of very rare vascular cancers involving cells that line the inside of blood vessels (endothelial cells). ‘Epithelioid’ refers to the elongated shape of the cells when seen under the microscope. Vascular cancers account for only a fraction of 1% of all cancers.

EHE affects approximately 4 people per year in every 10 million of population. It’s overall incidence is less than 1 in a million. EHE affects both biological genders, and can occur at any age, although paediatric EHE is rare. EHE tumours can appear anywhere in the body, but most frequently presents in the liver, lungs, bone, lymph nodes, and skin.

The disease can present with a single tumour, but in many cases presents with multiple tumours in one organ or in different locations. Doctors refer to this multiple-tumour presentation as multi-focal and can sometimes describe the disease as a grade 4 cancer. This frequently causes alarm, as for nearly all other cancers, grade 4 suggests very advanced disease. This is not the case for EHE, however, where the number and spread of tumours at presentation is not necessarily indicative of the severity and advancement of the disease as many patients will present with muti-focal but indolent EHE.

The nature of a patient’s disease is more accurately assessed by understanding how their EHRE is behaving, as outlined further down this page.

What causes EHE?

90% of EHE cases are caused by the specific WWTR1-CAMTA1 chromosomal rearrangement or translocation (swapping of genetic material) called the ‘WC Fusion’. This discovery was made in 2011 by dedicated scientists studying the molecular biology of EHE. The translocation (between chromosomes 1 and 3) was identified in the tumour cells of ~90% of EHE patients, but is not found in healthy people, nor in other types of vascular tumour, nor other cancers, and is therefore considered to be disease-defining. This translocation creates the TAZ-CAMTA1 fusion gene which in turn leads to the production of the TAZ-CAMTA1 fusion protein.

It was later discovered that the other 10% of EHE cases are caused by a different gene mutation called the YAP-TFE3 translocation, creating a YAP-TFE3 fusion gene and the YAP-TFE3 fusion protein.

While we do not yet fully understand the exact mechanisms involved, it is now strongly believed that the EHE fusion genes (TAZ-CAMTA1 and YAP-TFE3) upset key cell-controlling mechanisms in our cells, collectively known as the Hippo Pathway. To have this effect, scientists have discovered that both fusion proteins bind to members of a family of proteins called TEADs which then affects the transcription process at the start of protein generation in our cells. This binding to TEAD is now believed to be fundamental to the progression of the disease and is a major therapeutic target. Excitingly, the development of TEAD inhibitors is now a major focus of the pharmacological industry, not just for EHE, but because YAP and TAZ binding to TEADs also plays a role in other more common cancers. Phase 1 clinical trials of these new drugs are already underway, with early results appearing positive.

What actually causes the initial WWTR1-CAMTA1 and YAP-TFE3 gene translocations is not yet understood. However, there is a clinical signal that hormones may be involved as we see three distinct groups of female patients, one post puberty, one post pregnancy and one post menopause. Hormone involvement is an area of the ongoing research that we are funding.

How does EHE present and progress

EHE can be indolent (passive) and in this situation a patient may be totally asymptomatic. As a result, some of our patient community are diagnosed when progressing through a medical evaluation for completely different reasons. EHE can also present with slow tumour growth and mild symptoms. Rarely, EHE can even go into spontaneous remission. So, newly diagnosed EHE patients usually have time to learn about the disease, find experienced doctors, get second opinions if wanted and decide what to do.

The disease can however become more progressive at any time. Doctors do not know why this happens, nor can they predict when it will occur. This makes EHE a psychologically challenging disease to live with even in its indolent forms. Patients with the indolent form of the disease will typically be placed on an unusual care plan known as “active surveillance” or “wait and watch”, where the patient will initially undergo scans every two or three months so that doctors can see if the disease is progressing. These scans will become less frequent if the patient’s EHE remains indolent, and may ultimately become less than annual in frequency.

If scan results and/or disease symptoms are progressing then this is likely to be indicative of progressive EHE, doctors will consider a number of treatment options, including surgery, emobolisation, ablation, radiation therapy and systemic treatments. Which treatment is suggested will depend on where a patient’s EHE is located and whether it is a single tumour or multi-focal (a number of tumours). All of these factors will be taken into account. In its aggressive forms EHE tumours can grow rapidly, spread and/or exhibit destructive behaviour, even after long periods of indolence.

In short, EHE is a heterogeneous cancer, with unpredictable course. Routine surveillance scans are therefore a sensible precaution, helping to identify as soon as possible when the disease may be becoming progressive.

The ESMO consensus of experts

The above information is only a summary of some of the key facts about EHE. For more detailed information about the disease and its treatment, please see the ESMO Consensus Paper page in this section of the website. This paper was published in 2021 and represents the consensus of over 85 highly-experienced sarcoma specialists from across Europe, the UK, North America and Asia. Chaired by Dr Silvia Stacchiotti, and produced under the auspices of the European Society of Medical Oncology (ESMO), this paper is the only such recording of clinical understanding and agreed treatment options for the disease.