Epithelioid Hemangioendothelioma (EHE)

Epithelioid hemangioendothelioma (EHE) is a very rare vascular tumor or anomaly that arises from the cells lining the blood vessels. In some patients with more aggressive disease, EHE behaves like a low-grade (slow-growing) cancer. In patients with stable tumors, or tumors that shrink without treatment, EHE behaves more like a benign (non-cancerous) vascular tumor.

EHE typically appears in young adults, though the tumor may be diagnosed in younger or older adults. The symptoms of EHE depend on the tumor's location and can differ from patient to patient. Some patients experience no symptoms at all and learn that they have an EHE when undergoing an imaging test (such as an MRI or CT scan) for another reason.

EHE tumors can arise anywhere in the body but are most often found in the liver, lung, and bones.

• Tumors in the liver may cause abdominal pain, weight loss, blood work alterations, or an abdominal mass.
• Lesions in the lungs may cause chronic dry cough, shortness of breath, or other problems.
• EHE in the bone can cause pain or weaken the bone, leading to increased risk of fracture.
• Skin lesions may be confused with other skin conditions at first. Often, doctors do not consider the diagnosis of EHE involving the skin until after a biopsy.

Keep in mind, this condition is exceedingly rare, and the presence of any of these symptoms does not necessarily mean that your child has EHE.

The cause of EHE is currently unknown. It is not inherited, so relatives and future children are not at increased risk. However, researchers recently discovered genetic translocations (a problematic connection or fusion of two genes, leading to unregulated gene activity) that could serve as targets for future EHE therapies.

Diagnosing EHE is a process that happens in a few stages, in part because the skin lesions associated with EHE are often confused with more common skin conditions. Most often, the first step will be a complete medical history and thorough physical exam. Additional tests may include:

• Blood tests
• Magnetic resonance imaging (MRI)
• CT scan
• X-ray
• Biopsy

Certain characteristics of your child’s EHE may determine whether it requires more aggressive treatment, including:

• Its location
• The appearance of a biopsy under a microscope
• Whether the tumor has changed in size or spread to other tissues

Your child’s treatment depends on the size and location of the tumor and whether there are multiple tumor sites.

In rare cases, the tumor may shrink or go away without treatment. If not, there are multiple treatment options available. Your child’s care team will discuss the benefits of each one. They include:

• Watchful waiting: If your child has no symptoms and there are no signs the tumor is progressing, the doctor may want to observe the tumor for a period of time to determine whether treatment is necessary
• Surgery: Small or easily accessible tumors may be fully removed. Tumors completely removed with surgery most likely do not recur. Sometimes, complete removal is not possible due to the size, location, or presence of multiple tumor sites. In these cases, remaining tumors may require further therapy and can come back after treatment
• Medication management: A customized drug therapy plan can help relieve symptoms and prevent further growth of tumors that can’t be completely removed with surgery

Medications

Currently, no drug specifically targets EHE cells. However, some tumors shrink and even become invisible with therapy. Some of these medications are categorized as “chemotherapy,” meaning they may also be used for some types of cancer.

Medications used to treat EHE include:

• Sirolimus: Also known as rapamycin, this oral medication suppresses the immune system and slows the growth of abnormal lymphatic vessels that form the tumor. This can help shrink EHE tumors and improve symptoms, including pain
• Tyrosine kinase inhibitors: These drugs, designed as targeted therapies for cancers, have shown short-term success with EHE. Examples include sorafenib, sunitinib, and pazopanib.
• Vincristine: This chemotherapy drug targets all dividing cells within the body and is therefore used to treat many cancers. It is also used for aggressive benign vascular tumors.
• Interferon: The body produces interferon to combat infections or control inflammation. It has been formulated into a medication that targets blood vessel growth.
• Multi-agent chemotherapy: EHE tumors that grow rapidly, spread to other tissues, or do not respond to other medications may require more aggressive drug therapy. However, this combination of medications is rarely needed in children and young adults with EHE.

In very aggressive cases, or when tumors do not respond to these therapies, additional treatment options may include:

• Embolization: This minimally invasive procedure blocks the main artery that feeds the tumor. With the blood supply cut off, the tumor will often shrink. We do not attempt embolization in cases where several arteries feed into the tumor, which is often the case with EHE.
• Radiation: If we can’t remove your child’s tumor surgically and it doesn’t respond to chemotherapy or other medications, we may consider using radiation therapy in rare cases for solitary tumors or individual symptomatic tumors.

Your child should have regular follow-up appointments during and after treatment to check for:

• Recurrence of the tumor
• Any drops in platelet count
• Growth of the lesion

Your child’s care team will give you a schedule of follow-up care to see how your child is responding to therapy and to monitor for any late effects of therapy.

EHE is such a rare condition and behaves so differently from person to person that it’s difficult to determine the long-term outlook for your child.

The prognosis for your child greatly depends on:

• The extent of the disease (how large the tumor is and whether it has spread)
• The size and location of the tumor, which determine whether it can be surgically removed (tumors arising in the liver and those that are in multiple locations may be more aggressive)
• The results of the biopsied tissue (areas of cell death and markers of cell replication may indicate more aggressive tumors)
• Response to therapy
• The overall health of your child
• Your child's tolerance of specific medications, procedures, or therapies
• New developments in treatment

Because epithelioid hemangioendotheliomas are so rare, very few doctors have experience diagnosing and treating them. The Vascular Anomalies Center at Boston Children's Hospital, in partnership with the Dana-Farber/Boston Children's Solid Tumor Center, has evaluated more children with EHE than any other hospital in the world.

The VAC's physicians — representing 16 medical and surgical specialties, including radiologists and pathologists that specialize in diagnosing vascular anomalies — draw on those experiences to continually refine the therapies and achieve better long-term outcomes for children with EHE. Together, our team has the experience to make or confirm a diagnosis of EHE and recommend the best available treatment options.

The VAC currently cares for many EHE patients from afar, seeing them in person on an infrequent basis but coordinating closely with providers close to their homes.

Sometimes it’s difficult to determine the best treatment for EHE because it has such a wide spectrum of behavior. In some kids, the tumor remains stable or even goes away without treatment. In others, it grows, appears in other parts of the body — and it can even be fatal.

Understanding which types of therapy work for which kids will help us treat more children more effectively. With that in mind, our researchers and physicians have built an extensive and growing database with information on dozens of children and young adults referred to us for EHE, including their symptoms, the treatments recommended and the outcomes of those treatments. By systematically gathering this kind of information, we continually expand our understanding of the best therapies for patients with EHE. Additionally, we are always developing clinical trials for patients with rare vascular anomalies.