What is pulmonary epithelioid haemangioendothelioma?
Epithelioid haemangioendothelioma (EHE) is an ultra-rare tumour that arises from the cells lining blood vessels. It is classified as a malignant vascular tumour (a type of sarcoma), but its behaviour varies greatly: many patients have slow-growing disease that stays stable for years, while a smaller group has more aggressive disease.
When EHE involves the lungs it is called pulmonary epithelioid haemangioendothelioma (PEH). It typically appears as multiple small nodules scattered through both lungs. The liver and bone are other common sites, and some patients have disease in more than one organ at diagnosis.
PEH is more often diagnosed in women and in younger to middle-aged adults. Care is coordinated with oncology, sarcoma specialists, pathology and thoracic surgery.
Symptoms
Many people have no symptoms, and the nodules are discovered on a chest X-ray or CT performed for another reason. When symptoms occur they may include:
- Dry cough
- Breathlessness
- Chest pain, particularly pleuritic pain that is worse on breathing in
- Coughing up blood
- Tiredness, weight loss or fever
Symptoms, pleural effusion, coughing up blood and weight loss are associated with more active disease and are taken into account when planning treatment.
Causes
The cause of EHE is not known, and no lifestyle or environmental trigger has been established. It is not related to smoking, is not inherited and is not contagious. Most tumours carry a characteristic acquired gene fusion, WWTR1-CAMTA1, and a smaller group carries a YAP1-TFE3 fusion. These changes arise within the tumour cells and help pathologists confirm the diagnosis.
How PEH is diagnosed
Multiple small lung nodules have many possible causes, so a tissue diagnosis is essential.
| Test | What it shows |
|---|---|
| CT chest | Multiple small, well-defined nodules in both lungs, often near small blood vessels and airways |
| PET-CT | Activity in the nodules and whether the liver, bone or other organs are involved |
| Biopsy (CT-guided, bronchoscopic or surgical) | The tumour cells. A surgical (VATS) biopsy is often needed to obtain enough tissue |
| Immunohistochemistry | Vascular markers such as CD31, CD34 and ERG, and CAMTA1 or TFE3 staining |
| Molecular testing | The WWTR1-CAMTA1 or YAP1-TFE3 gene fusion |
| Liver imaging | Liver involvement, which is common |
Conditions to distinguish
Multiple nodules are more commonly caused by metastases from another cancer, tuberculosis and other infections, sarcoidosis or vasculitis. In India, nodules are often first treated as tuberculosis. Where microbiological tests are negative and the nodules persist, a biopsy is important. Bronchoscopy and EBUS-TBNA help exclude infection and sample enlarged lymph nodes.
Treatment
Because PEH is so rare, there is no single standard treatment. Plans are made by a multidisciplinary team, ideally including a sarcoma service, and are based on the extent of disease, symptoms and how quickly it is changing.
Active surveillance
Many patients with no symptoms and stable nodules are monitored with regular CT scans. This avoids treatment side effects in disease that may stay quiet for years.
Surgery
When there are only a few nodules confined to the lung, surgical removal by thoracic surgery may be considered.
Systemic treatment
For progressive or symptomatic disease, options include sirolimus (an mTOR inhibitor), anti-angiogenic drugs that target blood vessel growth, and chemotherapy. Responses are variable. Participation in clinical trials is encouraged where available.
Pleural disease
Recurrent fluid around the lung is drained and, where needed, controlled with procedures from pleural disease care.
Outlook and follow-up
The outlook ranges widely. Many people live for many years with stable or slowly growing disease, and occasional spontaneous regression has been reported. Pleural involvement, coughing up blood, weight loss and the YAP1-TFE3 subtype can be associated with a less favourable course. Lifelong follow-up with periodic imaging is usual.
When to seek urgent care
Seek urgent medical help for coughing up more than a small amount of blood, sudden or worsening breathlessness, sudden chest pain, or fever with feeling unwell while on systemic treatment.
Frequently asked questions
Is pulmonary epithelioid haemangioendothelioma a cancer?
Yes, it is classified as a malignant vascular tumour, a type of sarcoma. However, it often behaves much more slowly than most cancers, and some patients remain stable for many years without treatment.
Why might my doctor recommend watching rather than treating?
Many people with PEH have stable disease. Monitoring with regular scans avoids the side effects of treatment, and treatment is started if the disease grows or causes symptoms.
Why was I treated for tuberculosis first?
Multiple lung nodules are commonly caused by tuberculosis in India, and PEH is extremely rare. When nodules persist despite treatment or tests are negative, a biopsy is needed to reach the correct diagnosis.
Did smoking cause my PEH?
No link between smoking and PEH has been established. The cause is not known.
Is PEH inherited?
No. The gene fusions found in PEH develop within the tumour cells and are not passed on to children.
Are clinical trials available?
Clinical trials for EHE are run at specialist sarcoma centres internationally. The oncology team can advise whether any trial is suitable and accessible.
Related conditions and procedures
Consult Dr. Gogineni Ratnakara Rao
Apollo Hospitals, Financial District: Monday to Saturday, 8:30 AM to 5:00 PM. Anything in Lung Clinic, Chanda Nagar: Monday to Saturday (Thursday closed), 6:00 PM to 9:00 PM.