What are the other Names for this Condition? (Also known as/Synonyms)

• EHAE of Lung
• Pulmonary EHE
• Pulmonary Epithelioid Hemangioendothelioma (PEH)

What is Epithelioid Hemangioendothelioma of Lung? (Definition/Background Information)

• An epithelioid hemangioendothelioma (EHE) is a tumor involving the blood vessels and surrounding epithelioid cells. The blood vessels are lined by epithelioid cells, which grow abnormally to form the tumor
• Epithelioid Hemangioendothelioma of Lung is a malignant tumor affecting the lung. Studies indicate that the tumor may be low-to-intermediate grade malignancy. The tumor is observed in individuals (mostly females) of any age category
• The signs and symptoms of Epithelioid Hemangioendothelioma of Lung may include chest pain, labored breathing, and pleural effusion (fluid in the lungs). The tumor is known to invade lung tissues and metastasize to other sites (such as the liver)
• Combinations of surgery, radiation therapy, and/or chemotherapy are used in the treatment of Pulmonary Epithelioid Hemangioendothelioma. Due to its potential for metastasis and recurrence following surgery, the prognosis is typically guarded

Who gets Epithelioid Hemangioendothelioma of Lung? (Age and Sex Distribution)

• Epithelioid hemangioendothelioma involving the lung is seen in about 12% of the cases; lung-liver involvement is seen in about 18% of the cases
• The tumor may occur in individuals of all age group; the age range observed is 7-81 years, with 38 years being the median age of presentation
• The tumor affects both male and female genders, although a majority are observed in females (60-80% of the cases)
• There is no predilection to any ethnic group or a particular race

What are the Risk Factors for Epithelioid Hemangioendothelioma of Lung? (Predisposing Factors)

Currently, no definite risk factors have been identified for Epithelioid Hemangioendothelioma of Lung. However, the following risk factors are suggested for epithelioid hemangioendothelioma observed at other locations:

• Any developmental tissue abnormality involving the soft tissues may be a risk factor
• Some cases have been seen with myelodysplastic syndrome (MDS)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Epithelioid Hemangioendothelioma of Lung? (Etiology)

The exact cause of Pulmonary Epithelioid Hemangioendothelioma development is unknown; they are thought to arise spontaneously.

• It is suggested that the tumor may be related to abnormal blood vessel proliferations originating from the veins, due to unknown reasons
• Many studies have shown the presence of chromosomal translocations involving 2 genes, namely WWTR1 and CAMTA1
• A gene fusion involving the YAP1 and TFE3 genes have also been noted in some tumors

What are the Signs and Symptoms of Epithelioid Hemangioendothelioma of Lung?

The signs and symptoms of Epithelioid Hemangioendothelioma of Lung may include:

• The tumors may grow at a slow rate and appear as painless, nodular masses
• It can be locally-aggressive and damage the surrounding tissues
• Epithelioid hemangioendotheliomas may be present as single or multiple nodules
  • Solitary nodules, seen in about 10-19% of the cases, may grow up to 5 cm in size and are typically well-defined
  • Multiple nodules, less than or around 2 cm in size, may be seen in over 60% of the cases and may be well-defined or poorly-defined
• Bilateral involvement of the lung may be noted; the lung tissues are almost always involved
• Pleural wall thickening may occur when the tumor invades into the pleura; in such cases, they may be mistaken for a pleural mesothelioma (on imaging scans)
• Chest pain is the most common presentation
• If large tumors are present, it may cause cough (with blood in sputum), breathing difficulties, fatigue, and pleural effusion (fluid in the chest)

About 30-50% of the individuals may not present any symptoms and may be asymptomatic.

How is Epithelioid Hemangioendothelioma of Lung Diagnosed?

A diagnosis of Epithelioid Hemangioendothelioma of Lung is made using the following tools:

• Complete evaluation of family (medical) history, along with a thorough physical examination
• X-ray studies of the chest
• Imaging studies that may include MRI or CT scan of the lungs
• Arterial blood gases
• Lung function test
• Sputum cytology: This procedure involves the collection of mucus (sputum), coughed-up by the patient, which is then examined in a laboratory by a pathologist

A tissue biopsy refers to a medical procedure that involves the removal of cells or tissues, which are then examined by a pathologist. This can help establish a definitive diagnosis. The different biopsy procedures may include:

• Bronchoscopy: During bronchoscopy, a special medical instrument called a bronchoscope is inserted through the nose and into the lungs to collect small tissue samples. These samples are then examined by a pathologist, after the tissues are processed, in an anatomic pathology laboratory
• Thoracoscopy: During thoracoscopy, a surgical scalpel is used to make very tiny incisions into the chest wall. A medical instrument called a thoracoscope is then inserted into the chest, in order to examine and remove tissue from the chest wall, which are then examined further
• Thoracotomy: Thoracotomy is a surgical invasive procedure with special medical instruments to open-up the chest. This allows a physician to remove tissue from the chest wall or the surrounding lymph nodes of the lungs. A pathologist will then examine these samples under a microscope after processing the tissue in a laboratory
• Fine needle aspiration biopsy (FNAB): During fine needle aspiration biopsy, a device called a cannula is used to extract tissue or fluid from the lungs, or surrounding lymph nodes. These are then examined in an anatomic pathology laboratory, in order to determine any signs of abnormality. Nevertheless, FNAB is not a preferred method for the biopsy of lung tumors
• Autofluorescence bronchoscopy: It is a bronchoscopic procedure in which a bronchoscope is inserted through the nose and into the lungs and measure light from abnormal precancerous tissue. Samples are collected for further examination by a pathologist

Tissue biopsy from the affected lung:

• A biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, flow cytometric analysis and very rarely, electron microscopic studies, to assist in the diagnosis

A differential diagnosis with respect to other lung cancer types may be necessary prior to establishing a definite diagnosis, by excluding the following cancers:

• Benign lung tumors including sclerosing pneumocytoma and hamartoma
• Malignant lung tumors including several sarcomas, adenocarcinoma, and mesothelioma

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Epithelioid Hemangioendothelioma of Lung?

Complications of Epithelioid Hemangioendothelioma of Lung may include:

• The tumor is known to be simultaneously present/arise at various sites in the body (such as soft tissue, bone, liver, etc.), and hence, it is difficult to differentiate between a primary tumor and a metastatic tumor. Such tumors are called synchronous tumors
• Metastasis of the tumor to other sites in the body is not very common. The sites of metastasis of Pulmonary Epithelioid Hemangioendothelioma include the liver (most common site), spleen, kidney, retroperitoneum, skin, soft tissues, and bones
• Recurrence of epithelioid hemangioendothelioma after surgery; about 35% are generally known to recur
• Respiratory failure due to extensive spread of the tumor within the lungs
• Complications during surgery:
  • Blood loss during invasive treatment methods may be heavy
  • Damage to vital nerves, blood vessels, and surrounding structures 
• Side effects from chemotherapy (such as toxicity), radiation therapy

How is Epithelioid Hemangioendothelioma of Lung Treated?

Treatment measures for Epithelioid Hemangioendothelioma of Lung may include the following:

• Any combination of chemotherapy, radiation therapy, and invasive procedures (surgery), may be used treat the tumor
• Surgery: Complete excision where possible is attempted; although, it is hard to remove the tumor entirely
• Embolization (clotting the vessels in the tumor) may be used to provide temporary relief from the symptoms and reduce blood loss during a surgical procedure
• Lung transplantation may be undertaken in some rare cases, if necessary
• Follow-up care with regular screening and check-ups are important

How can Epithelioid Hemangioendothelioma of Lung be Prevented?

• Current medical research have not established a method of preventing Epithelioid Hemangioendothelioma of Lung formation
• Regular medical screening at periodic intervals with blood tests, radiological scans, and physical examinations are mandatory for those, who have already endured the tumor, due to its metastasizing potential and chances of recurrence. Often several years of active vigilance is necessary

What is the Prognosis of Epithelioid Hemangioendothelioma of Lung? (Outcomes/Resolutions)

• Epithelioid Hemangioendothelioma of Lung is a malignant tumor with metastasizing potential. The prognosis of the tumor is dependent upon several factors and is generally guarded
• The prognosis of similar tumors depend on a combination of factors, such as initial detection of the tumor, size and location, whether it has metastasized, its response to treatment, and medical therapy administered
• Tumors that are classified as low-grade malignancy typically have better prognosis than those that are termed intermediate-grade malignancy. The 5 year overall survival rate for low-grade tumors is 60%; for intermediate-grade tumors, it is about 20%
• Unfavorable prognostic factors include the following:
  • Extensive tumor involvement of the lungs and pleura: This is seen with intermediate-grade tumors and can result in respiratory failure and death
  • Anemia and weight loss
  • Pleural effusions with blood

Additional and Relevant Useful Information for Epithelioid Hemangioendothelioma of Lung:

• The most common location of epithelioid hemangioendothelioma (EHE) is the liver
• Generally, it is difficult to manage epithelioid hemangioendotheliomas, due to the following factors:
  • The extreme rarity of the tumor
  • Its differential behavior, since some tumors behave more aggressively than others
  • A lack of standardized treatment guidelines in the medical literature