Epithelioid haemangioendothelioma

Definitions

A low to intermediate grade vascular tumour composed of epithelioid endothelial cells with cytoplasmic vacuoles in short cords and nests within a myxohyaline matrix. Epithelioid haemangioendothelioma of similar appearance occurs in the lungs, liver, bone and soft tissue17,18.

Synonyms

This tumour was previously known as intravascular sclerosing bronchioloalveolar tumour, IVBAT2,5. Other proposed terms have been "sclerosing angiogenic tumour"19,

Epidemiology

Most patients are Caucasian with a 4:1 female predominance2, half less than 40 years of age2,20.

Clinical features

Half the patients are asymptomatic. Symptoms include pleuritic chest pain, dyspnea, cough, haemoptysis and clubbing. Pneumothorax may occur15. Infrequently, there is alveolar haemorrhage or thromboembolic disease. 15% of patients have liver involvement.

This tumour has a predilection for skin, soft tissues, liver11 and lung.

Radiology

There are usually multiple small bilateral nodules20. These may resemble tumour metastases, granulomatous disease or Langerhans' cell histiocytosis. They may be calcified10. Less often, there may be a single lung mass20.

Macroscopic appearances

The neoplasm usually forms a circumscribed mass. The cut surface has a cartilaginous consistency and there is often calcification. Pleural, pericardial or peritoneal involvement may be diffuse, resembling mesothelioma7,9.

Histopathology

There are nodules with central hypocellular sclerosis which may be calcified or ossified, and a cellular periphery. The tumour typically infiltrates bronchioles and alveolar spaces. A micropapillary architecture may be seen where lung parenchyma is infiltrated, but is not apparent in tumour elsewhere and is probably conferred by the pulmonary anatomy3. Lymphatic infiltration may mimic carcinoma. The cells show intracellular vacuoles, which may create a resemblance to signet ring cell carcinoma. There are often intranuclear cytoplasmic inclusions. The stroma varies from chondroid to hyaline to myxoid or mucinous.

Serosal disease may have a tubulopapillary and biphasic architecture, resembling mesothelioma9.

Immunohistochemistry

CD31	usually positive0, 12/15(12 cases positive, 1 case equivocal)8
CD34	positive0, 11/158
Ulex europaeus	positive
factor VIIIRA (von Willebrand factor)	positive0, 2/23, 2/36
At least two of the above	14/149
Fli-1	positive0, 8/91
FKBP12	positive0, 13/15(13 cases positive, 1 case equivocal)8
Vimentin	positive(strongly positive)0, 3/36, 14/14(strongly positive)9
SMA	up to 45% of cases
cytokeratin	20-30% of cases0, 3/36
CK7	50% of cases12
CK8	10% of cases12
CK14	negative12
CK18	positive12
CK19	negative12
EMA	usually negative
CEA	negative

heterogeneity of staining makes the use of a panel of endothelial markers obligatory.

Ultrastructure

The tumour cells are surrounded by an external lamina and occasional tight junctions. Intracytoplasmic lumina are seen. There are thick filaments of 100-150 nm. Pinocytotic vesicles may be present. Weibel-Palade bodies are variably present3.

Differential diagnosis

Metastatic epithelioid haemangioendothelioma; if there is a dominant mass elsewhere. It has been argued that combined lung and liver disease represents multicentric neoplasia14.
Epithelioid angiosarcoma
Carcinoma: the primitive intracellular vacuoles of epithelioid haemangioendothelioma may mimic adenocarcinoma and these tumours may be positive for cytokeratins. There may be a resemblance to lymphangitis carcinomatosa20.
Epithelioid sarcoma
With pleural involvement: mesothelioma20