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 tissue^17,18.

Synonyms

This tumour was previously known as intravascular sclerosing bronchioloalveolar tumour, IVBAT^2,5. 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 age^2,20.

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 mesothelioma^7,9.

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

Prognosis

Death occurs in half the patients, due to progressive pulmonary insufficiency². Metastases may occur to bone⁴. Serosal disease may be aggressive⁶.

References

Diagnostic histopathology of tumors. Edited by CDM Fletcher. 2nd edition. Churchill Livingstone. Page 67.

Diagnostic Immunohistochemistry edited by Professor D. J. Dabbs, pages 77

⁰Tumours of the Lung, Pleura, Thymus and Heart. WHO Classification of Tumours. IARC Press 2004.

¹Folpe, A. L., Chand, E. M., Goldblum, J. R., Weiss, S. W. Expression of Fli-1, a nuclear transcription factor, distinguishes vascular neoplasms from potential mimics. Am J Surg Pathol 2001;25:1061-1066.

²Dail DH, Liebow AA, Gmelich JT, et al. Intravascular, bronchiolar, and alveolar tumor of the lung (IVBAT). An analysis of twenty cases of a peculiar sclerosing endothelial tumor. Cancer 1983; 51:452-64

³Corrin B, Harrison WJ,Wright DH The so-called intravascular bronchioloalveolar tumour of lung (low grade sclerosing angiosarcoma): presentation with extrapulmonary deposits. Diagn Histopathol 1983; 6:229-37

⁴Dorfler H, Permanetter W, Kuffer G, et al. Sclerosing epitheloid angiosarcoma of bone and lung--intravascular sclerosing bronchioloalveolar tumor. Klin Wochenschr 1990; 68:388-92

⁵Eggleston JC The intravascular bronchioloalveolar tumor and the sclerosing hemangioma of the lung: misnomers of pulmonary neoplasia. Semin Diagn Pathol 1985; 2:270-80

⁶Ekfors TO, Joensuu K, Toivio I, et al. Fatal epithelioid haemangioendothelioma presenting in the lung and liver. Virchows Arch A Pathol Anat Histopathol 1986; 410:9-16

⁷Crotty EJ, McAdams HP, Erasmus JJ, et al. Epithelioid hemangioendothelioma of the pleura: clinical and radiologic features. AJR Am J Roentgenol 2000; 175:1545-9

⁸Higgins JP, Montgomery K, Wang L, et al. Expression of FKBP12 in benign and malignant vascular endothelium: an immunohistochemical study on conventional sections and tissue microarrays. Am J Surg Pathol 2003; 27:58-64

⁹Lin BT, Colby T, Gown AM, et al. Malignant vascular tumors of the serous membranes mimicking mesothelioma. A report of 14 cases. Am J Surg Pathol 1996; 20:1431-9

¹⁰Luburich P, Ayuso MC, Picado C, et al. CT of pulmonary epithelioid hemangioendothelioma. J Comput Assist Tomogr 1994; 18:562-5

¹¹Makhlouf HR, Ishak KG,Goodman ZD Epithelioid hemangioendothelioma of the liver: a clinicopathologic study of 137 cases. Cancer 1999; 85:562-82

¹²Miettinen M,Fetsch JF Distribution of keratins in normal endothelial cells and a spectrum of vascular tumors: implications in tumor diagnosis. Hum Pathol 2000; 31:1062-7

¹³Mukundan G, Urban BA, Askin FB, et al. Pulmonary epithelioid hemangioendothelioma: atypical radiologic findings of a rare tumor with pathologic correlation. J Comput Assist Tomogr 2000; 24:719-20

¹⁴Nerlich A, Berndt R,Schleicher E Differential basement membrane composition in multiple epithelioid haemangioendotheliomas of liver and lung. Histopathology 1991; 18:303-7

¹⁵Poletti V, Casadei G, Boaron M, et al. Epithelioid haemangioendothelioma of the lung imitating clinical features of pulmonary histiocytosis X. Monaldi Arch Chest Dis 1997; 52:346-8

¹⁶Sherman JL, Rykwalder PJ,Tashkin DP Intravascular bronchioloalveolar tumor. Am Rev Respir Dis 1981; 123:468-70

¹⁷Verbeken E, Beyls J, Moerman P, et al. Lung metastasis of malignant epithelioid hemangioendothelioma mimicking a primary intravascular bronchioalveolar tumor. A histologic, ultrastructural, and immunohistochemical study. Cancer 1985; 55:1741-6

¹⁸Weiss SW, Ishak KG, Dail DH, et al. Epithelioid hemangioendothelioma and related lesions. Semin Diagn Pathol 1986; 3:259-87

¹⁹Weldon-Linne CM, Victor TA, Christ ML, et al. Angiogenic nature of the "intravascular bronchioloalveolar tumor" of the lung: an electron microscopic study. Arch Pathol Lab Med 1981; 105:174-9

²⁰Yousem SA,Hochholzer L Unusual thoracic manifestations of epithelioid hemangioendothelioma. Arch Pathol Lab Med 1987; 111:459-63

²¹Zhang PJ, Livolsi VA,Brooks JJ Malignant epithelioid vascular tumors of the pleura: report of a series and literature review. Hum Pathol 2000; 31:29-34

This page last revised 6.4.2005.

©SMUHT/PW Bishop