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†, 12/158

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, 13/158

Vimentin

positive0, 3/36, 14/149

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

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