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Arch Pathol Lab Med. 2009 Jun;133(6):967-72. doi: 10.1043/1543-2165-133.6.967.

Utility of immunohistochemistry for endothelial markers in distinguishing epithelioid hemangioendothelioma from carcinoma metastatic to bone.

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  • 1Department of Laboratory Medicine, University of California, San Francisco, USA.



Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm of intermediate malignancy. Epithelioid hemangioendothelioma often presents a difficult diagnostic problem, especially in bone, because the epithelioid morphology and radiographic features raise the possibility of metastatic carcinoma. The current trend of small biopsies obtained with computed tomography-guided techniques exacerbates the problem. The markedly different treatment for EHE and metastatic carcinoma underscores the need for specific markers that can differentiate between these 2 entities.


To determine the relative utility of endothelial markers in differentiating EHE from metastatic carcinoma, with emphasis on bone biopsies.


We used immunohistochemistry in formalin-fixed paraffin-embedded tissue to compare the utility of Fli-1, CD34, CD31, podoplanin, and keratin cocktail in 13 EHEs and 13 morphologically similar carcinomas metastatic to bone. Immunohistochemical data were evaluated using Fisher exact test, and specificity and sensitivity were calculated.


Significant proportions of EHEs were positive for Fli-1 (100%), CD34 (85%), and CD31 (100%) compared with metastatic carcinoma (Fli-1, 15%; CD34, 15%; CD31, 38%) (P < .001, P = .005, and P = .01, respectively). However, these markers were not 100% specific for EHE. Cytokeratin cocktail stained significantly more metastatic carcinomas (100%) than EHEs (38%) (P = .01) but was not 100% specific. No significant difference was observed regarding immunostaining for podoplanin between the tumor types.


Fli-1 is most helpful in distinguishing EHE from metastatic carcinoma. However, the absence of complete specificity of any of the endothelial markers for EHE, or of keratin cocktail for carcinoma, suggests that these markers are best used in combination.

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