Malignant Vascular Tumors of the Serous Membranes Mimicking Mesothelioma

Abstract

Malignant endothelial neoplasms involving the serous membranes are rare, and only a few cases have been documented. We report 14 patients with epithelioid hemangioendothelioma (EHE) or epithelioid angiosarcoma (EA) diffusely involving the pleural, peritoneal, or pericardial cavities, resulting in a picture closely resembling mesothelioma. The mean age at diagnosis was 52 (range, 34-85). The patients included two women and one man with peritoneal tumors, eight men with pleural tumors, and three men with pericardial tumors. A shared histological appearance was a diffuse sheet-like and clustered pattern of tumor growth with variable degrees of vascular differentiation. A tubulopapillary growth pattern, often seen in mesothelioma, was prominent in four cases. Nine cases showed a variable number of spindle cells, some neoplastic, others reactive, focally producing a biphasic growth pattern, further suggesting mesothelioma. Initial interpretations included mesothelioma, adenocarcinoma, and, in one case with prominent spindle-cell components, leiomyosarcoma. Immunohistochemically, strong vimentin staining and negative or weak to moderate cytokeratin staining were observed in all 14 cases. The tumor cells coexpressed at least two of the four endothelial markers used in the study (CD31, CD34, von Willebrand factor, and Ulex europaeus agglutinin-I [UEA-I)]. Detection of abortive vessel formation was facilitated by staining for collagen type IV. Markers of mesothelial, epithelial, muscular, and neuronal differentiation were all negative in the subset of cases studied. As a control group, 39 mesotheliomas and more than 60 adenocarcinomas of various origins were studied using the same antibody panel. This group revealed strong keratin staining, moderate or negative vimentin staining, and no expression of any of the endothelial-lineage markers, with the exception of positive staining for UEA-I in occasional adenocarcinomas. Clinically, these endothelial tumors were highly aggressive; 12 patients presented with disseminated disease, and most died within months of the initial presentation. These findings indicate that, although uncommon, EHE/EA should be included in the differential diagnosis of serous membrane neoplasms with histological and clinical features of malignant mesothelioma. The diagnosis of an endothelial neoplasm can be suspected by the presence of abortive vessel formation and by the strong expression of vimentin, with absent or low-level expression of cytokeratin. The demonstration of immunoreactivity for two or more endothelial-associated markers is essential in confirming the diagnosis.

Malignant vascular tumours of the pleura in "asbestos" workers and endothelial differentiation in malignant mesothelioma

“…The expression of von Willebrand factor and CD34 has not been reported in malignant mesothelioma and the results of this study support previous investigations. 8 The present study indicates no definite immunohistochemical evidence of vascular diVerentiation in any of the cohort of 92 malignant mesotheliomas studied and we conclude that vascular marker expression (and endothelial diVerentiation) does not occur or is a very infrequent finding in malignant mesothelioma. The use of a combination of the vascular markers CD31 and CD34 would therefore allow eVective distinction of malignant mesothelioma from epithelioid angiosarcoma.…”

“…5 It has been described as originating from the pleura 6 and peritoneum. 7 In the pleura the main diVerential diagnosis is that of diVuse malignant mesothelioma 8 and clinicopathological distinction can be problematical. Firstly, a diVuse serosal growth pattern is a characteristic feature of malignant mesothelioma but this "mesotheliomatous" pattern is not specific and has been recognised in some non-mesothelial tumours, most notably carcinomas and, very rarely, sarcomas including epithelioid haemangioendothelioma.…”

“…Considering the aetiological role of asbestos, in the largest published series of 14 malignant vascular tumours involving the serous membranes 8 only one case of epithelioid angiosarcoma had a prior history of asbestos exposure. In order to ascribe mesothelioma to exposure to asbestos certain conditions must be met including (1) accurate diagnosis, (2) reliable evidence of exposure to amphibole asbestos, (3) an appropriate latent period, and (4) an absence of confounding aetiological factors such as irradiation or erionite mineral fibre exposure.…”

Pleomorphic mesothelioma: report of 10 cases

“…The two sarcomas with the greatest potential of being confused with pleomorphic mesotheliomas are angiosarcomas and the pleomorphic variant of malignant fibrous histiocytoma. Pleural angiosarcomas are often epithelioid and can easily be mistaken for a mesothelioma, both clinically and histologically, [27][28][29][30] and examples of epithelioid pleural angiosarcomas exhibiting marked pleomorphism that could easily be confused with pleomorphic mesotheliomas have been documented in the literature. 31 The pleural biopsy of one of the mesotheliomas cases in this study (case 1), in addition to being somewhat hemorrhagic, showed areas in which the neoplastic cells appeared to be lining irregular spaces resembling the vascular spaces seen in an angiosarcoma ( Figure 1a).…”

Epithelioid Lesions of the Serosa

“…Epithelioid hemangioendothelioma and epithelioid angiosarcoma may mimic epithelioid MM by clinical presentation, radiologic features, and morphology. [19][20][21] It has been recommended that a vascular tumor should be suspected in the presence of abortive vessel formation and in the absence or low-level expression of cytokeratin and mesothelial markers, such as calretinin, and confirmed with 2 or more vascular markers. 19,20 It is noteworthy that sarcomas and thymoma may be, at least to some extent, positive for mesothelial markers.…”