Neoplastic Angioendotheliomatosis: Immunopathologic and Morphologic Evidence for Intravascular Malignant Lymphomatosis

Abstract

Neoplastic angioendotheliomatosis (NAE) is a rare entity characterized by multifocal, intravascular proliferation of large pleomorphic cells within small vessels of most organs, with a particular affinity for the central nervous system. Clinically, patients with NAE present with focal neurologic signs and a progressive decline in mental status, followed by death in a few months. The histogenesis of NAE is controversial but has been previously thought to represent a malignant proliferation of endothelial cells. Three autopsy cases with clinical and histologic features of NAE were investigated by electron microscopic, standard histochemical, and immunohistochemical technics that included the use of three panleukocyte monoclonal antibodies (PLA), the endothelial-cell-specific reagents, FVIII-RAG anti-sera and Ulex europaeus agglutinin (UEA), and muramidase. The NAE cells in all three cases were stained positively by the PLA, whereas the adjacent endothelial cells and not the NAE cells were stained by FVIII-RAG and UEA. Muramidase by immunoperoxidase technic and nonspecific esterase (chloracetate) were not present in NAE cells. These results indicate that NAE is a leukocyte-derived neoplasm and not a malignant endothelial cell neoplasm. Based on these findings and on a review of the literature, it is proposed that NAE represents intravascular malignant lymphomatosis (IML). IML appears to be a primary manifestation and/or a major secondary form of disseminated malignant lymphoma. This would explain the spectrum of findings in previously reported cases.