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Neuro-Oncology 1999 1(2):89-100; doi:10.1093/neuonc/1.2.89
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© 1999 by the Society forNeuro-Oncology

The blood-brain barrier in primary CNS lymphomas: Ultrastructuralevidence of endothelial cell death

Peter P. Molnár, Brian P. O'Neill, Bernd W. Scheithauer and Dennis R. Groothuis2

Department of Neurology, Northwestern UniversityMedical School, Evanston Northwestern Healthcare, Evanston, IL 60201 [P.P.M.,D.R.G.]; Present address: Hungarian-Japanese EM Center (HJEMC), Department of Pathology, University Medical School ofDebrecen, P. O. Box 24, H-4012 Hungary [P.P.M.]; Department of Neurology [B.P.O.], and Department of Laboratory Medicine and Pathology [B.W.S.],Mayo Clinic and Foundation, Rochester, MN 55905; Department of Neurobiology and Physiology, NorthwesternUniversity and the Institute for Neuroscience, Northwestern University,Evanston, IL 60201 [D.R.G.]

2 Address correspondence and reprint requests to Dennis R. Groothuis, M.D.,Evanston Northwestern Healthcare, Department of Neurology, 2650 Ridge Avenue,Evanston, IL 60201.


  Abstract

The vasculature of 24 primary CNS B-cell lymphomas that were not related toacquired immunodeficiency syndrome was systematically studied by electronmicroscopy. Seven low-grade astrocytic tumors were included for comparison.Classical electron microscopy features of apoptosis were found in lymphomacells of 21 of 22 subjects. Capillaries of gliomas and lymphomas showedchanges reported previously: variability of endothelial cell (EC)-thicknessand number, basal lamina thickness and duplication, and fenestrations. PrimaryCNS B-cell lymphoma ECs showed two distinctive populations of electron-denseand electron-lucent cells. The electron-dense ECs occurred in 38% of allcapillaries, with changes consisting of chromatin condensation in bizarre andcontracted nuclei, cytoplasmic shrinkage with markedly increased electrondensity, and dilatation of the endoplasmic reticulum. We interpreted thesechanges as indicative of apoptosis. Cell death eventually resulted in completedisintegration of the endothelium with frank discontinuities of the ECcomponent of the blood-tumor barrier in capillaries and postcapillary venules.Another population of ECs had increased cell volume, conspicuous cytoplasmicelectron lucency, dispersed organelles, scattered vesicles, and apical stressfibers. We interpreted these changes as indicative of cellular regeneration.Individual apoptotic ECs often lay next to normal or regenerating ECs. Neithertype of EC change was observed in gliomas, which also lacked perivascularneoplastic lymphocytic cuffing. We believe that these populations of ECs,which have not been described in other disorders affecting the blood-brainbarrier, may be induced by cytokines released from necrotic and/or apoptotictumor lymphocytes and may explain the unusual imaging characteristics ofprimary CNS B-cell lymphomas treated with corticosteroids.

Received July 30, 1998; Accepted September 11, 1998


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