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Intracranial heterotransplantation in the nude, athymic mouse has been found to be an effective method for the experimental growth of human malignant lymphomas. Transplants of 11 primary lymphomas and six derived cell lines yielded a high take rate (90%) and a low mean latent period (36 days). Relatively small inocula produced extensive intracerebral infiltrates which could be identified as human in origin by immunofluorescence. Although confined to the central nervous system and meninges, the tumors were highly invasive and displayed morphologic features strikingly similar to those of the original primary tumors. Heterotransplantation of the lymphomas to extracranial sites was only rarely successful. Nude mice previously grafted with isologous neonatal thymuses failed to develop intracerebral tumors. Secondary cell cultures successfully established from several of the intracranial heterotransplants were found to be infected with NIH type-C xenotropic virus. The distinctive growth patterns and other neuropathologic features of the heterotransplants are described, and the relevance of these observations to the development of intracerebral lymphomas in immunosuppressed organ transplant recipients is noted. This method of studying human malignant lymphomas in vivo may permit better histopathologic characterization of the tumors, and may serve as a basis for further experimental lines of investigation, including viral, immunologic, and therapeutic studies.

This report describes a form of disseminated necrotizing leukoencephalopathy that has been observed in four children with acute lymphoblastic leukemia, and one child with Burkitt's lymphoma terminating in a leukemic phase. In addition to systemic vincristine, cytosine arabinoside, cyclophosphamide, and steroids, these patients received courses of intrathecal methotrexate, cytosine arabinoside, and hydrocortisone, because of meningeal tumor cell infiltration. Whole brain radiation was also given either before or during intrathecal therapy. Three of the children had a progressive irreversible neurologic illness, which developed either at or shortly after the completion of combined triple intrathecal therapy, death ensuing approximately 2 months later. The neuropathologic lesions consisted of discrete multifocal necroses of coagulative type, apparently extending by confluence, and disseminated in the cerebral white matter in a random manner. In one case, extensive symmetrical demyelinating and necrotizing lesions involved the centrum ovale bilaterally. There was a remarkable absence of inflammatory cellular response and a relative paucity of macrophage reaction, with usually little or no tissue breakdown. In addition to demyelination and glial cell loss, there was striking axonal damage, with conspicuous axonal swelling both within and around the necrotizing lesions. The surrounding white matter showed focal status spongiosus and a moderate astrocytic response. Vascular fibrinoid necrosis was inconstant and, except in one case, rarely observed. The possible causal relationship of these lesions to combined triple intrathecal antimetabolite therapy and brain radiation is discussed.