The central nervous system in childhood leukemia. III. Mineralizing microangiopathy and dystrophic calcification.

We determined the prevalence, histopathologic features, and clinical correlations of a distinctive vascular lesion within the central nervous system (CNS) of children who died with acute lymphoblastic leukemia (ALL). Of 163 brains examined at autopsy, 28 (17%) had a noninflammatory mineralizing microangiopathy, usually accompanied by varying amounts of necrosis and calcification in adjacent neural tissue. The lesion always involved the lenticular nucleus with or without additional involvement of cerebral cortex. It was not the cause of death in any patient. An analysis of clinical features common to patients with microangiopathy indicated that cranial irradiation, in doses as low as 1500 rad, had induced the degenerative process. Survival beyond 10 months from the time of irradiation and multiple postirradiation CNS leukemic relapses, both had significant influences on the development of the lesion. Chemotherapy, particularly systemic or intrathecal methotrexate, might have contributed to the disease process, but apparently was not the instigating factor. Patients at greatest risk for developing microangiopathy are those under 10 years of age at the time of cranial irradiation, who then live more than 10 months and develop multiple CNS leukemic relapses.