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Pathology of Leukemia in the Brain and Meninges: Postmortem Studies of Patients with Acute Leukemia and of Mice Given Inoculations of L1210 Leukemia

Pathologic Anatomy Branch, National Cancer Institute, Bethesda, Maryland

Data previously published were reviewed and compared with pathologic observations on more recently autopsied patients. Special consideration was given to the frequency of leukemic cell involvement of the brain and meninges and the effects of anti-leukemic chemotherapy on the amount and distribution of leukemic cells in the central nervous system at the time these patients died. The material from man was also compared with that from mice given inoculations of L1210 leukemia because meningeal leukemia of the mouse was found to be similar pathologically to meningeal leukemia of man.

There was little change in the amount of leukemic cell infiltration in the meninges of subjects autopsied during 2 periods, 1953–58 and 1961–63. Intracerebral leukostasis and leukemic nodule formation occurred with equal frequency in the 2 series.

Pathologically there did not appear to be any relationship between intracerebral leukostasis and leukemic nodule formation and the degree of leukemic cell infiltration in the meninges. Leukemic cell infiltration in the area postrema, the tuber cinereum, and other "non-neural" areas was usually associated with leukemic cell infiltration of the arachnoid.

Many of the histologic features of leukemic cell infiltration in the meninges and non-neural areas of the mouse after inoculations of L1210 leukemia were similar to those in man. Intracerebral leukostasis and leukemic nodules, and massive dural and arachnoidal hemorrhages, were occasionally seen in the brains of patients with acute leukemia; however, they were not observed in the central nervous system of mice inoculated with L1210 leukemia.

Diffuse meningeal leukemia will develop in mice given s.c. inoculations of L1210 leukemia if their life is prolonged with methotrexate treatment. In mice given s.c. inoculations of L1210 leukemia and treated with methotrexate, leukemic cells entered the arachnoid by direct migration and growth through the perivascular and perineural tissues of vessels and nerves which bridge the subdural space. Although direct observations about the route of spread of leukemic cells to the arachnoid cannot be made in the human, it was speculated after examination of the human material that direct spread of leukemic cells from dura to the arachnoid may occur in man as it did in the mouse. Pathologic observations in mice with diffuse meningeal leukemia confirmed the fact that most of the commonly used anti-leukemic drugs, when given parenterally, failed to cross the blood-brain barrier in sufficient quantity to eradicate leukemic cells from the central nervous system. One of the nitrosoureas, BCNU (given parenterally), did appear to be effective against meningeal leukemia cells in the arachnoid.