Meningeal involvement in B-cell chronic lymphocytic leukemia: report of two cases

Symptomatic central nervous system (CNS) involvement in chronic lymphocytic leukemia (CLL) or its variants is rare. We report two cases of CLL with leptomeningeal involvement. Patient one was an 81-year-old male who had CLL stage C (IV) at diagnosis and developed meningeal disease 29 months later. Patient 2 was a 42-year-old male with a diagnosis of CLL stage A (II) that evolved into mixed-cell CLL/prolymphocytic leukemia (PLL) 1.5 years later, with leptomeningeal infiltration of prolymphocytes developing 26 months after initial diagnosis. Meningeal leukemia was diagnosed by cerebrospinal fluid examination, with flow cytometry showing the same immunophenotypic findings of lambda-light chain restriction as the lymphocytes in bone marrow in one patient, and with morphologic characteristics exhibiting exclusively prolymphocytes in the other patient. The CNS disease of both patients responded effectively to intrathecal chemotherapy and cranial irradiation. However, both patients died of infection, a major cause of morbidity and mortality in patients with CLL. The clinicopathologic features of these two patients indicate that, despite the rarity of CNS involvement in CLL patients, any neurologic manifestation in CLL patients should arouse suspicion of meningeal leukemia and patients should be examined and managed accordingly.