Leukemia and Lymphoma Metastases

Central nervous system (CNS) metastases can occur with any primary systemic cancer, but some primary cancers such as melanoma have a specific predilection for the CNS. Brain metastasis is the most common CNS metastasis, occurring in 15% of all cancer patients (Posner, 1995). Leptomeningeal metastasis is less common, 3% to 8%, and epidural metastasis occurs in approximately 5% of cases (Posner, 1995; Byrne and Waxman, 1990). Leukemias and lymphomas do metastasize to the nervous system but rarely involve brain parenchyma and more characteristically involve the leptomeninges. Although epidural metastases do not represent nervous system metastases because they occur outside of the CNS, they typically have a neurologic presentation and for that reason are considered here. The overwhelming majority of CNS metastases are due to solid tumors rather than to lymphoreticular malignancies. Lymphoma accounts for only 10% of epidural metastases whereas solid tumors account for the remaining 90% (Posner, 1995; Byrne and Waxman, 1990); leukemia rarely causes epidural disease (Bower et al., 1997; Kataoka et al., 1995). In contradistinction, the lymphoreticular malignancies account for a preponderance of patients with leptomeningeal metastases. The overall incidence is difficult to ascertain because leukemias and lymphomas are often excluded from most series, but approximately 24% of patients with leptomeningeal metastasis have non-Hodgkin’s lymphoma (NHL) (Olson et al., 1974). Therefore, the pattern of CNS metastases from lymphoma and leukemia is different from that of solid tumors, and the differential diagnosis of these entities is different for patients with lymphoreticular malignancies. For example, leptomeningeal metastasis can mimic vincristine peripheral neuropathy, which is common among patients with lymphoma or leukemia. Patients with lymphoreticular malignancies are particularly vulnerable to opportunistic infections, which can mimic metastasis. Finally, isolated CNS metastasis is far more common with lymphoma or leukemia than with solid tumors where CNS disease typically occurs in the setting of widespread systemic metastases. Systemic therapy of leukemia and lymphoma can be highly effective and can eradicate extra-CNS disease. However, microscopic tumor within the CNS may be protected from circulating systemic chemotherapy by the blood–brain barrier. This disease can progress while the patient is in remission systemically, leading to an isolated CNS relapse. This pattern of recurrence is characteristic of the leukemias and lymphomas, making them different from the solid tumors and warranting special consideration.