Patients with AIDS and less-common immunodeficiency states, such as the Wiskott-Aldrich syndrome and ataxia-telangiectasia, and those who are receiving immunosuppressive drugs for long periods, as for example, in renal transplantation, are particularly liable to develop this type of lymphoma. Many of the tumors in immunosuppressed patients contain the EBV genome, suggesting a pathogenetic role for the virus (Bashir et al); however, the EBV genome has also been found in the tumors of a few immunocompetent patients (Hochberg and Miller). Sometimes this tumor appears as a complication of an obscure medical condition such as salivary and lacrimal gland enlargement (Mikulicz syndrome) and the related Sjögren syndrome. Another disorder, lymphomatoid granulomatosis (called by several different names), is also driven by EBV virus and has similarities to CNS lymphoma, as outlined in a later section.
Stereotactic needle biopsy is the preferred method of establishing the histologic diagnosis in sporadic cases. In immunosuppressed patients, the differential diagnosis of a solitary brain nodule that is suspected to be lymphoma is aided by the response, or lack thereof, to treatment for toxoplasmosis, the main alternative diagnosis (see “Toxoplasmosis” in Chap. 31). Reduction in the size of the lesion with antimicrobial drugs makes biopsy unnecessary.
Treatment Because the tumors are deep and often multicentric, surgical resection is ineffective. Treatment with cranial irradiation and corticosteroids often produces a partial or, transiently, a complete response, but the tumor recurs in greater than 90 percent of patients. At times, the response to corticosteroids can be striking, even eliminating imaging and histopathologic evidence of the tumor and making the diagnosis difficult. Paradoxically, clinicians use this dramatic disappearance as implicit evidence of the existence of CNS lymphoma, although other disorders such as demyelinating disease may do the same.
Until decades ago, the median survival of patients had been 10 to 18 months, and less in those with AIDS and in individuals who were otherwise immunocompromised. The treatment of CNS lymphoma is different in patients with AIDS than in patients who are immunocompetent in that chemotherapy creates an additional risk for infection. Restoring immune competence is advisable but, in contrast to the opportunistic infection that may be associated with immunosuppression, PML, there is little evidence that this restoration improves CNS lymphoma. While methotrexate, for example, had been eschewed, it has been tried in AIDS patients who also start antiretroviral treatment. Cranial irradiation is the predominant treatment.
There is currently no consensus on the optimal treatment of CNS lymphoma but methotrexate-based regimens are most effective. Single high dose intravenous therapy is widely used but multiple dose regimens in combination with whole brain radiation is also employed. Cranial irradiation has been studied heterogeneously as part of the initial treatment. More recently, methotrexate plus either cytarabine or a combination of rituximab and temozolomide has been assessed but not uniformly implemented. With these various regimens, despite high initial response rates, survival rates have been, at best near 50 percent. Survival in AIDS patients is far shorter but may be improved with the inception of aggressive antiretroviral treatment.
Ocular lymphoma is eradicated only by radiation therapy. Corticosteroids are added at any point to control neurologic symptoms. The median survival time with this approach in the non-AIDS patient is in the range of 3.5 years with intravenous methotrexate alone and 4 years or more if radiation is given subsequently. Some patients are alive at 10 years.