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contrast enhancement in response to corticosteroids Lymphocytic and mononuclear pleocytosis of CSF is more frequent than with gliomas and metastatic tumors The immunohistochemical demonstration in CSF of monoclonal lymphocytes or an elevated beta microglobulin points to leptomeningeal spread of the tumor (Li et al), but frequently the diagnosis is not possible from CSF cytologic examination alone As already indicated, patients with AIDS and less common immunode ciency states, such as the Wiskott-Aldrich syndrome and ataxia-telangiectasia, and those receiving immunosuppressive drugs for long periods, such as patients undergoing renal transplantation, are particularly liable to develop this type of primary cerebral lymphoma Many of the tumors in immunosuppressed patients contain the Epstein-Barr virus (EBV) genome, suggesting a pathogenetic role for the virus (Bashir and colleagues); however, the EBV genome has been found in the lymphoma cells in both immunocompetent and immunosuppressed 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) Stereotactic needle biopsy is the preferred method of establishing the histologic diagnosis in sporadic cases But in AIDS 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 to brain lymphoma (see page 646) Reduction in the size of the lesion(s) with antimicrobial drugs makes biopsy unnecessary Treatment Because the tumors are deep and often multicentric, surgical resection is ineffective except in rare instances Treatment with cranial irradiation and corticosteroids often produces a partial or, rarely, complete response, as remarked above, but the tumor recurs in more than 90 percent of patients Until recently the median survival of patients treated in this way has been 10 to 18 months,

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Figure 31-9 Cerebral lymphoma MRIs with gadolinium infusion Left: T1-weighted MRI of a nodular cerebral lymphoma after gadolinium infusion Right: Another typical appearance of a smaller ring-enhancing periventricular mass with subtle in ltration of the subependymal regions

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but less in those with AIDS or in individuals who are otherwise immunocompromised In immunocompetent patients, the addition of intrathecal methotrexate and intravenous cytosine arabinoside increases median survival to more than 3 years (DeAngelis), and apparent cure is not unknown However, this combined treatment is associated with a high risk of a leukoencephalopathy (see further on and Fig 31-23) and causes considerable unpleasant systemic side effects More recent regimens, as outlined by Glass and colleagues, consist of several cycles of intravenous methotrexate (35 g/m2) and citrovorum, administered at 2- to 3-week intervals and at times continued inde nitely if tolerated The side effects of these treatments are modest and there is no need for repeated lumbar punctures or the placement of an Ommaya reservoir Most of our patients have not developed mucositis or the other of the usual side effects of this type of chemotherapy Radiation treatment may be used subsequently, but there is then a higher incidence of delayed leukoencephalopathy and dementia Ocular lymphoma is eradicated only by radiation Corticosteroids are added at any point as needed to control prominent neurologic symptoms The median survival time has been in the range of 35 years with intravenous methotrexate alone and 4 years or more if radiation is given subsequently Some patients are alive at 10 years Metastatic Carcinoma Among secondary intracranial tumors, only metastatic carcinoma occurs with high frequency Occasionally one encounters a rhabdomyosarcoma, Ewing tumor, carcinoid, etc, but these tumors are so infrequent that their cerebral metastases seldom become a matter of diagnostic concern The pathophysiology of metastatic carcinoma the complex biologic mechanisms that govern the detachment of tumor cells from the primary growth, their transport to distant tissues, and their implantation on the capillary endothelium of the particular organ in which they will eventually grow has been well reviewed by Rusciano and Burger and by Posner Autopsy studies disclose intracranial metastases in approximately 25 percent of patients who die of cancer (Posner) About 80 percent of the metastases are in the cerebral hemispheres and 20 percent in posterior fossa structures, corresponding roughly to the relative size and weights of these portions of the brain and their blood ow Cancers of the pelvis and colon are exceptional in this respect, having a somewhat higher tendency than this to spread to the posterior fossa Intracranial metastases assume three main patterns those to the skull and dura, those to the brain itself, and those spreading diffusely through the craniospinal meninges (meningeal carcinomatosis) Almost as common as intracranial metastases are those to the spinal bones, which in time cause compression of the spinal cord This problem is discussed in Chap 44 Metastatic deposits in the spinal cord itself are infrequent but are seen from time to time; they are more common, for example, than a paraneoplastic necrotic myelopathy (see further on) Metastases to the skull and dura can occur with any tumor that metastasizes to bone, but they are particularly common with carcinoma of the breast and prostate and with multiple myeloma These secondary deposits usually occur without metastases to the brain itself and reach the skull either via the systemic circulation (as in carcinoma of the breast) or via Batson s vertebral venous plexus a valveless system of veins that runs the length of the vertebral column from the pelvic veins to the large venous sinuses of the skull, bypassing the systemic circulation (the route supposedly taken by carcinoma of the prostate) Metastatic tumors of the.

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