Smaller tumors at the base of the skull can be obliterated or reduced in size by focused radiation, probably with comparable or less risk than posed by surgery (see discussion by Chang and Alder). Conventional chemotherapy and hormonal therapy are probably ineffective, but the latter has been a subject of interest. Investigations are being undertaken with antiangiogenic antibodies for recurrent tumors.
This tumor has assumed increasing significance in the last few decades because of its increased incidence in patients with AIDS and other immunosuppressed states. There is a peak incidence in the fifth through seventh decades of life, or in the third and fourth decades in patients with AIDS and the incidence is increasing independent of this form of immunosuppression.
For many years, the cell of origin of this tumor was attributed to the reticulum cell, a histiocytic component of the germinal center of lymph nodes that produces the reticulum stroma of the nodes, and the tumor was termed “reticulum cell sarcoma.” The meningeal histiocyte and microgliacytes are the equivalent cells in the brain to the reticulum cell and considered then the origin of the tumor. Later, it was recognized that the malignant cells were lymphocytes and lymphoblasts, leading to its reclassification as a lymphoma (diffuse large cell type). It has been appreciated, on the basis of immunocytochemical studies, that the tumor cells are B lymphocytes. There is a fine reticulum reaction between the reticulum cells derived from fibroblasts and microglia or histiocytes. The disproportionate emphasis on this reticular stroma was in part the result of staining methods that brought it into relief with the lymphocytes. The B lymphocyte or lymphoblast is the tumor cell, whereas the fine reticulum and “microgliacytes” are secondary interstitial reactions.
In contrast, T-cell lymphomas of the nervous system are rare but do occur in both immunocompetent and immunosuppressed patients. Because the brain is devoid of lymphatic tissue, it is uncertain how this tumor arises; one theory holds that it represents a systemic lymphoma with a particular propensity to metastasize to the nervous system. This seems unlikely to the authors; systemic lymphomas of the usual kind rarely metastasize, as discussed further on, under “Involvement of the Nervous System in Systemic Lymphoma.”
Primary CNS lymphoma may arise in any part of the cerebrum, cerebellum, or brainstem, with 60 percent being in the cerebral hemispheres; they may be solitary or multifocal. A periventricular localization is common. Vitreous, uveal, and retinal (ocular) involvement occurs in 10 to 20 percent of cases; here vitreous biopsy may be diagnostic, but it is not often performed. (Two-thirds of patients with ocular lymphoma will have cerebral involvement within a year.) Lai and colleagues have presented evidence that, in advanced cases that were autopsied, microscopic deposits of tumor found their way to many regions of the brain and not solely in areas indicated by nodular enhancement on MRI. Whether this indicates a widespread or multifocal origin of brain lymphoma is not clear.
The pia and arachnoid may be infiltrated, and a meningeal form of B-cell lymphoma that involves peripheral and cranial nerves is also known. Cases of what has been termed neurolymphomatosis may or may not arise from systemic lymphoma (hence, primary neurolymphomatosis) and present with variably painful, predominantly motor polyradiculopathies. Lymphomatous metastases to the same regions are probably more common than the isolated peripheral nerve and meningeal form but give rise to a similar syndrome of multiple radiculopathies. One such patient of ours had a flaccid paraparesis and back and sciatic pain; MRI showed tumor infiltrating the cauda equina nerve roots and contiguous meninges.