Primary lymphoma of the central nervous system (CNS), including reticulum cell sarcoma, microglioma, and histiocytic lymphoma, represents less than 1% of all primary brain tumors. In the last 10 years, this tumor has tripled in frequency in the nonimmunosuppressed population. By 1991, the tumor will be the most common neurological neoplasm by virtue of the increase in sporadic occurrence and in the acquired immunodeficiency syndrome (AIDS) population. Three percent of AIDS patients will develop this tumor either prior to AIDS diagnosis or during their subsequent course. In addition to acquired immunosuppression, patients with inherited disorders (such as Wiskott-Aldrich syndrome, severe combined immunodeficiency, and X-linked immunodeficiency) and other acquired disorders of the immune system are predisposed to the development of CNS lymphoma. Immunological studies have suggested a role for Epstein-Barr virus in the production of this tumor. Although subtypes exist, non-Hodgkin's lymphoma of the CNS most commonly consists of histiocytic cells or large immunoblastic cells bearing B cell surface markers in close proximity to the lateral and third ventricles. Sixty percent of these deposits are multiple, and subarachnoid invasion is seen in one-quarter of patients. Vitreous involvement of the eye occurring prior to and during the course of CNS lymphoma has been noted in up to 25% of patients. The involvement of multiple areas of the neuraxis, the eye, and multiple intracranial sites often occurs in the absence of obvious systemic lymphoma. Therapeutic trials of brain radiation therapy are associated with median survivals of less than 1 year. Uniform complete responses of intracranial deposits are recorded following chemotherapy with high-dose intravenous methotrexate, CHOP (cyclophosphamide, hydroxydaunomycin/doxorubicin, Oncovin (vincristine), and prednisone), high-dose cytosine arabinoside, and intra-arterial methotrexate with barrier modification.

Primary central nervous system lymphoma

Objective: To compare the pathogenesis, clinical presentation, therapy, and prognosis of primary central nervous system lymphoma in immunocompetent persons with these characteristics of the disease...

Primary Central Nervous System Lymphoma

Therapeutic management of primary central nervous system lymphoma in immunocompetent patients: Results of a critical review of the literature

Primary CNS lymphomas (PCNSL), until recently representing about 1% of all brain tumors, show dramatically increased incidence both in high-risk groups (immunocompromised, AIDS) and in the general population. They are extranodal diffuse non-Hodgkin's lymphomas, the morphology and classification of which are identical to those of systemic lymphomas, although PCNSL show different biological behavior and diagnosis according to the New Working Formulation and updated Kiel classification may be difficult. The majority are large B cell variants of high-grade malignancy; low-grade subtypes and T cell lymphomas are rare. Sixty per cent occur in the supratentorial space (hemispheres, periventricular) and 12% in the posterior fossa; 30% are multiple (50%-70% in AIDS). PCNSL show a male preponderance with a peak incidence in the 5th-7th decade (3rd-4th in AIDS). The duration of diffuse or focal clinical symptoms averages 1-2 months. Computed tomography and magnetic resonance imaging scans show single or multiple or diffuse, often typical lesions. Diagnosis is achieved by evaluation of stereotactic biopsy material or cerebrospinal fluid cytology using immunocytological markers. Current therapy in immunocompetent patients, radiation plus corticosteroids and pre- or postradiation polychemotherapy, shows response rates of 85% with a median survival of 17-44 months, a prognosis similar to that for glioblastoma. Meningeal PCNSL is treated with intrathecal methotrexate or cytosine arabinoside. Transliquoral seeding of PCNSL is frequent, distant metastases occurring in 6%-8%. Therapy of AIDS-related PCNSL makes use of radiation and corticosteroids, and rarely of chemotherapy. The pathogenesis of PCNSL is unknown, but Epstein-Barr virus may be a contributory factor.

Primary central nervous system lymphomas--an update.

Thirteen patients with primary lymphoma of the central nervous system (CNS) were treated with high-dose intravenous methotrexate (MTX), 3.5 gm/sq m, followed by calcium leucovorin rescue, at 3-week intervals, for three cycles. Eleven patients subsequently received radiation therapy to the whole brain, 30 to 44 Gy. Before radiation therapy, eight patients responded completely and four partially; there was one non-responder. The median Karnofsky score before high-dose MTX therapy was 60 and increased to 90 after treatment. Five of the eight complete responders reached a Karnofsky rating of 100. The three longest responders (one of whom received MTX only) were without recurrence of their disease at 29+, 32, and 32+ months posttherapy. The median response period is 9+ months. The median survival time from the date of the first MTX treatment is 9+ months, and the three longest survival times are 29+, 32+, and 54+ months. All patients received corticosteroids in either unchanging or diminishing dosages during therapy. It is concluded that primary CNS lymphoma is sensitive to high-dose MTX, which provides a safe and easily administered adjuvant to radiation therapy for this neoplasm.

High-dose methotrexate for non-AIDS primary central nervous system lymphoma. Report of 13 cases.

This paper reports on 10 patients (4 male, 6 female) with primary non-Hodgkin's lymphomas of the brain (CNS-NHL--mean age 46.8 years, mean postdiagnostic survival 10 months). Pathological CSF (cerebrospinal fluid) was found in all 8 patients examined (positive cytology in 7/8 cases). Solitary tumors, diffuse periventricular infiltration or diffuse cerebral infiltration were demonstrated in cerebral computer-assisted tomography (CAT). Angiographical findings were unspecific. The histologic subtypes were lymphoplasmacytoid immunocytoma (4), unclassified low grade (1), centroblastic (1), B-immunoblastic (1), T-immunoblastic (1), lymphoblastic convoluted T-cell type (1), unclassified high grade (1) NHL. Patients who had received radiotherapy (+/- surgery) in this group had a mean survival of 15.66 months (sigma = 7.63). In addition, an overview of 83 well-documented, cases of the literature tries to characterize main histological and topographical distributions, histology-, patient's age-, and therapy-related survival. Patients with primary CNS-NHL have a 5-year survival expectancy of 30% compared with 2.3% in secondary CNS-manifestations of systemic non-Hodgkin's lymphomas. In this report, the beneficial effect of radiotherapy (mean survival 30.3 months) compared to surgery or symptomatic treatment (3.6 or 3.3 months) could be confirmed. It is concluded that primary CNS-NHL frequently present with atypical neuropsychiatric syndromes; diagnosis should be established preferentially with CAT and CSF-examinations or stereotactic biopsies, whereas open surgery should be avoided. An approach to exact classification should be attempted, as survival is clearly related to histological subtypes.

P.H. Wünsch

Papers

Primary non-Hodgkin's lymphomas of the CNS