Primary CNS lymphomas

General characteristics

Primary central nervous system lymphomas account for approximately 1% of all primary intracerebral tumours and are almost always B cell in origin. Although rare, an increasing incidence of this disease, up to 2%, has been seen among patients with acquired immunodeficiency syndrome (AIDS) and among other immunocompromised persons (Fine and Mayer 1993). The natural history of this disorder differs between patients with AIDS and those without AIDS. Both groups do equally poorly without therapy (1–3 month mean survival), but the overall survival for treated patients is much better for patients without AIDS (18.9 months) than for those with AIDS (2.6 months) (Pollack et al. 1989).

Central nervous systemic lymphomas are non-Hodgkin’s lymphoma in nearly all cases. In about 10%, a spread within the CNS was observed. When tumor progression occurs, it is usually confined to the CNS and/or the eye. Occult systemic disease can be excluded by staging with bone marrow biopsy and CT scans of the chest, abdomen, and pelvis (O’Neill et al. 1995; Abrey et al. 2005).

Although more than 95% of patients with primary CNS lymphoma have lymphoma of B-cell origin, 45 patients with CNS lymphoma of T-cell origin showed no difference in presentation or outcome in a retrospective series with data collected from 12 cancer centers.

Epidemiology and Aetiology

They occur in higher frequencies in patients with some form of immunosuppression. Approximately 2–6 per cent of patients with AIDS and 0.5–1 % of patients following transplantation will develop a primary CNS lymphoma. Primary CNS lymphomas are also found in association with Wiskott–Aldrich syndrome, systemic lupus, idiopathic thrombocytopenic purpura, Sjögren's syndrome, and sarcoidosis (Remick et al. 1990; Ling et al. 1997).

Despite the association with immunosuppressive states, primary CNS lymphoma more commonly occurs sporadically in the immunocompetent. Epstein–Barr virus (EBV) can be detected in all AIDS-related primary CNS lymphomas, raising the possibility of a direct EBV-related cause (MacMahon et al. 1991; Guterman et al. 1996).

Imaging and Location

The majority of primary CNS lymphomas have an intra-axial intraparenchymal location, whereas the secondary lymphomas mainly occur at the meninges (Scatliff et al. 1997; Thurner et al. 1997). The tumors are typically deep seated in the subependymal space and may present as a bilateral mass lesion.

Most lesions are solitary but a multifocal and/or necrotic appearance can be present in AIDS patients. Imaging may therefore show ring enhancement in 50% of AIDS patients while patients without AIDS usually show only homogeneous enhancement (Thurner et al. 1997).

The signal characteristics are iso- to slightly hypointense on T1-weighted imaging and hyperintense on T2-weighted scans. The extent of edema is normally less than observed in gliomas or metastases (Koeller et al. 2007). The enhancement is intense, and the detection of enhancement along the perivascular spaces is typical for lymphomas, with sarcoidosis as the only differential diagnosis. Calcification and hemorrhage are uncommon in primary CNS lymphoma.

Other differential diagnosis includes cerebral toxoplasmosis in the immunocompromised population with hemorrhage as a common finding. In the non-AIDS population, glioblastoma and metastases are the main differential diagnosis. Both can cross the corpus callosum and present comparable enhancement patterns.

Clinically, primary CNS lymphoma is classified as an extranodal lymphoma (stage 1E) and it most commonly presents as single or multiple contrast-enhancing space-occupying lesion(s) within the brain, or as cells in the eye (vitreous lymphoma) or CSF (leptomeningeal lymphoma).

Primary CNS lymphoma is most commonly confined to central nervous system or eye, and even at post-mortem only 10 per cent of patients are found to have disease outwith the CNS. The tumour is commonly in a periventricular site and this may explain the high incidence of CSF involvement. Approximately, 20 per cent of patients will have cerebrospinal fluid involvement at the time of presentation, and a further 20 per cent will have had, or develop, a uveitis with ‘floaters’ and progressive loss of vision due to lymphoma of the vitreous (Hochberg and Miller 1988).

The diagnosis may be suspected if the CT/MRI scan is typical, but biopsy is essential. There is no evidence that resection is superior to stereotactic biopsy. The tumours frequently lose their enhancement when steroids are given and it is not uncommon for the tumour to ‘disappear’ on CT scan after steroids, making stereotactic biopsy difficult. Anecdotally, these tumours have an increased propensity to bleed when biopsied compared with other intracerebral tumours.

CT/MRI scan of the chest and abdomen is almost always negative and bone-marrow biopsy is not required (Hochberg and Miller 1988).


In patients who do not have HIV/AIDS, biopsy and steroids confirm the diagnosis and usually produce a reasonable clinical and radiological response. Corticosteroids are cytotoxic to lymphocytes and prolonged remissions with steroids have been reported. The relative roles of radiation therapy and chemotherapy have not yet been researched adequately. Young patients (<60 years), treated with more than 40 Gy to the whole brain and a boost to 50 Gy to the tumour bed, along with chemotherapy, appear to have a better survival, with a median of around 2–3 years (Reni et al. 1997).

Escalating the boost to 60 Gy does not appear to produce any survival advantage (Nelson et al., 1992). Chemotherapy used to be kept in reserve for relapsed primary CNS lymphoma; however, more recently chemotherapy with high-dose methotrexate or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) has been found to be effective, and possibly has better CSF penetration if given prior to radiation (Glass et al. 1994; Lachance et al. 1994).

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