Final Diagnosis -- Primary CNS Lymphoma



Primary CNS lymphoma is a malignant extra-nodal lymphoma confined to the CNS. Peak incidence in non-AIDS patients is in the fifth to the seventh decade. The presentation is usually with a progressive cognitive decline and focal deficits. Progressive dementia and cognitive impairment is a feature of the slow infiltrative and diffuse nature of the tumor.

Radiographically, multifocal lesions in the supratentorial white matter are usually present. CT shows single or multiple isodense or hypodense lesions that enhance. Surrounding edema is usually less than that expected for a glioma or metastasis. MRI shows multiple enhancing lesions in T1 weighted images and hyperintense tumor and edema in T2 weighted images (4). The most common locations involved are the frontal lobes, basal ganglia and periventricular regions. FDG-PET shows areas of increased glucose uptake corresponding with metabolically active tumor.

Diagnosis is by brain biopsy. Recent use of steroids may decrease the diagnostic yield. Microscopic appearance shows an angiocentric growth pattern with cuffs of tumor cells around cerebral blood vessels. Tumor cells invade the surrounding brain tissue from these perivascular cuffs. There is no formation of follicles in contrast to non-CNS lymphoma. Cytological analysis shows large lymphoid cells of B-cell lineage. There is expression of B cell markers CD19, CD20, and CD79a. Variable numbers of T lymphocytes, macrophages, activated microglia and reactive astrocytes may be seen. Necrosis may be present, particularly if there was previous treatment with steroids. T cell lymphoma is rare but may occur (2% of cases) (3).

The molecular pathogenesis of the abnormal B cell is not fully understood. Intracerebral superantigens that have been associated with a variety of infectious agents may play a role in the expansion and persistence of abnormal B cells (1). Specific viruses that have a predilection for persistence within the CNS, such as Polyomavirus and Herpesviruses, have been proposed as possible candidates (4). Epstein Barr virus is particularly associated with CNS lymphoma in AIDS patients (1). HCV has been associated with several types of non-Hodgkin's lymphoma, as a trigger to B-cell clonal expansion, but this has not been shown in primary CNS lymphoma (5).

Histological subtype does not correlate with prognosis (2). Median survival without treatment is 2-3 months and with steroids is 4-5 months. Survival can be longer with chemotherapy and/or radiation. In our case, the patient responded well to two courses of intra-arterial methotrexate with improvement in MRI appearance of the lymphoma and has survived 8 months since biopsy.

In summary, the clinical presentation of progressive cognitive impairment along with several focal findings on neurologic examination suggested bilateral hemispheric involvement. EEG, MRI, and PET scans confirmed our clinical findings. The differential diagnosis for this presentation is limited to demyelinating disease such as multiple sclerosis, vascular dementia, and infiltrating neoplasm such as glioblastoma multiforme or lymphoma. Diagnosis was made by morphologic and immunohistochemical analysis of brain tissue.


  1. Amariglio N, Rechavi G (1996) Do superantigens play a role in lymphoproliferation? Leuk Lymphoma 22:237-243.
  2. Braus DF, Schwechheimer K, Muller-Hermelink HK, Schwarzkopf G, Volk B, Mundinger F (1992) Primary cerebral malignant non-Hodgkin's lymphoma: a retrospective clinical study. J Neurol 239:117-24.
  3. Paulus W, Jellinger K, Morgello S, Deckert-Schlueter M (2000) Malignant lymphomas. In: Pathology and Genetics of Tumors of the Nervous System, Kleihues P, Cavenee WK (Eds.), pp. 198-203, IARC Press: Lyon.
  4. Schlegel U, Schmidt-Wolf IG, Deckert M (2000) Primary CNS Lymphoma: clinical presentation, pathological classification, molecular pathogenesis and treatment. J Neurol Sci 181:1-12.
  5. Vallisa D, Berte R, Rocca A, Civardi G, Giangregorio F, Ferrari B, Sbolli G, Cavanna L (1999) Association between Hepatitis C virus and non-Hodgkin's lymphoma, and effects of viral infection on histological subtype and clinical cours

Contributed by Widdess-Walsh P, Nair A, Staugaitis SM

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