Primary central nervous system lymphoma

Primary CNS lymphoma is a primary intracranial tumor usually present in those with severe immunosuppression --- commonly in those with AIDS --- and represents around 20% of all cases of lymphomas in HIV infection (other types being Burkitt's lymphoma and immunoblastic lymphoma). Primary CNS lymphoma (PCNSL) is highly associated with Epstein-Barr virus infection (> 90%) in immunodeficient patients^[1] (such as those with AIDS and those iatrogenically immunosupressed) and does not have predilections for any age group. Mean CD4+ count at time of diagnosis is ~50/uL. Because of the severity of immunosuppression at the time of diagnosis, it is to no surprise that prognosis is usually poor. In immunocompetent patients (that is, patients that do not have AIDS or some other immunodeficiency) there is rarely an association with EBV infection or other infectious DNAs. In the immunocompetent population, PCNSL typically affects older patients in their 50's and 60's. Importantly, the incidence of PCNSL in the immunocompetent population has been reported to have increased more than 10-fold from 2.5 cases to 30 cases per 10 million population^[2][3]. The cause for the increase in incidence of this disease in the immunocompetent population is unknown.

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Classification

Most PCNSLs are diffuse large B-cell non-Hodgkin's lymphoma^[4][5].

Clinical manifestations

Primary CNS lymphoma usually presents with seizures, headache, cranial nerve findings, altered mental status, or other focal neurological deficits typical of a mass effect^{[6] [7]}. Systemic symptoms may include fever, night sweats, or weight loss.

Diagnosis

MRI or contrast enhanced CT usually shows multiple (1 to 3) 3- to 5-cm ring-enhancing lesions in almost any location, but usually deep in the white matter. The major differential diagnosis is cerebral toxoplasmosis, which is also prevalent in AIDS patients and also presents with a ring-enhanced lesion, although the contrast enhancement is more pronounced in toxoplasmosis and it presents with more lesions.

Because imaging techniques cannot distinguish the two conditions with certainty, patients usually undergo brain biopsy if the lesion is solitary or a trial of toxoplasmosis therapy is non-therapeutic. In the future, it may be possible to use PCR assay of cerebrospinal fluid for EBV DNA.

Treatment

Surgical resection is usually ineffective because of the depth of the tumor. Treatment with irradiation and corticosteroids often only produces a partial response, but tumor recurs in more than 90% of patients. Median survival is 10 to 18 months in immunocompetent patients, and less in those with AIDS. The addition of IV methotrexate and citrovorum may extend survival to a median of 3.5 years. If radiation is added to methotrexate, median survival may increase beyond 4 years. However, radiation is not recommended in conjunction with methotrexate because of increased risk of leukoencephalopathy and dementia in patients older than 60 years of age^[8].

References

1. ^ Fine HA, Mayer RJ. Primary central nervous system lymphoma. Ann Intern Med 1993; 119(11):1093-1104
2. ^ Eby NL, Grufferman S, Flannelly CM, Schold SC, Jr., Vogel FS, Burger PC. Increasing incidence of primary brain lymphoma in the US. Cancer 1988;62(11):2461-2465
3. ^ Corn BW, Marcus SM, Topham A, Hauck W, Curran WJ, Jr. Will primary central nervous system lymphoma be the most frequent brain tumor diagnosed in the year 2000? Cancer 1997;79(12):2409-2413
4. ^ Lukes RJ, Collins RD. Immunologic characterization of human malignant lymphomas. Cancer 1974;34:1488-1503
5. ^ Jellinger K, Radaskiewictz T, Slowik F. Primary malignant lymphomas of the central nervous system in man. Acta Neuropathol 1975;95-102 (suppl 6)
6. ^ Herrlinger U, Schabet M, Bitzer M, Petersen D, Krauseneck P. Primary central nervous system lymphoma: from clinical presentation to diagnosis. J Neurosurg 2000; 92:261-266
7. ^ Herrlinger U, Schabet M, Bitzer M, Petersen D, Krauseneck P. Primary central nervous system lymphoma: from clinical presentation to diagnosis.J.Neurooncol. 1999;43:219-226. (PMID: 10563426).
8. ^ Deangelis LM, Hormigo A. Treatment of primary central nervous system lymphoma. Semin Oncol 2004; 31:684-692. In AIDS patients, perhaps the most important factor with respect to treatment is the use of highly active anti-retroviral therapy (HAART), which affects the CD4+ lymphocyte population and the level of immunosuppression