Lymphoma, Primary CNS (PCNSL)
Mark Levis, M.D., Ph.D. and Nina Wagner, M.D.
- Incidence/prevalence of PCNSL in Africa is uncertain; cases occasionally reported from S. Africa where more expensive testing modalities more broadly available.
- In S. Africa, quantitative PCR for EBV DNA in CSF improves diagnostic specificity, though low positive predictive value precludes its use as an isolated marker for PCNSL.
- Dx in Zambia difficult without CSF PCR studies or brain imaging (CT or MRI); largely a Dx of exclusion made after failure of treatment for CNS toxoplasmosis ± CNS TB.
- Prognosis likely poor, but ART warranted.
Zambia Information Author: David Riedel, M.D.
EBV infection present in virtually 100% of HIV-associated PCNSL
- Absence of EBV-specific CD4+ T cell function may provide an immunological basis for HIV-associated PCNSL
- Late manifestation of disease, associated with CD4 < 50 (therefore, rarely an AIDS-defining illness).
- Incidence declining precipitously since advent of ART.
- Presents with variety of focal and non-focal neurological signs and Sx. In contrast to PCNSL in non-AIDS population, is often associated with B Sx.
- Histology is immunoblastic, high-grade B cell.
- Staging not necessary, as disease remains confined to CNS.
- Bx remains gold standard, but not always necessary for Dx. PCR for EBV DNA in CSF helpful in establishing Dx (see below).
- Enhancing lesions on CT or MRI (higher yield) generally have DDx of PCNSL vs.CNS toxoplasmosis. Radiographic features characteristic of PCNSL include 1) larger lesions; 2) multifocal lesions; 3) lesions involving corpus callosum; 4) inhomogenous enhancement (reflecting rapid growth rate with necrosis); 5) rarely involve posterior fossa.
- Thallium-201 SPECT or PET scans can be used to demonstrate metabolically hyperactive lesion.
- CSF cytology for neoplastic cells occasionally positive.
- In appropriate clinical setting of low CD4, Toxoplasma seronegativity, large or multifocal hyperenhancing radiographic CNS lesions, and no response to 10-14 days of toxoplasmosis treatment, PCR for EBV DNA in the CSF has high sensitivity and specificity for Dx of PCNSL, often precluding need for Bx.
- Outcome data limited in post-ART era, since incidence of HIV-related PCNSL has dropped dramatically.
- In absence of ART, med. survival 1-3 mos, and usually not improved with chemotherapy or radiation therapy (XRT).
- With ART (and chemotherapy/XRT), overall prognosis still poor (probably 12 to 18 mos), but long-term survival more common.
- Optimal treatment not yet defined.
- Initiation of ART essential for any chance of long-term survival.
- High-dose methotrexate (3-8 grams/m2 IV with leucovorin rescue beginning 24 hrs later) is current treatment of choice.
- Whole brain radiation with concomitant corticosteroids also effective.