Primary CNS Lymphoma (PCNSL)

Related Subjects: | Hodgkin Lymphoma | Non Hodgkin Lymphoma | Diffuse large B-cell lymphoma | Intravascular large B-cell lymphoma | Mantle cell lymphoma | Marginal Zone Lymphoma | Gastric (MALT) Lymphoma | Primary CNS Lymphoma (PCNSL) | Burkitt's lymphoma | Follicular Lymphoma

A late complication of HIV infection and associated with EBV virus.

About

• A rare form of extranodal non-Hodgkin B-cell (90%) lymphoma
• Usually confined to the brain, eyes, and CSF without evidence of systemic spread
• Increased with HIV infection - AIDS when CD4 count < 50 cells/microlitre

Aetiology

• High-grade B cell Lymphomas predominantly
• T cell Lymphomas of CNS very rare
• May be a role for the EBV virus in immunosuppressed

Epidemiology

• Can develop in immunosuppressed (HIV/AIDS, organ transplant, immunosuppressive agents) or immunocompetent patients

Location

• Cerebrum, cerebellum, brainstem
• Solitary or multifocal often periventricular
• Can invade cranial nerves
• Pink grey infiltrate mass highly cellular
• Grows around and into blood vessels - angiocentric
• May extend along the optic nerve to the eyes

Risks

• AIDS and low CD4
• Immunosuppressive drugs e.g. organ transplant
• Wiskott Aldrich syndrome, Ataxia telangiectasia

Clinical - also See Brain tumours

• Progressive CNS symptoms come on over weeks
• Disease may extend into the eyes so slit-lamp examination important

Differential

• Toxoplasmosis in AIDS

Investigations

• FBC, U&E, HIV test and CD4 count and viral load
• CT/MRI: one or more dense periventricular enhancing masses. May be ring-like enhancement. Vasogenic oedema. Lesions improve markedly with steroids. It is usually a homogenously enhancing mass lesion, most often a single brain lesion (66%), with a supratentorial location (87%) and involvement of the frontoparietal lobes (39%). Diffusion-weighted imaging (DWI) demonstrates restricted diffusion within the tumour.
• CSF - may show increase in WCC. Monoclonal lymphocytes. Increased B2 microglobulin. Epstein bar virus PCR for DNA in CSF is a very strong indicator of primary cerebral lymphoma. With mass effect, an LP may be unsafe.
• Stereotactic needle biopsy
• To detect the presence of non-CNS disease, a body PET CT and bone marrow biopsy should be performed.

Differential of Butterfly tumour across the Corpus: pre and post contrast

• High grade Astrocytoma, usually a Glioblastoma (WHO grade IV)
• Primary CNS lymphoma (consider HIV)
• Cerebral Toxoplasmosis (consider HIV)

Management

• Unlike other tumours PCNSL often has a favourable response to both chemotherapy and radiation therapy, but compared with lymphomas outside the CNS, survival is usually inferior. Main treatment is high-dose methotrexate (HD-MTX) and may include other chemotherapeutic agents with and without radiation
• Once tumour confirmed they are not typically resectable as deep and multicentric unless they are causing life-threatening mass effect where debulking may be done. Cranial irradiation and steroids can give partial or better results
• The role of surgery in PCNSL is generally restricted to stereotactic biopsy due to widespread and diffusely infiltrative tumor growth. No survival benefit from subtotal or gross total resection has been observed in retrospective studies
• Intrathecal chemotherapy e.g. methotrexate can increase median survival to 3 years but not without side effects.
• Rituximab may be given prior to this. Rituximab is a monoclonal antibody directed against the B-cell surface antigen CD20
• Trial of antimicrobials and HAART if Toxoplasmosis suspected in a patient with AIDS.

References

• Primary CNS Lymphoma Review