Primary CNS lymphoma (PCNSL)

It often starts with new problems such as weakness, confusion, changes in behavior, seizures or blurred vision. An MRI of the brain with contrast dye (gadolinium) usually shows the first sign. A brain surgeon (neurosurgeon) then takes a small tissue sample, often with a needle guided by a 3-D scan (stereotactic biopsy). Steroids given before the biopsy can hide the lymphoma, so teams try to take the sample first.

Other tests check every part of the brain and spine area, even places with no symptoms. An eye doctor looks inside the eyes with a slit lamp, because the lymphoma can grow there. If the eyes look involved, a sample from inside the eye (vitrectomy) may be needed. When it is safe, a spinal tap (lumbar puncture) tests the spinal fluid for lymphoma cells, often with flow cytometry.

A PET-CT scan of the body checks that the lymphoma has not started somewhere else. Blood tests look at blood counts, kidney function and HIV. Kidney function matters because the main medicine, high-dose methotrexate, is too harsh for people whose kidneys work poorly. A cancer team, a neurologist and an eye doctor often work together on the diagnosis.

Treatment is built around high-dose methotrexate, a chemotherapy medicine that can reach the brain, usually combined with other medicines such as rituximab. Which medicines are added, and how strong the treatment is, depends on age, fitness and kidney function. It differs from the usual treatment (R-CHOP) for large B-cell lymphoma elsewhere in the body.

When the lymphoma responds, a second phase of treatment aims to stop it coming back. For fit people, this is usually high-dose chemotherapy followed by their own stem cells (an autologous transplant). In the MATRix/IELSG43 trial of people aged 70 or younger, this worked better than more standard-dose chemotherapy. Whole-brain radiation is used much less than it was, because it can cause memory and thinking problems years later, especially after age 60. For people who cannot have a transplant, lower-dose radiation, more chemotherapy or no further treatment are weighed for each person.

If the lymphoma comes back, treatment depends on earlier treatment, how long the remission lasted and fitness. Options include more chemotherapy that reaches the brain, an own-cell transplant if there was none before, medicines such as ibrutinib or lenalidomide with rituximab, radiation, or a clinical trial. CAR-T cell therapy has been used in small studies; the evidence is still limited. A donor (allogeneic) transplant is not routine care for this lymphoma.

Primary CNS lymphoma is a serious cancer, but outlook has improved. In U.S. cancer registries, the share of people alive five years after diagnosis rose from about 28% in the late 1970s to about 45% in 2010–2017. Results are lower for people aged 60 and older: about 30% were alive five years later in the 2010s.

The NCI names older age and HIV infection as the factors that matter most. Others include a high LDH level, high protein in the spinal fluid and lymphoma deep in the brain. Fitness matters too, because it decides how strong a treatment a person can safely have.

For people up to about age 70 whose lymphoma responds, high-dose chemotherapy followed by their own stem cells has improved survival in a trial. European transplant guidelines say it can also be done in some fit older adults. Survivors may still need help with memory, movement or vision. Rehabilitation can be part of recovery.