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.

High-dose methotrexate-based combinations are central because they can reach the CNS. Additional medicines and the regimen’s intensity depend on age, fitness and organ function. Treatment differs from ordinary R-CHOP-based systemic lymphoma care.

For eligible patients who respond, high-dose chemotherapy followed by autologous stem cell rescue is an established consolidation option. Carefully selected radiotherapy or other consolidation approaches may be used in different circumstances, with attention to delayed neurological toxicity.

At relapse, treatment depends on previous therapy, the length of response and fitness. Options may include further CNS-active therapy, autologous transplantation if appropriate, targeted agents, radiotherapy or clinical trials. CAR-T is being used in selected specialist settings; donor stem cell transplantation is not routine CNS lymphoma treatment.

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.