Primary CNS Lymphoma

Primary CNS lymphoma is a rare type of cancer that occurs in the brain, spinal cord, or eyes without having spread to the brain from elsewhere in the body. The most important difference from other brain tumors is that it responds very well to drug (chemotherapy) treatment; therefore, it is not removed surgically, but only a tissue sample is obtained for diagnosis. It is most commonly seen in immunocompromised individuals and healthy people over 60 years of age. With modern treatments, the disease can be controlled in many patients, and complete remission is possible in some.

It is seen in two main groups: (1) Immunocompromised individuals - those with organ transplants, those taking immunosuppressive medications, and those with conditions that weaken the immune system. In this group, it can occur at a younger age and progress more rapidly. (2) Immunocompetent individuals, mostly over 60 years of age - the most commonly affected group. In immunocompromised individuals, a viral infection (Epstein-Barr virus) is associated with increased risk. Hereditary or familial risk has not been clearly demonstrated.

Diagnostic methods include: (1) Contrast-enhanced brain MRI - masses that enhance prominently in the deep brain regions are typical; (2) Tissue sample (biopsy) - mandatory for definitive diagnosis and must be obtained BEFORE starting corticosteroids, as these drugs can shrink the tumor and mislead diagnosis; (3) Ophthalmologic examination - to investigate ocular involvement; (4) Lumbar puncture - to examine cerebrospinal fluid; (5) Whole-body imaging (PET-CT) - to determine if lymphoma exists elsewhere in the body; (6) HIV testing. On tissue examination, a specific type of lymphoma (B-cell lymphoma) is most commonly seen.

No, the tumor is not removed surgically; only a small tissue sample is obtained for diagnosis. There are three main reasons for this: (1) The tumor responds very well to drug (chemotherapy) treatment; (2) The tumor is typically located in the deep brain regions and frequently presents as multiple foci, making surgical resection difficult and risky; (3) Studies show that removing the tumor does not contribute additional survival benefit. Usually, obtaining tissue through a closed technique (with a thin needle through a small opening) is sufficient. Chemotherapy is initiated directly after diagnosis is confirmed.

Methotrexate is one of the most effective drugs for this lymphoma and can reach the brain. It is given intravenously at high doses. To prevent kidney strain, abundant fluids and protective medications are administered before and after each course. It is typically given in several courses, every two to three weeks, often combined with rituximab. Possible side effects include: kidney involvement (which is why kidney values are closely monitored), mouth sores, decreased blood counts (increased infection risk), and elevated liver values. It is generally well tolerated in younger patients; dose adjustments may be needed in older age.

This transplantation (autologous stem cell transplantation) is a consolidation treatment applied in young and otherwise healthy patients after achieving good response with initial chemotherapy to make the outcome more durable. The process proceeds as follows: first, the tumor is reduced with chemotherapy, then the patient's own stem cells are collected, followed by intense chemotherapy, and the collected stem cells are reinfused. This method can improve long-term outcomes; however, it carries risks such as infection and organ involvement. It is not suitable for older patients or those with comorbidities; in these patients, low-dose radiation therapy is preferred for consolidation.

Yes, brain radiation (radiotherapy) treatment can be used for consolidation, especially in older patients where transplantation is not feasible. However, its use has decreased today because it may have long-term effects on the nervous system. Short-term effects may include fatigue, headache, and hair loss. Long-term effects (months-years later) may include cognitive impairment, gait disturbance, and urinary incontinence. For this reason, stem cell transplantation is preferred over radiation in younger patients; radiation therapy is more often used at low doses in recurrent disease or when transplantation is not feasible.

There is a high likelihood of recurrence in this lymphoma; a significant proportion of patients may experience recurrence within a few years. Recurrent disease treatment is planned based on the patient's general condition, previous treatment, and timing of recurrence. Options include: (1) Repeated chemotherapy - repetition of methotrexate-containing treatment or other drugs; (2) Oral targeted drugs - generally well tolerated; (3) Drug combinations; (4) Radiation therapy if not previously given; (5) Some novel treatments may be available in research protocols. Although recurrent disease is more challenging, promising results are being obtained with new targeted therapies.

Yes, lymphoma in immunocompromised individuals has different characteristics: it can occur at a younger age, may progress more rapidly, and frequently presents as multiple foci. Treatment includes: (1) Treatment addressing the underlying cause of immunosuppression is mandatory (for example, if HIV is present, appropriate antiretroviral therapy is initiated, which strengthens immunity and improves treatment response); (2) Methotrexate-based chemotherapy is given, although dose adjustments may be necessary; (3) Prophylactic medications are used to prevent infections. With advances in immunity-enhancing treatments, the course of these patients has improved significantly.

Supportive treatments include: (1) Corticosteroids to reduce brain edema - however, they must NOT be used BEFORE tissue sampling for diagnosis, as they shrink the tumor and complicate diagnosis; (2) Seizure medications in patients with seizures; (3) Gastroprotective medications; (4) Prophylactic antibiotics and antifungal medications when needed to prevent infections; (5) Bone marrow-supporting medications when blood counts drop; (6) Protective medications for kidney preservation following methotrexate and abundant hydration. Blood counts, kidney, and liver function are closely monitored throughout treatment. Signs of infection such as fever require immediate evaluation.