A rare cancer where lymphoma cells develop in the brain or spine. It starts in the central nervous system, not elsewhere in the body.
What is CNS lymphoma?
CNS lymphoma, or primary CNS lymphoma, is a rare type of cancer that affects your central nervous system (CNS). It occurs when cancerous lymphocytes develop in the brain, spinal cord, eyes, or leptomeninges (the membranes covering the brain and spinal cord). It is a non-Hodgkin lymphoma. Unlike lymphoma that spreads to the brain from other parts of the body, primary CNS lymphoma originates within the central nervous system.
The American Brain Tumor Association states that CNS lymphoma is very rare and accounts for 1 to 2% of non-Hodgkin lymphoma cases. The most significant risk for developing CNS lymphoma is a compromised or weakened immune system and advanced age.
Why choose AHN for your CNS lymphoma treatment?
Our highly experienced team of neuro-oncologists (brain cancer specialists) and neurosurgeons (brain surgeons) performs treatments that are only available at the very best hospitals in the country. By choosing AHN for your care, you will find:
- Improved survival rates: We use aggressive treatments while making sure you are feeling as well as you can. Helping you live a longer, more comfortable life is our priority.
- Advanced technology: Sophisticated tools, such as ChemoID®* and genome analysis, allow us to understand how the tumor will respond to different treatments before we prescribe them. At AHN, our goal is to tailor treatments that will be the most effective for your specific case.
- Minimally invasive treatments: Many of our treatment options are outpatient procedures that involve a short recovery time. Instead of spending all your time in a hospital, you can live your life and be surrounded by your support system.
- A collaborative approach: We discuss all our patients in a weekly meeting with our brain cancer experts. You benefit from the combined experience of a team that includes neuro-oncologists, radiation oncologists, neurosurgeons, medical oncologists, and neuroradiologists. Because we are always up to date on your progress, we are able to give you the best possible care.
- Robust support: We invite all patients with brain cancer to join our weekly support group to share feelings, discuss symptoms, and help one another cope. It may help you feel better during treatment and experience an improved state of mind.
- A convenient, after-hours cancer clinic: If you experience side effects from treatment, call your physician’s office first, then visit our After Hours Oncology Clinic, conveniently located at West Penn Hospital. We treat you quickly, without exposing your compromised immune system to the germs you may encounter at a traditional emergency room. Plus, our clinic is more affordable than a visit to the ER. And since our oncology specialists have access to your records, they may even be able to advise you over the phone and save you from making a trip.
- Clinical trials: If you meet the eligibility requirements, you may be able to participate in an experimental clinical trial. You could gain access to a groundbreaking treatment before it is widely available. Learn more about our clinical trial program.
CNS lymphoma symptoms and signs
Given the diverse locations where CNS lymphoma can manifest within the central nervous system, its symptoms can be highly varied and depend on the exact area affected. The symptoms often develop gradually and can mimic those of other neurological conditions. General symptoms and signs of CNS lymphoma include:
- Headaches: Often persistent, worsening over time, and not relieved by typical painkillers. They may be worse in the morning.
- Nausea and vomiting: Especially if accompanied by headaches, indicating increased pressure within the skull.
- Seizures: Can be generalized (affecting the whole body) or focal (affecting a specific part) and is a common symptom.
There are other symptoms and signs that can affect different parts of the body. These include cognitive changes such as:
- Memory loss: Difficulty remembering recent events or learning new information.
- Confusion or disorientation: Difficulty concentrating or processing information.
- Personality changes: Irritability, apathy, or changes in behavior.
- Difficulty with executive functions: Problems with planning, problem-solving, or decision-making.
- Fatigue: Unusual and persistent tiredness.
- Changes in mood or behavior: Depression, anxiety, or uncharacteristic emotional responses.
Causes and risk factors
Unlike many cancers where a clear, single cause is identified (e.g., smoking for lung cancer), CNS lymphoma does not have one definitive cause. Instead, it's understood to develop from a complex interplay of genetic, environmental, and immunological factors. The strongest established links are with impaired immune function and advanced age.
For a significant number of individuals who develop PCNSL, especially those who are immunocompetent (have a healthy immune system), the exact cause remains unknown. In these cases, it's considered "idiopathic." It's believed that a combination of subtle genetic predispositions and unknown environmental triggers might contribute.
The main risk factor for developing CNS lymphoma is a compromised immune system. There are certain health conditions that can cause a weakened or compromised immune system that can indicate a risk factor for CNS lymphoma. These include:
- HIV or AIDS
- Organ transplant recipients
- Autoimmune diseases and immunosuppressive therapies
- Epstein-Barr virus
CNS lymphoma screening and diagnosis
There is no routine screening for CNS lymphoma in the general population. People at higher risk due to immune deficiencies may undergo more frequent neurological evaluations, but there are no specific screening tests.
When CNS lymphoma is suspected, a thorough diagnostic workup is crucial, involving a combination of imaging, pathological examination, and sometimes other specialized tests. The goal is to not only confirm the diagnosis but also to rule out other conditions that can mimic PCNSL (e.g., toxoplasmosis, glioblastoma, metastatic cancer, infection, or other inflammatory conditions). Most often the diagnostic overview can include:
- Neurological examination: A detailed assessment of neurological function, including mental status, cranial nerves, motor strength, sensory perception, reflexes, and coordination. This helps localize the area of the brain or spinal cord affected and guides further imaging.
- Imaging studies: These can include an MRI or CT scan to get detailed images of the area of concern.
- Biopsy: A tissue biopsy is absolutely critical to confirm CNS lymphoma and differentiate it from other conditions.
- Cerebrospinal fluid (CSF) analysis (lumbar puncture): This checks for the presence of lymphoma cells in the fluid surrounding the brain and spinal cord (leptomeningeal involvement).
Types and stages of CNS lymphoma
CNS lymphoma types primarily refer how the lymphoma cells look under a microscope and their molecular characteristics. The vast majority (over 90 – 95%) of CNS lymphoma cases are B-cell non-Hodgkin lymphomas.
Unlike most systemic cancers, PCNSL does not follow the traditional TNM (Tumor, Node, Metastasis) staging system used for solid tumors, nor does it typically use the Ann Arbor staging system for systemic lymphomas. This is because PCNSL is, by definition, confined to the CNS at diagnosis, and its spread patterns are different. There are different evaluations that are done to determine the extent of CNS. These often include:
- Comprehensive neuroimaging: This may include an MRI of the brain or spine to detect lesions.
- Cerebrospinal fluid analysis: To check for the presence of malignant lymphoma cells in the CSF. If present, this indicates leptomeningeal involvement, which is a key factor in risk assessment and treatment planning.
- Ocular examination: This exam checks for involvement of the eyes, specifically the vitreous fluid or retina, which is considered part of the CNS for PCNSL purposes. If suspicious, a vitreous biopsy may be performed.
CNS lymphoma treatment
Treatment at AHN is tailored to you. Your AHN care team will discuss your options with you to help you feel confident in your treatment plan. We have the treatments and therapies that are at the forefront of technological advancements and pair those with supportive and comprehensive care. Some of the CNS lymphoma treatments available include:
- High-dose methotrexate-based chemotherapy: Methotrexate is a chemotherapy drug that can cross the blood-brain barrier and is a key component of treatment. Other chemotherapy drugs may be added.
- Radiation therapy: May be used to target areas of the brain or spinal cord affected by lymphoma.
- High-dose chemotherapy with autologous stem cell transplant: In some cases, particularly for younger, healthier patients, high-dose chemotherapy followed by a stem cell transplant using the patient's own stem cells may be considered.
- Targeted therapy: Drugs that target specific molecules involved in the growth and spread of lymphoma cells may be used, especially in relapsed or refractory cases.
- Clinical trials: Participation in clinical trials may be an option to access new and experimental therapies.
CNS lymphoma FAQs
Given the rarity of CNS lymphoma, a diagnosis can bring about many questions. Significant advancements in treatment options have improved curability rates. To help you understand your options and answer your specific questions, your AHN care team is here to help. Prior to meeting with your care team, many patients like to have reliable background information that can help guide their conversations. That’s why we’ve included some of our patients’ most frequently asked questions, so you can learn more about this rare condition and feel confident going into your meetings.
Is CNS lymphoma curable?
PCNSL is considered potentially curable, especially with modern, aggressive treatment regimens, although achieving a complete and durable cure can be challenging for some patients. Cure rates have significantly improved over the past few decades with advances in chemotherapy (particularly high-dose methotrexate-based regimens) and the strategic use of whole-brain radiation therapy (WBRT) or other consolidation therapies. For many patients, the goal of treatment is long-term remission, which can be equivalent to a cure. However, it's also known for its tendency to relapse, which can be more difficult to treat. Factors like age, performance status, extent of disease, and the specific treatment received influence the likelihood of achieving a cure.
What is the survival rate for primary CNS lymphoma?
The survival rate for PCNSL has improved considerably but varies significantly based on several factors, including the patient's age, overall health, specific treatment, and whether the disease relapses.
- Median overall survival (OS): Historically, without effective treatment, OS was often only a few months. With current standard therapies, the median OS for all patients (including older, frailer individuals) typically ranges from three to five years.
- Long-term survival: For younger, healthier patients (e.g., under 60 years old) who receive aggressive first-line treatment and achieve a complete response, five-year survival rates can be in the range of 40% to 60% or even higher in some studies.
Factors influencing survival:
- Age: Younger patients generally have better outcomes due to better tolerance of intensive treatments.
- Disease extent: Involvement of deep brain structures or the CSF is associated with a less favorable prognosis.
- Treatment response: Achieving a complete response to initial therapy is a strong predictor of long-term survival.
- Immunocompetence: Immunocompetent patients (those without HIV or who are not heavily immunosuppressed for other reasons) generally have better prognoses than immunocompromised patients.
How aggressive is CNS lymphoma?
PCNSL is generally considered an aggressive (high-grade) lymphoma. The most common subtype, diffuse large B-cell lymphoma (DLBCL), is known for its rapid growth and tendency to spread quickly within the central nervous system if left untreated.
- Rapid progression: Without treatment, PCNSL can progress quickly, leading to severe neurological deficits and a very short survival time (often just a few months).
- Infiltrative nature: It doesn't typically form well-defined, encapsulated tumors that can be easily removed. Instead, it often infiltrates brain tissue, making complete surgical resection difficult or impossible without causing significant neurological damage.
- Responsiveness to therapy: Despite its aggressive nature, PCNSL is often very sensitive to chemotherapy (especially high-dose methotrexate) and radiation therapy, which is why it can be highly treatable and potentially curable when caught early and treated aggressively. However, its aggressive nature also means that prompt and intensive treatment is critical to achieve good outcomes.
Contact us
To schedule an appointment or learn more about AHN neuroscience services, call 412-359-6200 in Pittsburgh or 814-452-7575 in Erie.
Second opinions
If you want a second opinion regarding a cancer diagnosis, treatment options, or prognosis, our team of oncology specialists can review your medical records at AHN. To get started, fill out our Second Opinion Request form. Our Navigation Team will contact you within the next 24 – 48 hours to discuss next steps and schedule.
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ChemoID is a registered trademark of Edwards Comprehensive Cancer Center.
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Optune is a registered trademark of Novocure.
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