Methotrexate, a common arthritis drug, can rarely trigger a lymphoma-type growth in the brain’s protective covering, and stopping the drug may be enough to shrink it. According to research reviewed by Gram, one 77-year-old woman’s dural thickening and lung lesions both regressed two months after she stopped methotrexate.
Methotrexate is a long-used medicine for rheumatoid arthritis that can, in rare cases, raise the risk of a type of lymphoma. A new case report describes a 77-year-old woman who took the drug for 20 years and developed a growth in the protective covering of her brain. Doctors confirmed the diagnosis with a small tissue sample from that covering. Two months after she stopped methotrexate, follow-up scans showed that both the brain thickening and spots in her lungs had shrunk. According to research reviewed by Gram, the case suggests that stopping the drug may be an important first step when this side effect appears. The report also shows that scans alone may not be enough, and a tissue biopsy can be critical for an accurate diagnosis. Because this involves only one patient, it cannot show how common the problem is.
Key Statistics
A 2026 case report in the NMC Case Report Journal described one 77-year-old woman who developed a lymphoma-type growth in the covering of her brain after 20 years of oral methotrexate for rheumatoid arthritis.
Two months after methotrexate was discontinued, follow-up brain MRI in that 2026 case report showed regression of both the dural thickening and the pulmonary lesions.
The Quick Take
- What they studied: Can long-term methotrexate use, a common arthritis drug, cause a lymphoma-type growth in the thin layer covering the brain, and does stopping the drug help?
- Who participated: One woman, age 77, who had taken oral methotrexate for rheumatoid arthritis for 20 years and was referred for worsening thickening of the brain’s outer covering.
- Key finding: A brain biopsy confirmed a lymphoma-type growth caused by methotrexate. Two months after stopping the drug, follow-up scans showed the brain thickening and lung spots had both shrunk. Because this is a single patient, the result shows what happened in one case rather than how often it happens.
- What it means for you: If you take methotrexate and notice new symptoms such as headaches, confusion, or unexplained lung problems, contact your doctor promptly. Do not stop or change your medicine on your own, because your doctor needs to weigh the risks and benefits for you.
The Research Details
This is a case report, which describes the medical history, test results, and outcome of a single patient. Case reports are often the first way doctors notice unusual side effects of a medicine. They tell a detailed story but cannot prove that one thing caused another across a population.
The patient had taken methotrexate by mouth for about 20 years to control rheumatoid arthritis, an inflammatory joint disease. When she developed progressive thickening of the dura, the tough membrane that wraps the brain, doctors ordered a contrast-enhanced MRI. The scan showed strong brightness in the thickened area over the front of the brain, which is a pattern that can look like several different conditions.
Because scans alone could not settle the question, the team performed a small surgical opening in the skull, called a craniotomy, to take a sample of the thickened membrane. Lab analysis identified mucosa-associated lymphoid tissue lymphoma, a slow-growing type of lymphoma. Doctors then stopped methotrexate and tracked the patient with follow-up imaging.
Describing a rare complication in detail helps other doctors recognize it sooner. The authors highlight that brain involvement of this condition is very uncommon, and most reported cases involve growths within brain tissue rather than the outer covering. Documenting a case where the covering was affected helps widen awareness.
The follow-up scans are especially useful. They show that the changes improved after the drug was stopped, which supports the idea that early recognition and stopping the medicine can matter.
This report is clearly documented, with imaging, a tissue biopsy, and follow-up results all described. A confirmed tissue diagnosis strengthens the conclusion that the growth was real and was linked to the drug.
However, a single case cannot establish cause and effect with certainty. Other factors, including the underlying arthritis or other medicines, may have played a role. Readers should treat this as a careful clinical observation, not as proof of how often the problem occurs.
What the Results Show
The main finding is that a 77-year-old woman who had taken methotrexate for 20 years developed thickening of the membrane covering the front of her brain. Contrast MRI showed strong enhancement in that area, meaning the affected tissue lit up brightly after a dye was given, which can signal inflammation or abnormal growth.
A small biopsy of the membrane showed mucosa-associated lymphoid tissue lymphoma. This confirmed the diagnosis of methotrexate-associated lymphoproliferative disorder, a condition in which the drug triggers abnormal growth of immune cells. The authors note that the scans alone were not enough to make this diagnosis.
After methotrexate was stopped, follow-up MRI about two months later showed that the brain thickening had regressed. Spots in the lungs, which were also linked to the condition, had improved as well. This matches the broader pattern in which this condition often gets better once the drug is discontinued.
The case highlights that this complication can affect the brain covering alone, without involving brain tissue itself. Earlier reports mostly described growths inside brain tissue, so this pattern is less familiar to clinicians.
The finding that lung lesions also improved suggests that the drug-related growth was affecting more than one part of the body, and that stopping the medicine treated the problem across sites.
Methotrexate has been linked to lymphoma since the early 1990s, and the authors note that brain involvement is considered rare. This report fits with earlier reports showing that these growths often shrink when methotrexate is stopped alone, without chemotherapy in many cases. It adds a less common location, the dural covering, to the list of known patterns.
The biggest limitation is the sample size: only one patient is described, so the results cannot be generalized. The follow-up period was short, about two months, so long-term outcomes are not known. Because the patient had rheumatoid arthritis, it can be hard to separate the effects of the disease from the effects of the drug. The report also does not show how often this complication happens among people taking methotrexate.
The Bottom Line
Based on this single case and the broader pattern the authors describe, doctors should consider methotrexate-related lymphoma when people on long-term treatment develop new brain or lung changes. Early recognition and prompt discontinuation of the drug, under medical supervision, appear to be important steps. Confidence is moderate for the general principle of early recognition and low for any specific rate or outcome, because the evidence comes from one patient.
People taking methotrexate for arthritis, psoriasis, or other conditions, along with their families and the clinicians who prescribe it, should find this useful. People who have never taken methotrexate will likely find it less relevant. Anyone on the drug should keep taking it as prescribed unless their doctor advises a change.
In this case, the brain and lung changes improved within about two months after methotrexate was stopped. Outcomes will vary from person to person, and some people may need further treatment. Anyone with new symptoms should speak with a doctor right away rather than waiting to see whether they improve.
Frequently Asked Questions
Can methotrexate cause lymphoma in the brain?
Rarely, yes. A 2026 case report described one 77-year-old woman who developed a lymphoma-type growth in the brain’s outer covering after 20 years of methotrexate. Brain involvement is considered uncommon, and most reported cases involve brain tissue itself.
What happens if you stop methotrexate after developing lymphoma?
In the reported case, both the brain thickening and lung lesions improved about two months after methotrexate was stopped. Many methotrexate-related lymphomas regress after the drug is discontinued alone, but any change should be managed with your doctor.
What symptoms should I watch for while taking methotrexate?
Contact your doctor about new headaches, confusion, persistent cough, shortness of breath, or unexplained swelling or fatigue. The reported case involved gradual brain thickening detected on MRI, so new neurological or lung symptoms warrant prompt medical evaluation.
Is a brain scan enough to diagnose methotrexate-related lymphoma?
Not always. In the 2026 case report, imaging alone was insufficient, and a small tissue biopsy of the dura confirmed mucosa-associated lymphoid tissue lymphoma. Biopsy was essential for establishing the diagnosis.
Want to Apply This Research?
- Log each methotrexate dose with the date and time taken, and record any new headaches, confusion, cough, shortness of breath, or unusual fatigue on a 1 to 5 severity scale. Note the date of each lab test and imaging result so you can review changes with your doctor.
- Set a weekly reminder to check your symptom log and to take your methotrexate on the schedule your doctor prescribed. If a new symptom appears, use the app to flag it and send a summary to your care team instead of waiting for your next appointment.
- Review your symptom and dose log with your rheumatologist at each scheduled visit, and keep a running list of any imaging or biopsy results. Over the long term, a consistent record makes it easier to spot patterns early and to share accurate information with your healthcare team.
This article summarizes a single-patient case report and is for general information only. It is not medical advice and cannot establish how often this condition occurs. Do not stop, start, or change methotrexate or any other medicine without talking to your doctor, and seek urgent care for new or worsening symptoms.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.