When Lymphoma Is Confused with Multiple Sclerosis

by Lisa Emrich Patient Advocate

Diagnosing multiple sclerosis is not as easy as undergoing an MRI scan and having a neurologist watch you walk; instead, it is a challenging process, and neurologists want to get it right. One thing that was considered even before I underwent MRI scans in 2000 for optic neuritis was the possibility of a brain tumor. It turned out not to be a tumor, but I wasn’t diagnosed with MS at the time, either. Over the years, several patients have reported similar “not a brain tumor” diagnoses when telling their MS stories.

Can a brain tumor be confused with MS?

An extremely rare form of multiple sclerosis, called tumefactive MS, involves brain lesions that look like tumors. These lesions are usually larger and more aggressive than normal MS lesions. Treatment usually begins with high-dose intravenous corticosteroids (e.g., Solumedrol) followed by disease-modifying therapies for MS and symptomatic treatments.

In a recent study, researchers investigated the unusual concurrence of MS and brain tumors. They point out, however, that it is difficult to determine whether brain tumors in MS are more common than in the general population. People with MS undergo more MRI scans than healthy individuals, thus the diagnosis of brain tumors in MS patients may appear to be more frequent (Platone et al. 2015). But not all cancer-related brain tumors appear large; they can also look like multi-focal enhancing white matter lesions which are the hallmark of MS.

Can MS be confused with lymphoma?

Absolutely, multiple sclerosis can be confused with lymphoma. In a recent case study, the MRI scans of a 57-year-old woman with unusual symptoms showed multi-focal enhancing white matter lesions that looked similar to MS under a microscope after a brain biopsy. Despite responding well to treatment with corticosteroids and rituximab for a presumed case of tumefactive MS, the woman got worse. Doctors repeated the brain biopsy six months later and diagnosed diffuse large B-cell lymphoma, a form of cancer (Kvarta et al. 2016).

Primary central nervous system lymphomas (PCNSL) are rare and account for less than one percent of all brain tumors. PCNSLs are most frequently diffuse large B-cell non-Hodgkin lymphomas and affect patients at a median age of 60. An early warning sign of PCNSLs may be inflammatory demyelinating brain lesions that mimic MS. Diagnosis can be a challenge due to the overlapping radiologic and clinical characteristics.

Signs that point to PCNSL rather than MS

Kvarta et al. (2016) examined the literature and found 16 cases where patients were initially diagnosed with demyelinating disease and later diagnosed with CNS lymphoma, on average two years later. Most of these patients were female (3:1) with an average age of 46.2 years (range: 20-65), and all patients responded to steroids. The most common signs and symptoms included hemiparesis (weakness or paralysis affecting one side of the body), visual symptoms (double vision, visual field defect, nystagmus), cognitive issues (memory problems, lack of concentration, confusion), and ataxia or gait disturbance. Each of these symptoms is common in MS.

In studying the cases, researchers identified some “red flags” that should raise clinical suspicion for PCNSL in patients who have white matter lesions:

  • Clinical: Middle to older age with no prior clinical episodes or radiographic lesions suggestive of MS; rapidly deteriorating disease course; steroid dependence; lack of spinal cord involvement

  • Imaging: Increased enhancement or lesion size over time; disproportionate mass effect (the effect of the growing mass on surrounding tissues)

  • Cerebrospinal fluid: Abnormal protein cells, including oligoclonal bands, a sign of nerve damage

If your doctor suspects MS, but seems reluctant to make a diagnosis, please remember that misdiagnosis is all too common in MS. It is much better for your doctor to carefully consider all possibilities, no matter how rare some of them may be, when making a diagnosis. Your health and well-being may depend upon it.


Kvarta MD, Sharma D, et al. Demyelination as a harbinger of lymphoma: a case report and review of primary central nervous system lymphoma preceded by multifocal sentinel demyelination. BMC Neurol. 2016;16:72. Published online 2016 May 21. doi: 10.1186/s12883-016-0596-1

Plantone D, Renna R, Sbardella E, Koudriavtseva T. Concurrence of Multiple Sclerosis and Brain Tumors. Frontiers in Neurology. 2015;6:40. doi:10.3389/fneur.2015.00040.

Lisa Emrich
Meet Our Writer
Lisa Emrich

Living with multiple sclerosis and rheumatoid Arthritis, Lisa Emrich is an award-winning, passionate patient advocate, health writer, classical musician, and backroad cyclist. Her stories inspire others to live better and stay active. Lisa is author of the blog Brass and Ivory: Life with MS and RA and founder of the Carnival of MS Bloggers. Lisa frequently works with organizations in support of better policies, patient-centered research, and research funding. Lisa serves on HealthCentral’s Health Advocates Advisory Board, and is a Social Ambassador for the MSHealthCentral Facebook page.