Biopsy-proven tumefactive demyelinating lesions: a systematic review and meta-analysis

A tumefactive demyelinating lesion (TDL) is an area of pathological changes in the central nervous system consistent with demyelination, larger than 2 cm, and can mimic tumors on imaging; hence the term "tumefactive." TDLs are often challenging, as they have been reported in isolation or in conjunction with demyelinating diseases.

To describe the clinical and radiological features of TDLs, explore the treatments used and outcomes, and describe different nomenclatures reported.

We followed PRISMA guidelines, and our protocol was registered on PROSPERO [CRD42024593078]. We searched PubMed, Web of Science, EMBASE, and Google Scholar. We included published cases with TDL (> 2 cm) on magnetic resonance imaging (MRI) in patients aged ≥ 18 years. We excluded a priori any established diagnoses of the lesions other than TDLs, cases without biopsy confirmation of demyelination, and cases lacking relevant data. The study framework is exploratory and descriptive in nature, and analyses are taken as hypothesis-generating. Comprehensive Meta-Analysis V3.0 was used for meta-analyses.

We examined 112 cases from 51 publications. The average age was 41.5 years, with women representing 54% of patients. MRI revealed solitary lesions in 65% of cases, mainly in the frontal (35%) and parietal (28%) lobes, with a mean lesion size of 4.25 ± 1.32 cm. CSF analysis showed oligoclonal bands in 20% of cases. The meta-analysis demonstrated a 72% pooled response rate to intravenous methylprednisolone (IVMP) (95% CI: 57.9% - 83.2%, p < 0.01), with moderate heterogeneity (I² = 62.4%), which should be interpreted cautiously given the small number of contributing studies. Subgroup analysis revealed no meaningful differences between nomenclatures. Publication bias assessments were exploratory and suggested potential bias, and that the observed variability may reflect study-level and reporting differences rather than disease-related effects.

Acute IVMP treatment had a high response rate and similar use rate. Despite variations in nomenclature and presentation, the broader pathological and clinical features, as well as the response to IVMP in TDLs, appear broadly similar across studies, acknowledging the methodological limitations of the available literature. Our study was also limited by the small sample due to the rarity of the condition.