Diffuse Infiltrative Non-mass-like Brain Parenchymal Lesions on MRI: Differentiating Lymphomatosis Cerebri from its Mimics

Abstract

Objectives: Diffuse infiltrative “non-mass-like” parenchymal lesions on MRI brain are a known presentation of an aggressive condition called lymphomatosis cerebri (LC) but are often misdiagnosed due to its non-specific clinical and imaging findings. We aim to identify clues to differentiate lymphomatosis from its less aggressive mimics based on imaging features. Material and Methods: MRI brain studies showing diffuse infiltrative “non-mass-like” parenchymal lesions between January 2013 and March 2020 were retrospectively identified and read for lesion location, signal characteristics, and enhancement pattern by two radiologists. Additional findings on MRI spine and whole-body fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) were recorded wherever available. The clinical diagnosis, patient demographics, symptoms, laboratory and histopathology results, treatment details, and follow-up details were also noted. Results: Of the 67 patients, 28 (41.7%) were diagnosed with lymphomatosis. The remaining 39 (13.4%) patients were classified as non-lymphomas (infective, vasculitis, and inflammatory conditions). Diffusion restriction on MRI (20/67, P = 0.007) and increased regional activity on FDG PET-CT (12/31, P = 0.017) were the two imaging parameters found to significantly favor lymphomatosis over other conditions, whereas the presence of microhemorrhages on susceptibility-weighted imaging was significantly associated with vasculitis (P = 0.002). Rapid clinical or imaging deterioration on a short trial of steroids (P = 0.00) was the only relevant clinical factor to raise an early alarm of lymphomatosis. Positive serological markers and non-central nervous system systemic diseases were associated with non-lymphomatous diseases. Conclusion: LC and its less aggressive mimics can be differentiated on diffusion-weighted imaging-MRI and PET-CT when read in conjunction with rapid progression of clinical features, serological workup, and systemic evaluation.

A very rare cause of leukoencephalopathy: Lymphomatosis cerebri

“…Initial FGD-PET was not relevant for pathologic accumulation of radiotracer within the brain (data not shown). 1 H-MRS revealed increased Cho/ Naa and Cho/cr ratios with reduced NAA absolute peak levels (Figure 1, f). We suspected a brain tumor and performed a brain biopsy.…”

“…A long list of different diseases such as vascular diseases, immune-mediated disorders, infections, neurodegenerative, dysmetabolic patterns, and myelin-dystrophic diseases may underlie such a condition. Although rare, lymphomatosis cerebri (LC) may be indistinguishable from other less aggressive and more frequent conditions responsible for diffuse leukoencephalopathy at an initial brain MRI assessment (1). Clinical presentation might not help in the orientation of the diagnostic work-up, as initial symptoms may include subacute cognitive impairment, focal motor deficits, movement disorders, and incoordination.…”

“…Such behaviour, although frequent, should be avoided when suspecting a brain LC unless necessary as a lifesaving therapy. Steroids may delay diagnosis and selection of resistant clones (1). Accurate microscopic analysis of specimens and immunohistochemical studies later revealed the presence of LC and allowed the application of internationally accepted therapeutic protocols.…”

“…Sugie et al (4) demonstrated that PNCSL may initially present as diffuse leukoencephalopathy without any T1W contrastenhancing nodular lesions on brain MRI, thus resembling the imaging features of LC. As a result, the brain imaging of LC may give rise to dangerous misdiagnosis, as it is not specific of any disease (1).…”

Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions

“…MR perfusion and MR spectroscopy may be non-contributory, and a brain biopsy may be required for definitive diagnosis. Changes in DWI may give clues to the diagnosis of lymphomatosis cerebri ( 107 ). Unmyelinated white matter beyond 2 years of age is not an uncommon finding, and these terminal zones of myelination are an important mimic to be considered ( 108 ).…”