A very rare cause of leukoencephalopathy: Lymphomatosis cerebri

Abstract

Leukoencephalopathy is a common finding on Magnetic Resonance Imaging (MRI), particularly in the elderly. A differential diagnosis may represent a very bet for clinicians when clear elements for diagnosis are lacking. Diffuse infiltrative "non mass like" leukoencephalopathy on MRI may represent the presentation of a very rare aggressive condition known as lymphomatosis cerebri (LC). The lack of orienting data, such as contrast enhancement on MRI or specific findings on examination of Cerebrospinal Fluid (CSF) or blood tests, may even far more complicate such a difficult diagnosis and orientate toward a less aggressive but time-losing mimic. A 69-old man initially presented to the Emergency Department (ED) complaining the recent appearance of unsteady walking, limitation of down and upgaze palsy, and hypophonia. Brain MRI revealed the presence of multiple, confluent hyperintense lesions on T2/Flair Attenuated Imaging Recovery (FLAIR) sequences involving either the withe matter of the semi-oval centres, juxtacortical structures, basal ganglia, or bilateral dentate nuclei. DWI sequences showed a wide restriction signal in the same brain regions but without any sign of contrast enhancement. Initial 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG PET) and CSF studies were not relevant. Brain MRI revealed a high choline-signal, abnormal Choline/ N-Acetyl-Aspartate (NAA), and Choline/Creatine (Cr) ratios, as well as reduced NAA levels. Finally, a brain biopsy revealed the presence of diffuse large B-cell lymphomatosis cerebri. The diagnosis of lymphomatosis cerebri remains elusive. The valorisation of brain imaging may induce clinicians to suspect such a difficult diagnosis and go through the diagnostic algorithm.

Keywords: 1H-MRS; MRI; Primary Central Nervous System lymphoma (PNCSL); leukoencephalopathy; lymphomatosis cerebri.

Figure 1.

Imaging of Lymphomatosis cerebri. Sagittal (a), coronal (b), and axial (c) FLAIR images of the brain showing diffuse high signal intensity involving deep and juxtacortical white matter, basal ganglia, dentate nuclei and cerebellar medulla. DWI (d) and ADC (e) images showing reduced water diffusivity in the same affected regions, thus suggesting high cellularity. ¹H-MRS disclosing high Cho/NAA and Cho/Cr ratio indicating enhanced cell membrane turnover and reduced neuronal viability (f).

Figure 2.

Microscopical Features of Lympomathosis cerebri. Hematoxylin-eosin staining of brain specimens showed diffuse infiltration of lymphocytes in the perivascular and in tissue brain (a). Immunohistochemistry showed infiltration of CD3+ reactive lymphocytes (b), CD20+ large lymphomatous cells (c,d), all characterized by increased expression of KI67 receptor, a marker of cellular proliferation (e).

Figure 3.

Imaging of Primary Central Nervous System Lymphoma as evolution of Lymphomatosis cerebri. T1-wheighed contrast enhanced sequences showed nodular lesions characterized by intense contrast enhancement in the cortex and subcortex of frontal left hemisphere (a,b). FDG-PET showed focal glucose hypermetabolism of the frontal lesions (c,d).