Neuroradiological features of lymphomatosis cerebri: A systematic review of the English literature with a new case report

Abstract

Lymphomatosis cerebri is a rare form of diffusely infiltrating primary central nervous system (CNS) lymphoma (PCNSL). The neuroradiological findings of lymphomatosis cerebri have not been adequately characterized, as the relevant literature consists only of case reports and small case series. The present study describes an unusual presentation of lymphomatosis cerebri in a 56-year-old immunocompetent woman who presented with diffusely infiltrating lesions with perivascular curvilinear enhancement on initial magnetic resonance imaging (MRI) and multiple nodules on the later follow-up computed tomography (CT) scan. A systematic review of the literature is also performed searching PubMed between January 1996 and December 2016 to collect all pertinent case reports and series written in the English language with pathologically confirmed lymphomatosis cerebri and diffuse infiltrative PCNSL without cohesive masses on initial MRI. A total of 45 cases were identified from 39 articles and the present case report. The patient ages ranged from 28 to 85 years (mean, 57.3 years). Only 3 patients (6.7%) were immunosuppressed (acquired immune deficiency syndrome patients). The most common clinical presentation was cognitive changes or dementia (46.7%). Cerebrospinal fluid analysis in all cases was non-specific. Diffuse and asymmetric abnormal T2-hyperintensity in deep and subcortical white matter was observed in all cases. Gray matter involvement (17.8%), spreading along the corticospinal tract (35.6%) and a slight mass effect (51.1%) also were observed. Contrast-enhanced patterns on MRI could be divided into three forms of non-enhancement (64.4%) and non-mass-like enhancement (35.6%) on initial MRI, as well as nodular or mass-like enhancement on the later follow-up MRI (15.6%). There were non-specific findings on magnetic resonance spectroscopy for 4 patients, on positron emission tomography/CT for 12 patients and on single-photon emission CT for 1 patient. Diagnosis was established by brain biopsy in 35 cases (77.8%) and autopsy in 9 cases (20%), involving B-cell lymphoma in 40 cases (88.9%) and T-cell lymphoma in 4 cases (8.9%). In conclusion, lymphomatosis cerebri, namely diffuse PCNSL or diffuse lymphoma of the CNS, is characterized by rapidly progressive dementia in the elderly, diffusely infiltrated CNS white matter along the corticospinal tract, possible involvement of the gray matter, a slight mass effect and varied contrast-enhancement patterns on MRI. Non-enhancement or non-mass-like enhancement on MRI may be a special form of diffuse PCNL during disease development and progression.

Keywords: diffuse tumorous infiltration; leukoencephalopathy; lymphomatosis cerebri; magnetic resonance imaging; neuroradiology; primary central nervous system lymphoma.

Figure 1.

CT findings of lymphomatosis cerebri from the present case report. (A-D) On February 25, 2015, the day of presentation to the neurological clinic, unenhanced CT showed (B) an abnormal low density in the right thalamus, external capsule and (C and D) parietal white matter. (E-H) On July 4, 2015, the follow-up unenhanced CT demonstrated abnormal hyperintensities that extended almost to all cerebral and cerebellar white matter, as well as the thalamus and brainstem. Multiple circular nodules were also observed in (E) the right cerebellar hemisphere, and (F and G) the bilateral occipital white matter and (H) right parietal white matter. CT, computed tomography.

Figure 2.

MRI findings of lymphomatosis cerebri from the present case report. (A-J) The initial MRI was performed on February 26, 2015. (A and F) FLAIR and (B and G) DWI showed diffuse multiple asymmetrical hyperintensity in (A) the bilateral basal ganglia and thalamus, (A, B and G) temporal white matter and (F and G) medial prefrontal cortex and periventricular white matter, as well as a slight mass effect on the posterior horn of the left lateral ventricle. (C and H) Apparent diffusion coefficient map showed mild hypotensity with no corresponding T2 hyperintensity, denoting a T2 shine-through effect and slight restricted diffusion. The lesions were (D and I) isointense on Tl-weighted spin-echo images, and (E and J) showed asymmetric perivascular curvilinear enhancement perpendicular to the lateral ventricle following gadolinium administration. (K-O) The follow-up MRI was performed on April 22, 2015. (K) FLAIR and (L) DWI demonstrated broader hyperintensity of the cerebral white matter. (O) The perivascular curvilinear enhancement on T₁-weighted imaging with gadolinium expanded markedly. MRI, magnetic resonance imaging; FLAIR, fluid-attenuated inversion recovery; DWI, diffusion-weighted imaging.

Figure 3.

[¹⁸F]FDG-PET/CT findings of lymphomatosis cerebri from the present case report. On April 23, 2015, the PET/CT fusion images revealed inhomogeneous and patchy distribution of ¹⁸F-FDG uptake, with an SUVmax of 20.5 and SUVave of 15.3 in (A and B) the cerebrum, (C) brainstem, (C) cerebellum and (C and D) cervical cord. (D) No sign of systemic lymphoma was present. FDG, fluorodeoxyglucose; PET/CT, positron emission tomography/computed tomography; SUV, standardized uptake value.

Figure 4.

Pathological findings of lymphomatosis cerebri from the current case. On May 12, 2015, a stereotactic brain biopsy of the left frontal lobe revealed (A) prominent diffuse perivascular infiltrates of atypical large B-cells with irregularly shaped nuclei, (B) with strong staining for the B-cell marker CD-20 and for (C) Ki-67, indicative of highly proliferating cells. This case was assigned to the non-germinal center B-cell immunophenotype, as it was negative for (D) CD-10 and (E) Bcl-6, but positive for (F) MUM-1. (A) Hematoxylin and eosin, ×400 magnification; (B) anti-CD20, ×400 magnification; (C) anti-Ki-67, ×200 magnification; (D) anti-CD10, ×400 magnification; (E) anti-Bcl-6, ×400 magnification; and (F) anti-MUM-1, ×400 magnification. CD, cluster of differentiation; Bcl, B-cell lymphoma; MUM-1, multiple myeloma oncogene 1.

Figure 5.

Preferred reporting items of systematic reviews and meta-analyses-style flow diagram of the literature search for the systematic review. MRI, magnetic resonance imaging; CNS, central nervous system.