Lymphomatosis cerebri: Multimodality imaging features and misdiagnosis analysis

Abstract

Lymphomatosis cerebri (LC) is a significant challenge in terms of its clinical diagnosis due to it being a rare disease. The purpose of the present study was to investigate the multimodality imaging characteristics, clinical features and reasons for misdiagnosis of LC with the goal of potentially facilitating early and accurate diagnosis of this frequently misdiagnosed disease. In the present study, clinical data and cerebral multimodality imaging findings from 11 patients with LC proven based on pathology were retrospectively analyzed and reviewed with consultation of the literature. The results indicated that the common symptoms included cognitive decline (8/11), gait disturbance (9/11) and behavioral abnormalities (5/11). Cerebrospinal fluid analysis indicated that the number of cells and level of protein increased (8/10). All patients had both deep and lobar lesion distribution of bilateral cerebral white matter with equal or slightly low-density shadows on CT plain scan and slightly longer signals on T1- and T2-weighted MRI. Most of the lesions (9/11) exhibited isointensity or slight hyperintensity on diffusion-weighted imaging and hyperintensity on apparent diffusion coefficient maps. In addition, five patients presented with a marked decrease in N-acetylaspartate/creatine (Cr) and increase in choline/Cr on ¹H-magnetic resonance spectroscopy, including an increase in lipid/Cr in 3 cases. Of these, one case exhibited no increase in lesion metabolism and 2 cases had slightly increased uptake on positron emission tomography/CT. The present study indicated that the multimodality imaging findings of LC have certain distinct characteristics and prompt recognition of these features may significantly improve early diagnosis and patient prognosis. Misdiagnosis may be mainly due to insufficient understanding knowledge of the condition and improper brain biopsy.

Keywords: diffuse cerebral white matter lesions; lymphomatosis cerebri; misdiagnosis analysis; multimodality imaging; primary central nervous system lymphoma.

Figure 1.

A 45-year-old male with diffuse T-cell lymphomatosis cerebri presented with memory loss, fatigue, lethargy and slow response for 4 months, which had been aggravated for 10 days. (A-F) Initial examination: (A) Plain axial CT scan indicated no obvious abnormalities. MRI: Patchy bilateral basal ganglia signals with slightly longer signals on (B) T1WI and (C) T2WI, and (D) high FLAIR signal. (E) DWI exhibited no diffusion limitation and (F) the T1WI enhanced scan revealed no enhancement. Re examination after 1 month of cortisol treatment: (G) FLAIR sequence indicated that the original abnormal patchy bilateral basal ganglia signals were significantly less pronounced on re-examination. Symptom recurrence re-examination after 2 months: (H-J) Axial FLAIR sequence indicated that the bilateral basal ganglia area had slightly higher signals than at the initial examination and the frontal lobe, temporal lobe, parietal lobe, radiation coronal area, corpus callosum and bilateral cerebellar hemispheres had new, similar lesions along the line; (K) the corticospinal tract was observed to infiltrate the cerebral feet and pons. (L) Sagittal T2WI revealed new, similar lesions in the cervical and upper thoracic spinal cord. (M) Cerebellar and brainstem lesions on DWI produced equal or slightly high signals and (N) apparent diffusion coefficient images displayed mainly slightly high signals. (O-Q) T1WI enhanced scan indicated that the abovementioned brain lesions were patchy and nodular with obvious enhancement. FLAIR, fluid-attenuated inversion recovery; T1WI, T1-weighted imaging; DWI, diffusion-weighted imaging.

Figure 2.

A 58-year-old female with diffuse large B-cell lymphomatosis cerebri presented with unstable gait on both lower limbs with memory loss and personality changes for 1 month. (A) Axial T2WI image revealed bilateral basal ganglia patches with slightly longer T2 signal lesions. (B) FLAIR image with a slightly higher signal and clearer display, and certain lesions exhibited limited spread and (C) a slightly high signal on DWI. (D) T1WI enhanced scan revealed no obvious abnormal enhancement. Disease progression was reviewed 4 months later. (E) In the axial FLAIR image, the bilateral basal ganglia area had flaky hyperintensity and (F) on DWI, more restricted diffusion than at earlier time points was observed. (G) The T1WI enhanced scan revealed small patchy and nodular enhancement. Re-examination after 2 months of cortisol treatment: (H) T1WI enhanced scan indicated that the original lesions were significantly reduced compared with the previous time-points and the enhancement range and degree were significantly reduced. (I) H&E staining showed that the brain specimen with large- to medium-sized lymphoid cells diffusely infiltrated along the white-matter tracts without mass formation with visible immunoblasts and central blasts. (J) Immunohistochemistry revealed that the atypical cells were positive for CD20, a marker for B cells (magnification, ×200). FLAIR, fluid-attenuated inversion recovery; T1WI, T1-weighted imaging; DWI, diffusion-weighted imaging.

Figure 3.

A 59-year-old male with diffuse large B-cell lymphomatosis cerebri presented with headache and bilateral lower extremity weakness with walking instability for 14 days. (A-C) Axial fluid-attenuated inversion recovery images revealed small patchy and equal slightly hyperintensive lesions in the bilateral basal ganglia, temporo-occipital areas, genu of the corpus callosum and pons. (D-F) T1-weighted imaging enhanced scan displayed the abovementioned lesions with small spot-like enhancement. (G) Positron emission tomography/CT indicated that the partial lesions were equal or had slightly low-density shadows. (H) ¹⁸F-fluorodeoxyglucose was slightly concentrated and (I) slightly high metabolism was indicated in PET.

Figure 4.

A 78-year-old male with diffuse large T-cell lymphomatosis cerebri presented with unresponsiveness for 1 year, weak right limb for 1 month and abnormal behavior for 10 days. (A) Axial fluid-attenuated inversion recovery image indicated diffuse patchy and large patchy hyperintensities throughout both cerebral hemispheres (mainly deep brain white matter). (B) Diffusion-weighted imaging revealed extensive and uneven hyperintensity in the lesions and the corresponding apparent diffusion coefficient maps (not shown) indicated water restriction. (C) T1-weighted imaging enhanced scan featured patchy and nodular enhancement. (D) H&E staining showed brain biopsy specimen with small to medium lymphoid cells that grew with a nodular or fuzzy nodular pattern (magnification, ×100; scale bar, 200 µm). (E) Immunohistochemistry revealed that the atypical cells were positive for CD3, a marker for T cells (magnification, ×100; scale bar, 200 µm).