Case report:
A 69-year-old Caucasian male presented with an impaired general condition with abdominal pain. He gradually exhibited a degradation of his neurological state with confusion, headache, hearing loss, and aphasia. His physical examination showed a static cerebellar syndrome associated with major ataxia and pyramidal syndrome.
An abdominal-chest computed tomography revealed enlarged spleen and liver, and an upper and under diaphragmatic polyadenopathy. Laboratory findings were the following: haemoglobin 10g/dL, a monoclonal gammopathy (IgM lambda 8g/L) with cryoglobulinemia type I activity and a serum free light chain ratio kappa/lambda at 0.08. The urine test found a Bence Jones proteinuria at 4.5 g/24h composed of 78% light chain lambda.
The cerebral MRI found hypersignal FLAIR in the supra-tentorial white matter with hypersignal on diffusion sequence without restriction in ADC induced by vasogenic edema. Moreover, there was a leptomeningeal contrast enhancement in Gadolinium sequences (Figure 1).
The lumbar puncture found a mild hyperproteinorachia (0.53 g/L; norm < 0,4 g/L) and 4 cells/mm3 composed of lymphocytes and plasma cells, with a pathological elevation of IgM at 14 mg/L and an IgM index at 0,42. Flow cytometry analysis failed to detect a monotypic B cell population in the cerebro-spinal fluid, but cellularity was very low.
Several histological specimens were studied:
1/ A colonoscopy was performed because of abdominal pain and showed a mild colitis with multiple small whitish lesions. The colonic biopsies showed submucosal clusters of histiocytes with abundant crystalline eosinophilic cytoplasm inclusions (Figure 2).
2/ The bone marrow biopsy was hypercellular, with a normal representation of the three hematopoietic lineages. There was a discrete lymphoid infiltrate, made of small B and T lymphocytes. The plasma cells represented 5 to 10% of the bone marrow cellularity and showed an inversion of their kappa/lambda ratio (Figure 3). A monoclonal B-cell population was found by polymerase chain reaction (PCR). Any mutation was detected by Next Generation Sequencing (NGS), in particular no MYD88 L265P mutation. Some clusters of histiocytes with abundant crystalline eosinophilic cytoplasmic inclusions were also identified.
3/ A cervical lymph node biopsy showed a massive infiltration by the same histiocytes as observed in colon biopsy and bone marrow (Figure 4). It was associated with small lymphoid B-cell nodules, lacking a specific phenotype by immunohistochemistry, and numerous monotypic lambda plasma cells. The PCR identified the same monoclonal B-cell population than in the bone marrow. No mutation was found by NGS, in particular no MYD88 L265P mutation. Cytogenetic analyses of the lymph node showed a complex caryotype with 2q, 3p, 10q, 17p deletions and 9p addition, any of these anomalies being specific of a B lymphoproliferative syndrome.
Finally, these clinical, biological, histological and imaging presentation were consistent with the diagnosis of a CNS involvement similar to BNS which usually occurs in the setting of WM, associated with CSH. However, in our case, underlying lymphoma was more accurately diagnosed as a marginal zone lymphoma (MZL) with plasmacytic differentiation.
The patient was first treated as a BNS by 3 cures of Rituximab-Bendamustine and intrathecal Methotrexate – Methylprednisolone - Aracytine. This treatment allowed an improvement of his clinical and cognitive state, with disappearance of cerebellar ataxia and pyramidal signs. An MRI realized after treatment find a stabilization of white matter lesions and a disappearance of the leptomeningeal contrast enhancement (Figure 1).