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).