Discussion:
To the best of our knowledge, this is the first reported case of a CNS
involvement similar to BNS associated with a generalized CSH in the
setting of a MZL.
Here we present a generalized form of CSH which represents 42% of
clinical presentation of this disease, whereas the localized pattern is
more frequent and often localized in the head and neck region [2].
CSH do not usually impair CNS: Dogan S. et al. report only 3% of dura
and pia mater involvement in patients with generalized CSH, and Flanagan
ME et al. report one case of CSH involving cerebellum and caudal brain
stem [2, 7].
In our case, neurological manifestations and MRI findings were highly
suggestive of BNS with signs of parenchymal and leptomeningeal
involvement. The lumbar puncture cellularity was consistent with a type
B BNS according to the Fintelmann’s proposed classification [8].
Type B BNS represents 25% of total BNS and is defined by a very low
cells rate (<5 cells/mm3) in the
cerebrospinal fluid. This suggested neurological manifestations being
associated with IgM deposition with an intrathecal secretion, as the
pathological CSF IgM index indicates, rather than lymphoplasmacytic
infiltration [8].
There is no clear causal link between CSH and BNS. We consider that they
are just two manifestations of an abnormal circulation of
immunoglobulins in quantity and quality.
In our case, definitive classification of the underlying small B-cell
lymphoma, which shows a striking plasmacytic differentiation, remains
difficult. Lymphoplasmacytic lymphoma (LPL) usually involves bone marrow
and sometimes lymph nodes and spleen. WM is defined as a LPL with bone
marrow involvement and an IgM monoclonal gammopathy. MYD88 L265P
mutation has been described in almost all, if not all (this is a point
of debate) LPL/WM, associated with a CXCR4 mutation in approximately
30% of cases. Conversely, this MYD88 L265P mutation is rarely
(~5% of cases) present in MZL. So, in our case,
polyadenopathy with minimal bone marrow involvement and absence of MYD88
L265P mutation would favor MZL with plasmacytic differentiation rather
than LPL/WM. However, because this neurological presentation similar to
BNS, which is, to our knowledge, exclusively described as a complication
of WM in literature, our patient was considered as having WM complicated
by a BNS for therapeutic decision. Nevertheless, one can legitimately
wonder why BNS could not also complicate a MZL with plasmacytic
differentiation and IgM paraprotein, knowing that neurological
manifestations in BNS type B are probably related to IgM rather than to
lymphoma cells infiltration.
The patient was treated as a BNS with R-Bendamustine associated and
intrathecal treatment allowing a clinical and radiological improvement.
Ibrutinib appears to be a good alternative as an oral treatment for this
disease [9]. CSH treatment depends of the causal pathology. There is
little information concerning specific response of CSH after
chimiotherapy but the histologic lesions persist in available
observations [10].