Extranodal manifestation of low grade non-Hodgkin lymhomas in the central nervous system is extremely rare. The synopsis of all diagnostic findings in the presented case resulted in the diagnosis of a splenic marginal zone lymphoma with meningeal lymphomatosis, infiltration of the temporal lobe and infiltration of the cauda equina despite the unavailability of a spleen histology as the diagnostic hallmark of this disease. The morphological features of the peripheral blood cells have been already very suggestive of SMZL and the differential diagnosis of variant form of hairy cell leukemia was excluded by immunophenotyping. Partial expression of CD5 as observed in this patient is found in approximately 20% of SMZL cells, mantle cell lymphoma is not plausible because of morphology and negativity for t(11;14) in FISH analysis. The translocation t(2;7)(p11;q21-22) is previously characterized in a few cases of SMZL and in CD5-negative MBL
[9, 10]. This translocation seems to link CDK6 to the IG kappa locus
. Trisomy 3 is a current but not specific chromosomal aberration which is found in a variety of B-cell lymphomas
. Summarized, the results of all analyses confirmed the extraordinary diagnosis of SMZL with involvement of the central nervous system.
Only three cases with CNS manifestation of a SMZL have been described in the literature so far. All of them suffered from meningeosis, one patient had additionally a cerebral manifestation and another patient an infiltration of the optic nerve. The treatment results have been different, two patients had good responses to chemotherapy and a third one had a refractory disease
Normally, splenic marginal zone lymphomas have a favorable prognosis. Conventional therapy (splenectomy, purine analogs or rituximab, antiviral therapy in concomitant HCV infection) is not curative, but can lead to long lasting remissions. Adverse prognostic factors have been identified. Chacón et al. found extranodal site involvement (apart from liver and spleen) after splenectomy reducing median overall survival to 52 months, while overall survival in patients without extranodal site involvement was not reached at 113 months
. Elevation of LDH at initial diagnosis is discussed as adverse prognostic factor in a published scoring system
. Aggressive treatment forms like high-dose therapy (HDT) followed by autologous stem cell transplantation (auto-SCT) is a valuable option for younger patients with high-grade NHL of central nervous system
. This therapeutical approach has no plausible curative potential in case of indolent lymphomas, however.
Due to the special features indicating the aggressiveness of the disease and the young age of our patient, we recommended an intensive proceeding including therapy with drugs penetrating excellently into the CSF (MTX, Busulfan, Thiotepa, Fludarabine) followed by allogeneic stem cell transplantation from an unrelated donor in order to cure from lymphoma. SMZL disappeared completely, even on the molecular level (Figure
Graft-versus-leukemia/lymphoma-effects are essential for the eradication of residual hematological malignancies after allogeneic BSCT
, but the information about GvL-acitivity within the CNS is still limited. A case of a PCNSL treated with allogeneic peripheral BSCT has been described: the manifestation of acute GvHD could be correlated with the disappearance of intracerebral lymphoma
. Another group described donor-derived lymphocytes in the cerebrospinal fluid after transplantation
. Furthermore, the successful treatment by allogeneic BSCT of patients with isolated CNS relapse of acute leukemia has been published
. In a prior publication we reported the successful therapy of CNS-relapse of high-grade NHL with alloSCT, immunomodulation and irradiation
. The clinical and molecular remission of SMZL in this case strongly suggest contribution of GvL-effects, however, the relative short follow-up of three years allows no definite conclusion.
The actual case in conjunction with preceding publications should encourage the physicians involved into therapy of lymphomas of the CNS to consider allogeneic stem cell transplantation as a valuable salvage therapy and as a possible primary therapy in high-risk patients. Investigation of this approach in clinical trials and further research about the activity of donor cells in the CNS after alloSCT are mandatory.
Informed written consent was obtained from the patient for allogeneic stem cell transplantation and for scientific evaluation of the transplantation and the results.