We analyzed PCNSL other than DLBCL, which is the most common type of PCNSL, in a single institution. There are few reports about primary CNS T-cell lymphoma, anaplastic large cell lymphoma, low-grade lymphoma, and Burkitt’s lymphoma [6
]. The incidence of those lymphomas is unknown precisely because of its rarity. It is known that in immunocompetent patients, the median age at diagnosis of PCNSL is 53–57 years. The highest risk group is those 60 years and older [25
], and the male to female ratio is 1.2–1.7:1. However, in this study, the median age of PCNSL other than DLBCL was 31 years (range 18–59) with a male-to-female ratio of 0.67:1. In Western countries, TPCNSL has been reported to constitute less than 4% of all PCNSLs, but in a nationwide survey of PCNSL in Japan, 8% of all cases were of T-cell origin [5
]. Out of 121 consecutive PCNSL patients that we have followed up in our center during the last 10 years, nine PCNSL patients had T-cell lymphoma (7.4%), and most of them were PTCL, including two patients with unspecified T-cell lineage. The incidence of TPCNSL in our study is more comparable with Japanese than Western data. These data may correlate with a generally higher incidence of T-cell lymphomas in Far Eastern regions [16
]. Shenkier et al. reported that among 45 patients, involvement of deep brain structures was seen in 16 patients (36%) and multiple lesions in 13 patients (29%) at diagnosis [27
]. In our study, of the nine patients with TPCNSL, three (30%) had deep structures and five (56%) had multiple lesions. Three patients (#6, 7, 8) had deep locations of disease sites and presented with multiple lesions at the same time. The prognosis for T-cell lymphoma is controversial. There are several reports about primary TPCNSL with poor prognosis [18
], and several with good response rates and overall survival time [10
]. Of our sample of nine patients, two died due to progressive disease after HD-MTX-based chemotherapy. The remaining six patients are alive in CR except one patient with SD at the 2.5-month follow-up. Although we could not draw conclusions on the prognosis of TPCNSL because of retrospective data and small patient numbers, our data showed equivocal or favorable clinical outcomes when compared with patients with DLBCL. It is meaningful that our study population was treated in a similar manner with HD-MTX-based treatment plus radiotherapy.
Uncommonly, MZBCL may present as a slowly growing localized mass arising from meningothelial cells of the dura (primary dural lymphoma), especially of the cerebral convexity, with rare cerebral parenchymal infiltration [13
]. The origin site was not the dura but a single lesion of the thalamus. It is known that MZBCL is very radiosensitive. Treatment options for primary CNS MZBCL have ranged from local therapy to a combination with systemic chemotherapy [22
]. Iwamoto et al. reported that eight patients with CNS MZBCL achieved complete response to treatment and no patient developed CNS recurrence during a median follow-up of 2 years (range 0.7–8.9 years). However, three patients developed systemic relapse after a median of 6.8 years (range 0.9–7.5 years). Bayraktar et al. showed that of six patients with primary CNS MZBCL, four achieved complete remission, and one relapsed at the same site after 5 years [6
]. The results show that primary CNS MZBCLs display indolent clinical behavior and have a generally favorable clinical outcome with long-term disease control and survival. In our study, one patient (#10) received systemic chemotherapy and radiotherapy and is alive in complete remission at 39.4 months. Our study also showed that primary CNS MZBCL had a good prognosis despite involvement of a deep structure (thalamus). A review of the literature indicates that local therapy with radiation alone shows favorable outcomes (Table ). Given these results, local treatment alone can be considered to be an effective modality for primary CNS MZBCL.
Primary CNS B-cell lymphoma other than DLBCL with literature review
We found two reports of primary CNS LPL [7
]. Carrasco et al. reported a pituitary LPL patient maintained complete remission for 4 years after transsphenoidal surgery, chemotherapy, and radiotherapy [7
]. We experienced one patient with a spinal cord LPL at T4 level. The patient (#12) received only surgical resection (corpectomy) without neurologic sequela and has lived without relapse for 51 months. Another patient, with LPL at the corpus callosum and left frontal lobe, is receiving the cohort 2 regimen. The interim evaluation is SD at 2.6 months. For these two patients, the prognosis of LPL seems to be satisfactory. Two patients did not show systemic symptoms and signs such as IgM paraproteinemia, neuropathy, and hyperviscosity.
Since Valsamis described the first case of primary CNS Burkitt’s lymphoma in an infant in 1976 [33
], there have been several case reports of primary CNS Burkitt’s lymphoma [11
]. The reported data showed poor clinical outcome. In our institution, one patient was diagnosed with primary CNS Burkitt’s lymphoma at the medulla and a leptomeningeal lesion with positive tumor cells in the CSF. Although the patient received HD-MTX-based chemotherapy, the final response was poor and the patient died at 7.6 months with progressive disease. Given other reports that show a poor outcome of primary CNS Burkitt’s lymphoma, HD-MTX-based chemotherapy does not appear to have an efficacious outcome. Therefore, more effective and aggressive treatment approaches for CNS Burkitt’s lymphoma are needed. In the literature review with our data, low-grade B-cell lymphoma, such as MZBCL and LPL, showed good prognosis, whereas Burkitt’s lymphoma showed an unfavorable clinical outcome (Table ).
Reported 5-year survival rates after conventional treatment with HD-MTX, either as a single agent or in combination, followed by WBRT, is close to 40% [8
]. Although heterogeneous and small number of cases does not warrant that these disease entities has the good prognosis than DLBCL, primary CNSLs, T-cell or B-cell lymphoma, other than DLBCL showed satisfactory treatment outcome in our series except for Burkitt’s lymphoma.
In this study, we described our experiences of primary CNS lymphoma other than DLBCL and made a historical comparison with previously reported DLBCL data from our institute. T-cell lymphoma showed equivocal or favorable clinical outcomes, and low-grade B-cell lymphomas such as MZBCL and LPL showed a good prognosis. However, CNS Burkitt’s lymphoma is more aggressive and presents a poor clinical outcome. Further research about treatment strategies for Burkitt’s lymphoma is needed. Additional analysis with a larger study population, including patients from other institutes, should be warranted.