Primary diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) is an aggressive disease with a poor prognosis. The status of the tumor immune microenvironment in CNS-DLBCL remains unclear. We investigated the prognostic implications of tumor-associated macrophages (TAMs), regulatory T-cells (Tregs), and indoleamine 2,3-dioxygenase (IDO)+ cells in primary CNS-DLBCL (n = 114) by immunohistochemical analysis. The numbers of tumor-infiltrating immune cells, including CD68+ TAMs, CD163+ or CD204+ M2 macrophages, FOXP3+ Tregs, and IDO+ cells were all significantly lower in CNS-DLBCL versus systemic DLBCL (n = 165; all P < 0.001), but with little difference in the ratio of CD163+/CD68+ or CD204+/CD68+ cells. An increase in CD68+ cell numbers was significantly associated with prolonged progression-free survival (PFS) and overall survival in patients with CNS-DLBCL (P = 0.004 and 0.021, respectively). In contrast, an increase in CD204+ cell numbers or a higher ratio of CD204+/CD68+ cells was related to a shorter PFS (P = 0.020 and 0.063, respectively). An increase in IDO+ cell numbers was associated with a significantly longer PFS (P = 0.019). In combination, the status of low IDO+ cell numbers combined with low CD68+ cell numbers, high CD204+ cell numbers, or a high CD204+/CD68+ cell ratio all predicted poor PFS in multivariate analyses. This study showed that an increase in CD204+ cell numbers, suggestive of M2 macrophages, was associated with poor clinical outcome in CNS-DLBCL, whereas increased CD68+ or IDO+ cell numbers were related to a favorable prognosis. The analysis of tumor-infiltrating immune cells could help in predicting the prognosis of CNS-DLBCL patients and determining therapeutic strategies targeting tumor microenvironment.

Diffuse leptomeningeal disseminated glioneuronal tumor (DL-GNT) is a rare brain tumor that presents as a plaque-like subarachnoid tumor, commonly involving the basal cisterns and interhemispheric fissure of children but lacking intraparenchymal tumor. Histologically, the tumors are composed of sheets of monotonous rounded cells. Here, we report three cases of DL-GNTs, focusing on clinicopathologic features. Two patients were adult male, but one patient was child. The patients presented with seizures (n = 1) or headaches (n = 2). In all patients, radiography revealed characteristic leptomeningeal thickening and enhancement with minor superficial parenchymal lesions. All three cases were diffusely positive for both GFAP and synaptophysin, and scattered positive for OLIG2 and NeuN, but negative for IDH-1 (H09). Electron microscopic examination showed astrocytic and neuronal differentiation. The patient with the anaplastic tumor died due to aggressive progression of the tumor, but the remaining two patients were stable without tumor recurrence for 23 and 37 months. Thus, these findings suggest that DL-GNT can occur in both children and adult and both supra- and infra-tentorial leptomeninges. It has unique radiological and histopathological features and biological behavior. Further clinicopathological data with molecular genetic study are required for establishing DL-GNT as a unique entity.

BackgroundPrimary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) is a distinct clinicopathological entity with a poor prognosis. Concurrent MYC and BCL2 overexpression predicts inferior prognosis in systemic DLBCLs. However, the prognostic significance of MYC and BCL2 in PCNS-DLBCL remains elusive.MethodsImmunohistochemistry (IHC) of MYC, BCL2 and BCL6 was performed on tumor samples from 114 patients with PCNS-DLBCL. IHC score was assigned based on the proportion of immunostained cells.ResultsMYC, BCL2, and BCL6 IHC scores were 18.16 ± 19.58, 58.86 ± 35.07, and 39.39 ± 37.66 % (mean ± SD), respectively. Twenty-one cases (18.1 %) were designated as MYC-positive with a cutoff score of 40. BCL2 positivity was found in 87 cases (75.0 %) using a cutoff score of 30. MSKCC (Memorial Sloan-Kettering Cancer Center prognostic model) class 2 and 3 had higher rates of MYC and/or BCL2 positivity (MYC, P = 0.012; BCL2, P = 0.008; dual-positive, P = 0.022). Poor KPS (Karnofsky Performance Status score <70), multifocal disease, Nottingham-Barcelona score ≥2, and MSKCC class 2 and 3 were related to shorter progression-free survival (PFS) (P = 0.001, 0.037, 0.001, and 0.008, respectively). Patients with older age (>60 years) showed poorer overall survival (OS) (P = 0.020). MYC positivity was associated with poor PFS (P = 0.027), while patients with BCL2 positivity exhibited a shorter OS (P = 0.010). Concomitant MYC and BCL2 positivity was related to poor PFS (P = 0.041), while the lack of both MYC and BCL2 expression was related to prolonged OS (P = 0.014). MYC and BCL2 expression had no independent prognostic implication by multivariate analysis in overall patients with PCNS-DLBCL. However, among patients treated with combined high-dose methotrexate, vincristine and procarbazine and radiotherapy, dual MYC and BCL2 overexpression (a cutoff score of 60) was an independent poor prognostic indicator (P = 0.010).ConclusionsEvaluation of MYC and BCL2 expression may be helpful for the determination of PCNS-DLBCL prognosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2397-8) contains supplementary material, which is available to authorized users.

Glioblastomas (GBMs) are the most aggressive type of primary brain tumors and provide a dismal prognosis. Thus far, several key genes have been identified in GBMs as prognostic and therapeutic targets. Mutations in two isocitrate dehydrogenase (IDH) genes, IDH1 and IDH2, commonly occur in low-grade gliomas and secondary high-grade gliomas, but are rare in primary GBMs. These mutations alter the catalytic activity of IDH proteins, promoting gliomagenesis. Gliomas with IDH1 or IDH2 mutation have better outcomes than do gliomas with wild-type IDH. The hot spots of IDH1 mutations (R132) and IDH2 mutations (R140 and R172) are well known and are considered as a possible biochemical explanation for the differing clinical characteristics of primary and secondary GBMs. We sought to find the incidence of IDH2 mutation and the characteristics of the gliomas with IDH2 mutation. Among 134 gliomas, which were operated in our hospital consecutively, we studied IDH1 and IDH2 mutations by Sanger sequencing and IDH2 mutation was identified in seven cases (5.2%, four oligodendrogliomas and three GBMs). IDH2 mutation was found in 3.3% of GBMs (3/90 cases) and 9.0% (4/44) of grades II to III gliomas. Here, we report the clinicopathological characteristics of the gliomas with IDH2 mutations including two cases of primary GBM carrying a novel missense IDH2 mutation (c. 484C>T, p. P162S).