Various mechanisms of treatment resistance have been reported for glioblastoma (GBM) and other tumors. Resistance to immunotherapy in GBM patients may be caused by acquisition of immunosuppressive ability by tumor cells and an altered tumor microenvironment. Although novel strategies using an immune-checkpoint inhibitor (ICI), such as anti-programmed cell death-1 antibody, have been clinically proven to be effective in many types of malignant tumors, such strategies may be insufficient to prevent regrowth in recurrent GBM. The main cause of GBM recurrence may be the existence of an immunosuppressive tumor microenvironment involving immunosuppressive cytokines, extracellular vesicles, chemokines produced by glioma and glioma-initiating cells, immunosuppressive cells, etc. Among these, recent research has paid attention to various immunosuppressive cells—including M2-type macrophages and myeloid-derived suppressor cells—that cause immunosuppression in GBM microenvironments. Here, we review the epidemiological features, tumor immune microenvironment, and associations between the expression of immune checkpoint molecules and the prognosis of GBM. We also reviewed various ongoing or future immunotherapies for GBM. Various strategies, such as a combination of ICI therapies, might overcome these immunosuppressive mechanisms in the GBM microenvironment.

Background: This study aimed to investigate what treatment are selected for malignant brain tumors, particularly glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL), in real-world Japan and the costs involved. Methods: We conducted a questionnaire survey regarding treatment selections for newly diagnosed GBM and PCNSL treated between July 2021 and June 2022 among 47 institutions in the Japan Clinical Oncology Group-Brain Tumor Study Group. We calculated the total cost and cost per month of the initial therapy for newly diagnosed GBM or PCNSL. Results: The most used regimen (46.8%) for GBM in patients aged ≤74 years was ‘Surgery + radiotherapy concomitant with temozolomide’. This regimen’s total cost was 7.50 million JPY (Japanese yen). Adding carmustine wafer implantation (used in 15.0%), TTFields (used in 14.1%), and bevacizumab (BEV) (used in 14.5%) to the standard treatment of GBM increased the cost by 1.24 million JPY for initial treatment, and 1.44 and 0.22 million JPY per month, respectively. Regarding PCNSL, ‘Surgery (biopsy) + rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy’ was the most used regimen (42.5%) for patients of all ages. This regimen incurred 1.07 million JPY per month. The three PCNSL regimens based on R-MPV therapy were in ultra-high-cost medical care (exceeding 1 million JPY per month). Conclusions: Treatment of malignant brain tumors is generally expensive, and cost-ineffective treatments such as BEV are frequently used. We believe that the results of this study can be used to design future economic health studies examining the cost-effectiveness of malignant brain tumors.

Osteoma is a common, slow growing bone tumor, and often affects the paranasal sinus. Typically, it shows a very hyperdense osseous lesion on computed tomography (CT) scan and low-intensity change on T2-weighted image on magnetic resonance imaging (MRI). No report has mentioned osteomas in blood supply on MRI. A 57-year-old male patient presented with a prolonged declined activity and a gigantic osseous tumor that originated from the frontal sinus, which markedly compressed the bilateral frontal lobe. MRI revealed a slightly enhanced front basal part of the tumor by gadolinium, with blood supply from ethmoidal arteries. The patient underwent surgery, and the diagnosis of osteoma was made based on histological findings. We reported a case of giant osteoma originating from the frontal sinus with unusual blood supply on 4-dimensional MR angiography.

Diffuse midline glioma (DMG), H3 K27-altered, is a newly defined “pediatric-type,” diffuse, high-grade glioma under current WHO classifications (updated in 2021). An essential diagnostic criteria of DMG is its occurrence in the midline structures; most intracranial DMG occurs in the brainstem or thalamus but can also occur in other midline structures. We experienced 2 adult cases of intracranial DMGs in areas other than the brainstem and thalamus that were initially difficult to diagnose. Case 1 was a 49-year-old man with extensive T2 high-signal lesions in the bilateral frontal lobes and corpus callosum on brain MRI. A Gd-based contrast medium partially enhanced the lesion and showed marked diffusion restriction, mimicking malignant lymphoma. Case 2 was a 24-year-old man who presented with paroxysmal olfactory abnormalities. The tumor extended mainly to the right temporal lobe, the right basal forebrain, and the bilateral hypothalamus, showing a T2/FLAIR mismatch sign suggestive of IDH-mutant astrocytoma without 1p/19q co-deletion. After a biopsy, both cases were properly diagnosed as DMG, H3 K27-altered (K27M-mutant). Diagnosing adult cases involving atypical midline structures is sometimes challenging before surgery; we discuss this phenomenon with both case details and a literature review.