Medulloblastomas are the most common malignant brain tumors in pediatric patients, typically arising from the cerebellar vermis within the posterior fossa. These neoplasms belong to the group of small round blue cell tumors and can be subdivided based on molecular profiling. While leptomeningeal spread is well recognized in advanced disease, primary leptomeningeal medulloblastoma (PLMB) without an identifiable intracranial mass is exceptionally uncommon and poses a diagnostic challenge due to overlap with infectious, inflammatory, and other neoplastic leptomeningeal conditions. Against this background, the recognition of atypical clinical presentations and subtle imaging findings is critical. In this setting, we report a 16-year-old boy who presented with progressive lower-extremity weakness. Brain magnetic resonance imaging (MRI) demonstrated cerebellar and parahippocampal diffusion restriction with minimal leptomeningeal enhancement and no discrete parenchymal mass. Spinal MRI revealed diffuse intradural-extramedullary nodules with widespread leptomeningeal involvement. Histopathology confirmed a desmoplastic/nodular medulloblastoma, non-wingless (WNT)/non-sonic hedgehog (SHH). When considered alongside the published literature, this case reflects the substantial variability in imaging findings, including inconsistent leptomeningeal enhancement, occasional diffusion restriction, and a high frequency of spinal metastases at presentation. Notably, clinical signs of intracranial hypertension, often anticipated in leptomeningeal disease, may be absent, further complicating timely diagnosis. By presenting this additional pediatric case and synthesizing current evidence, this report aims to refine the understanding of the radiological spectrum of non-mass-forming medulloblastoma and highlight the importance of recognizing subtle neuroaxis abnormalities suggestive of this rare entity.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant disorder associated with an increased risk of central nervous system tumors, particularly low-grade gliomas. However, the development of medulloblastoma in NF1 patients is extremely rare. Given the heightened risk of secondary malignancies following radiotherapy in this population, treatment strategies that minimize radiation exposure are important. We report a case of a two-year-old boy with a family history of NF1 who presented with headache and ataxia. Brain MRI revealed a 45-mm mass in the cerebellar vermis. Gross total resection was performed, and histopathology confirmed desmoplastic/nodular medulloblastoma. Postoperatively, the patient received multi-agent chemotherapy and intrathecal methotrexate without adjuvant radiotherapy. Consolidation therapy included high-dose chemotherapy with etoposide, carboplatin, and melphalan, followed by autologous peripheral blood stem cell transplantation. The treatment was completed successfully despite some toxicities. More than 10 years after treatment, the patient remains in complete remission without evidence of recurrence or late complications. This case highlights the potential of radiation-free, individualized treatment strategies for patients with NF1 to minimize the risk of secondary malignancies and achieve favorable long-term outcomes.

T cells and tumor-associated macrophages (TAMs) are critical immune components within the brain tumor microenvironment (TME), yet their precise roles in medulloblastoma remains unclear. In this study, we examined the infiltration characteristics of T cells in medulloblastoma tissues and analyzed the correlation between T cells and the clinical outcomes of medulloblastoma patients. Additionally, we further investigated the relationship between T cells and TAMs. We enrolled a total of 72 patients diagnosed with medulloblastoma and subsequently detected the T cell makers and programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) in paraffin-embedded sections using multiple immunofluorescence staining method. The correlation between T cell infiltration, clinical characteristics and prognosis were analyzed. Finally, we used Spearman correlation analysis to evaluate the correlation between T cells and TAMs. The median age at diagnosis of 72 patients (54 boys, 18 girls) was 7.5 years (range: 0.8-18 years). These patients included 43 cases of classic medulloblastoma (CMB), 24 cases of desmoplastic/nodular medulloblastoma (DNMB), 2 cases of medulloblastoma with extensive nodularity (MBEN) and 3 cases of large-cell/anaplastic medulloblastoma (LCA). The molecular subgroups consisted of 3 wingless (WNT), 29 sonic hedgehog (SHH) and 40 non-WNT/non-SHH cases. Twenty-five cases presented with metastasis at diagnosis, while 47 cases were without metastasis. Thirteen cases exhibited with high-risk genetic abnormalities. The total T cells (P = 0.031) and CD4 T cells (P = 0.045) were significantly elevated in the SHH subgroup compared to those in the non-WNT/non-SHH subgroup. Patients with increased CD4 T cells had better 5-year PFS (P = 0.000) and OS (P = 0.001), while patients without metastasis showed better 5-year PFS (P = 0.031) and OS (P = 0.015). Multivariate analysis showed that CD4 T cells were an independent prognostic factor affecting both the 5-year PFS (P = 0.004, HR = 0.230, 95% CI = 0.085-0.662) and OS (P = 0.017, HR = 0.180, 95% CI = 0.044-0.739). Additionally, it was observed that CD4 T cells exhibited a positive correlation with Mtotal (total macrophages) (P < 0.05, r = 0.249) and Mmix (M1/M2 mixed phenotype macrophages) (P < 0.01, r = 0.325), and CD3+CD8+PD-1+ cells showed a positive correlation with Mmix (P < 0.05, r = 0.258). The increase in CD4 T cells predicts a better prognosis in medulloblastoma patients, particularly within the SHH and non-WNT/non-SHH subgroups, and they may serve as a potential therapeutic target for medulloblastoma. Additionally, there may be a potential interaction between CD4 T cells and TAMs that warrants further investigation.

Tumor-associated macrophages (TAMs) constitute a significant proportion of the immune cell population within brain tumors. The polarization of macrophages exerts an important influence on the tumor microenvironment (TME). Nevertheless, the specific role of TAMs in sonic hedgehog (SHH) medulloblastoma remains unclear. To investigate the polarization characteristics and effects of TAMs in SHH medulloblastoma, we evaluated the infiltration of M1 and M2 macrophages in SHH medulloblastoma tissues and analyzed the correlation between TAMs recruitment and the clinical outcome of SHH medulloblastoma patients. We enrolled a total of 42 patients diagnosed with SHH medulloblastoma. Using multiple immunofluorescence staining on paraffin-embedded sections, we detected the activated phenotype (M1/M2) by monoclonal antibodies for CD68, HLA-DR and CD163. Subsequently, we analyzed the correlation between TAMs and clinical characteristics as well as prognostic factors. The median age of 42 patients (31 boys, 11 girls) was 5.3 years (range: 0.8-15.1 years). All patients had confirmed pathological types, including 4 cases of classic medulloblastoma (CMB), 33 cases of desmoplastic/nodular medulloblastoma (DNMB), 3 cases of medulloblastoma with extensive nodularity (MBEN), and 2 cases of large-cell/anaplastic medulloblastoma (LCA). Thirteen cases presented with metastasis at diagnosis, while twenty-nine cases were without metastasis. Four cases had high-risk genetic abnormalities. Different proportions of macrophages were found in the collected medulloblastoma tissues, and large amounts of CD68+HLA-DR+CD163+ cells were found. The study revealed that Mtotal (total macrophages) and Mmix (CD68+HLA-DR+CD163+ cells) were significantly higher in group of patients <5 years old (P < 0.05), and Mtotal in non-metastatic group were significantly higher than that in metastatic group (P = 0.043). M2 macrophages in CMB group were significantly higher than that in DNMB/MBEN group (P = 0.036), M1 macrophages were significantly higher in children without high-risk genetic abnormalities (P = 0.007). Five-year PFS was significantly poorer in patients ≥5 years old and metastatic group (P < 0.05). High Mtotal group had a better 5-year PFS (P = 0.000), whereas high M2 group had both better 5-year PFS and OS (P = 0.001, P = 0.001). Multivariate analysis showed that Mtotal and M2 macrophages were independent prognostic factors for 5-year PFS, and M2 macrophages were an independent prognostic factor for 5-year OS. The increase in total macrophages and M2 macrophages predicts a better outcome of SHH medulloblastoma. TAMs especially M2 macrophages might be a therapeutic target for SHH medulloblastoma.

To investigate the efficacy of immunohistochemical methods to determine molecular subgroups and prognostic predictions of medulloblastomas (MBs). β-catenin, GAB1, YAP1, filamin A and p53 were immunohistochemically stained, and MYC and MYCN fluorescent in situ hybridization (FISH) procedures were applied to 218 cases in our series. Based on the histomorphological characteristics of the cases, 67.9% were deemed classic MB; 15.6% as desmoplastic/ nodular medulloblastoma (DNMB); 12.8% as large cell/anaplastic (LC/A) MB; 3.7% as medulloblastoma with extensive nodularity (MBEN). Molecular characteristics revealed that 50.5% had non-WNT/non-SHH; 33.9% had SHH-activated and TP53-wildtype; 8.7% had WNT-activated; 6.9% had SHH-activated and TP53-mutant. According to the survival curves, LC/A MBs or non-WNT/ non-SHH tumors showed the worst prognosis, whereas DNMBs and WNT-activated tumors showed the best prognosis. Classic MBs or SHH-activated tumors showed a moderate course. MYCN amplification was found to act as an independent poor prognostic factor in the study. The distribution of histological subtypes and molecular subgroups, amplification rates, and prognostic data obtained through immunohistochemical methods in our study were consistent with those reported in the literature. It was therefore hypothesized that the determination of molecular subgroups by immunohistochemical methods can be useful in daily diagnostic practice, especially in centers with limited access to molecular techniques.