Background: Relapsed medulloblastoma (MB) poses a significant therapeutic challenge due to its highly immunosuppressive tumor microenvironment. Immune checkpoint inhibitors (ICIs) have struggled to mitigate this challenge, largely due to low T-cell infiltration and minimal PD-L1 expression. Identifying the mechanisms driving low T-cell infiltration is crucial for developing more effective immunotherapies. Methods: We utilize a syngeneic mouse model to investigate the tumor immune microenvironment of MB and compare our findings to transcriptomic and proteomic data from human MB. Results: Flow cytometry reveals a notable presence of CD45^hi/CD11b^hi macrophage-like and CD45^int/CD11b^int microglia-like tumor-associated macrophages (TAMs), alongside regulatory T-cells (T_regs), expressing high levels of the inhibitory checkpoint molecule VISTA. Compared to sham control mice, the CD45^hi/CD11b^hi compartment significantly expands in tumor-bearing mice and exhibits a myeloid-specific signature composed of VISTA, CD80, PD-L1, CTLA-4, MHCII, CD40, and CD68. These findings are corroborated by proteomic and transcriptomic analyses of human MB samples. Immunohistochemistry highlights an abundance of VISTA-expressing myeloid cells clustering at the tumor–cerebellar border, while T-cells are scarce and express FOXP3. Additionally, tumor cells exhibit immunosuppressive properties, inhibiting CD4 T-cell proliferation in vitro. Identification of VISTA’s binding partner, VSIG8, on tumor cells, and its correlation with increased VISTA expression in human transcriptomic analyses suggests a potential therapeutic target. Conclusions: This study underscores the multifaceted mechanisms of immune evasion in MB and highlights the therapeutic potential of targeting the VISTA–VSIG axis to enhance anti-tumor responses.

From the existing millions of fungal species, only a few cause disease. In this study, we investigated invasive fungal infections in the head and neck (H&N) over a 19-year period (2005 to 2024) at a large academic healthcare system. Among the 413 documented fungal H&N infections, 336 were noninvasive, and 77 were invasive. The highest incidence of invasive infections occurred in the sinonasal cavities, with a 15-fold difference compared to other sites. Most infections affected adults over 40 years old. The most common organisms were Mucorales (51%), hyaline molds (29%), and Candida (11%). Risk factors included malignancy, transplant, diabetes, and illicit drug use. Mortality was high in patients with malignancy and/or transplant. Infections affecting the mandible were usually a complication of osteoradionecrosis and were associated with the coinfection of Candida and Actinomyces. At other sites, infections were rare and were usually the result of penetrating injuries or immunosuppression. Treatment typically involved a combination of antifungals and surgical procedures.

From the existing millions of fungal species only a few cause disease. In this study, we investigated invasive fungal infections in the head and neck over a 19-year period (2005 to 2024) at a large academic healthcare system. Among 413 cases, 336 were noninvasive, and 77 were invasive. The highest incidence of invasive infections occurred in the sinonasal cavities, with a 15-fold difference compared to other sites. Most infections affected adults over 40 years old. The most common organisms were Mucorales (51%), hyaline molds (29%), and Candida (11%). Risk factors included malignancy, transplant, diabetes, and illicit drug use. Mortality was high in patients with malignancy and/or transplant. Infections affecting the mandible were usually a complication of osteoradionecrosis and were associated with coinfection of Candida and Actinomyces. At other sites, infections were rare and were usually the result of penetrating injuries or immunosuppression. Treatment typically involved a combination of antifungals and surgical procedures.

A 50-year-old man without a significant medical history developed progressive double vision from a partial right third nerve palsy, as well as right-sided hyperreflexia and decreased temperature sensation in his right hand. Initial contrast MRI of the brain revealed enhancement of the right oculomotor nerve. Cerebrospinal fluid and serologic studies were negative or normal. Over the next 6 weeks, he developed a left sixth nerve palsy and right-sided facial sensory changes, followed by a partial left third nerve palsy and right foot drop. The patient later disclosed a 2-year history of painful right hemiscrotum swelling. Abdominal imaging and testicular biopsy revealed a Stage IIA testicular seminoma and was treated with radical orchiectomy, steroids, intravenous immunoglobulin, and chemotherapy. He continued to deteriorate, with evidence of myelitis on thoracic MRI. Initial paraneoplastic studies were negative, and research-based antibody testing revealed leucine zipper 4 autoantibody positivity, indicating a paraneoplastic syndrome.

Background/Objectives: Adult-type diffuse gliomas (ADGs) are aggressive brain tumors with highly variable clinical outcomes. Prognostic assessment directly from routine hematoxylin and eosin (H&E)-stained whole-slide images (WSIs) could support personalized decision-making. Methods: To our knowledge, this is the first systematic benchmarking of pathology foundation models (FMs) and multiple instance learning (MIL) methods for overall survival (OS) risk stratification in ADGs under the 2021 World Health Organization (WHO) classification. A retrospective, multi-institutional cohort of 817 subjects from The Cancer Genome Atlas (TCGA) was analyzed. Following tissue segmentation and patch-level curation, we evaluated 77 pathology FM-MIL combinations (11 FMs × 7 MIL methods), together with seven ResNet-50 baseline configurations (84 encoder-MIL configurations in total), using patient-level 10-fold cross-validation. A perturbation-based evaluation assessed attention mechanism faithfulness. Results: UNI2 paired with MambaMIL achieved the highest cross-validated concordance index (C-index = 0.77), whereas its time-dependent AUC was modest (0.60–0.61 at 12–36 months), and several combinations performed comparably. Kaplan–Meier analysis demonstrated significant separation between high- and low-risk groups (log-rank p = 9.16 × 10⁻¹⁷; hazard ratio [HR] = 2.90, 95% confidence interval [CI]: 2.23–3.76), with a median OS of 16.6 months (95% CI: 15.0–20.4) versus 63.5 months (95% CI: 43.9-NR), respectively. Tertile stratification confirmed a monotonic OS gradient from 94.5 months to 14.7 months (p = 3.25 × 10⁻¹⁷). Risk stratification within individual WHO 2021 types was not significant. Most domain-specific FMs outperformed the ImageNet-pretrained baseline, and the removal of highly attended patches reduced performance, supporting attention faithfulness. Conclusions: The AI-derived risk score remained associated with OS after adjustment for individual clinical and molecular variables, but independent prognostic value was not demonstrated in the fully adjusted model (HR = 1.32, 95% CI: 0.94–1.85, p = 0.104), and its discrimination largely reflects differences between WHO 2021 types. This benchmarking framework provides guidance for FM-MIL design in computational pathology applications targeting survival prediction; external validation is required before clinical application.