Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and remains refractory to current therapies. Beyond profound immunosuppression, GBM is characterized by a complex tumor microenvironment (TME) in which neutrophils have emerged as critical yet understudied regulators of tumor progression and immune evasion. Tumor-associated neutrophils (TANs) display marked functional plasticity, acquiring pro-tumor or anti-tumor phenotypes depending on microenvironmental cues. GBM recruits and reprograms infiltrating neutrophils through chemokine-driven trafficking, hypoxia, and tumor-derived cytokines, promoting angiogenesis, glioma stem-like cell support, and immune suppression via vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 release (MMP-9), arginase-1, and neutrophil extracellular traps (NETs). Conversely, under inflammatory or therapeutically modulated conditions, neutrophils can exert cytotoxic and antibody-dependent anti-tumor functions and enhance T-cell responses. Clinically, elevated neutrophil-to-lymphocyte ratios and intratumoral neutrophil transcriptional signatures correlate with poor prognosis and resistance to immunotherapy. Emerging therapeutic strategies aim to modulate neutrophil recruitment, metabolism, polarization, and NET formation, often in combination with immune checkpoint blockade. This review synthesizes current knowledge of neutrophil biology in GBM, highlights their dualistic roles within the TME, and outlines translational opportunities for neutrophil-targeted therapies.

High-grade gliomas are aggressive, primary, central nervous system tumors with low survival rates due to recurrence and resistance to current therapy models. Recent studies have highlighted the importance between the interaction of glioma cancer cells and cells of the tumor microenvironment (TME). Cancer stem cells and immune cells play a critical role in the TME of gliomas. TMEs in glioma include the perivascular TME, hypoxic TME, and invasive TME, each of which have evolved as our understanding of the involved cellular players has improved. This review discusses the multidimensional aspects of the current targeted therapies and interactions between glioma cells and the TME with specific focus on targeted immunotherapies. Understanding the complexities of the TME and elucidating the various tumor-cell interactions will be critical for facilitating the development of novel precision strategies, ultimately enabling better patient outcomes.

Background: Pleural mesothelioma (PM) is typically diagnosed late during the disease. Earlier detection can increase the chance of effective therapy. Recurrent pleural effusions are the earliest symptoms displaying an array of cytomorphological changes from reactive atypia to malignancy. Diagnosis is possible on effusion cytology by applying molecular and immunocytochemical markers, the main difficulty being when to suspect PM and to differentiate PM from metastatic adenocarcinoma and reactive mesothelial proliferations.Methods: We evaluated the diagnostic performance of two immunocytochemical dual stains (BerEp4/Calretinin and Desmin/Epithelial Membrane Antigen (EMA)) on 149 ethanol‐fixed cytospin preparation as an initial step to solve the mentioned diagnostic difficulty. The immunocytochemical reactivity pattern was evaluated by two independent investigators. The final diagnosis corresponded to PM (n = 20), metastatic adenocarcinoma (n = 83), and mesotheliosis (n = 46) in these cases.Results: Calretinin had 99% specificity and 98% sensitivity for indicating a mesothelial phenotype, while BerEp4 distinguished the adenocarcinoma cases with 98% specificity and 99% sensitivity. EMA displayed 96% specificity and 99% sensitivity in malignant cases, while Desmin without EMA present showed 99% specificity and 96% sensitivity for indicating benign mesothelial proliferation.Conclusions: Interpretation of the four immunoreactions is improved when performed as dual stains. The dual staining is a useful tool in the initial handling of atypical effusions and guides the subsequent choice of antibody panels for more detailed subclassification of malignant effusions.

Background/Objectives: Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare neuroectodermal malignancy of the nasal cavity characterized by aggressive local invasion and variable metastatic potential, with diverse clinical behavior, often presenting at advanced stages. ONB poses challenges for targeted therapeutic strategies, despite advances in surgical and multimodal treatment strategies, because of the rarity of this disease and the limited understanding of its molecular pathophysiology. Methods: A comprehensive review of genomic, multi-omic, and molecular studies was performed to integrate known targeted sites in ONB with the current understanding of its pathophysiology. Results: Recent genetic and molecular studies have identified significant epigenetic and signaling pathway alterations that are critical in pathogenesis and treatment resistance and may serve as potential therapeutic targets. Additionally, novel discovered immunohistochemical and transcriptomic markers, such as IDH2, NEUROD1, and OTX2, offer improved diagnostic specificity and prognostication. Multi-genomic platforms (i.e., multi-omics), involving the combined integration of transcriptomics, epigenetics, and proteomics findings, have led to several recent insights, including the subclassification of neural and basal genomic subtypes, the identification of key driver mutations, and new insights into disease development. This review synthesizes current knowledge on the molecular landscape of ONB, including its tumor origin, immune microenvironment, genetic alterations, and key molecular pathways involved in its pathogenesis. Conclusions: Future research may benefit from integrating these findings into precision medicine approaches, enabling earlier diagnosis and more accurate prognosis.

Background/objectives: Non-small cell lung cancer and pleural mesothelioma are among the most lethal and therapy-resistant tumors in humans. These tumors are diagnosed late, frequently present pleural effusion and develop drug resistance, and the treatment is often inefficient and largely alliative. Therefore, there is an urgent need to refine the selection of drugs and patients for personalized treatment. Methods: To progress the field, we performed a systematic literature review in line with the PRISMA guidelines followed by a narrative synthesis approach to identify themes. Results: The literature to date shows, in general, a positive correlation between the drug-sensitivity of patient-derived cells ex vivo and the clinical outcome. However, only a handful of these studies show a numerical correlation. This, along with the vast diversity of correlated techniques and parameters makes it difficult to directly compare the findings. To build a common knowledge base for future studies, we therefore offer a comprehensive summary of the literature, identify gaps, and suggest future avenues for research. Conclusions: We present unified recommendations for the collection, preparation, and ex vivo sensitivity testing of samples for the future development of personalized medicine.

Background: Intracranial atherosclerotic disease (ICAD) remains a major global cause of ischemic stroke—particularly in Asian, Black, and Hispanic populations—and is characterized by high recurrence rates despite advances in intensive medical management. Objectives: This review synthesizes current evidence on surgical and endovascular approaches for ICAD, including extracranial–intracranial bypass, encephaloduroarteriosynangiosis, angioplasty, and hybrid revascularization strategies. Methods: We performed a structured narrative literature search of PubMed and Scopus. Searches were conducted up to 1 October 2025 using combinations of subject headings and keywords, including “intracranial atherosclerotic disease”, “ICAD”, “intracranial stenosis”, “bypass”, “encephaloduroarteriosynangiosis”, “angioplasty”, “stenting”, “revascularization”, and “stroke”. We also scanned reference lists of key articles and relevant reviews. Non-English language articles were excluded. Results: While randomized trials such as SAMMPRIS, VISSIT, and CASSISS reaffirm intensive medical management as first-line therapy, emerging data suggest that surgical revascularization may benefit select patients with hemodynamic compromise refractory to medical therapy. Recent studies incorporating physiologic imaging—such as PET, SPECT, and perfusion MRI—have refined patient selection, reducing perioperative risk and improving long-term outcomes. Innovations in indirect revascularization, hybrid procedures, and intraoperative imaging continue to expand therapeutic possibilities. However, evidence remains heterogeneous, underscoring the need for well-powered randomized trials integrating modern surgical techniques, objective hemodynamic endpoints, and AI-enhanced imaging analytics. Conclusions: While intensive medical management remains the first-line standard of care, select patients with refractory, hemodynamically significant ICAD may benefit from direct, indirect, or hybrid surgical revascularization. Future directions emphasize personalized, physiology-based management frameworks that combine medical, surgical, and technological advances to optimize stroke prevention and long-term vascular outcomes in ICAD.