Sellar region neurocytoma (SELN) is a rare neoplasm whose relationship to other neurocytomas within the central nervous system (CNS) has remained unclear. Prior reports have variably classified SELN as a variant of extraventricular neurocytoma (EVN), while immunohistochemical and ultrastructural studies have suggested a hypothalamic origin. Here, we performed unsupervised clustering of DNA methylation data across a large pan-cancer reference set and identified SELN (n = 20) as distinct from other neurocytomas and regional mimics, as well as clustering with neuroendocrine tumors from other organ sites. SELN exhibited a CIMP-like phenotype, TTF1 negativity (0/8), and AVP (vasopressin) promoter hypomethylation, implicating a magnocellular hypothalamic cell of origin. In evaluable cases, a neuronal/neuroendocrine immunophenotype was observed (synaptophysin 8/8, chromogranin A 5/5) with absent pituitary transcription factor expression (PIT1 and TPIT negative 0/4). DNA sequencing (n = 5) and RNA-based fusion profiling (n = 4) did not detect recurrent mutations or gene fusions, respectively. Patients often presented with visual disturbances or headaches and spanned pediatric and older age groups (median 42 years, range 12.5–75), with no sex predilection. Despite locally aggressive imaging features in some cases (cavernous sinus invasion, carotid encasement, hydrocephalus), disease-free survival (n = 13) was comparable to central neurocytoma, with no disease-related deaths during the limited follow-up. Together, these findings support SELN as a molecularly distinct hypermethylated neuroendocrine-like epitype and clinicopathologic entity.

MUTYH-associated polyposis (MAP) is an autosomal recessive tumor syndrome caused by biallelic mutations in the MUTYH gene, primarily associated with an increased risk of colorectal adenomas and carcinoma. However, the tumor spectrum in heterozygous MUTYH mutation carriers remains poorly defined. Here, we report the first case of a patient with a germline heterozygous MUTYH mutation who developed metachronous multiple primary tumors. The patient initially presented with a thyroid collision tumor (synchronous papillary thyroid carcinoma and medullary thyroid carcinoma) at age 55. Two years later, he was diagnosed with non-keratinizing squamous cell carcinoma of the thymus, accompanied by left cervical lymph node metastasis of papillary thyroid carcinoma (PTC). Subsequent next-generation sequencing of the lymph node metastasis revealed a novel heterozygous MUTYH frameshift mutation, c.848delT (p.M283Rfs*3), which was confirmed to be of germline origin by Sanger sequencing of the patient’s normal thyroid tissue. This case expands the disease spectrum associated with heterozygous MUTYH carriers and enhances the understanding of the phenotypic heterogeneity of tumors in this population.

Meckel’s cave (MC) epidermoid cysts (EC) are rare lesions. Extended endoscopic endonasal approaches (EEA) to the ventral skull base recently opened a minimally invasive corridor to MC. The aim of this study was to report our surgical experience and review the concerning literature. Our institutional registry was retrospectively reviewed, and patients who underwent an endoscopic endonasal approach for MC EC from 1998 to 2025 were included. Cases involving alternative surgical approaches or lesions with different histological diagnoses were excluded. A PRISMA systematic review of the literature was performed. The cohort consisted of 4 patients who underwent 6 endoscopic endonasal procedures (one patient experienced two recurrences and underwent two additional EEAs). Complete resection of the cyst content was achieved in 4 procedures (66.7

OBJECTIVE:An SF3B1 (Somatic splicing factor 3B subunit 1) mutation has been associated with prolactin-secreting pituitary neuroendocrine tumours (PitNET) with increased proliferation, invasion, dopamine agonist resistance and reduced progression-free survival. DESIGN:We screened a multi-centric cohort of 127 patients with prolactin-secreting PitNET for the SF3B1R625H mutation using digital PCR. METHODS:A comparative analysis was conducted between wild-type and mutated tumours, assessing clinical parameters, including age at diagnosis, sex distribution, prolactin levels, tumour size, extent of invasion, recurrence, and response to dopamine agonists. RESULTS:Somatic SF3B1R625H mutation was found in 21/127 patients (17%), who were diagnosed at a younger age (P = .04) and had larger tumour diameter (P = .03). Patients who needed transcranial surgery had a higher mutation frequency in their tumour samples compared to the transsphenoidal group (P = .01). The occurrence of mutation was similar in males and females. Preoperative and postoperative prolactin levels were comparable in patients with mutant and wild-type tumours. No associations were observed between mutation and tumour invasiveness, Ki-67 proliferation index, p53 expression, recurrence and dopamine agonist resistance. Hypopituitarism at presentation, visual deficits, number of surgeries and disease-free survival were not different between the groups. CONCLUSION:SF3B1 somatic mutation status in lactotroph tumours-as assessed by digital PCR technology-is associated with a younger age at diagnosis and larger tumour diameter. However, in our cohort, it does not appear to be associated with histological features, higher recurrence, treatment resistance, tumour invasiveness, or long-term outcomes in our multi-centric cohort.

OBJECTIVE:An endoscopic endonasal approach (EEA) is widely adopted for most craniopharyngioma surgeries due to its favorable clinical outcome. However, its role in recurrent tumors has not been fully assessed. The aim of this study was to analyze the surgical outcome of EEA in recurrent craniopharyngioma, assessing factors associated with radical resection and progression-free survival (PFS). METHODS:Consecutive patients with craniopharyngioma treated with surgery using an EEA at a single institution (1998-2024) were retrospectively reviewed. Those who met the inclusion criteria were divided into recurrent (prior treatment) and treatment-naive (no prior treatment) groups. Preoperative patient- and tumor-related features, surgical and clinical outcomes at follow-up, and complications were assessed and compared between the two groups. RESULTS:Overall, 126 patients (69 female, mean age 51.1 years) with craniopharyngioma treated using the EEA were included, 31 (24.6%) with recurrence and 95 (75.4%) who were treatment-naive. In the recurrent group, radical resection was achieved in 24 patients (77.4%), and the most common complication was CSF leakage (19.4%). No significant differences were observed for rates of resection and morbidity between the two groups. Radical resection of recurrent craniopharyngioma was associated with a previous transcranial surgical approach (p = 0.030) and a lower preoperative BMI (p = 0.014). In the overall cohort, longer PFS was correlated with no intraventricular extension (p = 0.004) and radical resection (p < 0.001). CONCLUSIONS:EEA proved to be a valid option for strictly selected patients with recurrent craniopharyngioma, with surgical and clinical outcome similar to those observed for treatment-naive patients. Radical resection and PFS were associated with both biological and technical factors, which should be taken into account in surgical planning and preoperative patient counseling.

Primary meningeal melanocytic tumors (PMMTs) are rare neoplasms currently stratified by the World Health Organization (WHO) into three grades of malignancy based exclusively on histopathological criteria, while the prognostic significance of molecular alterations remains poorly defined. This study aimed to investigate the prognostic relevance of histopathological and molecular features in PMMTs and to assess the diagnostic utility of immunohistochemical and molecular markers for distinguishing PMMTs from malignant melanotic nerve sheath tumors (MMNSTs). Thirty-six primary central nervous system (CNS) melanocytic tumors, including 24 PMMTs (10 grade 1, 12 grade 2, and 2 grade 3) and 12 MMNSTs, were analyzed through integrated histopathological, immunohistochemical, genetic, and epigenetic characterization. Among grade 2 PMMTs, descriptively defined CNS-invasive otherwise benign melanocytomas defined a clinically favorable subgroup, whereas SF3B1 mutations and chromosome 8q gains were associated with higher recurrence rates and shorter recurrence-free survival. Losses of chromosome 17 or 21q were observed exclusively in MMNSTs, supporting their potential diagnostic utility in distinguishing MMNSTs from PMMTs. These findings demonstrate biological heterogeneity among intermediate-grade PMMTs and identify molecular markers associated with adverse clinical outcomes. Integrated histopathological and molecular characterization may enhance prognostic stratification and diagnostic accuracy in primary CNS melanocytic tumors.

Purpose:Available prognostic scores for adult-type diffuse glioma with isocitrate dehydrogenase (IDH) mutant were validated before the evaluation of biomolecular features. The selection of patients who did not receive postoperative radiotherapy and chemotherapy would provide an ideal setting to describe the natural history of these tumors. Methods:We investigated the clinical outcomes of patients with adult-type diffuse glioma with isocitrate dehydrogenase IDH mutation approached with active surveillance after primary surgery. Results:We evaluated 61 patients consisting of 35 patients with IDH-mutant astrocytomas and 26 patients with IDH-mutant 1p19q oligodendrogliomas. The median follow-up was 13.1 years (95% CI 11.4-17.7). A total of 56 progression-free survival events were available at the time of analysis. The median age was 32.2 years, higher in IDH-mutant 1p19q oligodendrogliomas (39.5 years) compared to IDH-mutant astrocytomas (31.4 years; p = 0.003). Residual tumor [hazard ratio (HR) 2.63, 95% CI -1.23 to 5.58, p = 0.007], post-surgical diameter product (HR 1.11, 95% CI 1-1.22, p = 0.03), and midline crossing (HR 6.79, 95% CI 1.5-30.4, p = 0.005) were the only factors directly influencing progression-free survival in univariate analyses. No variables confirmed their predictive role in multivariate models. At the time of data analysis, we registered 22 overall survival (OS) events. In a multivariate Cox regression model, histo-molecular diagnosis (oligodendroglioma vs. astrocytoma; HR 0.28, 95% CI 0.10-0.8, p = 0.02) and initial tumor area assessed as continuous variables (HR 1.82, 95% CI 1.01-3.3, p = 0.05) independently affected the survival of patients (p = 0.01). Conclusions:In our series, the presence and dimension of residual tumors and midline crossing were the only independent variables predicting progression-free survival after primary surgery in grade 2 diffuse glioma.

Glioblastoma is the most aggressive and prevalent tumor of the Central Nervous System (CNS) with limited treatment options and poor patient outcomes. Standard therapies, including surgery, radiation, and chemotherapy, provide only modest survival benefits, highlighting the need for innovative therapeutic approaches. This study investigates a novel strategy targeting prelamin A processing in glioblastoma cells. By inhibiting the farnesyltransferase enzyme using SCH66336 (Lonafarnib), we promote the accumulation of lamin A precursor (prelamin A) in glioblastoma cells, thereby increasing their susceptibility to oxidative stress induced by Menadione administration, while sparing normal human astrocytes. Notably, the combined SCH66336-Menadione treatment reduced cell proliferation, modified the expression of stemness markers, and decreased viability in patient-derived glioblastoma stem cells, which represent the population responsible for tumor aggressiveness and recurrence. These findings indicate that inhibiting prelamin A processing could be a potential strategy to reduce glioblastoma aggressiveness and enhance therapeutic outcomes, particularly for treatment-resistant glioblastoma stem cell populations. This approach shows potential for integrating prelamin A processing disruption as a complementary strategy in glioblastoma therapy.

I tumori neuroendocrini ipofisari (PitNET)/adenomi ipofisari costituiscono un insieme eterogeneo di neoplasie la cui classificazione diagnostica anatomo-patologica è stata oggetto di numerose revisioni nonostante le quali diversi aspetti rimangono oggetto di discussione. L’obiettivo principale della presente rassegna è di fornire un riepilogo dell’attuale sistema classificativo, delle relative limitazioni, dei possibili algoritmi diagnostici e del ruolo della diagnostica molecolare.

Seizures are a common and challenging symptom in brain tumors, affecting approximately 60% of patients. Tumor-related epilepsy (TRE) in glioma patients requires personalized and dynamic management in a multidisciplinary environment, especially for its intricate pathophysiology and unpredictable disease evolution. This investigation provides an updated overview about the pathophysiological mechanisms and treatment options of TRE associated with gliomas, based on expert contributions belonging to different areas. By combining the most recent discoveries and expert opinions, this study seeks to provide useful advice for TRE management in glioma patients. To improve patient outcomes and quality of life, prospective, standardized, multicentric studies should be promoted to optimize TRE patient care and refine therapeutic approaches.

Introduction:Recently, the endoscopic endonasal approach (EEA) has been proposed as a possible surgical option for benign and malignant tumors, located in the infratemporal (ITF) and pterygopalatine fossae (PPF). The aim of this study is to analyze the surgical outcome of the EEA for these lesions, identifying the preoperative factors affecting tumor resection. Materials and methods:All consecutive cases of PPF and ITF tumors operated through an EEA have been retrospectively collected. Preoperative clinical and radiological features, surgical outcome, complications and patient follow-up have been analyzed. A systematic review of literature has been performed. Results:The series includes 100 patients (66 males, 66.0%, mean age: 43.7 ± 22.1). The most common histotypes were juvenile angiofibromas (36 cases, 36.0%), malignancies (26, 26.0%), and chordomas (14, 14.0%). Gross total resection of the PPF/ITF portion of the tumor was achieved in 88 (88.0%) patients. The most common complication was represented by 10 cases (10.0%) of V2 hypoesthesia (3 transient). At logistic regression, tumor location in the temporo-masseteric and tubo-pharyngeal zones proved negatively associated with the GTR rate (p:0.05, p<0.01). Conclusion:EEA is an effective and safe approach for both benign and malignant tumors involving the PPF and ITF. It is characterized by a favorable complications rate and a quick patients recovery. We observed that the tumor extensions in the temporo-masseteric area and in the tubo-pharyngeal space were the most relevant factors negatively associated with complete tumor removal.

Background: The androgen receptor (AR) is a ligand-dependent transcription factor of the nuclear steroid receptor superfamily, implicated in the pathogenesis of various solid tumors. The AR gene, located on chromosome Xq11–12, is accompanied by several X-linked genes that modulate AR expression and function, including FLNA, UXT, and members of the melanoma antigen gene (MAGE) family (MAGEA1, MAGEA11, MAGEC1, MAGEC2). While the AR has been investigated in multiple tumor types, its role in adult-type diffuse gliomas remains largely unexplored. Here, we characterized AR protein expression and the promoter methylation status of the AR and associated regulatory genes in adult-type diffuse gliomas. Methods: A retrospective analysis was conducted on 50 patients with adult-type diffuse gliomas, including IDH-mutant gliomas (grades 2–4) and IDH-wildtype glioblastomas (GBMs), classified according to the 2021 WHO criteria. AR nuclear expression was assessed by immunohistochemistry (IHC). Methylation-specific PCR and quantitative DNA methylation analyses were employed to evaluate promoter methylation of the AR and selected co-regulatory genes. Results: AR nuclear positivity correlated significantly with male sex (p = 0.04) and higher tumor grade, with the highest expression in IDH-wildtype GBMs (p = 0.04). In IDH-mutant gliomas, AR immunoreactivity was more prevalent in astrocytomas than in 1p/19q codeleted oligodendrogliomas (p = 0.02). AR expression was associated with unmethylated MGMT promoter status (p = 0.02). DNA methylation analysis revealed AR gene hypomethylation in tumors displaying nuclear AR positivity and in IDH-wildtype GBMs (Kruskal–Wallis p < 0.05). Additionally, methylation patterns of AR co-regulators located on the X chromosome suggest epigenetic regulation of AR signaling in gliomas. Conclusions: The findings reveal distinct AR pathway activation patterns in adult-type diffuse gliomas, particularly IDH-wildtype GBMs, suggesting that further exploration of antiandrogen therapies is warranted.

Background/Objectives: Astroblastoma is a rare glial neoplasm more frequent in young female patients, with unclear clinical behaviors and outcomes. The diagnostic molecular alteration is a rearrangement of the Meningioma 1 (MN1) gene. MicroRNAs (miRNAs) are important gene expression regulators with strong implications in biological processes. Here, we investigated microRNA expression, regulation, and biological processes correlated to target genes of deregulated miRNAs in MN1-altered astroblastoma. Methods: A cohort of 14 tumor samples, histologically classified as astroblastoma, was retrospectively collected and analyzed through their DNA methylation profiles. MiRNA expression profiles were then detected on MN1-altered astroblastomas (n = 8) and normal brain controls (n = 2) by Nanostring technology and validated by RT-qPCR; then, the expression of deregulated miRNAs was correlated with clinical-pathological characteristics. Subsequently, the methylation status of promoters of deregulated miRNAs was investigated through a methylation profiling microarray. Finally, bioinformatics analysis was conducted to explore the biological processes (BPs) and target genes of differentially expressed miRNAs. Results: Eight MN-altered astroblastoma were identified. Thirty-nine miRNAs were deregulated in tumor samples compared to normal brain tissue. Downregulated microRNAs exhibited an association with an increased risk of recurrence. The promoter methylation status was investigated in 32/39 miRNAs: 14/32 were epigenetically deregulated. None of them were genetically regulated. Conclusions: MN1-altered astroblastomas have an miRNA expression signature that identifies specific BPs and pathways. Our findings suggested that the involved pathways could be associated with clinical and pathological characteristics of MN1-altered astroblastomas. Also, the biology of this rare tumor could have potential implications on prognostic markers and therapy.

BACKGROUND:Glioblastoma isocitrate dehydrogenase IDH-wildtype (GBM IDHwt) in elderly patients presents challenges due to biological heterogeneity and under-representation in clinical trials. Despite rising incidence, prognostication remains inadequate, with treatment decisions based on subjective criteria. OBJECTIVE:To determine clinical, radiological, surgical, and molecular determinants of survival in elderly GBM IDHwt patients and explore prognostic utility of machine learning (ML) models using clinical and pretreatment data. METHODS:We analyzed 155 patients aged ≥70 years with confirmed GBM IDHwt who underwent neurosurgery at a tertiary care institution. We examined variables related to clinical presentation, imaging, surgery, and molecular markers using multivariate regression and Histogram Gradient Boosting Regression ML models. Two ML models were developed: one incorporating full dataset variables, and another focusing on preoperative features. RESULTS:Median overall survival (OS) was 11.3 months for patients undergoing resection and 3.7 months for biopsy. Independent predictors of prolonged OS included gross total resection (GTR), O6-methylguanine-DNA methyltransferase promoter methylation, nonacute symptom onset, and concomitant radiotherapy with temozolomide (RT + TMZ). ML models confirmed RT + TMZ and GTR as strongest predictors, while Karnofsky Performance Status showed negative importance. Body mass index (BMI) emerged as impactful; and the pretreatment model emphasized BMI and cognitive decline. CONCLUSIONS:This study confirmed prognostic relevance of GTR, O6-methylguanine-DNA methyltransferase methylation, and RT + TMZ combination. Baseline Karnofsky Performance Status and age did not demonstrate independent prognostic value, while BMI and cognitive decline were potential preoperative predictors. Our findings advocate a multidimensional, data-driven approach to preoperative risk stratification in elderly GBM patients, which may facilitate individualized treatment strategies.

Skull base osteosarcoma is an exceedingly rare malignancy. Unlike maxillofacial osteosarcomas, there are only few cases of skull base tumors reported in literature, and their clinical behavior and treatment outcome are not well defined. This study aims to characterize the clinical features and outcomes of primary skull base osteosarcoma based on our experiences of 9 cases and to review available literature data. A retrospective analysis was done on 9 cases of skull base osteosarcoma diagnosed at IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy, from 1995 to 2023. Clinicopathologic features were reported, and survival outcomes were analyzed. Literature review was performed by searching the PubMed database for published cases of skull base osteosarcoma. Kaplan–Meier survival analysis was used to calculate 1-year, 3-year, and 5-year survival rates. Patients were 5 males and 4 females, with an age range of 5–72 years (mean: 39 years). Tumor location was frontal (3), sphenoid/ethmoid (3), occipital (2), and temporal (1) bone. Seven patients had subtotal resections; Two had total resection, but only one achieved negative margin. Follow-up duration ranged from 4 to 256 months (median: 28 months). Local recurrence occurred in 4 patients. At last follow-up, 5 patients were alive, with 3 had no evidence of disease (NED) and 2 alive with disease (AWD), while 4 patients died of disease (DOD). One-year, 3-year, and 5-year survival were 88.9

Sphenoid wing meningiomas are slow-growing tumors arising in a region crossed by crucial neurovascular structures, for which surgery poses significant challenges. In the last decade, several cadaveric and clinical studies have proven the effectiveness of endoscopic transorbital surgery for skull base pathologies in accordance with the principles of minimal invasiveness. The ventral surgical corridor offered by this approach allows the early devascularization of the lesion without brain retraction, temporal muscle mobilization, and limited neurovascular structure manipulation. This 2D operative video describes the removal of a sphenoid wing meningioma using an endoscopic transorbital transpalpebral approach with minimal morbidity and quick recovery. The video can be found here: https://stream.cadmore.media/r10.3171/2025.1.FOCVID24179.

Compared to conventional morphological MR imaging, diffusion tractography may improve the visualization of the anterior optic pathway (AOP), thus enhancing the understanding of its anatomical relationship with surrounding sellar/parasellar tumors (SPTs). We aimed to develop a diffusion tractography pipeline for automatic and reliable reconstruction of the AOP and to investigate its microstructural alterations in SPT patients. A multishell diffusion protocol (b-values = 0,300,1000,2000 s/mm2; 64 maximum gradient directions; 2-mm isotropic voxel) on a 3T scanner, followed by a fully automated pipeline developed in-house to perform the probabilistic tractography, based on multishell-multitissue constrained spherical deconvolution modeling of the signal, was performed. It was first tested retrospectively in 10 healthy controls, then prospectively applied in 25 additional healthy controls and 35 SPTs patients. Microstructural parameters were compared between patients and controls using an along-tract approach. The study included 70 subjects: 35 healthy controls (18 females, mean age 50.7 ± 14.3 years) and 35 patients with SPTs displacing the optic chiasm (18 females; mean age 53.7 ± 16.4 years). The AOP reconstruction was successfully performed in all normal controls and patients. A correct correspondence with surgical inspection was identified in 84.7 % of patients who underwent surgery. Patients had significantly lower mean diffusivity (MD) values at the level of the chiasm (p < 0.01), that correlated with supero-inferior chiasmatic displacement (R = -0.49, p = 0.01). A novel, fully automated diffusion tractography pipeline for the AOP was developed and validated in patients with sellar/parasellar tumors. Reduced MD values at the chiasm level may indicate compression or gliosis in case of displacement.