Meningiomas are mostly benign tumors that, at times, can behave aggressively, displaying recurrence despite gross-total resection (GTR) and progression to overt malignancy. Such cases represent a clinical challenge, particularly because they are difficult to recognize at first diagnosis. SOX2 (Sex-determining region Y-box2) is a transcription factor with a key role in stem cell maintenance and has been associated with tumorigenesis in a variety of cancers. The purpose of the present work was to dissect the role of SOX2 in predicting the aggressiveness of meningioma. We analyzed progressive/recurrent WHO grade 1–2 meningiomas and WHO grade 3 meningiomas; as controls, non-recurring WHO grade 1 and grade 2 meningioma patients were enrolled. SOX2 expression was evaluated using both immunohistochemistry (IHC) and RT-PCR. The final analysis included 87 patients. IHC was able to reliably assess SOX2 expression, as shown by the good correlation with mRNA levels (Spearman R = 0.0398, p = 0.001, AUC 0.87). SOX2 expression was an intrinsic characteristic of any single tumor and did not change following recurrence or progression. Importantly, SOX2 expression at first surgery was strongly related to meningioma clinical behavior, histological grade and risk of recurrence. Finally, survival data suggest a prognostic role of SOX2 expression in the whole series, both for overall and for recurrence-free survival (p < 0.0001 and p = 0.0001, respectively). Thus, SOX2 assessment could be of great help to clinicians in informing adjuvant treatments during follow-up.

Medulloblastoma represents a rare yet complex embryonal tumor of the posterior cranial fossa that, while predominantly affecting pediatric populations, occurs with increasing recognition among adolescents and young adults (AYAs, 15–39 years). The scarcity of medulloblastoma within this demographic creates substantial obstacles in diagnosis, treatment selection, and psychosocial management that differ markedly from established pediatric approaches. Emerging data reveal that AYA patients exhibit distinctive tumor biology, including altered molecular subgroup patterns, variable therapeutic responses, and unique survival trajectories when compared to younger patients. Current investigations examining autologous stem cell transplantation following intensive chemotherapy protocols in metastatic cases demonstrate encouraging preliminary results. Evidence increasingly supports adapting pediatric treatment paradigms for adult application, potentially improving therapeutic outcomes while reducing treatment burden. These cross-disciplinary approaches between pediatric and adult oncology demonstrate considerable promise for enhancing clinical results and minimizing therapy-associated morbidity, emphasizing the critical need for collaborative care models in managing this challenging malignancy across diverse age groups.

Medulloblastoma is the most common malignant brain tumor in children, but it presents distinct challenges when occurring in adolescents and young adults (AYAs, aged 15–39 years). Recent molecular profiling has identified four principal medulloblastoma subgroups—WNT-activated, SHH-activated, Group 3, and Group 4—each demonstrating unique biological characteristics and clinical outcomes. AYA patients exhibit age-specific molecular patterns and therapeutic responses substantially different from those of younger children. This review synthesizes current evidence regarding epidemiology, diagnostic challenges, molecular characterization, risk stratification, treatment modalities, and outcomes specific to AYA medulloblastoma patients, highlighting the critical need for age-adapted therapeutic strategies and dedicated clinical research in this underserved population.

Background/Objectives: to compare and characterize the frequency and severity of treatment-related adverse events (TRAEs) experienced by pediatric and adult patients with medulloblastoma receiving the same pediatric-based treatments. Methods: a retrospective comparative study of TRAEs was conducted on 18 adult patients and 45 pediatric patients with medulloblastoma treated at the same institution with craniospinal/local radiotherapy and chemotherapy delivered according to pediatric regimens (i.e., PNET3, PNET4, PNET5 or high-risk protocols). Results: Grade ≥ 3 hematological TRAEs were significantly more frequent in adults (61.1% vs. 33.3%, p = 0.038). Adults also more frequently suffered from weight loss > 10% than children (72.2% vs. 40%, p = 0.018). The incidence of chemotherapy-induced peripheral neuropathy did not differ significantly between the two groups (27.7% in adults versus 22.2% in children, p = 0.65). These findings suggest that adult patients treated with pediatric-derived protocols may benefit from more proactive hematologic and nutritional supportive care to safely maintain treatment intensity. Objective severe ototoxicity was 22.2% and 17.8% in adults and children (p = 0.69), respectively. There were significantly more adults than children who needed a dose reduction (55.6% vs. 28.9% in children, p = 0.042) and who stopped treatment prematurely (44.4% vs. 20.1% in children, p = 0.048). There was no difference in 5-year overall survival between adults and the pediatric population (88.8% vs. 86.7%, p = 0.82). Conclusions: Adults are at an increased risk of hematological and nutritional toxicities when treated for medulloblastoma with identical treatment regimens. These age-related patterns of sensitivity demand protocol modifications (such as more supportive care, nutritional support, and possibly lower dose intensities). Although there were more treatment modifications due to more severe toxicity, adults had the same survival rates as children, suggesting pediatric-based protocols should still be employed with modifications to supportive care.

Grade 3 meningiomas are rare malignant tumors that can originate de novo or from the progression of lower grade meningiomas. The molecular bases of anaplasia and progression are poorly known. We aimed to report an institutional series of grade 3 anaplastic meningiomas and to investigate the evolution of molecular profile in progressive cases. Clinical data and pathologic samples were retrospectively collected. VEGF, EGFR, EGFRvIII, PD-L1; and Sox2 expression; MGMT methylation status; and TERT promoter mutation were assessed in paired meningioma samples collected from the same patient before and after progression using immunohistochemistry and PCR. Young age, de novo cases, origin from grade 2 in progressive cases, good clinical status, and unilateral side, were associated with more favorable outcomes. In ten progressive meningiomas, by comparing molecular profile before and after progression, we identified two subgroups of patients, one defined by Sox2 increase, suggesting a stem-like, mesenchymal phenotype, and another defined by EGFRvIII gain, suggesting a committed progenitor, epithelial phenotype. Interestingly, cases with Sox2 increase had a significantly shortened survival compared to those with EGFRvIII gain. PD-L1 increase at progression was also associated with worse prognosis, portending immune escape. We thus identified the key drivers of meningioma progression, which can be exploited for personalized treatments.