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Brain tumors are the most common solid neoplasms of childhood, but they are very rarely reported in children with Down Syndrome (DS), who develop more commonly different types of malignancies. In particular, we hereby report the case of an 8-years-old child with DS that presented to our attention for neurological and endocrinological issues. Brain imaging revealed the presence of a mass that was partially resected revealing a histological diagnosis of Pleomorphic Xanthoastrocytoma (PXA), a rare WHO grade II tumor extending from the diencephalic region into the surrounding brain tissue. These tumors can harbor the BRAF mutation p.V600E, targetable by the specific inhibitor Vemurafenib. After confirming the presence of the mutation in the tumor, the patient was treated with Vemurafenib. The treatment proved to be effective, leading to a partial response and a stabilization of the disease. Usually, in patients with DS a reduction of the dose of chemotherapeutic drugs is necessary. Vemurafenib was instead well-tolerated as the only observed adverse effect was grade I skin toxicity. This is, to our knowledge, the first case of a PXA reported in a child with DS and the first DS patient treated with Vemurafenib.

Background: Diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis. Magnetic resonance imaging (MRI) remains the gold standard for non-invasive DIPG diagnosis. MRI features have been tested as surrogate biomarkers. We investigated the direct involvement of cranial nerve V (CN V) in DIPG at diagnosis and its utility as predictor of poor overall survival.Materials and Methods: We examined MRI scans of 35 consecutive patients with radiological diagnosis of DIPG. Direct involvement of CN V was assessed on the diagnostic scans. Differences in overall survival (OS) and time to progression (TTP) were analyzed for involvement of CN V, sex, age, tumor size, ring enhancement, and treatment regimen. Correlations between involvement of CN V and disease dissemination, magnet strength and slice thickness were analyzed. Statistical analyses included Kaplan-Meier curves, log-rank test and Spearman's Rho.Results: After excluding six long-term survivors, 29 patients were examined (15 M, 14 F). Four patients presented direct involvement of CN V. Histological data were available in 12 patients. Median OS was 11 months (range 3–23 months). Significant differences in OS were found for direct involvement of CN V (median OS: 7 months, 95% CI 1.1–12.9 months for involvement of CN V vs. 13 months, 95% CI 10.2–15.7 for lack of involvement of CN V, respectively, p < 0.049). Significant differences in TTP were found for the two treatment regimens (median TTP: 4 months, 95% CI 2.6–5.3 vs. 7 months, 95% CI 5.9–8.1, respectively, p < 0.027). No significant correlation was found between involvement of CN V and magnet strength or slice thickness (r = −0.201; p = NS). A trend toward positive correlation was found between direct involvement of CN V at diagnosis and dissemination of disease at follow-up (r = 0.347; p < 0.065).Conclusions: In our cohort, direct involvement of CN V correlated with poor prognosis. Based on our data, we suggest that in DIPG direct involvement of CN V should be routinely evaluated on diagnostic scans.

Low-grade gliomas (LGG) are the most common central nervous system tumors in children. Prognosis depends on complete surgical resection. For patients not amenable of gross total resection (GTR) new approaches are needed. The BRAF mutation V600E is critical for the pathogenesis of pediatric gliomas and specific inhibitors of the mutated protein, such as Vemurafenib, are available. We investigated the safety and efficacy of Vemurafenib as single agent in pediatric patients with V600E+ LGG. From November 2013 to May 2018, 7 patients have been treated in our Institution; treatment was well-tolerated, the main concern being dermatological toxicity. The best responses to treatment were: 1 complete response, 3 partial responses, 1 stable disease, only one patient progressed; in one patient, the follow-up is too short to establish the clinical response. Two patients discontinued treatment, and, in both cases, immediate progression of the disease was observed. In one case the treatment was discontinued due to toxicity, in the other one the previously assessed BRAF V600E mutation was not confirmed by further investigation. Two patients, after obtaining a response, progressed during treatment, suggesting the occurrence of resistance mechanisms. Clinical response, with improvement of the neurologic function, was observed in all patients a few weeks after the therapy was started. Despite the limitations inherent to a small and heterogeneous cohort, this experience, suggests that Vemurafenib represents a treatment option in pediatric patients affected by LGG and carrying BRAF mutation V600E.