We report the first case of pleural mesothelioma (PM) occurring in a child affected by NF2-related schwannomatosis (NF2-SWN) and without any history of environmental exposure to asbestos. Mesothelioma is a rare secondary tumor in brain cancer patients and the association with NF2-SWN has been described only in a few anecdotal cases and never in the pediatric field. NF2-SWN is an autosomal dominant disease caused by inactivating germline mutations of the NF2 tumor suppressor gene, one of the most common mutations associated with human primary mesothelioma too. By MLPA assay, array-CGH analysis, and NGS on blood and tumor DNA, we determined the mutation profile of this rare NF2-driven PM and we identified several atypical chromosomal aberrations in tumor cells, suggesting a different genomic signature between pediatric and adult mesothelioma.

Background: Gorlin syndrome (GS) is a rare autosomal dominant disorder, associated with pathogenic PTCH1 or SUFU variants, predisposing to tumors such as basal cell carcinoma, medulloblastoma (MB), odontogenic keratocyst, and, rarely, cardiac fibroma (CF). MB occurs in ~5% of GS cases, typically in early childhood, while CF appears in 1–3%. Their coexistence in childhood is extremely rare. This report describes a pediatric GS case with synchronous MB and CF, focusing on the management priorities between oncologic and cardiac interventions. Methods: A 15-year follow-up is reported for a girl diagnosed at 22 months with desmoplastic/nodular MB and left ventricular CF. GS diagnosis was based on clinical features, imaging, and confirmation of a pathogenic PTCH1 variant (c.3306+1G>T). A literature narrative review on CF in GS was also conducted. Results: MB gross total resection was followed by chemotherapy, during which ventricular tachycardia episodes occurred, managed with cardioversion and antiarrhythmics. Given the favorable prognosis of early-treated MB in GS, oncologic therapy was prioritized. Cardiac status was monitored with ECG, Holter, echocardiography, and cardiac MRI. An adapted AIEOP protocol minimized cardiotoxicity. CF was managed conservatively, with no further arrhythmias and preserved ventricular function throughout 15 years. MB has not recurred. Conclusions: In GS patients with concurrent MB and CF, prioritizing MB treatment and adopting a conservative, closely monitored approach to CF can yield excellent long-term outcomes. In children with MB, especially syndromic forms, routine echocardiography is recommended to detect CF. This case underscores the value of multidisciplinary care in managing complex GS presentations.

Background/Objectives. Pediatric brain tumor survivors (PBTS) are at increased risk of cardiometabolic complications due to tumor- and treatment-related hypothalamic–pituitary (HP) damage and adverse body composition. We evaluated associations of the Single-Point Insulin Sensitivity Estimator (SPISE) with central adiposity, DXA-derived body composition, metabolic abnormalities, and HP involvement. Methods. In this retrospective study, 119 PBTSs (median age, 12.7 years; median time since therapy, 2.4 years) were evaluated. SPISE, BMI, waist-to-height ratio (WHtR), DXA-derived fat-to-lean ratio (FLR), and metabolic syndrome (MetS) were assessed. Multivariable logistic regression evaluated the association between SPISE and central adiposity. Exploratory receiver operating characteristic analyses compared the discriminatory performance of SPISE, BMI-SDS, HOMA-IR, and FLR. Results. Central adiposity was present in 58.8% of participants, whereas BMI-defined obesity occurred in 21.8%. Lower SPISE values were associated with central adiposity, obesity, MetS, HP damage, and multiple pituitary hormone deficiencies (all p < 0.05). SPISE declined across pubertal stages and remained associated with central adiposity after adjustment for age and selected HP variables (OR = 0.58, 95% CI 0.46–0.73). SPISE showed good discrimination of central adiposity (AUC = 0.81), with an exploratory, cohort-derived threshold of 7.82; FLR provided complementary information on body composition. Conclusions. Central adiposity was common and not fully captured by BMI-defined obesity. Lower SPISE values were associated with concurrent anthropometric and metabolic abnormalities, while DXA-derived FLR added descriptive information on body composition. Whether these indices improve cardiometabolic risk stratification beyond conventional measures requires prospective investigation.