High-grade astrocytoma with piloid features (HGAP) is a recently defined central nervous system (CNS) tumor, first introduced into the 2021 World Health Organization (WHO) classification. While predom Show more
High-grade astrocytoma with piloid features (HGAP) is a recently defined central nervous system (CNS) tumor, first introduced into the 2021 World Health Organization (WHO) classification. While predominantly observed in adults, pediatric cases remain rare and poorly characterized. This study aimed to review the epidemiology, clinical features, and molecular profile of pediatric HGAP. A comprehensive review of studies published from 2018 to 2025 was performed to identify methylation-confirmed HGAP cases in patients aged 18 years or younger. Data extracted from studies included subject demographics, tumor location, histological features, molecular alterations, and the implemented treatment sequence. The search identified 17 pediatric cases meeting the inclusion criteria. The median age at diagnosis was 15 years (range: 4-18 years), and a male predilection of approximately twofold was observed. Tumors most commonly arose in the posterior fossa (56.3%). Recurrent molecular alterations included CDKN2A/B loss (75%), FGFR1 mutations or fusions (55.6%), and ATRX loss (45.5%). This review did not identify definitive clinical or histomolecular differences between pediatric and adult HGAP, underscoring the need for further comparative studies. Pediatric HGAP may represent an underrecognized diagnostic entity within the glioma spectrum, emphasizing the critical role of methylation profiling for accurate diagnosis and classification. Retrospective reclassification of histologically and molecularly ambiguous gliomas is warranted and may reveal additional cases. Larger pediatric cohorts are urgently needed to inform clinical management and refine prognostic stratification. Show less
The improper expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) and the GIP/GIPR axis activation has been increasingly recognized in endocrine tumors, with a potential diagnost Show more
The improper expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) and the GIP/GIPR axis activation has been increasingly recognized in endocrine tumors, with a potential diagnostic and prognostic value. A high tumor-to-normal tissue ratio (T/N ratio) of GIPR was reported both in humans' and in rats' medullary thyroid cancer (MTC), suggesting a direct link between the neoplastic transformation and the mechanism of receptor overexpression. In this study, we evaluated the potential diagnostic and prognostic significance of GIPR expression in a large cohort of MTC patients by correlating GIPR mRNA steady-state levels to clinical phenotypes. The molecular effect of GIP/GIPR axis stimulation in MTC-derived cells was also determined. We detected GIPR expression in ~80% of tumor specimens, especially in sporadic, larger, advanced-stage cancers with higher Ki-67 values. GIPR stimulation induced cAMP elevation in MTC-derived cells and a small but significant fluctuation in Ca2+, both likely associated with increased calcitonin secretion. On the contrary, the effects on PI3K-Akt and MAPK-ERK1/2 signaling pathways were marginal. To conclude, our data confirm the high T/N GIPR ratio in MTC tumors and suggest that it may represent an index for the degree of advancement of the malignant process. We have also observed a functional coupling between GIP/GIPR axis and calcitonin secretion in MTC models. However, the molecular mechanisms underlying this process and the possible implication of GIP/GIPR axis activation in MTC diagnosis and prognosis need further evaluation. Show less