LAUSR

Dear Editor: IDH mutations represent an early event in diffuse glioma tumorigenesis and are present in the vast majority of lower grade (WHO II–III) diffuse gliomas and in secondary glioblastomas arising within the cerebral hemispheres in adult patients [1]. Although extremely common in adult brain tumors, IDH mutations are much less prevalent in pediatrics, where different genetic alterations have been identified, including MYB or MYBL1 rearrangement, FGFR1 alterations, BRAFV600E mutation, and mutations in the histone H3 variants [2]. Here, we report the case of a pediatric patient with an IDH mutant diffuse low-grade glioma characterized by a molecular signature usually found in the adult counterpart. The case is of a previously healthy 9-year-old girl referred to the department of pediatrics of our hospital because of a recent history of persisting frontal headache, with no other neurological symptoms. The physical examination was unremarkable. A brain magnetic resonance (MRI) was performed, showing a T2-hyperintense and T1-hypointense small lesion, located posteriorly and superiorly to the left Sylvian fissure, without contrast enhancement (Fig. 1a, b). The interpretation of this imaging finding was not straightforward, and a differential diagnosis between a focal cortical dysplasia and a lowgrade glial/glioneuronal tumor was considered. Therefore, an MRI follow-up program had been started. The clinical course slightly improved with the girl reporting to have less frequent and less severe headache attacks; however, no variation of the size of the lesion was appreciated. In the third surveillance MRI performed at the age of 11, the lesion appeared increased in volume, without other significant radiologic changes (Fig. 1c, d); this behavior was highly suggestive of a glial tumor, and the patient underwent surgical resection. A craniotomy with gross total resection was performed, without evidence of residual disease at the postoperative neuroimages. Pathology was consistent with a diffuse astrocytoma (WHO grade II), characterized by a moderately cellular population of infiltrative glioma cells with irregular ovoid nuclei, without significant mitotic activity, necrosis, or microvascular proliferation (Fig. 2a). The tumor cells were immunopositive for the IDH1-R132H mutant protein (Fig. 2b), had diffuse immunoreactivity for P53, and showed loss of ATRX nuclear expression. The patient did not receive adjuvant therapy and was monitored by serial MRIs. Follow-up images performed every 4 months demonstrated no recurrence of the disease at 1 year post-resection, and the patient continues to be followed with close surveillance imaging. This is a rare case of an IDH mutant diffuse low-grade glioma arising in a child of 9 years of age. The earliest age at which IDH mutation contributes to gliomagenesis is unknown, but was previously thought to be * Enrico Pegolo [email protected]