Case ReportA previously healthy 12-year-old boy was admitted to the hospital with vision loss, headache and dizziness over 1 month, which was aggravated in the last 5 days. Magnetic resonance imaging (MRI) of the head revealed a large (19.8 mm*18.5 mm*23.5 mm) irregular mass located in the suprasellar region abutting the left aspect of the optic chiasm. It appeared isointense on T1-weighted imaging (T1WI) and homogenously hyperintense on T2-weighted imaging (T2WI). After gadolinium administration, a well-circumscribed enhancing lesion was observed ( Figures 1A–E ). A small cerebellar lesion was also confirmed.Open in a separate windowFigure 1Brain MRI at admission (A–E). (A, B) Axial view (weighted sequence in T1, T2). (C–E) Sagittal, coronal, axial view after contrast injection, with the tumor marked. (F, G) Brain MRI after surgery. (H) Pancreatic cysts.The mother of the patient underwent surgery for HGB in the CNS (spine, cerebellum) and had pheochromocytomas and pancreatic cysts. On the basis of the mother’s medical history, clinical manifestations and imaging examinations, she was diagnosed with VHL disease, although she refused genetic sequencing. Therefore, the patient was examined for VHL disease before surgery. Sequencing of exon 1 of the VHL gene revealed a c.257C>T mutation (amino acid p.P86L). Ophthalmological examination revealed that the boundary of the optic disc in the left eye was pale and that there were no abnormalities in the right eye. Abdominal computed tomography (CT) was also performed to identify associated lesions and pancreatic cysts ( Figure 1H ). Based on these findings, the patient was definitely diagnosed with VHL syndrome.He underwent surgery to remove the tumor from the suprasellar region at our neurosurgical department, and histology confirmed the diagnosis of HGB ( Figures 2 and 3 ). The cerebellar lesion was not in the same surgical field as the suprasellar tumor and had no obvious mass effect, so they were not treated at the same time. Immunohistochemical analysis indicated that the Ki-67 index was approximately 2%. Furthermore, the neoplasm was positive for EGFR, NSE, CD34 and vimentin and negative for CK-pan, Pax-8, CD10, CD56, S-100, glial fibrillary acidic protein, inhibin, SSTR2, and epithelial membrane antigen ( Figure 2 ).Open in a separate windowFigure 2Representative postoperative pathological images. (A) Histologic examination of optic nerve HGB. (B–F) Immunohistochemical staining. (B) The proliferative fraction of tumor cells (Ki-67) was low, at approximately 2%. (C) CD-34 showed abundant blood vessels. Tumor cells showed positivity for EGFR (D), NSE (E) and vimentin (F).Open in a separate windowFigure 3Surgical pictures. Severe adhesion of the tumor and left optic nerve.The patient was transferred to the neurosurgery intensive care unit for postoperative monitoring and was ambulatory on postoperative day 1. Postoperative MRI ( Figures 1F, G ) demonstrated that the lesion in the suprasellar region was completely removed. He was discharged on postoperative day 7, and regular follow-up was performed. Unfortunately, the patient lost vision completely in the left eye after surgery.Go to:DiscussionHere, we reported a pediatric case of VHL disease presenting with HGBs in the optic nerve and cerebellum and pancreatic cysts. The diagnosis of VHL disease was confirmed by the identification of a familial germline mutation located in the first exon of the VHL gene (c.257C>T, p.P86L), which has been reported in the Human Gene Mutation Database and VHLdb databases (14, 15). To date, only 7 pediatric cases of sellar or suprasellar HGB (including optic nerve HGBs) have been reported ( Table 1 ). Regarding suprasellar HGBs, the pituitary stalk may be the site of origin in the vast majority of cases and, rarely, the intracranial portion of the optic nerve. In our case, we confirmed during surgery that the tumor was mainly located inside the optic nerve without a discernible tumor capsule and without the involvement of the leptomeninges. Given the rarity of suprasellar VHL-associated HGBs in childhood, we review the genotype-phenotype association of VHL disease, treatment, natural history and follow-up.