Craniopharyngiomas are the most prevalent nonneuroepithelial intracerebral tumor in pediatric practice. 1 They often cause debilitating damage to the endocrine system and are prone to recurrence. 2 Here we describe a case of adamantinomatous craniopharyngioma (adaCP) affecting 2 half-sisters, where whole exome sequencing (WES) produced evidence for a novel tumorigenic event in this condition. Patient 1 (19 years old) and Patient 2 (26 years old) are females of white European origin, born to unrelated parents. Both patients suffered from fatigue and growth retardation and presented with intense headaches, vomiting, and syncopes. In Patient 1, brain MRI detected a heterogeneous, enhancing sellar/suprasellar mass with a cystic component. She underwent a gross total tumor resection through the right subfrontal approach. The tumor was occupying the sella turcica, extending beneath the optic chiasma, lodging between the optic nerves and penetrating the III ventricle. As late as 2 years after the surgery, MRI scans detected no signs of relapse. Similarly, Patient 2 presented with a cystic sellar mass and signs of occlusive hydrocephalus. One year after a subtotal tumor resection, MRI scans detected post-surgery tumor growth, prompting radiation therapy with a cumulative dose of 54 Gy. By the age of 21, the tumor volume ceased further enlargement. The mother of the 2 siblings presented with no evidence for an intracranial tumor. Histopathologic findings in both tumor specimens were typical of an adaCP. The immunohistochemical analysis detected β-catenin nuclear and cytoplasmic localization throughout the whorl structures, as well as nuclear staining in a number of standalone cells (Fig. 1A).

After the institutional ethical committee approval and the patients’ written informed consent, genomic blood DNA samples from both siblings and their mother were analyzed using WES (Illumina NextSeq 550, Illumina TruSeq DNA Exome kit, paired-end libraries 2× 80 bp). Median target coverage was 72x with 92.14% of bases covered at> 10x, and 90.51% of bases covered at> 20x). Bioinformatics analysis was carried out using Genome Analysis ToolKit v4. 1.2. 0 (Broad Institute) and ANNOVAR 3 v2018Apr16 software packages. All 3 subjects shared a previously undescribed heterozygous NM_000038. 5: c. 7455_7458delTCCT: p. S2487fsFX28 variant in exon 16 of the