Papillary craniopharyngioma in a 4-year-old girl with BRAF V600E mutation: a case report and review of the literature

Abstract

Introduction: Craniopharyngiomas are one of the most frequently diagnosed hypothalamo-pituitary tumors in childhood. The adamantinomatous histological subtype accounts for most pediatric cases, while the papillary variant is almost exclusively diagnosed in adults. Here, we report a case of papillary craniopharyngioma in a very young child, confirmed by molecular tissue analysis.

Case report: A 4-year-old girl was being investigated for symptomatic central hypothyroidism. Brain MR imaging revealed a large solid/cystic suprasellar mass, splaying the optic chiasm and measuring 3 × 1.9 × 2.3 cm. The patient underwent a transsphenoidal near total resection of the lesion, which was encased within a tumor capsule. Post-operatively, the patient developed transient diabetes insipidus but otherwise recovered well. The pathology of the lesion was consistent with a papillary craniopharyngioma with regions of stratified squamous epithelium accompanied by superficial goblet cells and ciliated cells. Subsequent next-generation sequencing analysis of the lesion confirmed the presence of a BRAF V600E mutation (BRAFc.1799T>A p. (Val600Glu). To date, she remains free from progression 1 year following surgery.

Conclusion: This is the youngest case published to date of papillary craniopharyngioma with a confirmed BRAF V600E mutation. The case encourages discussion about the most appropriate adjuvant therapy for tumor progression in such cases, given the risks of radiotherapy to the developing brain and the increasing availability of oral BRAF inhibitor therapy.

Keywords: BRAF V600E mutation; Craniopharyngioma; Papillary; Pediatric.

Fig. 1

Sagittal pre-operative post-contrast T1 MRI brain scan image at presentation (a) revealing a large suprasellar lesion, measuring 3 × 1.9 × 2.3 cm. The lesion compromised a superior, solid component which had increased T1 signal pre-contrast (solid arrow head). This component also demonstrated high T2/FLAIR signal. An inferior, low FLAIR signal cystic component was noted. Peripheral rim enhancement of the lesion can be appreciated (white open arrow). b is a coronal T2 image also obtained at presentation which shows the upwards extend of the lesion (solid arrow) impinging onto and splaying the optic chiasm (open white arrow). Following transsphenoidal tumor surgery, follow-up sagittal T1 post-contrast MRI imaging (c) demonstrates improved appearances, with a small degree of non-enhancing residual tissue extending down into an enlarged pituitary sella (white arrow). The coronal T1 post-contrast image (d) now demonstrates a normal position of the optic chiasm (solid arrow) and a clearly discernable pituitary stalk which is slightly deviated to the left (white open arrow)

Fig. 2

Hematoxylin and Eosin staining at × 10 magnification (a). Histological assessment revealed fragments of stratified squamous epithelium and an absence of wet keratin. An acute inflammatory cell infiltrate was observed throughout the tissue. High power magnification (× 40; b) allows appreciation of both ciliated cells (black arrow) and goblet cells (white asterisk). The underlying stroma was composed of loose connective tissue and blood vessels. Immunohistochemistry revealed an absence of intranuclear Beta-catenin staining (a feature of adamantinomatous craniopharyngiomas)