**1. Introduction**

Pediatric Adamantinomatous Craniopharyngiomas (ACPs) are histologically benign brain tumors that often follow an aggressive clinical course. The tumors are most commonly centered in the suprasellar region and are believed to develop from remnants of Rathke's pouch. Radiologically and grossly, these tumors appear as mixed solid and cystic lesions often with areas of calcification (Figure 1). Histologically, ACPs are heterogeneous tumors of epithelial origin [1,2]. The classic features consist of palisading epithelium, stellate cells, nodules of anuclear "ghost cells" and "wet keratin" as well as large areas of regressive changes (i.e., inflammation and calcifications, multinucleated giant cells, hemosiderin deposits, cholesterol clefts) [1] (Figure 2). Their proximity to critical neurological and vascular structures often confers significant neuroendocrine morbidity on patients [3]. Surgery remains the primary treatment strategy, but can result in significant morbidity, specifically damage to the hypothalamus, pituitary and optic apparatus, which results in long-term sequelae that can greatly impact a child's quality of life [4–6]. In an era of personalized medicine and targeted therapies,

*J. Clin. Med.* **2020**, *9*, 519

ACP remains resistant to such advances. On the other hand, recent case reports of the response of papillary craniopharyngioma, a different tumor of the suprasellar region, to BRAF inhibitors have elucidated the great potential of targeted therapies in treating these tumors [7,8]. As a result, recent years have witnessed significant efforts to fully elucidate the genomic, transcriptomic and proteomic make-up of ACP in an attempt to identify potential therapeutic targets for the treatment of this disease [9–15].

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**Figure 1.** Classic histopathological findings in adamantinomatous craniopharyngioma: (**A**) H&E stained sections showing an epithelial tumor with palisading cells with aggregates of 'wet' keratin; (**B**) higher magnification view demonstrating keratinized 'ghost cells'; (**C**) Higher magnification view demonstrating calcifications and stellate reticulum; (**D**) Immunohistochemical staining for Beta-catenin that is nuclear positive in a subset of tumor cells. (**E**) The surrounding brain parenchyma shows extensive gliosis with Rosenthal fibers.

**Figure 2.** Computed Tomography (**Left**) andMagnetic resonance Imaging (**Right**) images from the same patient of a classic example of an adamantinomatous craniopharyngioma. This typical tumor is centered in the suprasellar region with mixed solid and cystic areas as well as areas of calcification as seen on the CT.
