What is a craniopharyngioma?

A craniopharyngioma (CRANE-eeh-oh-fair-IN-gee-OH-mah) is a localized tumor (abnormal growth or mass of cells) that occurs at the base of the brain behind the eyes near the pituitary gland.

Craniopharyngioma are benign tumors. This term means they do not have the features typically associated with cancer that invades or spreads (metastasizes) to other locations in the body.

Although not a malignant tumor that will spread through the body, craniopharyngiomas growing in the brain can present serious problems for the patient. Craniopharyngioma tumors can grow to large sizes, sometimes larger than a golf ball.

What causes a craniopharyngioma? Who is affected?

This type of tumor most commonly affects children between 5-10 years of age. The exact cause of craniopharyngioma tumors is unknown.

Craniopharyngiomas represent 2-5% of all primary brain tumors and 5-10% of all childhood brain tumors. This tumor is often found in two age groups: patients under 14 years of age and patients over age 45.

The outlook for patients diagnosed with a craniopharyngioma depends upon if the tumor can be completely removed and what type of nervous system issues and hormonal imbalances are present.

Where does a craniopharyngioma develop?

The location of craniopharyngioma tumors is very important. They tend to be located in the sellar area of the brain, which is close to the pituitary gland, hypothalamus, and carotid arteries.

The pituitary gland is a pea-sized organ at the bottom of the brain that controls hormone balance in the body. The hypothalamus is a small, cone-shaped organ connected to the pituitary gland. The hypothalamus is responsible for the production of many essential hormones, including those that govern body functions such as temperature regulation, thirst, hunger, sleep, mood, heartbeat, and more.

What is the structure of a craniopharyngioma?

Craniopharyngiomas are usually part solid mass and part fluid-filled cyst. The tumor typically consists of a combination of calcium deposits mixed with cysts (pockets) of fluid. They typically do not spread to other parts of the brain or body, but they will grow and put pressure on other areas of the brain including the pituitary gland, optic chiasm, optic nerves, and fluid-filled spaces in the brain.

How is a craniopharyngioma treated?

Treatment usually consists of surgery in some form, either full or partial resection (removal of the tumor during surgery) of the tumor or cyst. Surgery is usually followed by radiation therapy. Performing surgery in the sellar area of the brain is very high-risk. Stroke or death is possible if anything is nicked.

These procedures often result in after-effects including a non-functioning pituitary gland, hypothalamus dysfunction, and loss of vision.

Craniopharyngioma tumors may recur, even if the tumor was completely resected (removed during surgery) after initial diagnosis. Treatment of recurrent craniopharyngioma depends on the type of treatment used initially.

The Morgan Adams Foundation Leads the Way on Craniopharyngioma Research

In November 2015, The Morgan Adams Foundation hosted the first international symposium on adamantinomatous craniopharyngioma (ACP). The symposium was held at Children’s Hospital Colorado and attracted leaders in the craniopharyngioma field in both clinical research and basic science from the United States, the United Kingdom, Germany, Italy, France, and the Netherlands.

This conference established the University of Colorado as a primary focus in ACP research and promoted multiple national and international invitations for Todd Hankinson, MD, to speak on the topic.

Dr. Hankinson created and leads the only multi-center consortium in North America that focuses solely on improving therapies for pediatric craniopharyngioma.

Craniopharyngioma Research Funded by The Morgan Adams Foundation

Project: Verification of Therapeutic Targets and Assessment of Tumor Heterogeneity using Microdissection and Next Generation Sequencing in Adamantinomatous Craniopharyngioma 

PI: Todd Hankinson

This 2016 project was based on performing Next Generation Sequencing (RNA-Seq) on 4 Adamantinomatous Craniopharyngioma (ACP) specimens. The preliminary findings indicate that Dr. Hankinson’s group may be the first group to identify a gene fusion in ACP. This tumor was previously believed to be characterized by a single mutation, but the results of this project show two examples of a potential recurrent fusion between chromosomes 4 and 19. If these findings can be confirmed in a larger cohort of tumors, this would represent a completely novel and substantial leap forward in our understanding of ACP and may help us identify novel therapeutics.

This project was presented at the International Symposium on Pediatric Neuro-Oncology 2016 in Liverpool, England, and resulted in two publications.

Project: Pilot Study of IL-6 mediated inflammation in the cystic component of Adamantinomatous Craniopharyngioma (ACP)

PI: Todd Hankinson and Andrew Donson

An extension of previous work, this 2016 project identified new cytokine expression patterns in the cystic portion of Adamantinomatous Craniopharyngioma. In addition to identifying the overexpression of seven proteins and their receptors, the team also identified substantial overexpression of IDO-1, which contributes to inflammatory processes. The combination of findings in the cyst fluid and solid tumor tissues solidifies the belief that inflammation plays a critical role in the development of ACP.

Dr. Hankinson presented this work at International Symposium on Pediatric Neuro-Oncology, the American Academy of Neurological Surgeons, and the International Society for Pediatric Neurosurgery. Dr. Hankinson and his team are working in conjunction with Dr. Juan Pedro Martinez-Barbera at University College London to design experiments using their mouse model to test the pathways and possible medications identified in this project.

Project: Pre-clinical Trial of Anti-inflammatory Monoclonal Antibodies in a Mouse Model of Adamantinomatous Craniopharyngioma 

PI: Todd Hankinson and JP Martinez-Barbera

This 2017 project builds off several previous Adamantinomatous Craniopharyngioma projects funded by The Morgan Adams Foundation and progresses toward creating clinical trials of novel therapies for children with ACP. The project focuses on the proteins that promote inflammation and have been demonstrated to be present in ACP cyst fluid and tumor tissue.

Dr. Martinez-Barbera’s group at University College London was the first to describe and validate an embryonic mouse model of ACP back in 2011. Dr. Hankinson is working closely with Dr. Martinez-Barbera to complete a preclinical study of the two medicines that were determined to be pathway inhibitors of the proteins promoting inflammation. This project is the next step toward creating clinical trials for children with Adamantinomatous Craniopharyngioma.

Project: Developing a Clinically Translatable Interpretable 3D Radiographic and Transcriptomic Joint Domain Deep Learning Framework for Limited Datasets Using Adamantinomatous Craniopharyngioma as an Example

PI: Todd Hankinson

Building on previous machine learning work completed in 2019, this 2020 project looks to expand the deep learning model to one that can be interpreted using pediatric adamantinomatous craniopharyngioma (ACP) imaging data.

The previously developed black-box deep learning model created in 2019 can classify ACP using 2-dimensional imaging data with an accuracy equivalent to board-certified pediatric neuroradiologists.  Moving forward, the model will utilize full 3-dimensional datasets and allow for process analysis to better suit machine learning for high-stakes medical scenarios such as diagnosing brain tumors.

Project: Epithelial to Mesenchymal Transition (EMT) in Craniopharyngioma

PI: Todd Hankinson

Epithelial to mesenchymal transition (EMT) is a normal biological process whereby epithelial cells transition into mesenchymal cells in a well-orchestrated manner. The EMT process occurs during creation of the embryo and also in adult wound healing. EMT has been implicated in several epithelial cancers and is believed to facilitate tumor cells’ capacity for malignant behaviors such as invasion, recurrence, metastatic transformation, and resistance to therapy.

This 2020 project aims to demonstrate that EMT plays a role in craniopharyngioma development and may be a therapeutically targetable process.