Craniopharyngioma · What Is It, Signs & Symptoms, Treatment, and More

Craniopharyngiomas are related to distinct gene variants. Adamantinomatous craniopharyngiomas are characterized by activation of the Wnt signaling pathway, most commonly due to pathogenic variants activating CTNNB1. Pathogenic variants of the Wnt signaling pathway lead to excessive formation of β-catenin and its associated oncogenic effects, like cell proliferation and invasion, and tumor formation. Papillary craniopharyngiomas are usually associated with pathogenic variants in the BRAF oncogene, specifically BRAF V600E (i.e., a specific variant in the BRAF gene, where the amino acid valine (V) is replaced by glutamate (E) at position 600). BRAF activates the mitogen-activated protein kinase (MAPK) pathways, which are commonly upregulated in cancers. 

Craniopharyngioma may cause symptoms due to compression of nearby structures. Compression of the optic chiasm where the optic nerves cross, for example, can lead to visual deficits, most commonly bitemporal hemianopsia (i.e., loss of vision in the outer visual fields). Damage or compression of the anterior pituitary can lead to hormonal deficiencies, such as growth hormone deficiency, leading to growth restriction in children. Pressure on the posterior pituitary can lead to vasopressin (i.e., antidiuretic hormone, or ADH) deficiency, formerly known as central diabetes insipidus, which can lead to polyuria and polydipsia. Adults may have a growth hormone deficiency, presenting with weight gain, central obesity, and fatigue; gonadotropin deficiency, manifesting as amenorrhea in genetic females and erectile dysfunction or loss of libido in genetic males; TSH deficiency, causing weight gain, fatigue, cold intolerance, and constipation; and adrenocortical hormone (ACTH) deficiency, presenting with weight loss, arthralgia, dizziness, and hypotension. When the tumor is large, it can obstruct the aqueduct or foramina of Monro and lead to hydrocephalus (i.e., excess buildup of cerebrospinal fluid in the brain ventricles) with a consequent increase in intracranial pressure. Invasion and pressure on the hypothalamus can lead to diencephalic syndrome (i.e., failure to thrive in young children) and obesity. 

Additionally, individuals may present with moderate or severe headaches, sometimes accompanied by nausea, vomiting, and lethargy. Depression and cognitive impairment are also common. 

Since craniopharyngiomas are typically slow-growing tumors and the symptoms are related to compression of local structures, diagnosis usually occurs when the associated symptoms begin. The diagnostic process typically includes an assessment of the individual’s medical history and an endocrinological evaluation that includes laboratory tests to evaluate the thyroid and adrenal function (e.g., thyroid-stimulating hormone, ACTH), as well as any hormonal deficiencies that may be present (e.g., follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone). A neuro-ophthalmologic examination assessing visual fields, acuity, and optic disc color and texture may also be performed to evaluate the severity of compression on the optic pathways and identify papilledema. The presence of the mass can be confirmed through magnetic resonance imaging (MRI) or computed tomography (CT scan). CT scan can detect the presence of calcifications, which are a feature of the adult, PCP tumor type. Pathological examination and molecular analysis may confirm the exact diagnosis of the mass. 

The differential diagnoses for other tumors located in the sellar and suprasellar region include pituitary adenoma, germ cell tumors, astrocytomas, and other rare neoplasms and infiltrative disorders. 

Craniopharyngiomas are challenging to treat due to their location near important anatomical structures and frequently recur because they often adhere to nearby structures. Therefore, craniopharyngiomas are typically managed by a multidisciplinary team (MDT) that includes specialists from ophthalmology, endocrinology, neurosurgery, and more, who can collaborate to discern the best course of treatment for the individual.  

Craniopharyngiomas are usually treated with surgical removal, to alleviate the mass-related symptoms. Surgery aims to remove as much of the tumor that can be safely removed. Nonetheless, aggressive surgery, especially for tumors invading the hypothalamus, may lead to significant neuro-endo-vascular-ophthalmological damage. Therefore, a more conservative surgical approach combined with adjuvant therapy is often attempted.   

Since craniopharyngiomas are sensitive to radiotherapy, surgery combined with radiation therapy (using various techniques, such as stereotactic radiosurgery, stereotactic radiotherapy, intensity-modulated radiotherapy, or proton beam radiotherapy) may be the chosen approach. Alternatively, in PCP tumors with the BRAF V600E gene variant, targeted therapy (e.g., vemurafenib and cobimetinib or dabrafenib and trametinib) may be applicable. Histological and molecular assessment of the tumor specimen are necessary to guide treatment. Cystic parts of a tumor can be managed with various operative or nonoperative techniques, such as percutaneous aspiration, intracystic irradiation or chemotherapy, or surgical removal. When hydrocephalus is present, a temporary or permanent shunt can be placed, inserting catheters into the ventricles to drain excess cerebrospinal fluid and relieve pressure.  

All the aforementioned treatment options may result in long-term side effects, especially in children. Damage to the hypothalamus or pituitary stalk, for example, caused by the tumor or exacerbated by treatment, can lead to altered pituitary function that may require long-term treatment with hormone replacement therapy (e.g., levothyroxine in cases of thyroid deficiencies) especially in childhood. Those with vasopressin deficiency may require life-long treatment with vasopressin. Radiotherapy may lead to late visual, endocrine, cognitive, and psychological sequelae, as well as vasculopathies (e.g., Moyamoya disease) and secondary neoplasms (e.g., meningiomas, glioblastomas). The long-term sequelae increase the complexity of craniopharyngioma management and are considered by the MDT when collaborating on the individualized treatment plan.