What Is A Craniopharyngioma

Overview

Craniopharyngioma is a rare but complex brain benign tumour (neoplasm) derived from embryonic tissue from the sellar region and its surroundings (parasellar region). Despite its rarity, understanding craniopharyngioma is paramount due to its potential to impact vital brain structures and hormone regulation.¹ This comprehensive article will delve into the intricacies of craniopharyngioma, exploring its anatomy, causes, signs and symptoms, diagnostic methods, treatment options, prognosis, coping strategies, and current research efforts.

Anatomy and location

To comprehend craniopharyngioma, we first need to understand the basic anatomy of the brain. The brain comprises of three main regions; they are the cerebrum, cerebellum, and brainstem, each responsible for various functions.²

Craniopharyngiomas usually consist of a solid mass part and a fluid-filled cyst part. They are benign (not cancerous) and do not spread to other parts of the brain or to other parts of the body. Typically they develop near the pituitary gland and the hypothalamus, specifically in a region known as the sellar and suprasellar areas. This location can lead to various complications as the tumour exerts pressure on nearby structures, such as the pituitary gland, the optic nerves and the optic chiasm. As a result, some functions of the brain become comprised, these encompass the deregulation of the hormone-making process, growth, and vision.¹

Causes

Craniopharyngiomas have a bimodal age distribution, with an increased incidence between 5 and 1 years old and between 50 and 74 years old. They are caused by malformations of embryonic tissue in the sellar and parasellar regions of the brain. There are two main types of craniopharyngiomas: adamantinomatous craniopharyngioma and papillary craniopharyngioma.¹

Adamantinomatous craniopharyngioma

Adamantinomatous craniopharyngioma, commonly found in children, results from the transformation of cells from the craniopharyngeal duct, an embryological structure connected to Rathke’s pouch which gives rise to part of the pituitary gland (located in the brainstem), into tumour cells - a process known as neoplastic transformation. Whilst the exact cause of the condition remains unclear, it has been noted that there may be a potential genetic cause as more than 70% of the tumours have a mutation (changes in the genetic material) in the CTNNB1 or APC genes which are responsible for the production of a protein called beta-catenin. This protein is fundamental for the growth of the embryo, leading to the conclusion that mutations in these genes might therefore play a role in the development of adamantinomatous craniopharyngioma.¹

Papillary craniopharyngioma

Papillary craniopharyngiomas, frequently found in adults, result from the change in the cell type of cells in the anterior pituitary gland which leads to the formation of nests made from cells known as squamous cells (cells that make up the middle and outer layers of the skin). Similarly to adamantinomatous craniopharyngiomas, the cause of papillary craniopharyngiomas remains unknown.¹

Signs and symptoms

Craniopharyngiomas, despite being benign tumours, can cause a wide range of symptoms, which often depend on the tumour's size and location due to the compression posed to important anatomical structures such as the pituitary gland, the hypothalamus, and the optic chiasm. Common symptoms include:

• Paresis (limb weakness)
• Difficulty walking
• Seizures
• Psychiatric symptoms such as paranoid delusions
• Increase in intracranial pressure
• Headaches
• Nausea

As craniopharyngiomas are difficult to treat due to being located in areas that are difficult to access and close to many important structures. As a result, patients can experience many symptoms that are related to the treatment of the disease rather than the disease itself.

Symptoms specific to tumour location

Tumour near the pituitary gland

Patients with a tumour compressing the pituitary gland may experience pituitary gland dysfunction. Some of the symptoms include:

• Decreased growth rate due to growth hormone (GH) deficiency
• Delayed puberty and absence of menstrution in people assigned female at birth (amenorrhea) due to deficiencies in folicle stimulating hormone (FSH) and lutenising hormone LH (reproductive hormones)
• Feeling weakness and tiredness due to adrenocorticotropic hormone (ACTH) deficiency
• Fatigue, generalized weakness, menstrual irregularity, and forgetfulness can result from thyroid stimulating hormone (TSH) deficiency
• Central diabetes insipidus, characterised by excessive thirst and urination

Tumour near hypothalamus

Patients with tumours compressing the hypothalamus may develop hypothalamus dysfunction. The hypothalamus is connected to the pituitary gland and regulates its hormone secretion, as well as other numerous biological processes. Some of the symptoms include:

• Hypothalamic obesity which is a type of obesity that occurs even with caloric restriction and lifestyle changes
• Froelich’s syndrome which is a combination of hypothalamic obesity delayed sexual development, and small testes
• Changes in behaviour
• Imbalances in body temperature
• Changes in thirst
• Changes in heart rate and blood pressure
• Sleep disorders such as non-24-hour sleep-wake syndrome, characterised by night-time insomnia and excessive daytime sleepiness

Other tumour pressure-related symptoms

Pressure on optic nerves

The craniopharyngioma might also exert pressure on the optic nerves and optic chiasm. The optic nerves are responsible for carrying visual information to the brain and they partially cross right above the pituitary gland to form a structure called the optic chiasm. When compressed it can lead to the following symptoms:

• Decreased visual acuity (blurry vision)
• Visual field defects (loss of vision in certain areas of the visual field)

Pressure on brain ventricles

Some individuals might also experience foramen of Monro occlusion; this is when there is an occlusion of some of the channels that connect ventricles. The ventricles are part of the brain ventricular system which is composed of four cavities (ventricles) where cerebrospinal fluid (CSF) is produced and circulates. When the foramen of Monro is occluded, the CSF will not flow adequately and will accumulate (this is called hydrocephalus). The symptoms derived from this occlusion vary depending on the age of the affected individual; these include:

• Babies might feed poorly, be irritable, and have an enlarged head
• Children and adults can have neck pain, headaches, vomiting, and blurred vision

Treatment-associated symptoms

In addition to these symptoms, as mentioned previously, the individuals affected by the condition may experience treatment-associated complications. Depending on the course of treatment adopted by each patient their symptoms will vary. Here is a list of the procedures and their consequential symptoms:

• Surgical removal of craniopharyngioma - due to the tendency to recur multiple surgeries are required. These may lead to damage to close anatomical structures, as well as develop deficits in cognition, memory and attention
• Radiation therapy - this procedure can lead to the damage of the internal carotid arteries resulting in potential cerebrovascular complications such as dilatation and weakening of the blood vessel wall (aneurysm), and Moyamoya disease where the internal carotid arteries are narrowed resulting in potential headaches, strokes, and seizures. Moreover, the radiation exposure may also increase the likelihood of developing brain tumours such as gliomas³

Diagnosis

In order to diagnose a craniopharyngioma three main methods are used:

• Medical History and Physical Examination - this includes a thorough inquiry about the patient’s symptoms, family history, and conduction of a neurological exam. Symptoms of headache, visual impairment, decreased growth rate, increased thirst and urination, and other signs of hormonal deficiency will raise the suspicion of craniopharyngioma
• Laboratory testing - this is necessary to confirm clinical suspicion of endocrine deficiency. The tests that are normally conducted include an evaluation of serum electrolytes (minerals in the body), and hormones that would be affected by pituitary dysfunction, such as GH, IGF-1, TSH, free thyroxine, cortisol, FSH, LH, testosterone, oestradiol, and prolactin
• Images techniques - the main two techniques used are computed tomography (CT) scan and magnetic resonance imaging (MRI). A CT scan is used to detect tumour calcification, while an MRI can be used to detect fluid accumulation inside cystic tumours

Eye examinations and biopsy are other methods that healthcare practitioners might use to help confirm the diagnosis.¹ 

Treatment options

Surgical removal

Often, craniopharyngioma treatments start with surgery, where, when possible, all or most of the tumour is removed. The type of surgery an individual would have would be in accordance with the location of the craniopharyngioma. There are two main types:

• Open craniopharyngioma surgery or craniotomy is a procedure that involves the opening of the skull to access the tumour
• Minimally invasive craniopharyngioma surgery, also known as a transsphenoidal procedure which is when the surgical tools are inserted through the nose. This method minimises the effects on the brain

To ensure a good quality of life post-operation, surgeons attempt to remove as much of the tumour as possible, however, this isn’t always possible and therefore other treatments may be used after surgery.³

Radiation therapy

Some individuals might also be recommended to undertake radiation therapy, where powerful energy beams, obtained from X-rays, protons and other sources, are used to control tumour cells. This treatment is frequently used post-operation to treat any remaining tumour cells. There are three main types of radiation therapy:

• External beam radiation therapy - through the aim of the radiation beam to tumour cells it reduces the chances of hurting healthy tissue
• Stereotactic radiosurgery - the aim of multiple beams at different angles to the tumour.
• Brachytherapy - placing radioactive material directly into the tumour where it can radiate the tumour from the inside³

Other treatments

Chemotherapy may also be recommended to some individuals; this is when a medicine is used to kill the tumour.⁴In addition, for papillary craniopharyngioma, targeted medicine therapies might be used. This is when medicines attack specific chemicals in the tumour cells, which via the blocking of certain chemicals, can cause the death of the tumour cells.⁵

Prognosis

Craniopharyngiomas have an optimistic prognosis as it has high survival rates of 83% to 96% of five-year survival and 65% to 100% of ten-year survival. However, it also carries similar rates of morbidity with almost all patients developing some post-craniopharyngioma complications or conditions (sequelae) and has a very high rate of recurrence of approximately 50%.¹

Summary

Craniopharyngioma is a rare but complex benign brain tumour that originates from embryonic tissue in the sellar and parasellar regions. It can lead to a wide range of symptoms and complications, affecting vital brain structures and hormone regulation. The causes of craniopharyngioma are still not fully understood, but it is classified into two main types. Diagnosis typically involves a combination of medical history, physical examination, laboratory testing, and imaging techniques. Treatment options include surgery, radiation therapy, chemotherapy, and targeted therapies, depending on the tumor's location and size. Despite its high survival rates, craniopharyngioma often leads to long-term sequelae and has a significant risk of recurrence. Therefore, continued research efforts are essential to improve treatment outcomes and enhance the quality of life for affected individuals.