Craniopharyngioma: Symptoms, Treatment, Prognosis, Pathophysiology, Epidemiolgy, Complications

Craniopharyngioma is a rare type of cancer. It is a primary brain tumor which is benign and later may become malignant. It mainly affects children and is occasionally observed in adults. Craniopharyngioma is of great concern since it’s a childhood cancer.

Craniopharyngioma is a tumor that occurs near the pituitary gland and the hypothalamus region of the brain. It is present in the form of a large cyst or multiple cysts filled with turbid, proteinaceous and yellow colored fluid. Generally, Craniopharyngioma is a localized benign tumor. However, it may become large, malignant and can spread in an anterior, posterior and lateral manner to different regions of the brain. Presence of tumor affects the functions of the brain. Although treatment facilities are available, it is difficult to treat Craniopharyngioma due to the location.

Craniopharyngioma occurs in both children of age 5-14 years and in adults of age 65-75 years. Craniopharyngioma found in children is of type Adamatinomatus and is not a solid tumor. While in case of adults, it occurs as a papillary type (solid tumor). Due to the difference in types of tumors, the treatment in both cases varies.

Craniopharyngiomas affect functions of the brain and due to their presence there is also an increase in the intracranial pressure. These tumors interfere with the hormone production, growth and vision. The effects are manifested in form of symptoms as:

• Morning headache which goes away after vomiting
• Changes in the vision (eventually there is vision loss)
• Loss of balance or problems while walking
• Short stature (symptoms due to growth hormone deficiency)
• Hypersomnia (unusual sleepiness)
• Increase in thirst (polydipsia) or frequency of urination (polyuria)
• Fever and nausea
• Loss of hearing.
• In 20-40% of the cases the hypothyroidism symptoms are observed in the form of lethargy, weight gain, myxedema, dry skin, fatigue, brittle hair, and cold intolerance.

• Craniopharyngioma has an incidence of 1.8 in one million people. It accounts for 1-3 per cent of intracranial tumors while 13 per cent of suprasellar tumors.
• It shows no predilection for race, ethnicity or gender. It occurs at the same frequency in both males and females.
• The association of craniopharyngioma has been reported in very limited number of familial cases. No genetic basis has been found till date.
• It has a bimodal age distribution pattern. Craniopharyngioma occurs in children of age 5-14 years and in adults older than 65 years.

Generally the prognosis of Craniopharyngioma depends on the size, type and location of the tumor in the brain. It is observed that after surgical treatment, the rate of recurrence for both benign and malignant (rare) craniopharyngiomas is very high. Overall, it shows poor prognosis.

During diagnosis, the overall 2 year survival rate for a patient is 86% and 5 years survival rate is 80%. This rate varies by age group as good prognosis (5 year survival rate is 99%) has been observed in case of children and patients below 20 years of age. While, in case of the older patients i.e., above 65 years, an overall poor prognosis (38% at 5 years) was observed.

Like many other cancers, the cause of craniopharyngioma and its risk factors is not known.

There is still limited knowledge on the genetic basis of this tumor. Although, there is loss of tumor suppressor genes, activation of oncogenes, which takes place in craniopharyngiomas too, however, the specific genetic details still remain elusive. Some research studies have shown that beta-catenin and Want pathway may have a significant role in the pathogenesis of these tumors. The exact mechanisms underlying pathogenesis needs to be elucidated.

• The tumor may recur even after surgical and radiation therapy.
• After treatment, most of the problems with hormones and vision do not improve. In some cases, the symptoms become worse.

The diagnosis of Craniopharyngioma involves:

• Physical examination and past history
• Neurological examination
• Visual field examination
• Tests to be performed includes:
  • Histopathological analysis is performed to know the type of craniopharyngioma. Adamatinomatus type shows calicifcation, which is rarely seen in case of Papillary tumors.
  • Blood tests to determine the levels of hormones.
  • A CT scan or MRI scan of the brain is done to know the location of the tumor in the brain and to check if the tumor has spread to various parts of the brain or has spread extracranially.
  • Use of PCR analysis shows that Adamatinomatus type is characterized by CTNNB1 mutations and papillary tumors are characterized by BRAFv600E mutations.

The treatment for children with craniopharyngioma should be planned by a team of health care providers, preferably an inter-disciplinary team who are experts in treating children with brain tumors. Various types of treatments used for treating craniopharyngioma in children are:

• Surgery for Treating Craniopharyngioma: It is the first step and the main type of treatment for craniopharyngioma. Surgery means resection or removal of the tumor mass. The main types of surgeries used are Transsphenoidal surgery and Craniotomy. If there is hydrocephalus (excess of fluid), then a shunt (drainage system) surgery is used. It is also used to drain tumors which are made of fluid-filled cysts. Sometimes the entire tumor can be removed only by surgery and requires no further treatment.
• Radiation Therapy for Craniopharyngioma: For small tumors, radiation therapy along with surgery is used. At times due to its location or its size, the tumor cannot be removed by surgery, in which case radiation therapy is applied to kill the remaining tumor cells. While treating small children, the radiation therapy is properly chosen to cause minimum side effects. Some types of radiation surgeries include Stereotactic radio surgery for small craniopharyngiomas. For treatment of solid tumors, Intracavitary Radiation therapy is used where the radioactive substance is injected in the solid tumor mass and fluid filled cysts. Intensity modulated proton therapy is also used.
• Treating Craniopharyngioma with Chemotherapy: It involves use of anti-cancer drugs to inhibit or kill the tumor cells. As mentioned in the literature, the current effective treatment strategy for malignant tumors is combination of gross total respective surgery with adjuvant chemo-radiotherapy. Drugs like Paclitaxel and Carboplatin have shown to increase the survival rates. In addition, intracavitary chemotherapy is used that places drugs directly at the tumor site, for example a cyst. It is used to treat cases of tumor recurrence.
• Biological Therapy for Treating Craniopharyngioma: It is also called Immunotherapy. It makes use of the immune system’s defence products such as Monoclonal antibodies, Interleukins and Interferon to treat cancer. This type of therapy is used in case of recurrent tumors.

Craniopharyngioma is a rare cancer and mainly affects children. For good treatment outcomes, it should be treated at a centre with many years of experience in treating the patients. The cause and underlying molecular pathogenesis of this cancer needs to be elucidated to enable better treatment management in the future.

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