Craniopharyngiomas

Also known as: Rathke pouch tumors, adamantinomas

Related conditions: Endocrinological and neurological dysfunctions

Definition: A craniopharyngioma is a slow-growing, histologically benign tumor that has been found above and below the sella turcica (depression in the upper surface of the sphenoid bone) and in ectopic locations in the brain. Most craniopharyngiomas are found in the sella turcica and the area above it, home to the pituitary gland and hypothalamus. Although generally benign, craniopharyngiomas, like malignant tumors, can metastasize to areas outside the brain. When discovered, they typically range from 1 to 4 inches in size. They grow by expansion and can cause compression of structures such as the optic chiasm and nerves and the pituitary stalk and gland. The three subtypes are adamantinomatous or pediatric type, which is the classic and most common form of this tumor, having primarily a cystic composition, usually with a solid component; papillary or adult type, which has a more encapsulated, solid component that typically has no calcifications; and mixed type, which is composed of transitional features between the adamantinomatous and papillary variants.

Risk factors: The cause of craniopharyngioma is not known, and there are no known environmental or infectious risk factors. More than 50 percent of people with craniopharyngiomas are younger than eighteen (adamantinomatous type), and most cases occur in children between the ages of five and ten. The second most common age range in which craniopharyngioma occurs is between forty and sixty years (papillary). Craniopharyngiomas do not appear to be more prevalent in a particular gender or ethnicity, nor do they appear to be inherited.

Etiology and the disease process: Although the etiology of craniopharyngiomas has not been determined with certainty, several theories exist as to their origin. One theory is that craniopharyngiomas are another form of a congenital tumor known as an epidermoid cyst. (Epidermoid cysts can arise anywhere in the body and are proven to be congenital.) Another theory suggests that they arise from embryonic dental or jaw tissue (dental anlage). A third theory, and the one that seems to be the most popular, purports that craniopharyngiomas are remnants of Rathke’s pouch (a depression in the roof of the developing mouth that gives rise to the anterior pituitary) and arise from squamous cell nests found at the junction of the pituitary stalk and the distal portion of the anterior pituitary.

Craniopharyngioma appears as a single, large cyst or multiple cysts filled with a cloudy, proteinaceous, brownish-yellow material that glitters because it contains floating cholesterol crystals. This kind of tumor most frequently arises in the pituitary stalk and projects into the hypothalamus. Craniopharyngioma causes symptoms in three different ways: first, as it grows it increases the pressure on the brain; second, as it enlarges it interferes with the normal function of the pituitary gland; and third, as it grows upward, it damages the optic nerve.

Incidence: Craniopharyngioma is a rarely occurring, nonheritable cancer. According to the National Cancer Data Base, the overall incidence of craniopharyngioma in the United States is 0.13 per 100,000 persons per year. Craniopharyngiomas account for 1 to 3 percent of all intracranial tumors and 4.2 percent of all childhood intracranial tumors. The incidence does not vary by sex or race. Approximately 340 cases of craniopharyngiomas occur annually in the United States, with 96 occurring in children between birth and fourteen years of age. Recurrences usually occur at the primary site. Ectopic and metastatic recurrences are extremely rare and have been reported after surgical removal. Recurrence rates can be as high as 20 percent.

Symptoms: Symptoms frequently develop slowly and become obvious only after the tumor enlarges to about 1.5 inches in diameter. Craniopharyngiomas produce symptoms by compression of adjacent neural structures, leading to endocrine and visual problems; they obstruct cerebrospinal fluid pathways, causing hydrocephalus and increased intracranial pressure, which lead to headaches and nausea.

The most common symptoms are headache (55 to 86 percent of patients), endocrine dysfunction (66 to 90 percent of patients), and visual disturbances (37 to 68 percent of patients). Headaches are slowly progressive, dull, continuous, and positional, becoming severe when endocrine symptoms become obvious. Endocrine dysfunction includes hypothyroidism, adrenal failure, and diabetes insipidus; young patients typically display growth failure and delayed puberty. Nearly three-quarters of patients suffer some sort of damage to the optic pathway.

Other manifestations relate to the various connections of the hypothalamic-pituitary complex and surrounding structures. Tumors located in the thalamus and frontal lobes are often accompanied by corresponding endocrine, autonomic, and behavioral problems, such as hyperphagia and obesity, short-term memory deficits, psychomotor retardation, emotional immaturity, and lethargy.

Screening and diagnosis: Computed tomography (CT) scanning and magnetic resonance imaging (MRI) are the screening methods of choice for craniopharyngioma. MRI, with or without administration of contrast enhancement, is generally preferred over CT scanning but may not be as readily available. Although CT can clearly demonstrate the characteristic calcifications and size of the tumor, MRI can demonstrate the size and extent of the tumor as well as any ventricular involvement. MRI results can confirm cystic features of the tumor. Various MRI sequences, such as fluid-attenuated inversion recovery (FLAIR), gradient echo, and diffusion-weighted imaging, can aid in making the correct diagnosis.

The diagnostic workup for craniopharyngioma also includes complete endocrinological and neuroophthalmological evaluation with visual-field examination and neuropsychological assessment. The endocrinological tests will include serum electrolytes, serum and urine osmolality, thyroid studies, morning and evening cortisol levels, growth hormone levels, and luteinizing and follicle-stimulating hormone levels.

Postoperatively, CT scanning is performed to establish a baseline from which follow-up scans will be judged. MRI is often performed to determine whether there is any residual tumor.

Treatment and therapy: There is no medical therapy per se for craniopharyngioma. There is little debate that the standard treatment of this tumor is surgical excision followed by adjuvant radiotherapy; however, controversy does exist about the optimal degree of excision. Some physicians believe that complete resection is the best treatment and that every effort should be made to remove as much of the tumor as possible. Others advocate a planned partial tumor excision, leaving radiotherapy or radiosurgery to complete the removal. The controversy stems from the fact that nearly all craniopharyngiomas are located in eloquent areas of the brain; removal necessitates maneuvering around very delicate anatomical structures, which, if damaged during the course of tumor removal, could fail to perform normally, leaving the patient with severe deficits. Craniopharyngiomas tend to adhere to the structures and tissues that surround them, making them difficult to excise without disturbing or damaging these other entities. It is especially challenging to resect a craniopharyngioma that is adhering to the pituitary gland, the hypothalamus, or the optic chiasm and nerves. For example, damage to the pituitary gland, which controls the activity of many other endocrine glands, such as the thyroid, the ovaries, and the adrenal glands, can result in a cascade of endocrine-related disorders including hypothyroidism, obesity, diabetes, and, in children, failure to thrive. Damage to the hypothalamus, which controls the activity of the pituitary by releasing various hormones to regulate it, can result in a host of problems from interrupted circadian rhythm to impaired immune system function. Damage to the optic chiasm and optic nerves can cause visual disturbances ranging from mild hemianopsia (in which each eye is able to send images from only half its field of vision to the brain) to complete blindness. Because of these issues, treatment of craniopharyngioma is complex.

The surgical approach used is dictated by the tumor’s location. If the predominant portion of the tumor is intrasellar, the approach is usually transsphenoidal (through the sphenoid bone). The transsphenoidal approach is less invasive than craniotomy (in which part of the skull is removed to provide access to the brain) and therefore preferable. Craniotomy is necessary when the predominant component is suprasellar. Certain suprasellar masses may be approached through an extended transsphenoidal craniotomy.

The pterional craniotomy is the standard approach to suprasellar lesions because it allows the surgeon to see the optic nerves and chiasm. A subfrontal approach is used for lesions that are anterior to the optic chiasm, but this may be difficult to determine preoperatively. Cyst aspiration combined with instillation of radioactive isotope phosphorus-32 is the alternative to traditional resection; however, a tumor with significant solid components is not likely to respond to this type of treatment.

Prognosis, prevention, and outcomes: The survival rate for patients who undergo surgery for craniopharyngioma is estimated to be 86 percent at two years and 80 percent at five years postdiagnosis. Survival varies by age group, with excellent survival rates for patients younger than twenty years old and poorer survival rates for those older than sixty-five. Molecular and genetic studies focusing on the treatment and prevention of craniopharyngioma are ongoing.

Bibliography

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Merchant, T. E., et al. “Craniopharyngioma: The St. Jude Children’s Research Hospital Experience, 1984–2001.” International Journal of Radiation Oncology, Biology and Physics 53.3 (2002): 533–42. Print.

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