BASICS
DESCRIPTION
- Benign epithelioid tumor, usually suprasellar, partially calcified, solid, or mixed solid-cystic that arises from remnants of the craniopharyngeal duct or Rathke pouch
- Histologic subtypes
- Adamantinomatous craniopharyngioma; more common in children
- Papillary craniopharyngioma; more common in adults
EPIDEMIOLOGY
Bimodal age distribution
- Children between 5 and 14 years
- Older adults between 50 and 74 years
Incidence
0.5 to 2.0 new cases/million population/year (1)
Prevalence
- ~2/100,000 persons
- More common in countries other than the United States (e.g., Africa and Japan)
ETIOLOGY AND PATHOPHYSIOLOGY
- Eye: Pressure on the optic chiasm results in visual changes.
- Endocrine: Pressure on hypothalamus/pituitary results in deficiencies of growth hormone (GH), gonadotropins (Gn), thyroid-stimulating hormone (TSH), antidiuretic hormone (ADH), and adrenocorticotropic hormone (ACTH)
- GH deficiency: growth failure
- Gn deficiency: erectile dysfunction (ED), amenorrhea, delayed puberty
- TSH deficiency: hypothyroidism
- ADH deficiency: diabetes insipidus (DI)
- ACTH deficiency: hypoadrenalism
- Pain: headaches (from increased intracranial pressure), hydrocephalus (tumor compression of the 3rd ventricle), or meningeal irritation by escaped cyst contents
- GI: nausea, vomiting
- Cardiovascular: hypertension (HTN) and/or orthostatic hypotension
Not well understood. Theories include the following:
- Adamantinomatous type may result from altered embryogenesis, in which remnant squamous cells proliferate from their origin in the sellar region into the median eminence while Rathke pouch is transforming into the anterior pituitary.
- Papillary type may result from metaplasia of cells in the pars tuberalis of the adenohypophysis.
RISK FACTORS
Unknown
COMMONLY ASSOCIATED CONDITIONS
- DI: common when pituitary stalk is involved
- Sexual dysfunction (common)
- Depression
- Sleep apnea
- Turner syndrome (rare)
DIAGNOSIS
A craniopharyngioma may go undiagnosed for years.
HISTORY
- Eye: visual changes, blurriness, loss of peripheral vision (visual symptoms will vary depending on how the tumor affects the optic chiasm)
- GI: anorexia, nausea, vomiting, constipation
- Endocrine: extreme weight gain, lethargy, thirst, urination, cold intolerance, early/delayed puberty, failure to thrive
- Neurologic: headaches
- Reproductive: decreased sexual drive, impotence, amenorrhea
- Psychiatric: depression
PHYSICAL EXAM
- Vital signs (note HTN/orthostatic hypotension)
- Height, weight, and body mass index (BMI)
- For children: growth curves (note excessive weight gain; failure to thrive) and Tanner staging
- Visual acuity and visual field (e.g., bitemporal hemianopsia)
- Funduscopic exam: optic atrophy or papilledema (present in ~20-35% of cases) (1)
- Signs of hypothyroidism: coarse and thinning hair, dry skin, brittle nails, yellowish tint to the skin, cold skin, myxedema
- Neurologic exam: noting any focal deficits, deep tendon reflexes, and balance problems
DIFFERENTIAL DIAGNOSIS
- Rathke cleft cyst
- Suprasellar arachnoid cyst
- Pituitary adenoma
- Astrocytoma/glioma of the hypothalamus/optic chiasm
- Hypothalamic hamartoma
- Teratoma
- Meningioma
- Epidermoid and dermoid tumors
- Eosinophilic granuloma
- Lymphocytic hypophysitis
- Sarcoidosis
- Infections: syphilis, tuberculosis
- Aneurysm of the internal carotid/anterior communicating artery
- Arteriovenous malformation
DIAGNOSTIC TESTS & INTERPRETATION
Assess serum electrolytes (which may be high) and endocrine functions (which may be low).
Initial Tests (lab, imaging)
- Serum electrolytes/water balance: Patients may have elevated serum electrolytes due to ADH deficiency. Glucose may be high due to co-occurring insulin resistance/obesity.
- GH: may be low; can also be appropriately low if patient is nonpubertal. If patient is peripubertal, expect higher GH levels.
- Insulin-like growth factor 1 (IGF-1): may be low. Hyperinsulinemic states (insulin resistance) may also lead to lower IGF-1 levels.
- Luteinizing hormone/follicle-stimulating hormone (LH/FSH): may be low throughout the month for menstruating women (although would normally vary). Tumors secreting sex steroids and type 2 diabetes with obesity may also cause low levels. FSH levels may be high in Klinefelter syndrome, 46,XY/XO and 47,XYY karyotypes, mutations in the FSH receptor gene, and cryptorchidism. Both LH and FSH would be high in menopause/premature ovarian failure.
- Testosterone/estradiol: may be low. Estradiol is also lower after menopause/premature ovarian failure. Cryptorchidism, testicular torsion, increasing age, ketoconazole use, and type 2 diabetes with obesity are all associated with lower testosterone.
- Prolactin: may be low; higher in patients taking antidopaminergic drugs, including antipsychotic medications, metoclopramide, domperidone, cisapride, α-methyldopa, and reserpine; also higher in patients with prolactin-secreting pituitary adenomas
- Total serum cortisol: may be low. Pregnancy, oral contraceptive pills, hydrocortisone, and spironolactone can falsely elevate total serum cortisol and may mask underlying adrenal insufficiency.
- TSH: may be low. Exogenous dopamine can also cause low TSH. Amiodarone stimulates the thyroid and may cause elevated/low TSH. Lithium, thioamides, potassium iodide, and prednisone can increase TSH.
- Urine osmolality: may be low if patient has DI resulting from craniopharyngioma; may also be low if patient is taking a diuretic; may be high if patient is volume depleted and has functioning ADH activity or if patient receives desmopressin and has functioning renal ADH receptors
- Noncontrast CT or MRI
- Look for solid, cystic, and calcified components to the brain lesion.
- More commonly occurs in suprasellar regions; can also occur in infrasellar regions
- A sellar/parasellar mass detected on MRI should then be imaged with a noncontrast CT to better visualize calcifications (1)[C].
Test Interpretation
- Adamantinomatous: Peripheral palisading of the epithelium is a pronounced feature; contains nodules of keratin ("wet" keratin), which are the hallmarks of this tumor subtype
- Papillary: contains islands of squamous metaplasia embedded in a connective tissue stroma, with infrequent cystic degeneration and calcification
TREATMENT
GENERAL MEASURES
- Avoidance of driving, operating machinery, playing sports, or other activities that heavily depend on visual abilities
- Avoidance of gastric irritants; symptomatic treatment of nausea or vomiting
MEDICATION
Many patients with a craniopharyngioma have pituitary hormone dysfunction and will need lifelong hormone replacement under the ongoing care of an endocrinologist.
ISSUES FOR REFERRAL
- Long-term follow-up with an endocrinologist for monitoring hormone deficiencies and treatment
- Neuro-ophthalmology exam immediately following treatment, then annually
- Periodic cognitive testing for cognitive/neuropsychiatric problems
ADDITIONAL THERAPIES
- Modafinil for somnolence and obesity
- Patients more commonly have obstructive sleep apnea or secondary narcolepsy; modafinil may help (2,3)[A].
- Pain control for headaches
- Laxatives for constipation
- Continuous positive airway pressure (CPAP) for patients with obstructive sleep apnea (3)[A]
- Alternative reinforcement for behavior issues; appropriate psychosocial counseling (4)[B]
- Transitional services in adulthood
- Rehabilitation programs
SURGERY/OTHER PROCEDURES
- Treat adrenal insufficiency and DI prior to surgery.
- Resection is the main treatment; gross total resection is associated with increased rates of endocrinopathies compared with subtotal resection and radiotherapy; consider this when planning goals of surgery (5)[A].
- Risks of surgery: anesthesia; pituitary damage (particularly posterior, resulting in DI); vascular damage, causing severe, permanent neurologic damage (although this outcome should be avoidable) (2)[A]; hypothalamic and frontal lobe damage, resulting in problems with behavior, concentration, motivation, and socialization; and hyperphagia
- Hypothalamic obesity can occur posttreatment in up to 40% of cases. (6)[B]
- Limitations of surgery: Recurrence rate is significant, even with complete "radical" resections (1)[C]
- Other procedures
- Stereotactic radiosurgery and conformal radiation therapy are safe and effective minimally invasive options for additional management of residual or recurrent craniopharyngiomas (7)[B]
- Intracystic catheter insertion
- Bleomycin: No definitive recommendations for the use of intracystic bleomycin in the treatment of cystic craniopharyngiomas in children (8)[A]
- Interferon: currently the intracystic substance with the best benefit-to-risk ratio (9)[A]
INPATIENT CONSIDERATIONS
IV Fluids
May further increase urination, augmenting DI effects
Nursing
- Strict bed rest is encouraged to offset balance problems.
- Extra blankets for cold intolerance
- mood stabilizing agents for behavioral problems
- Pain control
- Antiemetics and treatment for constipation
Discharge Criteria
- General postsurgical stable status recommendations
- Pituitary hormones (e.g., TSH) will likely be abnormal, but the patient can be discharged with plans for any needed hormone replacement.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Postoperative MRI, within 2 months of surgery, to confirm that the extent of the resection was as planned; follow-up MRI every 6 to 12 months
- Biannual or annually follow up with MRI/CT scans to assess for recurrence of tumor
- Formal visual field evaluation by a trained professional 3 months after surgery then annually
- Monitor endocrine function: TSH, ACTH, ADH, Gn, and GH.
- Consider hormone supplementation for hypothyroidism, adrenal insufficiency, or delayed growth.
- Periodic cognitive testing for those with neuropsychiatric or cognitive disturbances
PATIENT EDUCATION
- National Cancer Institute. Childhood craniopharyngioma treatment (PDQ). http://www.cancer.gov/cancertopics/pdq/treatment/child-cranio/patient/page1. Modified May 22, 2014. Accessed 2014. Bethesda, MD: National Cancer Institute.
- High likelihood of recurrence; need for long-term surveillance with MRI/CT and for hormone supplementation
PROGNOSIS
- Long-term morbidity and mortality may include tumor recurrences, secondary malignancies, and endocrine and neuropsychiatric dysfunction.
- Prognostic factors for poor functional outcomes may include the following:
- Age <5 years
- Hypothalamic invasion by tumor
- Large tumor size
- Tumor site near vital structures
- Recurrent surgical procedures
- Poor surgical judgment
- Prognostic factors decreasing risk of recurrence/regrowth in craniopharyngioma include the following:
- Size <4 cm
- Favorable site
- Complete surgical resection
- Age >5 years
- Absence of hypothalamic disturbances
COMPLICATIONS
- Chronic/common: endocrine dysfunction, behavioral abnormalities, tumor recurrence, secondary malignancies, and hydrocephalus
- Acute/less common: seizures
- Acute/rare: chemical meningitis from rupture of cyst contents into the subarachnoid space
REFERENCES
11 Bartels U, Laperriere N, Bouffet E, et al. Intracystic therapies for cystic craniopharyngioma in childhood. Front Endocrinol (Lausanne). 2012;3:39.22 Bretault M, Boillot A, Muzard L, et al. Clinical review: bariatric surgery following treatment for craniopharyngioma: a systematic review and individual-level data meta-analysis. J Clin Endocrinol Metab. 2013;98(6):2236-2246.33 Clark AJ, Cage TA, Aranda D, et al. Treatment-related morbidity and the management of pediatric craniopharyngioma: a systematic review. J Neurosurg Pediatr. 2012;10(4):293-301.44 Crowley RK, Woods C, Fleming M, et al. Somnolence in adult craniopharyngioma patients is a common, heterogeneous condition that is potentially treatable. Clin Endocrinol (Oxf). 2011;74(6):750-755.55 Fang Y, Cai BW, Zhang H, et al. Intracystic bleomycin for cystic craniopharyngiomas in children. Cochrane Database Syst Rev. 2012;4:CD008890.66 Kalina M, Wilczek M, Kalina-Faska B, et al. Carbohydrate-lipid profile and use of metformin with micronized fenofibrate in reducing metabolic consequences of craniopharyngioma treatment in children: single institution experience. J Pediatr Endocrinol Metab. 2015;28(1-2):45-51.77 Klimo PJr, Venable GT, Boop FA, et al. Recurrent craniopharyngioma after conformal radiation in children and the burden of treatment. J Neurosurg Pediatr. 2015;15:499-505.88 Hammond JL, Hall SS. Functional analysis and treatment of aggressive behavior following resection of a craniopharyngioma. Dev Med Child Neurol. 2011;53(4):369-374.99 M ¼ller HL. Childhood craniopharyngioma: current controversies on management in diagnostics, treatment and follow-up. Expert Rev Neurother. 2010;10(4):515-524.
CODES
ICD10
D35.3 Benign neoplasm of craniopharyngeal duct
ICD9
227.3 Benign neoplasm of pituitary gland and craniopharyngeal duct
SNOMED
- Craniopharyngioma (disorder)
- Adamantinous craniopharyngioma
- Craniopharyngioma, papillary
CLINICAL PEARLS
- Although considered a "benign" tumor, a craniopharyngioma is associated with significant morbidity and mortality. Management of these tumors requires a multidisciplinary approach.
- Hormonal disturbances are common and patients typically need lifelong hormonal replacement.
- Surgical resection is the definitive treatment.