Craniopharyngioma

Craniopharyngioma is a benign-appearing epithelial tumor of the sellar and suprasellar region arising from remnants of the Rathke pouch. It makes up 2 to 5% of intracranial tumors, with an incidence of about 0.13 in 100,000 people a year and a bimodal age peak at 5 to 14 years and 50 to 74 years.

Two types

• Adamantinomatous (children): CTNNB1 mutation, cystic with "machinery oil" fluid, calcification and finger-like brain invasion
• Papillary (adults): BRAF V600E mutation in about 95%, solid, with no calcification

Though histologically grade 1, its location in the hypothalamus and optic chiasm causes major morbidity. Recurrence occurs in 20 to 50% after subtotal resection. Ten-year survival is 80 to 90%. Complications: visual loss, hypopituitarism (80 to 90% after surgery), diabetes insipidus, hypothalamic obesity (up to 50%), memory and sleep disturbance, and cerebrovascular events.

• Children: headache and vomiting from hydrocephalus, growth failure, delayed puberty and visual decline
• Adults: bitemporal hemianopia, hypogonadism, fatigue and cognitive or mood change
• Polyuria and polydipsia (diabetes insipidus) in a minority at presentation
• Red flags: rapid visual loss, hypothalamic obesity, acute pituitary hemorrhage and signs of raised pressure

1. MRI sellar region with gadolinium: a suprasellar cystic mass with enhancing solid components (adamantinomatous) or a solid enhancing mass (papillary).
2. CT: calcification in about 90% of children.
3. Visual assessment: acuity, fields, color vision and fundus.
4. Endocrine evaluation: 8 am cortisol (under 100 nmol/L deficient, over 450 nmol/L excludes deficiency) or a short synacthen test with 250 micrograms, TSH and free T4, IGF-1, LH, FSH, testosterone or estradiol, prolactin, plasma and urine osmolality, serum sodium.
5. Histology with BRAF V600E and CTNNB1 testing.

Differentials: Rathke cleft cyst, pituitary adenoma, germinoma, hypothalamic glioma, arachnoid cyst, meningioma.

• Perioperative cortisol cover: hydrocortisone 100 mg IV before induction then 50 mg IV every 6 hours (children 50 to 100 mg/m2 IV then 50 to 100 mg/m2 a day in 4 divided doses), then taper to 15 to 20 mg a day orally in 2 to 3 divided doses (children 8 to 10 mg/m2 a day).
• Surgery: endoscopic endonasal transsphenoidal resection (for retrochiasmatic midline tumors) or transcranial resection (for large lateral tumors). Aim for gross total resection when the hypothalamus is not at risk, and otherwise limited resection followed by radiotherapy.
• Radiotherapy: 54 Gy in 30 fractions of 1.8 Gy (conformal or proton) after subtotal resection or at recurrence, with 10-year disease control of 80 to 90% versus 30 to 40% with surgery alone. Cystic recurrence can be managed with an Ommaya reservoir and aspiration.
• BRAF-mutant papillary tumors: dabrafenib 150 mg orally twice daily with trametinib 2 mg orally once daily, for 4 to 8 weeks before surgery or until progression. Monitor for fever, rash and ventricular function.
• Diabetes insipidus: desmopressin 100 to 200 micrograms orally at night, titrated to a maximum of 1200 micrograms a day in divided doses (or 10 to 20 micrograms intranasally), with sodium checked in the first week since the triphasic pattern causes hyponatremia.
• Hormone replacement (after cortisol is replaced): levothyroxine 1.6 micrograms/kg orally daily, titrated to free T4 in the upper half of normal. Growth hormone: children 0.025 to 0.035 mg/kg SC daily, adults starting 0.2 mg SC daily. Sex steroids at the appropriate time.
• Hypothalamic obesity: structured diet and exercise, and metformin 500 mg orally twice daily with food, increasing to a maximum of 2 g a day.
• Sick day rules: double or triple the glucocorticoid dose in febrile illness, with IM hydrocortisone 100 mg for vomiting or collapse, and a medical alert bracelet.

Follow-up: MRI at 3 months, 6 months, then annually for 10 years. Review endocrine, visual and neurocognitive status every 6 months.