Craniopharyngioma

INTRODUCTION

Craniopharyngiomas are rare solid or mixed solid and cystic tumors that arise from remnants of Rathke's pouch along a line from the nasopharynx to the diencephalon. Historically, these have also been referred to as "Rathke pouch tumors" or "hypophyseal duct tumors."

●Epidemiology – Craniopharyngiomas are rare suprasellar brain tumors arising from the remnants of Rathke’s pouch. There is a bimodal age distribution, with peak incidence between 5 and 14 years and later between 50 and 75 years of age.

●Pathology and genetics – Histologically, craniopharyngiomas are either adamantinomatous (more common in childhood) or papillary (predominant in adults). All tumors should be tested for BRAF V600E mutations by immunohistochemistry or sequencing. Nearly all papillary craniopharyngiomas have BRAF V600E mutations.

●Clinical features – Craniopharyngiomas are slow-growing tumors that usually arise along the pituitary stalk in the suprasellar region adjacent to the optic chiasm. Common presenting symptoms include visual changes, endocrine abnormalities, and headache.

Neuroimaging shows a suprasellar enhancing mass, often cystic and, in the case of adamantinomatous tumors, calcified.

●Multidisciplinary planning – Individuals should be managed by a multidisciplinary team experienced in the treatment of craniopharyngioma that includes neurosurgery, radiation oncology, neuro-oncology, endocrinology, ophthalmology, neuroradiology, and neuropathology.

●Surgical management – When neuroimaging suggests craniopharyngioma in a patient with clinical characteristics suggestive of a papillary subtype (eg, adult age, lack of tumor calcification) and there is an intent to offer BRAF-targeted therapy to lessen need for risky surgery and large radiation fields, biopsy or conservative resection is an alternative to upfront aggressive surgery. However, decisions should be individualized, since BRAF therapy does not replace the role of adjuvant radiation and is sometimes poorly tolerated, and gross total resections, when safe, can be curative and obviate the need for adjuvant therapy of any kind.

For all other patients, initial management involves surgical resection to establish diagnosis, alleviate mass-related symptoms, and remove as much tumor as is safely possible.

●Postoperative therapy

•BRAF-mutant tumors – For most patients with newly diagnosed BRAF-mutant papillary craniopharyngioma who have residual disease after surgical management, we suggest treatment with BRAF-targeted therapy (eg, vemurafenib/cobimetinib or dabrafenib/trametinib) and/or adjuvant radiation therapy (RT), rather than watchful waiting (Grade 2C). Adjuvant RT improves local control and may be associated with less morbidity than use as a salvage therapy.

For patients who elect BRAF-targeted therapy, treatment decisions after four to six cycles should be individualized after discussion of the potential risks and benefits of RT, surgery, continued targeted therapy, and observation.

●All other tumors – For most other patients, postoperative decisions are individualized based on the extent of tumor residual, patient age and comorbidities, and the potential risks of RT. RT after subtotal resection reduces the risk of recurrence. Some patients require additional procedures to manage symptomatic cysts.

●Treatment complications – A wide range of endocrine and neurologic complications are observed in patients with craniopharyngioma following treatment; these likely contribute to the increased mortality of patients with craniopharyngioma and thus the rationale for lifelong surveillance for these patients.

●Prognosis – The long-term prognosis following treatment is influenced both by the ability to control tumor and the development of treatment-related complications. In long-term follow-up studies, rates of 10-year overall survival range from 80 to 96 percent.