Adamantinomatous craniopharyngioma

Adamantinomatous craniopharyngiomas are WHO grade 1 tumours of the pituitary region typically presenting as cystic masses with peripheral calcifications in children. They are a distinct entity from the far less common papillary craniopharyngioma found in adults ^1,4. 

Terminology

Until the 5^th Edition (2021) of the WHO classification of CNS tumours, adamantinomatous craniopharyngiomas were considered a subtype of craniopharyngiomas along with papillary craniopharyngiomas ¹. 

Increasing molecular evidence has demonstrated that they have distinct and mutually exclusive mutations of CTNNB1 (adamantinomatous) and BRAF (papillary) ^1,2,4. As such, they are now considered separate entities and are discussed separately.  

Epidemiology

Adamantinomatous craniopharyngiomas are far more common than papillary craniopharyngiomas and are identified in all age groups, but predominantly in children with a second, less pronounced, peak between 40-59 years of age ⁹. No sex or racial predilection has been identified ⁹. 

Importantly, even though adamantinomatous craniopharyngiomas are thought of as tumours of childhood whereas papillary craniopharyngiomas are considered tumours of adults, adamantinomatous craniopharyngiomas are more common than papillary craniopharyngiomas at all ages ^9,10. 

Clinical presentation

Clinical presentation is variable on account of the variable precise location and size of the tumour. Presenting complaints include:

• headaches and raised intracranial pressure
• visual symptoms
• hormonal imbalances
  • short stature and delayed puberty
  • amenorrhoea
  • diabetes insipidus
• behavioural change due to frontal or temporal extension

Pathology

Adamantinomatous craniopharyngiomas consist of palisading peripheral columnar epithelium, wet keratin and stellate reticulum that have appearances reminiscent of the enamel pulp of developing teeth, with many similarities with ameloblastomas ^2-4.

There may be single or multiple cysts filled with thick oily fluid rich in protein, blood products, and/or cholesterol, giving the so-called "motor oil" fluid appearance. "Wet keratin nodules" are a characteristic histological feature. Calcification is usually present (~90%) ³.

Adamantinomatous craniopharyngiomas have β-catenin gene (CTNNB1) mutations that prevent degradation of β-catenin protein ^2,4. 

Radiographic features

Adamantinomatous craniopharyngiomas are primarily suprasellar tumours (75%) while a small intrasellar component is present in 20-25% of cases ⁵. Purely intrasellar location is quite uncommon (<5%), and may be associated with the expansion of the pituitary fossa ^3,6. Larger tumours can extend in all directions, frequently distorting the optic chiasm or compressing the midbrain with resulting obstructive hydrocephalus.

Rare or ectopic locations reported include nasopharynx, posterior fossa, extension down the cervical spine.

These tumours typically have a lobulated contour as a result of usually being multiple cystic lesions. Solid components are present, but often form a relatively minor part of the mass and enhance vividly on both CT and MRI. Overall, calcification is very common (~90% are calcified) ⁷. 

These tumours have a predilection to being large, extending superiorly into the third ventricle, encasing vessels and even adhering to adjacent structures ⁷. 

CT

• cysts
  • near-CSF density
  • typically large and a dominant feature
  • present in 90%
• solid component
  • soft tissue density
  • enhancement in 90%
• calcification
  • seen in 90% ¹¹
  • typically stippled and often peripheral in location

MRI 

• cysts
  • T1: iso- to hyperintense to grey matter ¹¹ (due to high protein content "motor oil cysts")
  • T2: variable but ~80% are mostly or partly T2 hyperintense
• solid component
  • T1 C+ (Gd): vivid enhancement
  • T2: variable or mixed 
• calcification
  • difficult to appreciate on conventional imaging
  • susceptible sequences may better demonstrate calcification
• MR angiography: may show displacement of the A1 segment of the anterior cerebral artery (ACA)
• MR spectroscopy: cyst contents may show a broad lipid spectrum, with an otherwise flat baseline ⁸

Treatment and prognosis

Treatment is usually surgical with radiotherapy, especially useful for incomplete resection. The surgical approach depends on the size and sellar vs suprasellar extent. Some lesions can be accessed via a transsphenoidal approach, whereas others require a craniotomy. 

Prognosis is similar to that of papillary craniopharyngiomas, most affected by the age at diagnosis, with progressive worse prognosis with advancing age ^9,10. In children, the overall 3-year survival of all craniopharyngiomas is ~95% whereas it drops to ~45% for elderly patients >80 years of age ⁹.   

Differential diagnosis

General imaging differential considerations include:

• Rathke cleft cyst
  • no solid or enhancing component
  • calcification is rare
  • unilocular
  • the majority are completely or mostly intrasellar
• pituitary macroadenoma (with cystic degeneration or necrosis)
  • can look very similar
  • usually has intrasellar epicentre with pituitary fossa enlargement rather than the suprasellar epicentre
  • despite the occasional presence of T1 bright cystic regions, calcification in these cases is often absent (whereas most adamantinomatous craniopharyngiomas are calcified)
• pituitary apoplexy 
  • the presentation will usually be acute
• intracranial teratoma
  • presence of fat is helpful but requires fat-saturated sequences or CT to confirm