Adamantinomatous craniopharyngioma

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Types of craniopharyngioma

General

• Adamantinomatous craniopharyngioma is a mixed solid and cystic squamous epithelial tumour.

• It is typically localized to the hypothalamic-pituitary axis.

• It is histologically characterized by stellate reticulum and wet keratin and is molecularly characterized by activating CTNNB1 mutations.

Definition

• Essential criteria
• Location within the sellar region.
• Presence of benign, non-keratinizing squamous epithelium.
• Presence of stellate reticulum and/or wet keratin.

• Desirable criteria
• Nuclear immunoreactivity for p-catenin.
• Identification of a mutation in the CTNNB1 gene.
• Absence of a BRAF p.V600E mutation.

Numbers

• It is the most common non-neuroepithelial intracerebral neoplasm in children, accounting for 5–11% of intracranial tumours in this age group.

• There is a bimodal age distribution with peaks in children (5–15 years) and adults (45–64 years).

• There is no reported sex predilection.

WHO grade

• This tumour is regarded as CNS WHO grade 1.

Histopathology

• Macroscopic
• The tumours are solid and cystic; the cyst fluid is often dark greenish-brown and resembles "machinery oil".
• Masses are often lobulated with irregular surfaces that adhere strongly to surrounding brain structures.
• Calcifications are common.

• Microscopic
• The well-differentiated epithelium forms cords, lobules, ribbons, and irregular trabeculae.
• Prominent peripheral crowding and palisading of cells is characteristic.
• Hallmarks include "wet keratin" (nodules of anucleate ghost-like squamous cells) and a loose microcystic stellate reticulum.
• Finger-like tumour protrusions often extend into surrounding gliotic brain tissue.

• Immunophenotype
• p63 is expressed in all epithelial layers.
• Expression is positive for high-molecular weight cytokeratins (34BE12, CK5/6) and low- to intermediate-weight cytokeratins (CK7, CK17, CK19).
• Nearly all cases show nuclear accumulation of p-catenin protein, though often only in scattered individual cells or small clusters.
• SOX9 is widely expressed, while SOX2 is present in a small proportion of cells.

Pathogenesis

• These tumours are proposed to arise from cellular elements related to the Rathke pouch.

• Pathogenesis is driven by activating mutations in exon 3 of CTNNB1, which encodes p-catenin.

• Rare cases occur in the setting of Familial Adenomatous Polyposis 1, associated with germline APC mutations.

Localisation

• Most occur in the sellar and infundibulotuberal region.

• Approximately 95% have a suprasellar component.

• Rare ectopic occurrences have been documented in the cerebellopontine angle.

Clinical features

• Incidental detection is rare (< 2%); most present with symptoms of headache, visual field deficits, and endocrine dysfunction.

• Almost half of patients develop "hypothalamic syndrome," which includes morbid obesity, cognitive impairment, and psychiatric symptoms.

Radiological features

• Features follow a "90% rule": approximately 90% are predominantly cystic, 90% have prominent calcifications, and 90% show contrast enhancement in the cyst walls.

Management

• Treatment strategies are debated, ranging from gross total resection to limited surgery focused on preserving hypothalamic and visual integrity.
• Radiotherapy and hypothalamus-sparing surgical approaches are often recommended to maintain quality of life.

• Surgery resection + radiotherapy

• Cystic component of craniopharyngioma commonly presents a problem for radiotherapy and radiosurgery

• Tumour growth and cyst enlargement can be independent:
• Solid component can usually be controlled by radiation
• Cystic component may require treatment with
• Stereotactic aspiration (e.g. acute presentation or poor surgical candidate)
• Placement of Ommaya reservoir allowing intermittent aspiration pf a cyst that cannot be completed resected
• Sclerosis of cyst wall by chemotherapy agents for treatment-resistant cysts (e.g. bleomycin, interferon alpha)
• Internal irradiation (brachytherapy) with implanted radioisotopes for treatment resistant cysts (Phosphorus-32)

Prognosis

• While biologically grade 1, the prognosis is often complicated by the tumour's tendency to invade adjacent vital structures, which can preclude safe total resection.

• Overall survival rates are high (e.g., 62–92% at 20 years), but long-term morbidity from hypothalamic damage or metabolic syndrome is significant.

• Late mortality may occur due to cardiovascular disease or infections rather than tumour progression.