Craniopharyngioma is a benign but complex brain tumor that occurs near the pituitary gland. It can cause vision problems, hormone deficiencies, and other issues due to its location near critical structures. Treatment involves maximal safe surgical removal combined with radiation therapy or other adjuvant therapies. While surgery and radiation can control the tumor, long-term management of complications is challenging due to the effects on pituitary and hypothalamic function. Future treatments may involve targeted molecular therapies based on genetic mutations in some craniopharyngiomas.

1. CRANIOPHARYNGIOMA
Dr RE Anto
Dept of Neurosurgery

2. • “The most formidable of all intracranial
tumours”
• “The kaleidoscopic tumours, solid and
cystic....” whose management is “one of the
most baffling problems to the neurosurgeon”
-Harvey Cushing (1936)

3. Craniopharyngioma
-Benign intracranial tumour
-Intimate relationship with critical structures
• Visual apparatus
• Pituitary
• Hypothalamus
• Limbic system
-Devestating clinical and psychosocial consequences

6. PATHOPHYSIOLOGY
Two hypotheses
• Embryogenic
• Transformation of the squamous cell epithelium along the
path of the craniopharyngeal duct
• Metaplastic
• Metaplasia of adenohypophyseal cells in pituitary stalk or
gland “Rathke’s Pouch”
Defect in Wnt signaling pathway reactivation
• β-Catenin gene mutations effecting exon 3 suggesting nuclear
β-Catenin accumulation

8. EPIDEMIOLOGY
• 3% of all intracranial tumours
• >50% suprasellar tumours in childhood
• Most common nonglial tumour of childhood
• Bimodal distribution
– Children (5-15 years)
– Late adulthood (45-60 years)
• Slight male predominance (55%)

9. PATHOLOGY
Adamantinomatous (WHO Grade 1)
• More common variant
• Epithelium of tooth
primordia
• Cysts in these tumours
contain “motor oil” liquid
• Associated with CTNNB1
mutation

11. Papillary (WHO Grade 1)
• Adults
• Predominantly solid tumours
• Cyst – fluid less oily and dark
• Derived from buccal mucosa
primordia
• Associated with BRAF V600E
mutation
Mixed
• 15% of craniopharyngiomas

12. SUPRASELLAR
(most common)
INTRAVENTRICULAR
(rare)
INTRASELLAR
(less common)
Hoffman et al

13. • Anterior pituitary
deficiency (>85%)
Paediatric
• Visual dysfunction
(>85%)
Adult
• Diabetes insipidus
• HCP
• Cognitive dys
• Memory impx
Both

14. Hypothalamic syndrome
• Obesity
• Sexual dysfunction
• Sleep/Wake cycle
• Pituitary failure
• Temperature dysregulation
• Behavioral (Depression/Aggression)
• Social / Emotional withdrawal

15. NEUROIMAGING
Various imaging modalities
• Skull Xray/CT/MR sequences
• 60-80%: calcifications in the suprasellar region
• 75%: one or more cysts
CT
• Better at evaluating the calcifications
• The skull base (enlargement of the sella turcica or erosion of the dorsum
sella)
MR
• Better evaluation of the relationships of tumour to surrounding
structures

16. MRI
• Cysts are uniformly hyperintense on T2
• Heterogenous on T1
MR Angiography
• Relationship between the tumour and the surrounding
vessels and the circle of Willis
MR Spectroscopy
• Shows a dominant peak consistent with lactate or lipids

17. • 7 year old boy with
2/12 hx of visual
problems and
headaches.
CT scan

18. T1WI Sagittal T2WI Sagittal

19. T1WI C+ Sagittal T1WI C+ Coronal

20. Perfusion MR MR Spectroscopy

21. Autopsy

22. Role of surgery
Maximal safe resection
• Transcranial vs Endoscopic
endonasal
• Gross total vs Subtotal
Management of cysts
• Drainage vs Ommaya reservoir
Management of hydrocephalus
• Shunt placement

23. Transcranial approaches
• Subfrontal
• Pterional
• Orbitofrontal
• Lamina terminalis
• Transcallosal
• Transcortical

25. Endoscopic Endonasal Approach

27. Intracystic therapy
• Reserved for tumours with one big dominant cyst
• Delay time to defintive surgery or radiation
• Requires surgery for placement and CT “leak test”
• Radiation - P32 (one time)
• 79.5-96% regression of cysts
• Chemotherapy - Bleomycin (3 week course)
• 50% of cyst regression
• Chemotherapy - Interferon-α (4 week course)
• 78% of cysts shrunk by 50% or more

28. • 2 x Ommaya reservoir
insertions in 2020 at
Polokwane Hospital

29. • A series of 17 children, intracystic bleomycin was
well tolerated, with five complete remissions and a
median progression-free interval of 1.8 years

30. • A series of 47 patients, given a radiation dose of 250 Gy,
The overall response rate was 78% and the mean
survival was 10 years.
• The survival rate at 1, 3, 5, and 10 years after p32
therapy was 91%, 77%, 73%, and 52%, respectively.

31. Radiation
LINAC
• Linear Accelarator (external beam RT)
• TruBeam
• CyberKnife
Stereotactic radiosurgery
• GammaKnife
Proton Beam
• Uses charged particles rather than photons to deliver high
doses of radiation to the target volume while limiting the
"scatter" dose received by surrounding tissues

32. Radiation therapy
• 54 Gy in 30 fractions
• 6 weeks of treatment
• Adverse events
• Cyst enlargement
• HCP
• Pituitary failure
(20-60% at 5 years)
• Cognitive decline
• Total dose temporal lobes
• Radiation necrosis

33. Evidence favouring radiation
• Study of 122 patients, looked at those treated
with GTR, STR and STR + RT, and the primary
endpoints were PFS and OS.

34. UCSF database

35. Progression Free Survival

36. Timing of radiation
• Controversial
• Immediate post-op (adjunctive) vs recurrence
(salvage)
• Another series noted control rate did not depend
on timing of RT
– DI and Visual impx (delayed > immediate)
• General recommendation is immediate
adjunctive therapy
– Cautious in children (delay) because of the greater
sensitivity to carcinogenic and adverse neurocognitive
effects of RT

37. SUMMARY
Surgery
• Maximum safe resection is 1st line Rx
• Cyst may require Ommaya reservoir
• HCP may require shunt
Radiation
• No proven difference between GK, CK, LINAC
• SBT + RT = GTR with low morbidity
• Radiation may be delayed until recurrence vs immediately post op.
Chemotherapy
• Intracystic interferon-α, bleomycin or p32
Medical therapy
• Hormone replacement

38. FUTURE DIRECTION
• Targeted molecular therapies
• Genetic studies
– CTNNB1 (B-catennin) : Adamantinomatous
– BRAF : Papillary
• Inhibitors of BRAF Proto-oncogene
– Dabrafenib/Vemurafanib
• MEK inhibitors
– Trametinib
• Multicenter phase-2 clinical trials at the
National Cancer Institute are currently
underway evaluating BRAF/MEK inhibition
in the treatment of craniopharyngioma

39. CONCLUSION
• Regardless of the therapeutic
strategies that are utilized, it is
evident that craniopharyngiomas
continue to present a distinct
challenge that still needs to be
overcome.
• Quality of life is a key consideration
in this disease, and long-term follow
up, involving a multidisciplinary
team, is a necessary element of care
of these patients.