Craniopharyngioma

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.