This document discusses craniopharyngioma and vestibular schwannoma. It provides details on the epidemiology, pathology, clinical presentation, investigations, treatment and complications of craniopharyngioma. It discusses the various treatment options for craniopharyngioma including surgical resection with or without radiotherapy. It also discusses vestibular schwannoma including its epidemiology, pathology, clinical features, investigations and treatment options such as surgery and radiotherapy.

1. Craniopharyngioma &
Vestibular Schwannoma
DR.KIRAN

2. Craniopharyngioma
Synonyms
Rathke's pouch tumour, Craniopharyngeal duct tumour,
Adamantinoma, Dysodontogenic epithelial tumour.
The first description of a craniopharyngioma was in 1857 by
Zenker.
The term craniopharyngioma was introduced in 1932 by Cushing.
Craniopharyngioma is a slow-growing, extra-axial, epithelial-
squamous, calcified, cystic tumor. ( WHO grade I).

3. Craniopharyngiomas arise from epithelial remnants of the
Rathke pouch and are typically found in the suprasellar
region in children or adolescents.
They often have solid and cystic components, the latter
filled with lipoid, cholesterol-laden (“crankcase oil”)
fluid.
Although appearing well encapsulated, craniopharyngiomas
typically demonstrate invaginations into adjacent brain.

4. Craniopharyngiomas most frequently arise in the pituitary
stalk and project into the hypothalamus.

5. Epidemiology
The incidence of newly diagnosed craniopharyngiomas ranges
from 0.13 to 2 per 100,000 population per year.
There is no variance by gender or race.
Distribution by age is bimodal with the peak incidence in
children at 5–14 years and in adults at 65–74 years of age.
In children, craniopharyngiomas account for 5% of all tumours
and 50% of all sellar/para sellar tumours.
They account for <5% of all CNS neoplasms in adults.

6. MOLECULAR BIOLOGY
• Some craniopharyngiomas are monoclonal in origin,
and cytogenetic abnormalities have been reported in
chromosomes 2 and 12.
• Mutations of the β-catenin gene have been identified
in 70% of adamantinomatous craniopharyngiomas.

7. Pathophysiology
Embryogenetic theory
Transformation of embryonic squamous cell structures along
the path of the craniopharyngeal duct (adamantinomatous
type)
Metaplastic theory
Metaplasia of adenohypophyseal cells in pituitary stalk or
gland * Rathke’s pouch * (squamous papillary type)
Defect in Wnt signaling pathway reactivation
β-Catenin gene mutations effecting exon 3 suggesting
nuclear β-Catenin accumulation.

8. Macroscopic Appearance
• GROSS: smooth lobulated capsule
• Solid- calcified
• Cystic-machine oil appearance
(crankcase oil)

9. Microscopy:
Adamantinomatous (90%)
Epithelial lesion with peripheral
palisading of basal squamous
epithelium surrounding loosely
arranged epithelial cells, the
so-called "stellate reticulum"
Papillary(10%)
Resembles oropharyngeal
mucosa, composed of simple
squamous epithelium .
Mixed type – 15%

10. Differences between adamantinomatous and papillary
craniopharyngiomas
Adamantinomatous :
• More common
• Occur at a younger age
• Commonly calcified
• Commonly cystic.
• A palisading layer of basaloid
epithelium surrounds
irregularly arranged cells that
resemble the stellate reticulum
of the epidermis.
• Keratin nodules are
commonly seen.
Papillary:
• Less common
• Occur at an older age
• Calcification is less common
• Commonly solid.
• Squamous epithelial nests that
surround loose fibrovascular
tissue rather than microcysts
create a solid tumor with a
pseudopapillary pattern.
• Keratin nodules are not seen.

11. Clinical Presentation
Symptoms manifest due to mass effects
Neurologic
Brain parenchyema
cognitive deficits
Visual Optic pathways
Visual disturbances
Ventricular system
Headaches, nausea/vomiting, hydrocephalus
Hypothalopituitary (Endocrinological)
growth failure (children) hypogonadism (in adults)

12. Tumour classification
Sammi et al: vertical projection
• Grade I- intra sellar/infra diaphragmatic
• Grade II-Occupying cistern with/without an intrasellar
component.
• Grade III- Lower ½ of 3rd ventricle
• Grade IV- Upper ½ of 3rd ventricle
• Grade V- Reaching the septum pellucidum or lateral ventricle.

13. Prognostic Factors
Favorable:
Lack of calcifications
Extent of surgical resection
Unfavorable:
Age younger than 5 years old
Size > 5 cm
Hydrocephalus
Need for CSF shunting
Merchant et al., 2013

14. Radiologic Findings
General:
Well encapsulated tumor, mixed cystic and solid component
CT
Detect calcifications
MRI
Most important used to plan surgical approach
Show relationship between tumor, vasculature, and optic
apparatus

15. Adamantinomatous
CT
Cysts -near CSF density, typically large and a dominant.
solid component-enhancement in 90%.
Calcification-seen in 90%,often peripheral in location.
MRI
cysts
T1: iso-hyperintense to brain (due to high protein content "machinery oil
cysts")
T2: hyperintense.
solid component
T1 C+ (Gd): vivid enhancement
T2: variable or mixed
MR spectroscopy: cyst contents may show a broad lipid spectrum.

17. T1
T1C

18. Coronal T1 C+ Coronal T2

19. Papillary
More spherical in outline and usually lack the prominent cystic
component; most are either solid or contain a few smaller cysts.
Calcification is uncommon.
MRI
Cysts-T1: 85% T1 hypointense.
solid component
T1: slightly hypointense to brain,
T1 C+: vivid enhancement
T2: variable/mixed
CT
Cysts-small and not a significant feauture, near CSF density.
solid component-soft tissue density, vivid enhancement.
MR spectroscopy: cyst contents does not show a broad lipid spectrum.

21. T1

22. T1C

23. T2

24. Pretreatment evaluation
Pre-contrast CT and MRI, occasional cerebral angiography
Endocrinologic Evaluation
baseline serum electrolytes,
Serum and urine osmolality,
thyroid profile,
Cortisol levels
GH, LH and FSH levels in adolescent and adults.
Neuro-ophtalmologic
Important to establish pre-treatment baseline

25. Treatment options
•Surgical resection +/- EBRT
-Mainstay Treatment
•Intracystic RT
•Chemotherapy
-Bleomycin – reduce tumor size
•Aspiration
-Purely cyst mass with goal of delaying treatment

26. Surgical
•Craniotomy
Pterional,
Bifrontal and interhemispheric
•Transsphenoidal route
Originally only dedicated to intrasellar masses due initial
difficulty with CSF leaks, and difficulty visualizing with
microscope.
90% of intrasellar and parasellar tumors approached
transphenoidally.

28. Complete resection
▫Potentially curative associated with local control and longterm
survival in 70% to 90% of patients
▫Rate of recurrence after imaging confirmed total resection 15-30%
•Complications
▫Extensive resection associated with DI in 90% and hypothalamic
obesity in 50%
Partial resection/cyst aspiration
▫Rapid symptom relief
▫Progression in 70% within 3 years
▫Second surgery higher surgical morbidity and lower quality of life

29. • Role Of Radiotherapy

30. With a limited surgical procedure (partial resection or cyst
aspiration plus biopsy) followed by radiotherapy, local control
and survival rates are nearly equivalent to those achieved with
complete resection.
Typically, doses of 50 to 54 Gy in 25 to 30 fractions (1.8 Gy)
over 6 weeks are delivered to the preoperative tumor volume
with a 1- to 1.5-cm margin.

31. With these dose recommendations (i.e., 1.8-Gy fractions to 50 to 54
Gy), the risk of visual impairment is very low (1% and 1.5%).
Radiosurgery may be useful in ablating small residual or recurrent
tumors.
Radiosurgery dose to the optic chiasm and nerves must be kept below 8
Gy, estimated to be radiobiologic tolerance for optic neuropathy
with single-fraction radiosurgical doses.
As a result, radiosurgery use should be restricted to tumors <3 cm in
size and located >3 to 5 mm from the optic apparatus.

32. Target volumes

33. 10 case reports of patients treated between 1952 and 1954
By 1986 reported total of 77 patients
• Median total dose of 56Gy w/ median dose of (1.5Gy/fx)
• PFS @ 5 years 83% PFS @ 10 years 79%

34. Radiation
Children’s hospital in Boston
• August 1976 - March 2003, n=79
• Median dose 54Gy
• LC at 10 years (no difference in OS)
▫Surgery alone: 52%
▫Surgery + planned RT: 84%
Winkfield et al. 2011.

35. Treatment related morbidity and management of
Craniopharyngioma (Clark et al. J Neurosurg 2012) :
•2012 Systematic Review
•109 studies describing extent of resection for 531 patients
•Morbidity difference between extent of resection +/- radiation Therapy
▫Gross-total resection (GTR)
▫Sub-total resection (STR) -Suggested reduced endocrine dysfunction

37. Intracystic RT and Chemotherapy
•β emitter 32 P, Yttrium-90
•To Treat residual or recurrent cyst formation
Used in patients to delay definitive treatment
(ie. Surgery GTR or STR +EBRT) for young patients
Bleomycin – limited success
Preoperative intralesional bleomycin may be effective at
decreasing cyst size and fibrosing cyst wall
Associated with vasogenic edema
Direct leakage of the drug to surrounding tissues during the
installation procedure, diffusion though the cyst wall

38. Complications
•90% will have at least one hormone deficiency
-Panhypopituitarism: hypogonadism, hypothyroidism,
adrenal insufficiency, GH deficiency
-Hypothalamic dysfunction: obesity, sleep disorders, DI .
-Post-treatment visual acuity highly dependent on pre-
treatment status
•Some patients might have improved vision
•Majority will remain the same
-

39. Treatment overview
•Complete resection remains the goal of primary surgery
▫High percentage of recurrences if tumor not radically
removed
•Maximal safe resection
-If GTR – observe (LC 80 -100%)
-If STR:
adjuvant EBRT to 54 Gy at 1.8Gy/fx (LC 75-90%)
Observation (LC 30%)
Consider deferring RT for children < 3 years

41. Evidence-Based Treatment Summary
1. Surgical resection is recommended, when feasible.
2. The use of postoperative radiotherapy has not been tested in
prospective trials but reduces the risk of recurrence and improves
survival in incompletely resected tumors.
3.Cyst decompression and biopsy followed by radiotherapy may
be an acceptable treatment for patients for whom resection is not
considered feasible.
4. Intracavitary bleomycin or radiocolloids may be useful in
cystic tumors.

42. Vestibular Schwannoma

43. INTRODUCTION:
• Acoustic Neuroma
• 1833- Sir Charles Bell- first clinical case report of
vestibular schwanoma.
• 1894- First successful removal of vestibular
schwanoma by Charles A Balance.
• Benign tumour arising from abnormally
proliferative schwann cells, which envelope the
lateral portion of the vestibular nerve in the
internal acoustic meatus.

44. Epidemiology
• 6 % of all Intracranial tumors
• 80 - 90% of CPA tumors
• Vast majority in adulthood
• No known race, gender predilection
• 95% Sporadic (unilateral, around 50 yrs)
• 5% Neurofibromatosis type 2 (bilateral, younger age)- 95% chance
of b/l VS, meningioma, ependymoma, spinal cord & peripheral
schwannoma.
• WHO grade I tumours.

45. Pathology
• Benign
• well circumscribed
• unencapsulated tumors
• In over 90% of cases these tumours arise from
the inferior division of the vestibular nerve .
• Malignant degeneration exceedingly rare
• Majority originate near the fundus of IAC

46. ASSOCIATION : NF2
• 1822, Wishart-bilateral VS-NF-2
• sporadic cases of VS-tumor occur unilaterally
• Faster growth rate , Early age.
• Autosomal dominant, 22q12.2
• merlin protein

47. Macroscopic appearance
• Yellow pinkish grey
• Soft Consistency
• Large tumour
• Cystic

48. Microscopic appearance
• Antoni A - closely packed
cells with small spindle-
shaped and densely stained
nuclei. A whirled appearance
of Antoni type A cells is
called a Verocay body
• Antoni B -looser cellular
aggregation of vacuolated
pleomorphic

49. CLINICAL FEATURES

51. Phases of Tumor Growth
• Intracanalicular:
– Hearing loss, tinnitus, vertigo
• Cisternal:
– Worsened hearing and dysequilibrium
• Compressive:
– Occasional occipital headache
– CN V: Midface, corneal hypersthesia
• Hydrocephalic:
– Fourth ventricle compressed and obstructed
– Headache, visual changes, altered mental status

52. Investigations:
Routine
Specific :
CT scan brain
MRI brain with contrast
Relevant :
Pure tone audiometry
Brainstem auditory–evoked responses
Audiological tests

53. Pure tone and speech audiometry are the most useful screening
tests. Selective loss of speech discrimination in excess of pure
tone loss is particularly suggestive of vestibular schwannoma.
Brainstem auditory–evoked responses typically demonstrate a
slowing of conduction, and electronystagmography may detect
a decrease in caloric response on the ipsilateral side.
Audiological tests:
Asymmetric unilateral SNHL
Tone decay –high ,retrocochlear hearing loss
Stapedial reflex absent

55. Radiographic features:
• Most vestibular schwannomas have an intracanalicular
component, solid, Cystic degeneration seen, Calcification is
typically not present.
• Widening of the porus acousticus resulting in
the trumpeted IAM sign.
– present in up to 90% of cases .
• Extracanalicular extension into cerebellopontine angle can
lead to "ice cream cone" appearance

56. CT
• Erosion and widening of the internal acoustic
meatus.
• Variable density.
• Hard to identify due to adjacent bone artefact.
• Contrast enhancing.
– Variable

57. Normal SideTrumpeted IAM

58. MRI
• T1
– slightly hypo-intense compared to adjacent brain -
63%
– iso intense compared to adjacent brain - 37%
• T2
– heterogeneously hyper intense c.f to adjacent brain
• T1 C+ (Gd)
– contrast enhancement is vivid

59. T1+C
T1

61. Treatment options
Goals: local control and preservation of function.
• Surgery
– Translabyrinthine
– Retrosigmoid
– Middle cranial fossa
• Radiotherapy
– Conventional
– Stereotactic

63. Radiation:
Conventional:
In patients with a medical contraindication to surgery, treatment
with external-beam irradiation alone is an option.
In patients with a medical contraindication to surgery, treatment
with external-beam irradiation alone is an option. A dose of 50
to 55 Gy in 25 to 30 fractions over 5 to 6 weeks is
recommended.

64. Stereotactic Radiosurgery
The first report of SRS for vestibular schwannoma was published by
Leksell in 1971.
Because of the minimally invasive nature and excellent clinical
outcomes achieved with SRS, practice patterns at some institutions
are shifting to favor SRS over resection. The ideal candidates have
tumors less than 3 to 4 cm in size.
Using modern techniques and doses, local control rates with SRS are
generally greater than 90% and significant cranial nerve
toxicity(hearing loss )rates are less than 10%.
Several retrospective reports have compared outcomes of patients
treated with surgery versus SRS demonstrating that both approaches
achieve comparable local control rates but SRS produces equivalent
or superior functional outcomes.

66. Fractionated Stereotactic Radiation Therapy
Fractionated stereotactic radiation therapy (FSRT) has been a part of
the treatment for vestibular schwannoma at selected institutions.
The hypothesized radiobiologic advantage of FSRT, therefore, is based
on reducing late toxicity to surrounding normal structures.
Typical candidates are those with tumors too large for radiosurgery or
rare patients with malignant schwannomas.
Serviceable hearing preservation rates may be higher than those
achieved with SRS.

68. IRRADIATION TECHNIQUES AND TOLERANCE:
High-resolution MRI images should be used during treatment
planning, either as the primary dataset or through fusion with a
treatment planning CT scan.
The dose is typically prescribed to the 70% to 90% isodose line.
The ideal SRS prescription dose is typically 12 to 13 Gy; local
control appears to be compromised with doses below this
range and cranial nerve toxicity increases with higher doses.

69. Fractionated Stereotactic Radiation Therapy:
The objective of FSRT is to combine the radiobiologic
advantages of conventional EBRT with the reduced
normal tissue exposure of radiosurgery.
Common regimens prescribed are on the order of 45 to
50 Gy at 4-6 Gy per fraction, or 20 to 25 Gy at 4 to 5
Gy per fraction.

71. Proton Therapy
• Data are now emerging on the use of fractionated proton
therapy.
• Weber et al. reported on 88 patients treated with fractionated
proton therapy with a median dose of 12 cobalt Gy equivalent.
• The five-year local control rate was 94%. However, only 33%
of patients were able to maintain serviceable hearing.
• Vernimmen et al. reported on 51 patients treated with
hypofractionated (three fractions) proton therapy with a mean
dose of 26 cobalt Gy equivalent.
• The five-year local control rate was 98%; however, the hearing
preservation rate was only 42% .

72. Targeted Therapy
Very recent data indicate that antiangiogenic agents
such as bevacizumab can induce tumor regression and
also, in some patients, restore hearing.
Larger trials with this agent are therefore planned in
NF2-associated vestibular schwannoma.

74. Evidence-Based Treatment Summary
1.Small nonprogressive tumors can be observed.
2. Surgical resection is generally considered the standard of care for symptomatic
lesions.
3. Radiosurgery produces outcomes equivalent to surgery, although these modalities
have not been prospectively compared.
4. Fractionated stereotactic radiotherapy is being increasingly employed, with
institutional reports suggesting a lower incidence of cranial neuropathies than
radiosurgery, but this has not been prospectively validated.
5. The role of bevacizumab in NF-2-associated progressive bilateral vestibular
schwannomas is being explored.
6. Trials of proton therapy for vestibular schwannoma are ongoing,

75. •Thank you.