Craniopharyngioma and vestibular schwanoma

1. Craniopharyngioma &
Vestibular Schwannoma
DR.KIRAN KUMAR BR

2. 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
and may provoke vigorous glial reaction.

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)
Metaplasia of squamous epithelial cell rests that are remnants of
the part of the stomadeum that contributed to the buccal
mucosa.
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:
Two main histological subtypes:
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 .
Less infiltration of adjacent brain
tissue .
Mixed type – 15%

10. Differences between adamantinomatous and papillary
craniopharyngiomas
Adamantinomatous :
• More common
• Occur at a younger age
• Commonly calcified
• Commonly cystic and filled
with cholesterol-rich fluid or
soft necrotic debris.
• 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 to various brain
structures
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. Three major clinical syndromes based on location
Prechiasmal/chiasmal
Compression of optic apparatus
optic atrophy (eg, progressive decline of visual acuity and
constriction of visual fields) bitemporal vision loss
Retrochiasmal
3rd ventricle obstruction
hydrocephalus, with signs of increased intracranial
pressure (eg, papilledema and horizontal double vision)
Intrasellar
Compression of pituitary stalk and hypothalamic region
Endocrinopathy and headache

13. 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.

14. Grading
Based on degree of hypothalamic displacement:
Grade 0 = None
Grade 1 = Abutting/displacing
Grade 2 = Involving/Infiltrating – marked by absence of
hypothalamus on imaging
Puget et al.

15. Differential Diagnosis
-Rathke Cleft Cyst
-Suprasellar Arachnoid Cyst
-Hypothalamic/Chiasmatic Astrocytoma
-Pituitary Adenoma
Can mimic CP when cystic and hemorrhagic
-Thrombosed Aneursym
-Germinoma or Mixed Germ Cell Tumor with Cystic
Components

16. Prognostic Factors
Favorable:
Lack of calcifications (esp in adults)
Extent of surgical resection
Caucasian race
Unfavorable:
Age younger than 5 years old
Size > 5 cm
Hydrocephalus
Need for CSF shunting
Merchant et al., 2013

17. 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

18. Adamantinomatous
CT
Cysts -near CSF density, typically large and a dominant.
solid component-soft tissue density, 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: 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 spectroscopy: cyst contents may show a broad lipid spectrum.

21. T1
T1C

22. Coronal T1 C+ Coronal T2

23. Sagittal T1 C+ Axial T1
Axial DWI
Axial FLAIR

24. Papillary
Papillary craniopharyngiomas tend to be more spherical in outline and
usually lack the prominent cystic component; most are either solid or
contain a few smaller cysts. Calcification is uncommon.
CT
Cysts-small and not a significant feauture, near CSF density.
solid component-soft tissue density, vivid enhancement.
MRI
Cysts-when present they are variable in signal
T1: 85% T1 hypointense.
solid component
T1: iso- to slightly hypointense to brain, T1 C+: vivid enhancement
T2: variable/mixed
MR spectroscopy: cyst contents does not show a broad lipid spectrum
as they are filled with water fluid

26. T1

27. T1C

28. T2

29. Work-up
•Pretreatment evaluation
Pre-contrast CT and MRI, occasional cerebral angiography
Endocrinologic Evaluation
baseline serum electrolytes,
serum and urine osmolality, thyroid profile,
AM/PM cortisol levels
GH, LH and FSH levels in adolescent and adults.
Neuro-ophtalmologic
Important to establish pre-treatment baseline
Neuropsychological Assessment

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

31. 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

32. Surgical
•Craniotomy
Pterional,
Bifrontal and interhemispheric
•Transsphenoidal route – 1990’s
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

34. Complete resection
▫Potentially curative associated with local control and longterm
survival in 70% to 90% of patients
▫Post-op imaging indicates residual calcifications or obvious tumor in
15-50% of “totally resected” cases
▫Rate of recurrence after imaging confirmed total resection 15-30%
•Complications
▫Given location of tumor many adverse effects and could increase
morbidity of patient
▫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

35. • What role does radiation play in treating
CP???

36. 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.
In patients with compressive symptoms, surgical
decompression before irradiation is essential because
the tumor typically responds slowly to radiotherapy,
and radiation-induced edema may worsen compressive
symptoms.

37. 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%).
Radiotherapy may be given as salvage rather than
immediately after subtotal resection. Radiosurgery may
be useful in ablating small residual or recurrent tumors.
With 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.

38. 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%

39. 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.

40. Radiation
•St. Jude Children’s Research Hospital experience -Surgery
alone. 1984-2001
Retrospective, n=30, f/u = 5 years.
-Surgery + RT (55.8 Gy) 1.8Gy/fx )
Surgery group had more endocrine, neurologic,
ophthalmologic complications and IQ deficit .
-Surgery alone - lost ~ 9 IQ pts
-Surgery + RT - lost ~ 1.25 IQ pts
Merchant et al.

41. Radiation
•St. Jude Children’s Research Hospital experience (Merchant
et al.)
•Prospective study, n=88, Median f/u = 5 yrs
Surgery + RT (55.8 Gy) 1.8Gy/fx
-CTV Margins > 5mm n=26
-CTV Margins < 5mm n=62
(88.1% vs 96.2% [P=.6386]) no difference
Outcome
-CTV may be safely reduced w/o affecting rate of PFS
-Reduced PTV for future treatments to 3mm .

42. 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

45. 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
-Vascular injury (1-2%): temporal cavernomas, aneurysms.
-Cognitive dysfunction

46. 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

47. Treatment overview

49. Hormone Abnormality Threshold Dose to Hypothalamic Axis
Growth hormone deficit 18–25 Gy
ACTH deficit 40 Gy
TRH/TSH deficit 40 Gy
Precocious puberty 20 Gy
LH/FSH deficit Hyperprolactinemia

50. Vestibular Schwannoma

51. INTRODUCTION:
• Synonym: Acoustic Neuroma
• 1777- First observed on autopsy.
• 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.

52. 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.

53. 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

54. 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
• bevacizumab

55. • Autosomal dominant
• 22q12.2
• merlin protein
• 2015 : 9 clinical trails
• bevacizumab

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

57. 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

58. CLINICAL FEATURES

59. Jackler Staging System
Stage Tumor Size
Intracanalicular Tumor confined to IAC
I (small) < 10 mm
II (medium) 11-25 mm
III (Large) 25-40 mm
IV (Giant) > 40 mm

61. 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

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

63. 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

64. 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 .
– Helps in differentiating it from meningoma.
• Extracanalicular extension into cerebellopontine angle can
lead to "ice cream cone" appearance

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

66. Normal SideTrumpeted IAM

67. Contrast
Plain

68. MRI:
• T1
– slightly hypo-intense c.f. adjacent brain - 63%
– iso intense c.f adjacent brain - 37%
– may contain hypo intense cystic areas
• T2
– heterogeneously hyper intense c.f to adjacent brain
– cystic areas fluid intensity
– may have associated peri-tumoural arachnoid cysts
• T1 C+ (Gd)
– contrast enhancement is vivid
– but heterogeneous in larger tumours

69. T1+C
T1

71. Treatment options
The primary goals of therapy are local control and
preservation of function
• Surgery
– Translabyrinthine
– Retrosigmoid
– Middle cranial fossa
• Radiotherapy
– Conventional
– Stereotactic

73. 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.

74. 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%.
Proposed mechanisms of hearing loss following SRS resulting from direct
radiation injury to the vestibulocochlear nerve or cochlea, compression of
the vestibulocochlear nerve or internal auditory artery from tumor edema,
or thrombosis of the internal auditory artery.
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.

76. Fractionated Stereotactic Radiation Therapy
Fractionated stereotactic radiation therapy (FSRT) has been a part of
the treatment arm amentarium for vestibular schwannoma at
selected institutions.
Vestibular schwannomas are slowly proliferating tumors with a low
estimated α/β ratio of 2.5 to 4.
The hypothesized radiobiologic advantage of FSRT, therefore, is
based on reducing late toxicity to surrounding normal structures,
such as the cranial nerves and brainstem by Stereotactic localization
techniques .
Typical candidates are those with tumors too large for radiosurgery or
rare patients with malignant schwannomas, although FSRT can
certainly be performed for patients with smaller tumors.
Serviceable hearing preservation rates may be higher than those
achieved with SRS.

78. 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.
Multiple isocenters may be used to achieve a high degree of
conformality while simultaneously sparing normal tissues, and 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.
Facial, trigeminal, and auditory toxicities have also been shown to
correlate with the length of nerve irradiated.
Most cranial neuropathies develop within 2 years of SRS, but hearing
loss can occur much later.

79. 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 1.8 to 2 Gy per fraction, or 20 to 25 Gy at 4
to 5 Gy per fraction.

81. 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.