craniopharyngiomas revised
TRANSCRIPT
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Dr. A. Ramcharan’s FirmThursday 31st Match 2011
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Demographics
•NAME: V.R.
•AGE: 5 years old
•SEX: Male
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• Referred by a private physician to Paediatric OPC with complaints of :-
• Intermittent frontal headaches
• Vomiting
• Photophobia
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Clinic Notes
• 22/07/09
• PC• headaches ×4/12
• HPC• Pt. was previously well up until 4 months ago• Frontal in nature• Each episode lasting ‘few’ hours• Frequency:• once per week and usually at school
• Associated orbital pain during episodes of headache• Exacerbated by:• Dietary: chocolate, cheese, coca cola
• Alleviated by Cataflam PRN
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Clinic Notes
• Past Medical History:• Repeated visits to private physicians being managed with antibiotics
and gravol• No history of head trauma• No known medical illnesses
• Past Hospitalisations
• Past Surgical History NIL
• Drug History: • Cataflam• Gravol• Antibiotics• Unable to recall name• Completed course prior to clinic visit
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Clinic Notes
• Allergies o
• Immunizations • Up to date
• Antenatal History• Fyzabad Health Centre• History of headaches, scoliosis
• Birth History:• Full term pregnancy• Lower Segment C-Section: 2 o to failure to progress• Birth weight: 8lbs• NNJ o ,Respiratory problems o
• Discharged 2/7 following birth
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•Nutritional History• Breast fed x 11/12
•Developmentally appropriate for age• At the time attending pre-school
•Immunizations reportedly up to date
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Examination
• Patient comfortable, no CPD
• Weight: 20kg ( 75th centile)
• Height :110cm
• BP- 95/67
• Anicteric, acyanotic, afebrile
• CVS• √S1 √S2
Ø M
• RESP• AE=bilateral
Ø rhonchi Ø crepitations
• ABD:• Soft, non-tender, o masses, √BS
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Examination
• CNS: • GCS: 15/15• Power• Tone normal• Reflexes
• Fundoscopy: • Right and left fundi normal
• No facial tenderness noted• SKIN: NAD
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• Impression: ? Migraine• Plan:
• CT skull & sinuses• Bloods
• CBC, RFT, LFT, HbEp, CRP, Ca 2+, Mg2+, , PO 3- 4
• Cataflam PRN• Gravol PRN• Diary record of headaches• OPC x 3/52
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Investigations
Wbc 6.4
Hb 11.6
MCV 84.1
MCH 30.4
Platelets 273
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Investigations
TSH 2.91
T4 9.7
T-uptake 0.9
T3 1.9
Prolactin 6.96
FSH 0.65
LH 0.1
Glucose 81
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Investigations
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Investigations
HbEp- AA
Patient was Followed up at Dr. ‘R’ POPC Each visit- patient continued to have
complaints of headaches
CT scan and MRI brain were performed
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01/11/10
• CT sinuses:• The sphenoid, maxillary and left ethmoid sinuses
are clear and pneumatized. The frontal sinuses are not yet pneumatized. The sinus ostia are patent bilaterally. The nasal turbinates are normal. The nasal septum is centred on the midline. There are soft tissue/fluid densities noted in the right ethmoid sinus, suggestive of a sinusitis.
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01/11/10
• CT brain with contrast: • There is a 2.40cm x 2.40cm hyperdense poorly
enhancing mass noted in the suprasellar region, within the interpeduncular cistern and extending anteriorly between the frontal lobes. There is calcification noted in the right anterior margin of the mass. There is no midline shift. The ventricles and CSF spaces appear normal. There are no acute intracerebral hemorrhages.There are no intra or extra axial fluid collections. The calvarium is normal.
• Impression- Suprasellar mass• Differential diagnosis:• Craniopharyngioma • Astrocytoma• Hypothalmic harmatoma
• URGENT MRI BRAIN ORDERED
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MRI BRAIN:◦ Reviewed by Dr. Maharaj (EWMSC)◦ Consistent with craniopharyngioma
Case was discussed with Dr.Akan and Dr.Spann and plan was as follows:◦ Do baseline bloods◦ FSH, LH, RBS, TFT, prolactin◦ Opthalmology assessment◦ Neurosurgical referral
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• Opthalmology review• Formal visual assessment normal
• Currently being followed up in POSGH- neurosurgical
• POPC ‘R’
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Case 1
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Brain Tumours
the US, about 2000 children and adolescents younger than 20 years of age are diagnosed with malignant brain tumors each year
In children under 2, about 70% of brain tumors are medulloblastomas, ependymomas, low- grade gliomas
The CNS cancer survival rate in children is approx 70% (rate varies with type of cancer and age of onset: younger patients have higher mortality)
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Classification
POSTERIOR FOSSA TUMOURS Cerebellar astrocytomas Medulloblastoma Ependymoma
BRAIN STEM TUMOURS Brainstem gliomas
SUPRATENTORIAL TUMOURS Cerebral astrocytoma Ependymoma Optic glioma craniopharyngiomas
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Craniopharyngiomas
a type of brain tumour derived from pituitary gland embryonic tissue (Rathke’s pouch)
Occurs most commonly in children but also in men and women in their 50’s and 60’s
Prevalence of 2/100 000 Rare, slow growing, benign by
histology, usually suprasellar, may be cystic
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Genetics
Adamantinomatous craniopharyngiomas have been consistently reported to show alterations in the beta-catenin gene expression
Beta catenin is a transcriptional activator of the Wnt signaling pathway which is involved in determining cell fate, proliferation, adhesion, migration, polarity and behaviour during development
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Theories
Embryogenetic theoriesRelates to development of the
adenohypophysis and transformation of the remnant ectoblastic cells of the craniopharyngeal duct and the involuted Rathke pouch
Metaplastic theoryRelates to the residual squamos epithelium
(derived from stomodeum and normal parts of the adenohypophysis) which may undergo metaplasia
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Dual theoryExplains the craniopharyngioma
spectrum attributing the adamantinous (most prevalent in children) to embryonic remnants and the adult type (ie squamos papillary) to metaplastic foci derived from mature cells of the hypophysis
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Pathophysiology
Several inflammatory cytokines have been shown to be elevated in the craniopharyngioma cyst fluid when compared with CSF
IL-1alpha and TNF-alpha were significantly elevated but lower than 10-fold
IL-6 was greater than 50,000 times more concentrated in the cystic fluid than CSF
This supports the hypothesis that biomodulation of the cytokine profile could lead to long periods of stability and even tumor regression. IFN-alpha exerts diverse influences mainly on cytokine antagonists and soluble adhesion molecules and has been shown to play a role in the treatment of craniopharyngioma in some limited trials, both after systemic use and local, direct intracystic use
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Recurrences usually occur at the primary site
Ectopic and metastatic recurrences are extremely rare and have been reported after surgical removal
The two possible mechanisms of seeding are dissemination of tumor cells along the surgical paths during the procedure and migration of tumor cells through the subarachnoid space or Virchow-Robin spaces (which would explain ectopic recurrences distant from the surgical bed and within brain parenchyma)
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Histology
2 distinct types Adamantinomatous
craniopharyngioma- calcifications are visible on neuroimaging
Papillary craniopharyngioma- rarely calcifies
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Symptoms
Symptoms at presentation may include:
Raised intracranial pressure Headache Vomiting (classical projectile
vomiting) Visual loss Those of pressure on critical adjacent
neuronal structures
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Hypothalamic/pituitary axis Anterior pituitary dysfunction with hormone deficiency (may involve GH,TSH, ACTH and FSH/LH) Posterior pituitary damage leading to DI (Diabetes Insipidus)
Optic pathways Visual field deficits (often bitemporal hemianopia). Optic atrophy and visual loss
Frontal lobes DementiaApathy
Temporal lobes SeizuresAmnesia
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Visual field deficits Often go unnoticed initially, usually picked up through
routine eye checkups at school Patients may notice: decreased clarity of vision Diplopia blurred vision subjective visual field defectsVisual field defect: Bitemporal hemianopsia (may be unilateral) is most
common, following by homonymous hemianopsia and homonymous quadrantanopia
When unilateral loss of vision occurs with optic atrophy, the tumor is most likely anterior and lateral to the chiasm
Due to the slow, progressive nature of the tumor, patients may not complain of visual loss
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Endocrine Dysfunction Hormonal abnormalities occur in 43-90% of children
at the time of diagnosis of a craniopharyngioma
The following endocrine problems may occur:
Growth hormone (GH) deficiency results in short stature
Luteinizing hormone (LH)/follicle-stimulating hormone (FSH) deficiency may lead to delayed or arrested puberty
Adrenocorticotropic hormone (ACTH) deficiency TSH deficiency and hypothyroidism leads to poor
growth, cold intolerance and fatigability Hyperprolactinemia Diabetes insipidus
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Tumour location Associated symptoms
prechiasmic Optic atrophyDecreased visual field acuityConstriction of visual field
retrochiasmic HydrocephalusPapilledemaCompression of the optic tractsHorizontal double vision
intrasellar Endocrinopathy• Panhypopituitarism (growth hormone and ACTH deficiency)• Diabetes insipidus Headaches
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Investigations
Endocrinologic studies baseline serum electrolytes serum and urine osmolality thyroid studies morning and evening cortisol levels growth hormone levels luteinizing and follicle-stimulating
hormone levels (in adolescent and adult patients)
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Radiology
CT scan Often used as the initial diagnostic
procedure Identifies the tumor as a craniopharyngioma
and provides some basic information as to its location and extent
Common characteristics of CT images of craniopharyngiomas are
Calcification (unenhanced CT shows this well) Low density lesion Cyst formation Contrast enhancement Sellar enlargement and erosion
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MRI scan MRI provides information
delineating the relationship of the tumor to adjacent anatomic and vascular structures
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Comparative roles of CT and MRI for CraniopharyngiomasCT MRI
role Identification of craniopharyngioma
Determine location and extent of tumor
appearance Calcification for adamantanous tumors onlyContrast enhancement in nodular regions
Heterogeneous
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Neuro-ophthalmologic evaluation with formal visual field documentation
Neuropsychological assessment
Histology
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Therapy
The optimal treatment of craniopharyngiomas remains controversial and the approach taken depends on tumor characteristics
Usually therapy involves a combination of surgical resection, cyst aspiration, radiation therapy (usually stereotactic radiotherapy or proton therapy), intracavitary irradiation and chemotherapy (given directly into the tumor cysts)
In most centers the standard of care is either: Surgery alone if the tumor can be completely
resected without unacceptable morbidity A combination of surgery to debulk the cystic
component principally followed by radical radiotherapy.
To delay surgery and radiation therapy, intracystic bleomycin can be used.
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Chemotherapy
Systemic chemotherapy is not used for craniopharyngiomas
However there is often a role for initial intra-cystic bleomycin
A catheter can be placed into the cystic component of the tumor, the contents aspirated and then intra-cystic bleomycin is given. It is important to check that there is no "leakage" of cyst contents prior to bleomycin installation into the ventricles
Leakage of bleomycin into the ventricles can be associated with a severe and life threatening arachnoiditis
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Intracystic bleomycin can lead to prolonged reduction in cyst size and in young children can be used to control disease (cyst expansion only) until they are older – when either a combination of radiotherapy and surgery or radiotherapy alone can be used
The solid component of the tumor is not treated with this technique
There is no direct injury to the hypothalamus and pituitary gland using this technique
Radioisotopes like Yttrium90 can also be instilled into craniopharyngioma cysts with the same results as bleomycin
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Surgery
Complete (radical) surgical resection of the tumor is associated with a more favorable outcome
Only 50-80% of patients are suitable for attempted complete resection
In general, smaller tumors could be completed resected without injury to adjacent structures
Surgical treatment is used for diagnosis, decompression and prevention of recurrence
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Surgical technique indications
Bifrontal and subfrontal approach
Supraseller tumors (prechiasmatic and large retrochiasmatic lesions)
Trans-sphenoidal approach Cystic infradiaphragmatic lesions Symmetrical and well-defined suprasellar and retrosellar lesions with enlarged sella Tumors without calcification
Lowers surgical morbidity and postoperative visual loss
Stereotactic aspiration of cyst Cystic tumors
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Cyberknife Radiosurgery
Abstract Microscopic and endoscopic techniques requiring superior skills are required for the examination of parasellar tumors
However, the parasellar region is surgically inaccessible, and complete excision of parasellar tumors remains a challenge
CyberKnife (CK) enables frameless radiosurgery and provides chronological and spatial freedom
CK was found to be feasible for parasellar tumors, although its safety and efficacy must be observed in long-term follow up
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Frequency of some post- operative sequelaeresidual calcification or tumor after resection
15-20%
Clinical recurrence 10-30%
Diabetes insipidus 50-80%
Panhypopituitarism 75-100%
Neuropsychologic and behavioural disturbances
36-60%
Morbid hypothalamic obesity 50%
Visual deterioration 2-45%
Fusiform dilation of internal carotid artery
15%
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Radiation therapy
RT planning: As this tumor is benign, the
standard of care is to use very small margins around the tumor in order to treat effectively and also spare surrounding normal critical structures
This is generally achieved with stereotactic therapy or proton technique
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Apoptosis in alpha interferon (IFN-alpha) intratumoral chemotherapy for cystic craniopharyngiomas.Ierardi DF, Fernandes MJ, Silva IR, Thomazini-Gouveia J, Silva NS, Dastoli P, Toledo SR, Cavalheiro S. IFN-alpha was able to induce Fas-
mediated apoptosis together with a reduction in the tumor size
such an observation may suggest the importance to investigate still unexplored mechanisms to be exploited in craniopharyngioma therapy
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Prognosis
The prognosis in this disease is very variable The natural history can be indolent or these tumors can be associated with
persistent cyst formation and growth Even though they are classified as histologically benign tumors,
craniopharyngiomas tend to shorten life, and can more aptly be called low-grade malignancies.
One of the most important prognostic factors is recurrence. The 20 year survival is around 60%, but once recurrence occurs the survival
rate drops to 25%. There are several factors that correlate with a more negative prognosis: Presence of calcification Incomplete tumor resection (based on postoperative imaging and presence of
gross residual disease) Severe hydrocephalus Adverse intraoperative events Age of less than 5 year
S
The prognostic significance of tumor type remains controversial.
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Initial Visual Field as a Predictor of Recurrence and Postoperative Visual Outcome in Children with Craniopharyngioma-PubMed Lee MJ, Hwang
The size of the tumor was not correlated with the preoperative visual field defects (P = .15)
Preoperative visual field defects were associated with
polyuria and polydipsia (P = .01) higher recurrence (P < .001) poorer postoperative visual acuities
(P < .001)
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References
pedsoncologyeducation.com Wikipedia pubmed
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Thank you
Questions?