Dr. A. Ramcharan’s FirmThursday 31st Match 2011

Demographics

•NAME: V.R.

•AGE: 5 years old

•SEX: Male

• Referred by a private physician to Paediatric OPC with complaints of :-

• Intermittent frontal headaches

• Vomiting

• Photophobia

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

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

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

•Nutritional History• Breast fed x 11/12

•Developmentally appropriate for age• At the time attending pre-school

•Immunizations reportedly up to date

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

Examination

• CNS: • GCS: 15/15• Power• Tone normal• Reflexes

• Fundoscopy: • Right and left fundi normal

• No facial tenderness noted• SKIN: NAD

• 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

Investigations

Wbc 6.4

Hb 11.6

MCV 84.1

MCH 30.4

Platelets 273

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

Investigations

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

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.

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

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

• Opthalmology review• Formal visual assessment normal

• Currently being followed up in POSGH- neurosurgical

• POPC ‘R’

Case 1

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)

Classification

POSTERIOR FOSSA TUMOURS Cerebellar astrocytomas Medulloblastoma Ependymoma

BRAIN STEM TUMOURS Brainstem gliomas

SUPRATENTORIAL TUMOURS Cerebral astrocytoma Ependymoma Optic glioma craniopharyngiomas

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

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

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

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

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

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)

Histology

2 distinct types Adamantinomatous

craniopharyngioma- calcifications are visible on neuroimaging

Papillary craniopharyngioma- rarely calcifies

Symptoms

Symptoms at presentation may include:

Raised intracranial pressure Headache Vomiting (classical projectile

vomiting) Visual loss Those of pressure on critical adjacent

neuronal structures

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

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 

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 

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

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)

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

MRI scan MRI provides information

delineating the relationship of the tumor to adjacent anatomic and vascular structures

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

Neuro-ophthalmologic evaluation with formal visual field documentation

Neuropsychological assessment

Histology

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.

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

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

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

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

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

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%

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

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

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. 

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)

References

pedsoncologyeducation.com Wikipedia pubmed

Thank you

Questions?