Craniopharyngioma

Introduction

Craniopharyngiomas are benign epithelial cell tumors derived from remnants of Rathke’s pouch.

  • They may be found in the suprasellar region, in the pituitary stalk, sella, optic system, or third ventricle.
  • Most craniopharyngiomas are partly cystic, filled with fluid containing cholesterol crystals.

Pathophysiology

  • Rathke’s pouch refers to a particular anatomical region of the roof of the mouth, that later gives rise to the anterior pituitary gland.
  • Remnants from this ectodermal layer may go on to develop benign cysts and neoplasms in children and adults.

Epidemiology

  • 1-3% of all brain tumors are craniopharyngiomas
  • They constitute a larger proportion (5-10%) of brain tumors in children.
  • The age distribution is bimodal
    • Occuring between 4 and 14 years and between 50 and 75 years.

Types

  • Adamantinomatous
    • More common in children
    • Histological features include peripheral palisading epithelium bordering underlying hydropic vacuolization (“stellate reticulum”), and scattered, plump keratin nodules, some with calcifications.
  • Papillary
    • More common in adults.
    • Histologically, composed of simple squamous epithelium and fibrovascular islands of connective tissue.
  • Both variants are surrounded by Rosenthal fibers, bundles of glial filament formed from chronic compression of neutrophils due to mass affect.
  • These fibers are also seen in juvenile pilocytic astrocytomas, which also arise in this region.
  • This is important to bear in mind when biopsy results are interpreted!

 

Clinical Features

As the tumor presses on adjacent structures, some of the many symptoms below may develop, depending on the tumor’s location. 

  • Visual disturbances: 20-30% of children with craniopharyngioma.
    • Papilledema (from increased intracranial pressure) may be detectable on physical exam.
    • Bitemporal hemianopsia (missing vision in the periphery of the right and left visual fields due to pressure on the optic chiasm),
    • Double vision
  • Endocrine abnormalities:
    • Hypothyroidism (40% of cases):
      • Weight gain
      • Fatigue
      • Cold intolerance
      • Constipation
      • Nonpitting edema noted on physical exam.
    • Adrenal failure (25% of cases):
      • Orthostatic hypotension
      • Hypoglycemia
      • Hyperkalemia
      • Cardiac arrhythmias
      • Lethargy
      • Confusion
      • Anorexia
      • Nausea and vomiting
    • Diabetes insipidus (20% of cases):
      • Excessive fluid intake and urination
    • Growth failure (11-18% of cases)
    • Delayed puberty
  • Neurologic
    • Headache (55-86% of cases):
      • slowly progressive, dull, continuous, and positional
    • Hyperphagia and obesity (11-18% of cases)
    • Psychomotor retardation
    • Short-term memory deficits
    • Incontinence
  • Changes in behavior:
    • Emotional immaturity and apathy

 

Diagnosis

Definitive diagnosis is made histologically, based on surgical biopsy.

Differential Diagnosis

  • Tumors: pituitary macroadenoma, meningioma, optic glioma, germinoma, teratoma, lymphoma, metastasis
  • Infectious or inflammatory processes: sarcoidosis, systemic histiocytosis, syphilis, tuberculosis
  • Vascular malformations: carotid-cavernous fistula, cavernous sinus hemangioma
  • Congenital defects: non-neoplastic cyst

Screening

  • Look for mass on CT or MRI

800px-Craniopharyngioma1_0.jpg
CT scan showing a craniopharyngioma https://en.wikipedia.org/wiki/Craniopharyngioma

 

  • 80-87% have calcifications, which may be detected on CT
    • Calcifications are more common in the pediatric population (90% in children, 50% in adults)
  • 75% have at least one cyst

Treatment

  • Pre-surgical evaluation and treatment:
    • Adrenal and thyroid function testing:
      • Serum electrolytes
      • Serum and urine osmolality
      • Thyroid studies
      • Cortisol levels
      • Growth hormone levels
      • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels.
        • Diabetes insipidus and hypoadrenalism are treated preoperatively
    • Visual field testing, to compare with post-operative testing
    • Control of peri-tumoral edema and increased intracranial pressure
      • May require temporary or permanent shunt
    • Percutaneous aspiration of large cystic components, if present, to prevent intraoperative hemorrhage
    • MRI for surgical planning and visualization of vessels

 

  • Treatment Options:
    • There are 2 competing approaches to initial treatment:
      • Complete surgical resection: when the tumor doesn’t infiltrate surrounding structures, total resection is feasible.
        • However, this aggressive surgical approach is associated with an increase in treatment complications.
      • Partial resection, followed by radiation therapy to treat residual disease, has been show to have equivalent rates of tumor control, without fewer rates of anterior hypopituitarism, diabetes insipidus, growth disturbance, and behavioral and feeding problems.
        • Initial surgical treatment confirms the diagnosis and decreases the compression of the tumor on surrounding structures.
        • Radiation therapy: radiation creates free oxygen radicals that damage DNA.
          • When targeted at tumor cells, which have a limited ability to repair DNA, the damage is significant and the cells undergo apoptosis.
        • Several different radiation therapy approaches may be used to vary the dosage size, treatment field, and number of treatments, depending on the tumor size and location.
    • Radiation therapy may also be used to treat recurrences, which are common especially in the pediatric population (53-62%).
    • When surgery isn’t feasible, treatment focuses on symptomatic control of the cystic component to avoid compression of visual, hypothalamic, or third ventricle structures
      • Aspiration: Catheters may be placed with CT guidance by the Ommaya reservoir system (see below), allowing for repeat aspirations if needed.
      • Alternatively, percutaneous needle aspiration may be performed on a one-off basis.
      • Intracavitary irradiation with brachytherapy: after draining the cyst, beta-emitting isotopes are placed in the cystic cavity.
      • Additional aspirations and refills are used to control cystic growth over time.
      • Intracavitary chemotherapy with bleomycin: reduces cyst size and thickens cyst wall

 

Outcomes

Treatment complications, treated symptomatically with medication when possible

  • Endocrine:
    • Panhypopituitarism (90% of patients after 10 years):
      • Hypogonadism
      • Hypothyroidism
      • Adrenal insufficiency
      • Growth Hormone Deficiency
    • Hypothalamic dysfunction:
      • Obesity
      • Secondary Type 2 Diabetes
      • Temperature dysregulation
      • Sleep disorders
      • Diabetes insipidus
  • Neurologic
    • Impaired intellect
    • Behavioral problems
  • Visual disturbances
  • Vascular: may include temporal cavernoma, moyamoya syndrome, aneurysms, and decreased caliber of arteries.
    • Increased risk of stroke.
  • Secondary malignancy: meningioma and malignant glial tumors

 

Prognosis

  • Prognosis is influenced mostly by treatment-related complications, rather than by tumor progression.
  • Overall survival rates published in the literature range from 85-95% at 5 years and 81-91% at 10 years. P
  • atients with craniopharyngioma have 3- to 5-fold increase in expected mortality, compared to the general population, due to cerebrovascular disease, type 2 diabetes, myocardial infarction, and severe infection. 

 

References

  1. Bunin GR, Surawicz TS, Witman PA, et al. The descriptive epidemiology of craniopharyngioma. J Neurosurg. 1998 Oct. 89(4):547-51.
  2. Clark, Aaron J, et al. Treatment-related morbidity and the management of pediatric craniopharyngioma: a systematic review. Journal of Neurosurgery 10.4 (2012): 293-301.
  3. Hukin J, Steinbok P, Lafay-Cousin L, Hendson G, Strother D, Mercier C, et al. Intracystic bleomycin therapy for craniopharyngioma in children: the Canadian experience. Cancer. 2007 May 15. 109(10):2124-31.
  4. Müller HL. Craniopharyngioma. Handb Clin Neurol. 2014. 124:235-53.
  5. Pereira AM, Schmid EM, Schutte PJ, et al. High prevalence of long-term cardiovascular, neurological and psychosocial morbidity after treatment for craniopharyngioma. Clin Endocrinol (Oxf). 2005 Feb. 62(2):197-204.
  6. Sands SA, Milner JS, Goldberg J, et al. Quality of life and behavioral follow-up study of pediatric survivors of craniopharyngioma. J Neurosurg. 2005 Oct. 103(4 Suppl):302-11.
  7. Van den Berge JH, Blaauw G, Breeman WA, et al. Intracavitary brachytherapy of cystic craniopharyngiomas.J Neurosurg. 1992 Oct. 77(4):545-50.

 

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