Ocular Features of Craniopharyngioma
Craniopharyngiomas (CP) are uncommon, typically suprasellar neoplasms either derived from the craniopharyngeal duct epithelium of the Rathke pouch or squamous metaplasia with consequent formation of cell nests. CP comprise 1.2 – 4.6% of intracranial tumors, and there are 0.5–2.5 new cases per 1 million per year globally. There is no particular gender, race, or geographical area that is more susceptible to CP.
There are two histologic types of CP: adenomatous and papillary. Adenomatous CP typically present in a bimodal distribution of age, from 5-15 years and less commonly from 45-60 years. Papillary CP are typically found in adults aged 45-60 years. Adenomatous CP have both solid and cystic components. The solid components contain dense nodules of squamous epithelium bordered by loose stellate reticulum. The cystic portion contains cholesterol and thus has a yellow-brown appearance. Another distinct feature of adenomatous CP is the presence of eosinophilic, calcium-rich desquamated cells known as wet keratin. In contrast, papillary CP are often non-calcified, less likely to contain loose reticulum, and more pedicle in form.
CP are considered benign World Health Organization (WHO) Grade I tumors and malignant transformation is rare. Most incidences of malignant CP occur after radiation therapy or multiple recurring intracranial tumors. The recurrence rate is roughly 50%, but 65-100% of individuals have 10-year survival. Morbidity rates parallel survival rates, with nearly all individuals developing some form of either short-term or long-term sequelae. These sequelae can include pituitary hormone deficiencies, obesity, and ophthalmic symptoms, due to the close proximity to the pituitary gland and optic chiasm. Additionally, pituitary abscesses can occur inside of CP albeit very rarely, further complicating endocrine and visual deficits.
Individuals with CP often present with complaints of dull, continuous headaches, endocrine abnormalities, or visual disturbances. Because of the slow-growing nature of the tumor, symptoms typically do not arise until after growing greater than 3 cm. Common ophthalmic manifestations include decreased visual acuity, visual field reduction, and/or diplopia, often noticeable by the patient in 40-70% of cases. One of the most common visual presentations of CP is bitemporal hemianopsia due to compression of the optic chiasm. Other visual field defects that localize to the optic chiasm are also possible from direct compression (e.g., optic neuropathy, junctional visual field loss, or rarely optic tract).
Because of the comprehensive involvement of surrounding structures, both a focused neurological examination and general examination are warranted if CP is suspected. Besides the endocrine presentations which will not be discussed here, a complete ophthalmic exam can point towards the appropriate diagnosis. Visual loss (especially bitemporal hemianopsia) and abnormal pupillary responses may suggest a chiasmal lesion such as CP. Signs of increased intracranial pressure, including papilledema or optic disc atrophy if intracranial pressure increase has been prolonged, may be non specific features.
Both computerized tomography (CT) and magnetic resonance imaging (MRI) scans can be utilized to diagnose CP. Cranial MRI with contrast is the preferred imaging source due to greater detail in regard to soft tissues, cystic component, tumor location and relationship to adjacent structures. However, calcifications are more evident on CT imaging, particular in pediatric cases where calcifications are more common. Cystic components, if present, appear similar in density to cerebrospinal fluid (CSF) on MRI. A sellar or suprasellar mass comprised of calcified cysts is the principal radiologic feature of a CP. A full eye exam including formal visual field testing with automated static or kinetic perimetry is recommended for CP.
Endocrine evaluation should be performed in every patient with CP. Histopathological evaluation of the lesion can include an MIB-1 labeling index to measure the proliferative capacity of the tumor. MIB-1 is a monoclonal antibody most often used for planning therapy and predicting reoccurrence. As mentioned above, histological findings can diagnose the subtype of CP.
Rathke cleft cyst
Cavernous sinus hemangioma
The general approach to treating CP includes conservative approaches, surgical intervention (e.g. subtotal or complete resection or cyst drainage), radiotherapy, and intracystic therapy. Intracystic therapy is typically reserved for adenomatous craniopharyngiomas, whereas radiation and surgery can be used for either subtype. Surgical removal of the tumor typically alleviates visual disturbances.
Surgical resection is the treatment of choice for CP. Endoscopic endonasal transsphenoidal (EET) or transcranial surgical approaches are common. If increased intracranial pressure or hydrocephalus is apparent on physical exam or imaging, a shunt should be considered prior to operation. Preoperative optical coherence tomography (OCT) and formal visual fields should ideally be performed pre-operatively to provide baseline information.
Due to the close proximity to the pituitary gland, craniopharyngiomas often cause various manifestations of hypopituitarism. Therefore, any of the anterior or posterior pituitary hormones may need to be replaced. This may still be required if surgery is performed and there is evidence of hypopituitarism. Systemic chemotherapy is not utilized in the treatment of craniopharyngiomas. However, in a mass composed of only cystic components, interferon alpha and localized bleomycin has shown to be successful in some reports. There are no medications currently that improve or prevent visual disturbances.
Proton beam radiotherapy or external beam radiation may follow subtotal resection. Proton therapy has been demonstrated to reduce secondary incidence by up to 15-fold as compared to traditional external beam radiation using photons.
Recurrence of craniopharyngioma after surgical excision, with rates documented from 9% up to 51%, emphasizes the need for regular follow-up imaging. Consistent ophthalmic evaluations with visual fields and OCT is also recommended.
Because of the location of a CP, pre- and post-treatment complications can occur. Besides tumor recurrence, a number of pituitary-specific complications may arise. Pituitary apoplexy or secondary empty sella syndrome have been reported, characterized by hemorrhage or chiasmatic herniation into the newly vacated space, respectively. Both complications produce endocrine and visual symptoms, such as ophthalmoplegia and visual loss, and are medical emergencies. Quality of life can be greatly compromised following treatment of a craniopharyngioma, due to hormonal and ophthalmic disturbances, and any abnormalities should be promptly evaluated.
The overall prognosis of a CP is contingent on size, classification type, location, and treatment chosen. Survival rates for craniopharyngiomas are roughly 89.5% at 2 years and 83.9% at 5 years (both medical and surgical). Prognosis is better for individuals under the age of 20 years as compared to older individuals.
- Torres MO. Craniopharyngioma. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK459371/. Published May 4, 2020. Accessed November 30, 2020.
- Erfurth EM. Diagnosis, Background, and Treatment of Hypothalamic Damage in Craniopharyngioma. Neuroendocrinology. 2020;110(9-10):767-779. doi:10.1159/000509616
- Müller HL, Merchant TE, Warmuth-Metz M, Martinez-Barbera JP, Puget S. Craniopharyngioma. Nat Rev Dis Primers. 2019;5(1):75. Published 2019 Nov 7. doi:10.1038/s41572-019-0125-9
- Narla S, Govindraj J, Chandrasekar K, Sushama P. Craniopharyngioma with malignant transformation: Review of literature. Neurology India. 2017;65(2):418. doi:10.4103/neuroindia.ni_528_16.
- Jeong TS, Yee GT, Kim NR. Malignant Transformation of Craniopharyngioma without Radiation Therapy: Case Report and Review of the Literature. J Korean Neurosurg Soc. 2017;60(1):108-113. doi:10.3340/jkns.2015.0707.022
- Wijnen M, van den Heuvel-Eibrink MM, Janssen JAMJL, et al. Very long-term sequelae of craniopharyngioma. Eur J Endocrinol. 2017;176(6):755-767. doi:10.1530/EJE-17-0044
- Bhaisora KS, Prasad SN, Das KK, Lal H. Abscess inside craniopharyngioma: diagnostic and management implications. BMJ Case Rep. 2018;2018:bcr2017223040. Published 2018 Feb 3. doi:10.1136/bcr-2017-223040
- George I Jallo MD. Craniopharyngioma Clinical Presentation: History, Physical Examination. https://emedicine.medscape.com/article/1157758-clinical. Published October 26, 2020. Accessed November 30, 2020.
- Nuijts MA, Veldhuis N, Stegeman I, et al. Visual functions in children with craniopharyngioma at diagnosis: A systematic review. PLoS One. 2020;15(10):e0240016. Published 2020 Oct 1. doi:10.1371/journal.pone.0240016
- Lai KE, Duong A. Pituitary Adenoma. EyeWiki. https://eyewiki.org/Pituitary_Adenoma. Published December 16, 2019. Accessed November 30, 2020.
- Garnett MR, Puget S, Grill J, Sainte-Rose C. Craniopharyngioma. Orphanet J Rare Dis. 2007;2:18. Published 2007 Apr 10. doi:10.1186/1750-1172-2-18
- Gil-Simoes R, Pascual JM, Casas AP, de Sola RG. Intrachiasmatic craniopharyngioma: Assessment of visual outcome with optical coherence tomography after complete surgical removal. Surg Neurol Int. 2019;10:7. Published 2019 Jan 21. doi:10.4103/sni.sni_292_18
- Thompson CJ, Costello RW, Crowley RK. Management of hypothalamic disease in patients with craniopharyngioma. Clin Endocrinol (Oxf). 2019;90(4):506-516. doi:10.1111/cen.13929
- O'steen L, Indelicato DJ. Advances in the management of craniopharyngioma. F1000Res. 2018;7:F1000 Faculty Rev-1632. Published 2018 Oct 11. doi:10.12688/f1000research.15834.1
- Shohdy KS, Rashad W. Endocrine Disorders Developing after Surgical Intervention of Craniopharyngioma in Children. Pediatr Endocrinol Rev. 2017;14(3):298-301.
- Bishokarma S , Shrestha S , Ranabhat K , et al. Outcome of Surgical Resection of Craniopharyngioma:Single Center 12 Years' Experience. Kathmandu Univ Med J (KUMJ). 2018;16(64):328-332.