13 Natural History and Management Options of Craniopharyngioma

Harshad R. Purandare and Basant K. Misra

Abstract

Craniopharyngioma is benign, slow-growing, cystic epithelial tumor that arises from the remnants of the Rathke’s pouch. Most tumors grow out of the sella with variable midline suprasellar extension, compressing the optic chiasma and tracts, and may reach the floor of the third ventricle. There remains ongoing controversy relating to the type of treatment, surgical approaches, and the need for postsurgical adjuvant therapy. Specific treatment strategy should be tailored according to the institution and surgical expertise, with increasing emphasis on the quality of life in contemporary practice.

Craniopharyngioma is among the most challenging intracranial lesions to manage surgically and medically, with significant morbidity and recurrence, despite advances in surgical techniques, adjuvant therapy, and endocrinological care.1 The tumor is thought to arise from the squamous cell rests of the embryonic hypophyseal–pharyngeal duct (craniopharyngeal duct; Fig. 13.1). Another hypothesis suggests origin of the tumor due to squamous metaplasia of the existing cells of the adenohypophysis. This is supported by predominant development of papillary tumors in adults.²

●Craniopharyngioma accounts for 2 to 5% of all primary intracranial tumors and up to 10 to 15% of intracranial tumors in children.³ It is a World Health Organization (WHO) grade I tumor. There is no genetic susceptibility or predisposition. The disease has a slight male preponderance and has a bimodal peak with increased incidence between 5 and 14 years and 65 and 74 years of age.⁴

●There are two distinct histological and genomic types: adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP). ACP is a more common subtype (86.2% cases), predominantly occurring in children and exhibits characteristic microcystic spaces, palisading columnar epithelium with basal nuclei, stellate reticulin, and wet keratin. PCP shows monomorphic papillary growth pattern with nonkeratinizing squamous epithelium over fibrovascular cores and scattered capillary network. Mixed or transitional forms (2.5% cases) have occasionally been reported. Tumors in the pediatric population are almost exclusively ACPs, whereas papillary tumors constitute 15 to 40% of all adult craniopharyngiomas.^{5,​ 6}

●Most lesions are heterogenous with predominantly solid (18–39%), predominantly cystic (46–64%), or mixed solid and cystic (8–36%) morphology.7^{,​ 8} The cyst contains fluid described in appearance variably from “machinery oil” to “shimmering yellow cholesterol-laden” fluid. It consists of desquamated epithelium, membrane lipids, and cytoskeletal keratin. Calcification (seen in 40% of adults and 95% of pediatric cases) can be diffuse and speckled to firm, large, and chunky.^{2,​ 9} The latter is difficult to resect and amounts to significant morbidity if the same is attempted.¹⁰

●Craniopharyngiomas form micropapillary extensions into surrounding neuroparenchymas, which elicit a gliotic reaction causing adhesion and subsequent surgical difficulty and morbidity with attempted gross total resection (GTR).¹¹ The difference in rate of recurrence in the adult and pediatric groups may be explained by the predominant pathological variants occurring among these tumors. PCPs and tumors in adults tend to be more indolent. ACPs are more aggressive and exhibit more brain invasion with extensive and firmer adhesions to adjacent structures.^{5,​ 6,​ 10}

●Ninety-four percent of ACPs exhibit dysregulation of the nucleocytoplasmic Wnt/β-catenin pathway in the form of CTNNB1 mutation, whereas BRAF-V600E mutations are characteristic of 96% PCPs.^{1,​ 12} Although histologically benign, rare cases of malignant transformation have been reported. While the mechanism of anaplastic transformation is unclear, animal studies suggest delayed p53 mutation developing after radiation as a possible cause.¹³

●The location of the tumor in close proximity to the visual pathways, hypothalamic pituitary axis, and the limbic systems results in a wide spectrum of visual, endocrine, vegetative, and cognitive dysfunction either at presentation or as a consequence of treatment.^{2,​ 9,​ 14}

●The most common clinical presentation is visual deterioration (67%), followed by raised intracranial pressure (hydrocephalus with headache, vomiting) in 29 to 45% cases, endocrinopathies in 30 to 65% cases (panhypopituitarism with gonadal insufficiency being the commonest), hypothalamic dysfunction, and neurocognitive impairment.^{9,​ 10,​ 15} Headache is also a common symptom, seen in 50% cases. Neurological deficits in the form of seizures, ataxia, cranial nerve palsies, and altered sensorium are seen in 17% of cases.¹⁶ The various endocrinopathies at presentation include growth hormone (GH) deficiency (35–95%), follicle-stimulating hormone (FSH)/luteinizing hormone (LH) deficiency (38–82%), adrenocorticotropic hormone (ACTH)/cortisol (21–62%), thyroid-stimulating hormone (TSH; 21–42%), and antidiuretic hormone (ADH) diabetes insipidus (6–38%). In numerous studies, the predominant endocrine presentation in 93% of children was growth dysfunction (delayed puberty, obesity, short stature, precocious puberty), whereas the most prevalent disorders in adults were related to menstruation and sexual function.¹⁷ Hydrocephalus is seen in 29 to 45% cases. Definitive long-term treatment for hydrocephalus was needed in 40% cases.^{4,​ 7,​ 14}

●Diagnosis and referral are often delayed for months or years (mean duration: 10 months; range: 1–108 months) due to slow growth of the lesion and insidious onset of symptoms.^{17,​ 18} Patients with hydrocephalus and neurological deficits presented earlier. Patients presenting only with endocrine deficits had a longer duration of symptoms before diagnosis. Visual impairment, hydrocephalus, and neurological deficits at initial presentation were usually associated with poorer long-term survival and outcomes. Among the pediatric population, infants and young children more frequently presented with features of raised intracranial pressure and neurological deficits, whereas elder children presented with growth failure, weight gain, or endocrine dysfunction.¹⁹

●Computed tomography (CT) scan in ACP shows cysts of near cerebrospinal fluid (CSF) density, soft-tissue density solid component with enhancement seen in 90% cases, and stippled calcification, which is often peripherally located. Occasionally, large and chunky basally located calcification is seen. Cysts in PCP are small and often insignificant; the solid component is the dominant element and shows a more vivid and homogenous enhancement and calcification is uncommon. Magnetic resonance imaging (MRI) is the definitive diagnostic imaging to characterize the lesion and study its location and relation to the adjacent structures. Solid tumor is iso- to hypointense on T1 and mixed hypo- to hyperintensity on T2 images with patchy and reticular enhancement. Cysts have an enhancing wall, and the content shows variable T1 and T2 intensities based on their protein and cholesterol content. Giant craniopharyngiomas are tumors greater than 5 cm in diameter and have a multicompartmental extension.^{18,​ 20}

●Numerous classification and grading systems have been proposed by Hoffman, Samii, Yasargil, Pudget, Kassam, etc. Although none have gained widespread acceptance, all the systems are primarily based on location and anatomical relations guiding the surgical approach.²

13.2 Selected Papers on the Natural History of Craniopharyngioma

●Karavitaki N, Brufani C, Warner JT, et al. Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up. Clin Endocrinol (Oxf) 2005;62(4):397–409

●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

●Zacharia BE, Bruce SS, Goldstein H, Malone HR, Neugut AI, Bruce JN. Incidence, treatment and survival of patients with craniopharyngioma in the surveillance, epidemiology and end results program. Neuro-oncol 2012;14(8):1070–1078

13.3 Natural History of Craniopharyngioma

Literature data on the natural history of craniopharyngioma are sparse as almost all tumors undergo inevitable treatment following diagnosis.² The age-adjusted incidence rate of craniopharyngioma ranges between 1.3 and 1.7 cases per 1,000,000 person-years.²¹

●Most tumors grow out of the sella with variable midline suprasellar extension (94% cases), compressing the optic chiasma and tracts, and may reach the floor of the third ventricle. Purely intrasellar tumors occur in 4% cases only, whereas 75% cases are purely suprasellar. Posterior growth results in extension to the interpeduncular cistern with splaying of the peduncles. Supratentorial hydrocephalus results from occlusion of the foramen of Monroe or the aqueduct of Sylvius. Lateral extensions would result in subfrontal or mesial temporal mass effect and even occasional extension to the lateral ventricle. Rare locations include purely third ventricular, purely mesial temporal, pineal, and cerebellopontine angle.22

●The huge heterogeneity regarding the location, shape, speed of growth, formation of cysts, and compliance of brain tissue to progressive displacements makes us reconsider the classic division into pediatric and adult subgroups of lesions in favor of the concept of “individual” lesion, based on clinical and pathological objective data. It highlights the requirement for multidisciplinary follow-up involving neuropsychological and psychosocial assessment and support, exercise, and lifestyle counseling commencing early in the postoperative period and regular medical review by the treating neurosurgeon, radiation oncologist, endocrinologists, and ophthalmologists.²³

●The growth rate of craniopharyngiomas is variable, and hence, no reliable clinical, histological, or radiological predictors of recurrence or behavior exist. A good evaluation of risk of recurrence requires a long follow-up as it is a slow-growing tumor. A minimum follow-up of 5 years is required, with a 10-year follow-up being preferred.⁸ Most recurrences occur within the first 3 to 5 years.^{4,​ 24,​ 25} Risk of recurrence is noted to be higher with incomplete primary resection, cystic tumors (due to capsular adhesion), supradiaphragmatic lesions, hypothalamic involvement (leading to incomplete resection), and in tumors with higher MIB index.^{4,​ 15,​ 19,​ 26}

●Recurrent tumors are associated with decreased rates of GTR and overall survival (OS) with increased rate of mortality and morbidity, including higher risk of visual deterioration, due to severe adhesions to the surrounding critical structures.^{8,​ 17,​ 19,​ 26,​ 27}

●Because of the benign nature of the disease and excellent short-term survival, data on OS are scant in the literature. Because these lesions often exhibit aggressive local recurrence, progression-free survival is typically used as the benchmark when evaluating various treatment paradigms. Yet craniopharyngiomas have a substantially reduced OS, with mortality risk being three to six times that of the general population.²⁸

●The OS rates, which reflect the effect of multiple treatments described in exclusively pediatric series, ranged from 83 to 96% at 5 years, 65 to 100% at 10 years, and averaging 62% at 20 years. In adults or a broad age range population (adults and children) series, the OS rates ranged from 54 to 96% at 5 years, 40 to 93% at 10 years, and 66 to 85% at 20 years.¹⁶ Younger age, small tumors, subtotal resection, and radiation therapy were found to be associated with improved OS in a multivariate analysis. Men and women had similar survival rates. Black patients had poorer OS.²³

●Despite the survival data, the long-term morbidity is quite severe. A prospective study of craniopharyngioma survivors demonstrated that whereas cognitive function per se was not severely impacted, behavioral problems and affect disturbances were prominent, resulting in significant impairment of global functioning in most patients.²² Numerous studies have confirmed a high incidence of reduced quality of life and social functioning.^{29,​ 30} A cohort of 128 patients having a median follow-up of 13 years exhibited pituitary deficiencies in 98% cases, visual disturbances in 75% cases, and obesity in 56% cases.³¹ Morbid obesity was seen in 16% cases.³²

●Hypothalamic obesity in craniopharyngioma is significant not only because it has been shown to severely impact quality of life but also due to the associated high risk of metabolic syndrome, cardiovascular disease, and multisystem morbidity. Weight gain results from damage to the ventromedial hypothalamus, which leads, variably, to a low resting metabolic rate, autonomic imbalance, endocrine deficits, reduced physical activity and impaired functional capacity, and insomnia.¹⁶ Patients with higher body mass index (BMI) prior to surgery are at particular risk. Pharmacotherapy is ineffective in controlling obesity and hence surgical preservation of hypothalamic integrity is mandatory to minimize this devastating sequelae.^{26,​ 27}

●Disease-related mortality can occur even many years after treatment. Causes of late mortality include progressive disease with multiple recurrences, chronic hypothalamic insufficiency, hormonal deficiencies, cerebrovascular disease, and seizures; decreased mineral bone density with fractures; and nonalcoholic steatohepatitis, leading to liver cirrhosis in some cases.^{4,​ 7,​ 14,​ 33}

13.4 Selected Papers on the Management of Craniopharyngioma

●Fahlbusch R, Honegger J, Paulus W, Huk W, Buchfelder M. Surgical treatment of craniopharyngiomas: experience with 168 patients. J Neurosurg 1999;90(2):237–250

●Van Effenterre R, Boch AL. Craniopharyngioma in adults and children: a study of 122 surgical cases. J Neurosurg 2002;97(1):3–11

●Morisako H, Goto T, Goto H, Bohoun CA, Tamrakar S, Ohata K. Aggressive surgery based on an anatomical subclassification of craniopharyngiomas. Neurosurg Focus 2016;41(6):E10

●Yaşargil MG, Curcic M, Kis M, Siegenthaler G, Teddy PJ, Roth P. Total removal of craniopharyngiomas. Approaches and long-term results in 144 patients. J Neurosurg 1990;73(1):3–11

●Cavallo LM, Frank G, Cappabianca P, et al. The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients. J Neurosurg 2014;121(1):100–113

13.5 Treatment Options

Optimal therapeutic approach for craniopharyngiomas is not well defined. Some authors recommend GTR as a primary goal if it can be attained with minimal or limited morbidity, thus aiming to limit long-term recurrence. On the contrary, other authors routinely advocate a subtotal resection followed by adjuvant therapy to minimize complications and preserve maximum functionality.^{6,​ 7,​ 20,​ 34,​ 35} The risk of recurrence and regrowth is as high as 80%; hence, adjuvant therapy is often essential.

●GTR is associated with increased risk of developing neurological deficits and endocrinopathies (three to five times).6^{,​ 14,​ 36} Patients undergoing surgery for tumor more than 3 cm in size and those with hypothalamic invasion experienced more endocrine and neurological morbidity such as panhypopituitarism (32–48% cases), diabetes insipidus (40–55% cases), morbid obesity (25–30% cases), disorders of hunger and thirst, poikilothermia, somnolence, and a range of neurocognitive deficits.^{10,​ 14,​ 19,​ 37} Patients with postoperative deficits report an overall deterioration of quality of life.^{38,​ 39} Many studies have shown that less aggressive resection does not have a significant impact on overall recurrence rates and has an overall superior functional outcome. Hence, decision-making has to be individualized with the contemporary strategy of maximal but safe resection, followed by RT being favored by a majority.^{4,​ 6,​ 10,​ 31,​ 40,​ 41,​ 42,​ 43}

13.5.1 Surgery

Patients presenting with obtundation and obstructive hydrocephalus will need to undergo an external drainage to save life before definitive tumor treatment can be undertaken. An upfront shunt procedure before tumor excision is usually avoided. Preoperatively, stabilization of the endocrine axis with administration of steroids and thyroxine supplementation and correction of electrolyte abnormalities related to diabetes insipidus are essential and may take around 3 to 7 days to do so. Detailed neuro-ophthalmological evaluation including assessment of visual acuity and perimetry is mandatory for prognostication and as a baseline for follow-up evaluation after treatment.2

●Transcranial microsurgical resection forms the first line of treatment for most craniopharyngiomas. A select subset can be resected through an endonasal approach. The transcranial approaches include anterior approach (unilateral subfrontal, bifrontal basal interhemispheric, bifrontal transbasal), anterolateral approaches (pterional, frontotemporal, and orbitozygomatic), and superior approach (interhemispheric transcallosal transventricular and transcortical transventricular; Fig. 13.2). To achieve maximal safe resection, the choice of surgical approach is critical and this is determined by a detailed preoperative evaluation of the imaging studies for tumor size, location, extent, calcification, cystic components, invasion, presence or absence of hydrocephalus, and relation to adjacent structures, specifically the optic apparatus, the circle of Willis, and the hypothalamus.^{2,​ 3,​ 4,​ 7,​ 30,​ 44,​ 45,​ 46} The surgeon’s preference, comfort, and experience are also other relevant factors.

●Table 13.1 compares surgical outcomes and complications in some of the large series of surgical management of craniopharyngiomas published in literature.

Table 13.0 Surgical outcomes and complications in major case series

Transcranial Microsurgical Approaches

The unilateral subfrontal approach is the least traumatic due to limited cortical handling and can be used for small to moderate-sized midline lesions in prechiasmatic location with extension to anterior fossa and suprasellar region (Fig. 13.3).^{2,​ 4,​ 7,​ 47,​ 48,​ 49,​ 50,​ 51,​ 52,​ 53} It maintains midline orientation. Tumor in the third ventricle can be approached through the lamina terminalis. Ipsilateral olfactory nerve is at risk of damage in the approach. Conventionally, the pterional approach has been favored for most small to moderate-sized craniopharyngiomas having superior or lateral extensions. With multiple trajectories through the interoptic, opticocarotid, and lateral carotid corridors combined with translamina terminalis corridor, tumor going up to the anterior aspect of the third ventricle, the interpeduncular fossa, and the lateral regions can be resected (Fig. 13.4). The approach is limited by “blind areas” under the ipsilateral optic nerve limiting retrochiasmatic resection, ipsilateral posterior and superior third ventricular regions, and ipsilateral extreme lateral mesial temporal regions. The visualization of the contralateral carotid is compromised, and operating between perforator vessels may prove hazardous. A modified approach combining the pterional and lateral subfrontal approach is often sufficient for more radical extensions, whereas a combination approach with transcallosal or transcortical transventricular surgery may be employed for large suprasellar and intraventricular extensions. The orbitozygomatic approach, an extension of the pterional approach, provides a more anteroinferior to posterosuperior trajectory to approach suprasellar lesions with reduced brain retraction.

Related posts:

Natural History and Management Options for Cushing’s Disease Natural History and Management Options of Angionegative Subarachnoid Hemorrhage Natural History and Management Options of Chronic Subdural Hematoma Natural History and Management Options of Ruptured Brain Arteriovenous Malformation Natural History and Management Options of Cranial Dural Arteriovenous Fistulas Natural History and Management Options of Unruptured Brain Arteriovenous Malformation

Stay updated, free articles. Join our Telegram channel

Join