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craniopharyngioma

Craniopharyngioma (CP)

A craniopharyngioma (CP) is an embryonic malformation of the sellar region and parasellar region.

Its relation to Rathke's cleft cyst (RCC) is controversial, and both lesions have been hypothesized to lie on a continuum of cystic ectodermal lesions of the sellar region.

Craniopharyngiomas frequently grow from remnants of the Rathke pouch, which is located on the cisternal surface of the hypothalamic region. These lesions can also extend elsewhere in the infundibulohypophyseal axis.

These tumors can also grow from the infundibulum or tuber cinereum on the floor of the third ventricle, developing exclusively into the third ventricle.

Jakob Erdheim (1874-1937) was a Viennese pathologist who identified and defined a category of pituitary tumors known as craniopharyngiomas. He named these lesions “hypophyseal duct tumors” (Hypophysenganggeschwülste), a term denoting their presumed origin from cell remnants of the hypophyseal duct, the embryological structure through which Rathke's pouch migrates to form part of the pituitary gland. He described the two histological varieties of these lesions as the adamantinomatous and the squamous-papillary types. He also classified the different topographies of craniopharyngiomas along the hypothalamus-pituitary axis. Finally, he provided the first substantial evidence for the functional role of the hypothalamus in the regulation of metabolism and sexual functions. Erdheim's monograph on hypophyseal duct tumors elicited interest in the clinical effects and diagnosis of pituitary tumors. It certainly contributed to the development of pituitary surgery and neuroendocrinology. Erdheim's work was greatly influenced by the philosophy and methods of research introduced to the Medical School of Vienna by the prominent pathologist Carl Rokitansky. Routine practice of autopsies in all patients dying at the Vienna Municipal Hospital (Allgemeines Krankenhaus), as well as the preservation of rare pathological specimens in a huge collection stored at the Pathological-Anatomical Museum, represented decisive policies for Erdheim's definition of a new category of epithelial hypophyseal growths. Because of the generalized use of the term craniopharyngioma, which replaced Erdheim's original denomination, his seminal work on hypophyseal duct tumors is only referenced in passing in most articles and monographs on this tumor.

Jakob Erdheim should be recognized as the true father of craniopharyngiomas 1).

Epidemiology

Incidence of 0.13 cases per 100,000 people every year. They represent approximately 2%–5% of all primary brain tumors and have a bimodal presentation in children aged 5–14 and adults aged 55–65 years

The incidence of craniopharyngioma in the United States was estimated from two population-based cancer registries that include brain tumors of benign and borderline malignancy: the Central Brain Tumor Registry of the United States (CBTRUS) and the Los Angeles county Cancer Surveillance Program. Information on additional pediatric tumors was available from the Greater Delaware Valley Pediatric Tumor Registry (GDVPTR). The overall incidence of craniopharyngioma was 0.13 per 100,000 person years and did not vary by gender or race. A bimodal distribution by age was noted with peak incidence rates in children (aged 5-14 years) and among older adults (aged 65-74 years in CBTRUS and 50-74 years in Los Angeles county). Survival information was available from GDVPTR and the National Cancer Data Base (NCDB), a hospital-based reporting system. In the NCDB, the 5-year survival rate was 80% and decreased with older age at diagnosis. Survival is higher among children and has improved in recent years.

Craniopharyngioma is a rare brain tumor of uncertain behavior that occurs at a rate of 1.3 per million person years. Approximately 338 cases of this disease are expected to occur annually in the United States, with 96 occurring in children from 0 to 14 years of age 2).


The Childhood Cancer Registry of Piedmont, Italy, estimates an incidence of 1.4 cases per million children per year. Similar data are provided by other registries in Western countries, while higher rates have been observed in Asia and Africa. There are no known specific environmental risk factors for craniopharyngioma, and genetic predisposition is not demonstrated 3).


Zacharia et al., used the surveillance, epidemiology and end results program (SEER) database to identify patients who received a diagnosis of craniopharyngioma during 2004-2008. They analyzed clinical and demographic information, including age, race, sex, tumor histology, and treatment. Age-adjusted incidence rates and age, sex, and race-adjusted expected survival rates were calculated. They used Cox proportional hazards models to determine the association between covariates and overall survival. We identified 644 patients with a diagnosis of craniopharyngioma. Black race was associated with an age-adjusted relative risk for craniopharyngioma of 1.26 (95% confidence interval [CI], 0.98-1.59), compared with white race. One- and 3-year survival rates of 91.5% (95% CI, 88.9%-93.5%), and 86.2% (95% CI, 82.7%-89.0%) were observed for the cohort; relative survival rates were 92.1% (95% CI, 89.5%-94.0%) and 87.6% (95% CI, 84.1%-90.4%) for 1- and 3-years, respectively. In the multivariable model, factors associated with prolonged survival included younger age, smaller tumor size, subtotal resection, and radiation therapy. Black race, on the other hand, was associated with worse overall survival in the final model. They demonstrated that >85% of patients survived 3 years after diagnosis and that subtotal resection and radiation therapy were associated with prolonged survival. They also noted a higher incidence rate and worse 1- and 3-year survival rates in the black population. Future investigations should examine these racial disparities and focus on evaluating the efficacy of emerging treatment paradigms 4).

Origin

Its relation to Rathke's cleft cyst (RCC) is controversial, and both lesions have been hypothesized to lie on a continuum of cystic ectodermal lesions of the sellar region.

It grows close to the optic nerve, hypothalamus and pituitary gland.

Types

Adamantinomatous craniopharyngioma, the most frequent histological variety in children.

Papillary craniopharyngioma

Localization

Most craniopharyngiomas can be classified as either “prechiasmatic” or “retrochiasmatic” according to their growth patterns.

Retrochiasmatic craniopharyngioma

Subdiaphragmatic craniopharyngioma

Supradiaphragmatic craniopharyngioma

Intraventricular craniopharyngioma

Appearance

Clinical Features

Typical manifestations at diagnosis are some combination of headache, visual impairment, Polyuria/Polydipsia, growth retardation, and significant weight gain.

Presence of hydrocephalus, distortion of circle of Willis, and large tumor volume were associated with headache, and the last 2 variables were also associated with more severe and frequent headaches. Radiation treatment and insertion of Ommaya reservoir were associated with reduced headache frequency. In conclusion, headaches are common in patients with craniopharyngioma and are likely related to tumor size and volume. In most patients, headaches improve with successful tumor treatment 5)

CP is frequently diagnosed after long duration of history (DOH), especially in older children. However, DOH was not associated with tumor size, hypothalamic involvement (HI), survival, or functional capacity (FC) 6).

Visual and neurological deficits necessitate rapid diagnostic workup.

Infundibulo tuberal syndrome

see Hydrocephalus in craniopharyngioma


A significant number of patients with craniopharyngioma are GH deficient. The safety of GH replacement in these subjects has not been established.

Differential diagnosis

Compared with craniopharygiomas, sellar gliomas presented with a significantly lower ratio of visual disturbances, growth hormone deficiencies, lesion cystic changes, and calcification. Sellar gliomas had significantly greater effects on the patients' mentality and anatomical brain stem involvement 7).

Co-occurrence

Simultaneous sellar-suprasellar craniopharyngioma and intramural clival chordoma, successfully treated by a single staged, extended, fully endoscopic endonasal approach, which required no following adjuvant therapy is reported 8).

Treatment

The treatment paradigm for craniopharyngioma has evolved over time, as our treatment options have expanded and our understanding of the long-term consequences of radical resection has grown. Originally, aggressive resection was the only hope of controlling this tumor; in spite of the often severe morbidity of such an approach, it remained the mainstay of treatment. But as the natural history of this tumor is recurrence, it may be considered a chronic disease, with the goal of maximizing control but minimizing patient morbidity. Our desire as surgeons to obtain tumor-free postoperative imaging may overlook the impact on our patient. Weighing risks, benefits, and alternatives to surgical goals and approaches are crucial in the treatment of this challenging tumor.

To date, no class I recommendations exist for the best treatment of these tumors. Management should be by a multidisciplinary team (neurosurgery, endocrinology, ophthalmology, psychology, oncology, and radiation oncology) and be individualized for each patient. There are some practical surgical considerations to keep in mind. In cases where total resection can be obtained without significant morbidity (i.e., cases where the tumor is not invading or adherent to the hypothalamus), GTR remains the treatment of choice. In cases where the tumor is small and the solid portions are primary intrasellar, without significant extension laterally in the suprasellar space or without encasement of vessels, an endoscopic approach may provide good outcomes. In cases where the tumor is densely involved in critical structures and has a significant cystic component causing mass effect, an Ommaya placement with or without chemotherapy infusion may represent a less invasive way to decompress neural structures and control tumor progression.

Finally, in cases of subtotal resection (STR) or recurrent disease, particularly with a favorable margin between the tumor and the optic chiasm, adjuvant RT or SRS is likely to improve progression-free survival. Promising treatments from PBTC trials may offer hope for future therapies with lower side effect profiles. Ultimately, this tumor remains one of the most difficult pediatric neurosurgical problems, and recommendations will continue to evolve 9).

Surgical management

Intensity modulated radiation therapy (IMRT)

IMRT is a viable treatment option for pediatric craniopharyngioma. Despite the use of IMRT, the majority of the craniopharyngioma patients experienced long-term toxicity, many of which present prior to radiotherapy. Limitations of retrospective analyses on small patient cohort elicit the need for a prospective multi-institutional study to determine the absolute benefit of IMRT in pediatric craniopharyngioma 10).

Proton beam therapy

Currently there is no clear evidence that proton beam therapy will improve survival or reduce morbidity for children with craniopharyngioma. However, proton therapy has the potential to reduce RT dose to the Circle of Willis, which may reduce the risk of future cerebrovascular complications. We propose that more resources should be allocated to ensuring these patients are managed by experienced multidisciplinary teams through the continuum from diagnosis to long-term follow-up 11).

Outcome

Recurrence

Malignant Transformation

Books

Case series

2017

Wijnen et al. from Rotterdam studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since presentation was 13 years (interquartile range 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection (n=25), subtotal resection without radiotherapy (n=44), subtotal resection with radiotherapy (n=25), cyst aspiration without radiotherapy (n=8), and 90Yttrium brachytherapy (n=21).

Pituitary hormone deficiencies (98%), visual disturbances (75%), and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy, and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma.

Long-term health conditions were comparable after different initial craniopharyngioma treatment approaches and were generally more frequent in patients with childhood- compared with adult-onset disease 12).

2016

A retrospective analysis of the clinical data of 92 children who underwent surgical treatment from May 2011 to January 2005. Long-term follow-up was performed from 12 months to 8 years. The pterional approach was used in 49 patients, the interhemispheric approach in 20 patients, the corpus callosum approach in 16 patients, and the butterfly approach in 7 patients. Pathological classification was performed by hematoxylin and eosin stain staining of the pathological tissues and evaluated according to the different surgical approaches, MRI calcification status, calcification type, pathological type, whether radiotherapy was performed, postoperative recurrence, and death.

For the pterion approach resection, there was near total resection in 46 patients (93.9%) with the lowest recurrence rate. The operative approach and postoperative recurrence rates were compared; the difference was statistically significant (P <0.05). For comparison of the operative approach and postoperative mortality, the difference was not statistically significant (P >0.05). There was not a significant difference between the MRI classification and postoperative recurrence rate (P >0.05). Comparing the degree of tumor calcification with the recurrence rate after operation and the mortality rate, the difference was statistically significant (P <0.05). The recurrence rate and mortality rate of adamantimous craniopharyngioma and squamous papillary craniopharyngioma in 2 groups following operation were compared, and the differences were statistically significant (P <0.05). Postoperative adjuvant radiotherapy was compared with the postoperative recurrence rate and mortality; the differences were statistically significant (P <0.05).

The main effects on tumor recurrence include the choice of surgical approach and degree of calcification. The adamantimous craniopharyngioma relapse rate is higher, which could be because invasion of craniopharyngioma only occurs with adamantimous craniopharyngioma. Postoperative radiotherapy can significantly prolong the recurrence time and reduce the mortality rate of patients with craniopharyngioma 13).


Clinical data from 226 consecutive patients with primary CP were retrospectively reviewed. Tumor location and the relationship of the tumor to the third ventricle floor and the pituitary stalk were evaluated using preoperative MRI and intraoperative findings. A topographic classification scheme was proposed based on the site of tumor origin and tumor development. The clinical relevance of this classification on patient presentation and outcomes was also analyzed.

The growth of CPs can be broadly divided into 3 groups based on the site of tumor origin and on tumor-meningeal relationships: Group I, infrasellar/infradiaphragmatic CPs (Id-CPs), which mainly occurred in children;

Group II, suprasellar subarachnoid extraventricular CPs (Sa-CPs), which were mainly observed in adults and rarely occurred in children; and Group III, suprasellar subpial ventricular CPs (Sp-CPs), which commonly occurred in both adults and children. Tumors in each group may develop complex growth patterns during vertical expansion along the pituitary stalk. Tumor growth patterns were closely related to both clinical presentation and outcomes. Patients with Sp-CPs had more prevalent weight gain than patients with Id-CPs or Sa-CPs; the rates of significant weight gain were 41.7% for children and 16.7% for adults with Sp-CPs, 2.2% and 7.1% for those with Id-CPs, and 12.5% and 2.6% for those with Sa-CPs (p < 0.001). Moreover, patients with Sp-CPs had increased hypothalamic dysfunction after radical removal; 39% of patients with Sp-CPs, 14.5% with Id-CPs, and 17.4% with Sa-CPs had high-grade hypothalamic dysfunction in the first 2 postoperative years (p < 0.001).

The classification of CPs based on growth pattern may elucidate the best course of treatment for this formidable tumor. More tailored, individualized surgical strategies based on tumor growth patterns are mandatory to provide long-term tumor control and to minimize damage to hypothalamic structures. Differences in the distribution of growth patterns between children and adults imply that hierarchical comparison is necessary when investigating outcomes and survival across treatment paradigms in patients with CP 14).

2014

103 patients underwent the endoscopic endonasal approach at two institutions (Division of Neurosurgery of the Università degli Studi di Napoli Federico II, Naples, Italy, and Division of Neurosurgery of the Bellaria Hospital, Bologna, Italy), between January 1997 and December 2012, for the removal of infra- and/or supradiaphragmatic craniopharyngiomas. Twenty-nine patients (28.2%) had previously been surgically treated.

The authors achieved overall gross-total removal in 68.9% of the cases: 78.9% in purely infradiaphragmatic lesions and 66.3% in lesions involving the supradiaphragmatic space. Among lesions previously treated surgically, the gross-total removal rate was 62.1%. The overall improvement rate in visual disturbances was 74.7%, whereas worsening occurred in 2.5%. No new postoperative defect was noted. Worsening of the anterior pituitary function was reported in 46.2% of patients overall, and there were 38 new cases (48.1% of 79) of postoperative diabetes insipidus. The most common complication was postoperative CSF leakage; the overall rate was 14.6%, and it diminished to 4% in the last 25 procedures, thanks to improvement in reconstruction techniques. The mortality rate was 1.9%, with a mean follow-up duration of 48 months (range 3-246 months).

The endoscopic endonasal approach has become a valid surgical technique for the management of craniopharyngiomas. It provides an excellent corridor to infra- and supradiaphragmatic midline craniopharyngiomas, including the management of lesions extending into the third ventricle chamber. Even though indications for this approach are rigorously lesion based, the data in this study confirm its effectiveness in a large patient series 15).

2010

From 1990-2008, 90 patients (64 adults and 26 children) underwent standard transsphenoidal surgery (TSS) for craniopharyngioma (34 subdiaphragmatic and 56 supradiaphragmatic). TSS was performed as the initial surgery in 62 patients and as the second procedure in 28 patients.

Total tumor removal was achieved in 70 (77.8%) patients, subtotal removal was achieved in 17 (18.9%), and partial removal was achieved in 3 (3.3%). Total removal was more often accomplished in initial surgery (56 of 62 [90.3%]) than second surgery (14 of 28 [50.0%]). Postoperative deterioration of anterior pituitary hormones developed in 31 of 47 (66.0%) patients with preoperative normal function or partial anterior pituitary loss. New-onset postoperative diabetes insipidus (DI) developed in 35 of 67 (52.2%) patients. Of 61 patients with preoperative visual loss, 55 (90.2%) noted some degree of visual improvement after surgery. The early postoperative mortality rate was 2.2% (2 of 90 patients). Cerebrospinal fluid (CSF) leakage occurred in 11 patients (12.2%), and 5 patients required surgical repair of the leak. Tumor recurrence was observed in seven (7.8%) patients during a mean follow-up period of 4.6 years.

Most craniopharyngiomas including the supradiaphragmatic type can be removed safely by TSS with a good outcome, although endocrine function frequently worsens after surgery. Dural fascia graft is a very effective technique to prevent CSF leaks, especially after eTSS 16).


14 patients underwent a purely endoscopic, endonasal approach for resection of newly diagnosed craniopharyngiomas. These procedures represent index surgeries; no patient had undergone previous tumor resection. A retrospective review of endocrinological and ophthalmological outcomes, extent of resection, and complication prevalence was completed. Additionally, a review of the English literature was performed to evaluate outcomes of similar endoscopic techniques for resection of craniopharyngiomas.

Four patients (28.6%) underwent gross-total resection; near total resection or better was achieved in 9 patients (64.3%). All patients presented with some form of visual field or acuity deficit. Postoperatively, 12 patients (85.7%) experienced visual improvement, with 6 patients (42.9%) having complete visual recovery. One patient experienced worsening of her visual deficit. Visual acuity improved in 8 patients (57.1%), while visual field defects improved in 11 (78.6%). The pituitary stalk was preserved in all cases. Eight (57.1%) of 14 patients experienced some form of anterior pituitary dysfunction postoperatively. Although 9 patients (64.3%) were documented to have either transient or permanent new diabetes insipidus immediately after surgery, at 1-month follow-up only 1 patient met clinical criteria. Five patients (35.7%) developed CSF leaks that were successfully treated by subsequent endoscopic revision. All CSF leaks occurred early in the series. Two patients (14.2%) were treated for presumed meningitis postoperatively.

The endoscopic endonasal approach is a minimally invasive alternative to open transcranial approaches for select craniopharyngiomas. Similar to previous transcranial series, rates of endocrinopathy and gross-total resection were dependent upon the adherence of the tumor capsule to the hypothalamus, pituitary stalk, and associated vasculature. A review of the literature suggests that the results of the current series are similar to other published series on this topic 17).

2000

Eight patients who were surgically treated for craniopharyngiomas located exclusively within the third ventricle were considered. The initial symptoms were acute hydrocephalus in two cases, psychological disturbances in two, amenorrhea in two, headaches in one, and hypopituitarism in one. The diagnoses were established, in all cases except one, with magnetic resonance imaging. In all cases, the tumor completely filled the third ventricle.

Total removal of the lesion was achieved in seven cases. One patient underwent partial removal. In the immediate postoperative period, no major complications were observed. Five patients required replacement hormonal therapy. All patients returned to a normal life. Many months after surgery, two patients exhibited psychological disturbances and died, the first because of voluntary withdrawal of replacement therapy (12 mo after surgery) and the second because of a severe imbalance in body fluids and electrolytes, with a subsequent hyperosmolar coma (27 mo after surgery). Only one patient who underwent initial total removal experienced a small recurrence of the lesion (30 mo after surgery); after 3 years, the lesion exhibited unchanged size.

The translamina terminalis approach is a valid choice for the removal of purely intraventricular craniopharyngiomas. These tumors can be removed without significant sequelae related to the surgical approach. The proximity to the hypothalamus requires accurate neuroendocrine and electrolyte control in the postoperative period, in some cases even years after surgery 18).

1)
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2)
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8)
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18)
Shirane R, Ching-Chan S, Kusaka Y, Jokura H, Yoshimoto T. Surgical outcomes in 31 patients with craniopharyngiomas extending outside the suprasellar cistern: an evaluation of the frontobasal interhemispheric approach. J Neurosurg. 2002 Apr;96(4):704-12. PubMed PMID: 11990811.
craniopharyngioma.txt · Last modified: 2017/04/11 16:13 by administrador