Neurogenic myocardial dysfunction post craniopharyngioma resection: A diagnostic dilemma.

Endoscopic transsphenoidal resection of craniopharyngioma is a commonly used technique. Cerebral vasospasm may occur in nearly 10% of cases leading to adverse neurological outcomes. Cardiopulmonary dysfunction may be seen in patients with severe vasospasm. The literature describing the occurrence of neurogenic stunned myocardium following craniopharyngioma resection in pediatric patients is very sparse. Here, we describe such a case managed with a combination of milrinone (to relieve vasospasm and improve cardiac pump function), noradrenaline (to obtain target blood pressure), and vasopressin (to control urine output). This case report proposes the treatment plan of neurogenic stunned myocardium following vasospasm in pediatric patients.

Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans.

Wingless (Wnt)/ß-catenin signaling plays an essential role during normal development, is a critical regulator of stem cells, and has been associated with cancer in many tissues. Here we demonstrate that genetic expression of a degradation-resistant mutant form of ß-catenin in early Rathke's pouch (RP) progenitors leads to pituitary hyperplasia and severe disruption of the pituitary-specific transcription factor 1-lineage differentiation resulting in extreme growth retardation and hypopituitarism. Mutant mice mostly die perinatally, but those that survive weaning develop lethal pituitary tumors, which closely resemble human adamantinomatous craniopharyngioma, an epithelial tumor associated with mutations in the human ß-catenin gene. The tumorigenic effect of mutant ß-catenin is observed only when expressed in undifferentiated RP progenitors, but tumors do not form when committed or differentiated cells are targeted to express this protein. Analysis of affected pituitaries indicates that expression of mutant ß-catenin leads to a significant increase in the total numbers of pituitary progenitor/stem cells as well as in their proliferation potential. Our findings provide insights into the role of the Wnt pathway in normal pituitary development and demonstrate a causative role for mutated ß-catenin in an undifferentiated RP progenitor in the genesis of murine and human craniopharyngioma.

Pathology and pathogenesis of craniopharyngiomas.

Craniopharyngiomas are benign but locally invasive tumours of the sellar region that occur as two subtypes. The adamantinomatous type (aCP) occurs mainly during childhood while the papillary type (pCP) is found almost exclusively in adults. It is thought that aCPs arise from ectopic embryonic remnants of Rathke's pouch and these tumours share features with odontogenic tumours suggesting a common origin. The pathogenesis of pCPs is less understood but these tumours may arise from metaplastic transformation of anterior pituitary epithelial cells. Mutations in CTNNB1 that encodes ß-catenin are found in around 70 % of aCPs. These mutations stabilise ß-catenin, which evades destruction and accumulates in the nucleus and cytosol leading to constitutive activation of the Wnt signaling pathway. Expression of mutant ß-catenin early in mouse pituitary development promotes the formation of tumours similar to aCPs. However, accumulation of ß-catenin occurs only in small clusters of tumour cells even though the mutation is ubiquitous. These cell clusters are slow-growing and share some characteristics with pituitary stem cells. They are often present at the invading edge and express growth factors that may participate in paracrine signaling to surrounding cells. ß-Catenin nuclear translocation may also occur in the absence of CTNNB1 mutations, suggesting that other genetic or epigenetic events can activate Wnt signaling in aCP. These mechanisms, as well as those underlying the molecular pathogenesis of pCPs remain to be identified.

[Biology of the craniopharyngioma].

In the recent years a considerable number of different studies devoted to craniopharyngioma morphology were performed. There are more than 35 factors known up to date that could be related to the craniopharyngioma growth (Ki-67, p53, beta-catenin, p63, Retinoid acid receptors, Galectin-3, MIF, MVD, CK et al.). Despite the such a variety of factors, none of them, except for the Ki-67, strongly correlates with the risk of tumour recurrence and none can be associated with a particular tumour type. Most studies, by the way, focused on a very small number of factors and were performed in relatively small groups of patients. Most publications are devoted to the Ki-67, beta-catenin and p53 studies, and the highest number of patients enrolled to the study was 67. This survey made an attempt to review the literature on the craniopharyngioma biology and to identify further areas of research to obtain data that could affect the choice of treatment and outcome in this complex disease.

Coexistence of adamantinomatous and squamous-papillary type craniopharyngioma: case report and discussion of etiology and pathology.

Craniopharyngiomas are histopathologically classified as adamantinomatous type (AD) and squamous-papillary type (SP). However coexistence of a mixed type seen on histopathologic specimens has not been reported. In this report, a patient diagnosed with mixed type craniopharyngioma is presented and the etiology and pathologic features are discussed.

Rathke cleft cysts: a review of clinical and surgical management.

The aim of this paper is to provide a comprehensive review of clinical, imaging, and histopathological features, as well as operative and nonoperative management strategies in patients with Rathke cleft cysts (RCCs). A literature review was performed to identify previous articles that reported surgical and nonsurgical management of RCCs. Rathke cleft cysts are often incidental lesions found in the sellar and suprasellar regions and do not require surgical intervention in the majority of cases. In symptomatic RCCs, the typical clinical presentation includes headache, visual loss, and/or endocrine dysfunction. Visual field testing and endocrine laboratory studies may reveal more subtle deficiencies associated with RCCs. When indicated, the transsphenoidal approach typically offers the least invasive and safest method for treating these lesions. Various surgical strategies including cyst wall resection, intralesional alcohol injection, and sellar floor reconstruction are discussed. Although headache and visual symptoms frequently improve after surgical drainage of RCCs, hypopituitarism and diabetes insipidus are less likely to do so. A subset of more aggressive, atypical RCCs associated with pronounced clinical symptoms and higher recurrence rates is discussed, as well as the possible relationship of these lesions to craniopharyngiomas. Rathke cleft cysts are typically benign, asymptomatic lesions that can be monitored. In selected patients, transsphenoidal surgery provides excellent rates of improvement in clinical symptoms and long-term cyst resolution. Complete cyst wall resection, intraoperative alcohol cauterization, and sellar floor reconstruction in the absence of a CSF leak are not routinely recommended.

Craniopharyngioma, Chronotypes and Metabolic Risk Profile.

AIM: To investigate the potential association among Craniopharyngioma (CP), chronotypes and metabolic risk profile. SUBJECTS AND METHODS: The study population included 28 patients (46.4% males; 42.6 ± 15.8 years) and 28 controls, age, gender and BMI matched (46.4% males; 46.5 ± 12.9 years). In this study sample, we evaluated: anthropometric measurements (waist circumference, WC; BMI), plasma glucose, lipid profile, and systolic (SBP) and diastolic (DBP) blood pressure. Morningness-Eveningness was measured with the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ), which included 19 questions about preferred sleep time and daily performance. RESULTS: in both patients and controls grade I obesity was detected in 15 subjects (53.6%), grade II obesity in 13 subjects (46.4%). In the patient group, the mean score of chronotype was 47.8 ± 12.6. In particular, 9 patients (32.1%) exhibited the morning chronotype, 6 (21.4%) the intermediate chronotype and 13 (46.4.%) the evening chronotype. No significant difference was found in gender and age among the chronotype categories. Patients with the evening chronotype had higher blood pressure values and worse metabolic parameters than those with the morning chronotype. In the control group, the mean score of the chronotype was 57.6 ± 9.5. In particular, 16 (57.1%) subjects exhibited the morning chronotype, 10 (35.7%) the intermediate chronotype and only 2 (7.1.%) the evening chronotype. The prevalence of intermediate and evening chronotypes was higher in females than males (p = 0.021), while males have a higher prevalence of the morning chronotype. Subjects with intermediate and evening chronotypes had worse metabolic parameters than those with the morning chronotype. In patients, the chronotype score was inversely correlated to WC, BMI, SBP, DBP, plasma glucose, total cholesterol, triglycerides, LDL cholesterol and positively correlated with HDL cholesterol. No correlation was found between age and chronotype. In controls, the chronotype score was inversely correlated to WC, BMI, plasma glucose, total cholesterol, LDL cholesterol. No correlation was found among chronotype and age, blood pressure, triglycerides, HDL cholesterol. Considering the whole population of the study (patients and controls), at logistic regression the chronotype score was significantly associated with the presence of CP. CONCLUSIONS: for the first time thus far, our study puts the light on the association of the CP with chronotypes and metabolic alterations in this disease, which are the main determinants of the reduced quality of life, higher morbidity and mortality in this setting of patients. This finding suggests that alterations of chronotype might represent an adjunctive risk for CP patients and a possible target for their integrate management.

Ciliated craniopharyngioma--case report and pathological study.

BACKGROUND: Craniopharyngioma has two subtypes: adamantinomatous and squamous-papillary. Squamous-papillary craniopharyngioma may develop from remnants of the craniopharyngeal duct, anterior pituitary cells with squamous metaplasia, suprasellar epidermoid cyst, or Rathke cleft cyst. AIM: While ciliated craniopharyngioma is considered to represent a transitional stage between Rathke cleft cyst and squamous-papillary craniopharyngioma, ciliated craniopharyngioma following Rathke cleft cyst at the same site has not previously been described. RESULTS: We report a case of ciliated craniopharyngioma developing from Rathke cleft cyst. CONCLUSION: The clinical course for this case is discussed together with a review of the pathological literature for ciliated craniopharyngioma.

Interleukin-1α leads to growth hormone deficiency in adamantinomatous craniopharyngioma by targeting pericytes: implication in pituitary fibrosis.

BACKGROUND: The incidence of growth hormone deficiency (GHD) in adamantinomatous craniopharyngioma (aCP) is significantly higher than in other sellar region tumors, but the possible mechanism is still elusive. A high level of inflammatory responses is another feature of aCP. We investigated the internal connection between interleukin-1α (IL-1α) and GHD, while focusing on its biological activities in pituitary fibrosis. MATERIALS AND METHODS: To diagnosis of GHD, the Body Mass Index (BMI), Insulin Like Growth Factor-1(IGF-1) and peak growth hormone (GH) values after insulin stimulation test of 15 aCP patients were recorded. Histological staining was performed on the aCP samples. Levels of 9 proinflammatory cytokines in tumor tissue and cell supernatant were detected using Millipore bead arrays. The effect of IL-1α on GH secretion was evaluated in vivo and in vitro. Western blot, qRT-PCR and cell functional assays were used to explore the potential mechanism through which IL-1α acts on GH secretion. The stereotactic ALZET osmotic pump technique was used to simulate aCP secretion of proinflammatory cytokines in rats. Recombinant IL-1α (rrIL-1α) and conditioned media (CM) prepared from the supernatant of aCP cells was infused directly into the intra-sellar at a rate of 1 µl/h over 28 days, and then the effects of IL-1α treatment on pathological changes of pituitary gland and GH secretion were measured. To further confirm whether IL-1α affects GH secretion through IL-1R1, an IL-1R1 blocker (IL-1R1a, 10 mg/kg body weight, once daily) was administered subcutaneously from the first day until day 28. RESULTS: There was a significant positive correlation between pituitary fibrosis and GHD (rS = 0.756, P = 0.001). A number of cytokines, in particular IL-1α, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1), were elevated in tumor tissue and cell supernatant. Only IL-1α showed a significant difference between the GHD group and the No-GHD group (P < 0.001, F = 6.251 in tumor tissue; P = 0.003, F = 1.529 in cell supernatant). IL-1α significantly reduced GH secretion in coculture of GH3 and pericytes. The activation of pericytes induced by IL-1α was mediated by the IL-1R1 signaling pathway. In vivo, IL-1α induces pituitary fibrosis, further leading to a decreased level of GH. This pathological change was antagonized by IL-1R1a. CONCLUSION: This study found that the cross talk between aCP cells and stroma cells in the pituitary, i.e. pericytes, is an essential factor in the formation of GHD, and we propose that neutralization of IL-1α signaling might be a potential therapy for GHD in aCP.

Epidemiological aspects of craniopharyngioma.

Craniopharyngioma is a benign intracranial tumor that can be clinically aggressive. The descriptive epidemiology of this tumor is not fully known, in part because of its borderline nature between a benign and malignant tumor, and in part because of its rarity. It has a bimodal age distribution with a peak between 5 and 14 years of age, and a second one in adults older than 65 years. 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. Survival has dramatically improved in the last years.

Origin of craniopharyngiomas: implications for growth pattern, clinical characteristics, and outcomes of tumor recurrence.

OBJECT Craniopharyngiomas are associated with a high rate of recurrence. The surgical management of recurrent lesions has been among the most challenging neurosurgical procedures because of the craniopharyngioma's complex topographical relationship with surrounding structures. The aim of this study was to define the determinative role of the site of origin on the growth pattern and clinical features of recurrent craniopharyngiomas. METHODS The authors performed a retrospective analysis of 52 patients who had undergone uniform treatment by a single surgeon. For each patient, data concerning symptoms and signs, imaging features, hypothalamic-pituitary function, and recurrence-free survival rate were collected. RESULTS For children, delayed puberty was more frequent in the group with Type I (infradiaphragmatic) craniopharyngioma than in the group with Type TS (tuberoinfundibular and suprasellar extraventricular) lesions (p < 0.05). For adults, blindness was more frequent in the Type I group than in the Type TS group (p < 0.05). Nausea or vomiting, delayed puberty, and growth retardation were more frequent in children than in adults (p < 0.05). Overall clinical outcome was good in 48.07% of the patients and poor in 51.92%. Patients with Type TS recurrent tumors had significantly worse functional outcomes and hypothalamic function than patients with the Type I recurrent tumors but better pituitary function especially in children. CONCLUSIONS The origin of recurrent craniopharyngiomas significantly affected the symptoms, signs, functional outcomes, and hypothalamic-pituitary functions of patients undergoing repeated surgery. Differences in tumor growth patterns and site of origin should be considered when one is comparing outcomes and survival across treatment paradigms in patients with recurrent craniopharyngiomas.

Multiple primary brain tumors of different cell types.

Eighteen cases of multiple primary brain tumors of different histological types were found in a review of Mayo Clinic records from 1950 to 1978. The predisposing factors, clinical presentation, location, and type of tumor are discussed. The clinical significance and etiology of these multiple tumors are considered.

Postoperative ectopic craniopharyngioma. Case report.

The case of an ectopic craniopharyngioma arising from a seed of tissue deposited along the operative track is reported. The uniqueness of this lesion is addressed. Ideal therapy and controversies regarding radiation therapy of craniopharyngiomas are discussed in light of this new variation in recurrence.

Comparative genomic hybridization analysis of craniopharyngiomas.

OBJECT: Craniopharyngioma is the most common childhood brain tumor and is thought to arise from embryonic remnants of the Rathke pouch. Some craniopharyngiomas are monoclonal in origin and hence presumably harbor somatic genetic alterations, although the precise molecular mechanisms involved in craniopharyngioma development are unknown. The goal of this study was to identify genetic alterations in craniopharyngiomas. METHODS: To gain insight into the molecular mechanisms involved in development of these tumors, the authors analyzed nine adamantinomatous craniopharyngiomas by using comparative genomic hybridization. Six tumors (67%) displayed at least one genomic alteration, and three had six or more alterations. Only two tumors displayed a decrease in DNA copy number, and in all others an increase in DNA copy number was noted. CONCLUSIONS: The authors conclude that a subset of craniopharyngiomas consists of monoclonal tumors arising from activation of oncogenes located at specific chromosomal loci.

Traumatic suprasellar arachnoid cyst.

The case is reported of a suprasellar archnoidal cyst in a five-year-old boy who developed symptoms of hypothalamic involvement. It appears to have been of traumatic origen. It was operated upon, resulting in a remission of symptoms.

Mortality, neoplasia, and Creutzfeldt-Jakob disease in patients treated with human pituitary growth hormone in the United Kingdom.

OBJECTIVE: To determine the cause of death and incidence of neoplasia in patients treated with human pituitary growth hormone. DESIGN: A long term cohort study established to receive details of death certification and tumour registrations through the Office of Population Censuses and Surveys and NHS central register. PATIENTS: All patients (1246 male, 662 female) treated for short stature with pituitary growth hormone under the Medical Research Council working party and health services human growth hormone committee. MAIN OUTCOME MEASURES: Death or development of neoplasia. RESULTS: 110 patients died (68 male, 42 female; aged 0.9-57 years) from 1972 to 1990. Fifty three death were from neoplasia responsible for growth hormone deficiency (27 craniopharyngioma, 24 other intracranial tumour, two leukaemia); two from histiocytosis X; and 13 from pituitary insufficiency. Six patients died of Creutzfeldt-Jakob disease, six of other neurological disorders, and eight of acute infection. Other deaths were apparently unrelated to growth hormone deficiency or its treatment. Seventeen tumours (in 16 patients) were identified during or after growth hormone treatment. Four were in patients with previous intracranial neoplasia and two were after cranial irradiation. Thirteen were intracranial, the others being Hodgkin's lymphoma, osteosarcoma, carcinoma of colon, and basal cell carcinoma. CONCLUSIONS: Recurrence or progression of intracranial tumours and potentially avoidable metabolic consequences of hypopituitarism were the main causes of death. Growth hormone treatment probably did not contribute to new tumour development. Creutzfeldt-Jakob disease after pituitary growth hormone treatment continues to occur in the United Kingdom. This cohort must remain under long term review.

[Neurosurgery and pituitary tumors: etio-pathogenic considerations]. / La neurochirurgie et les tumeurs hypophysaires. Considérations étio-pathogéniques.

PITUITARY ADENOMA: Based on the experience of nearly 5000 cases of surgically treated pituitary tumors at the neurosurgery department of the Foch Hospital, the pituitary adenoma is the most frequent pituitary tumor. Secreting tumors lead to a clinical syndrome depending on the level of hormone overproduction. Gonadotrop or non-functioning pituitary adenomas are mainly macroadenomas presenting with visual symptoms, hypopituitarism or as an incidentaloma. Anatomical features dictate the surgical approach. OTHER TUMORS: The other types of hypophyseal tumors, such as craniopharyngioma, Rathke's cleft cyst or others are usually surgical tumors because medical treatment is ineffective. Malignant pituitary tumors are unusual.