Pediatric craniopharyngiomas: magnetic resonance imaging assessment for hypothalamus-pituitary axis dysfunction and outcome prediction.

BACKGROUND: In adamantinomatous craniopharyngiomas, tumor topographical categories, cystic component volume, and magnetic resonance signal intensity may impact prognosis. OBJECTIVE: To identify magnetic resonance imaging (MRI) variables associated with pituitary-hypothalamic axis dysfunction and predictive of outcome in children with cystic adamantinomatous craniopharyngiomas. MATERIALS AND METHODS: We evaluated 40 preoperative MRIs of adamantinomatous craniopharyngiomas to classify tumor topography, volume, and signal intensity of the cystic components and peritumoral edema. Volumes and normalized signal intensity minimum values were extracted from coronal T2-weighted images (nT2min). Radiological variables were compared to pituitary-hypothalamic axis dysfunction-related clinical data and surgical outcomes. RESULTS: Adamantinomatous craniopharyngiomas were categorized into five topographic classes (12 patients, sellar-suprasellar; seven patients, pseudo-intraventricular; six patients, strict intraventricular; 14 patients, secondary intraventricular; one patient, not strict intraventricular). All cases exhibited a predominant (30 patients, 80%) or total (10 patients, 20%) cystic tumor component and displayed low nT2min percentage values compared to cerebrospinal fluid (42.3% [interquartile range 28.4-54.6%]). Significant associations between tumor topographic classes and pituitary dysfunction (P<0.001), and between peritumoral edema and hypothalamic dysfunction (P<0.001) were found. Considering extent of surgical removal and tumor relapse, volume of the cystic tumor component displayed a positive correlation (P=0.002; r=0.48; P=0.02; r=0.36), while nT2min intensity values exhibited a negative correlation (P=0.01; r= - 0.40; P=0.028; r= - 0.34). CONCLUSION: Severe hypothalamic-pituitary axis dysfunction is associated with tumors along the pituitary stalk and peritumoral edema. Tumor invasion of the third ventricle, tight adherence to the hypothalamus, larger volumes, and lower nT2min intensity of the tumor cystic component are independent predictors of extent of adamantinomatous craniopharyngioma excision and recurrence.

Adamantinomatous craniopharyngioma: evolution in the management.

BACKGROUND: In spite of the continuous progresses in pediatric neurosurgery, adamantinomatous craniopharyngioma (AC) remains a challenging tumor due to its proximity to optic pathways, pituitary gland, hypothalamus, and Willis' circle, which can result in significant endocrine, cognitive, and neurological morbidity after treatment with subsequent impact on the patient's quality of life (QoL). The relevance that QoL has today explains the changes in the management of AC observed over the time. The goal of the present article is to provide a historical background, to show the milestones in the changes of the AC treatment, and to analyze the current main options to manage such a challenging tumor. MATERIAL AND METHODS: The pertinent literature has been reviewed. Moreover, a comparison between the past and recent personal series is reported. RESULTS: Three main eras have been identified. The first (named Cushing era) was characterized by the need to realize a harmless surgery and to define the best way to approach AC; the second (microscope era) was characterized by a tremendous technical and technological development, with remarkable results in term of safe tumor resection and control but relatively poor QoL outcomes; and the third one (current period) is characterized by an increasing integration between surgery and adjuvant treatments, with relatively minor tumor control but significant improvement of QoL (comparable overall survival). The authors' experience reflects these changes. Two groups of children were compared: 52 cases (mean follow-up: 17.5 years) belong to the historical series (group 1, 1985-2003, aggressive surgical management) and 41 (mean follow-up: 8.5 years) to the current one (Group 2, 2004-2021, integrated management). No significant differences between the two groups were detected about recurrence rate, surgical mortality, and overall survival. However, Group 2 showed significant lower rates of postoperative panhypopituitarism, obesity, and visual deterioration. CONCLUSIONS: Radical surgery allows for a good AC control with a low rate of recurrence but high risk of permanent morbidity. Despite the greater number of recurrences and surgeries, the more conservative policy, based on a combination of treatments, seems to provide the same tumor control with a better QoL. The advances in trans-nasal and trans-ventricular endoscopy, in proton therapy and in the management of the AC cyst are the main factors that allowed such an improvement.

Prognostic Factors and Treatment Impact on Overall Survival in Adult Craniopharyngioma.

OBJECTIVE: To examine the demographics, tumor characteristics, treatments, and clinical outcomes of a large adult craniopharyngioma population. METHODS: The 2004-2018 National Cancer Database was queried to investigate adult patients with craniopharyngioma. Univariable and multivariable Cox hazard ratio analysis was conducted to analyze the overall survival (OS) impact of demographic and clinical variables. RESULTS: A total of 666 adult patients with craniopharyngioma were identified with a mean age of 51 years (standard deviation 16 years). On multivariable analysis, independent of demographic and clinical variables, increased age, uninsured status, Medicaid, Medicare, Charlson-Deyo Comorbidity Index of 2, and tumor size greater than 40 mm were independently associated with worse OS. There was no significant difference in survival between histologic subtypes. Gross total resection (GTR) (hazard ratio [HR] 0.602, 95% confidence interval [CI] 0.384-0.942, P = 0.026) and subtotal resection (STR) with adjuvant radiotherapy (HR 0.316, 95% CI 0.140-0.710, P = 0.005) were independently associated with improved OS. GTR with radiotherapy trended towards improved OS (HR 0.601, 95% CI 0.334-1.083, P =0.090), but STR alone and radiotherapy alone demonstrated no significant difference in survival compared with no treatment on multivariable analysis. Kaplan-Meier survival models demonstrated improved survival with GTR, GTR + radiation therapy, and STR + radiation therapy. Patients undergoing endoscopic resection had significantly lower GTR rates and greater rates of adjuvant radiotherapy compared with open approaches but no difference in OS. CONCLUSION: Adult patients with craniopharyngioma who underwent GTR or STR with adjuvant radiotherapy had significantly improved overall survival. Endoscopic approaches had lower rates of GTR but no difference in OS.

In-Hospital Costs for Open versus Endoscopic Endonasal Approach for Craniopharyngioma Resection.

OBJECTIVE: To determine the in-hospital cost implications of an expanded endoscopic endonasal approach (EEEA) for craniopharyngioma resection relative to the traditional open transcranial approach. METHODS: All craniopharyngioma surgeries performed at a single institution over a period from January 1st 2001 to October 31th 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate regression analysis was performed using R software. RESULTS: Thirty-six patients met study criteria, including 22 undergoing an open approach and 14 undergoing an EEEA. There was a significantly longer average length of stay among patients undergoing open resection (21.5 vs. 10.6 days, p = 0.024). The average total in-hospital cost of a patient undergoing an EEEA was $58979.3 compared to $89142.3 for an open approach (p = 0.127). On univariate regression analysis, the total in-hospital cost for a patient undergoing an open approach relative to an EEEA was $30163.0 (p = 0.127). The open approach was exclusively performed from study onset until April 2010 (16 patients). From April 2010 to August 2013, 6 open approaches and 5 EEEA were performed. The EEEA has been exclusively performed from August 2013 until the conclusion of our study period (9 patients). CONCLUSIONS: There has been a shift toward surgical resection of craniopharyngioma via an EEEA approach for amenable tumors. Our study demonstrates that the EEEA has become the preferred surgical approach at our institution, and shows that the EEEA is associated with shorter postoperative length of stay and lower total in-hospital cost. Laryngoscope, 133:83-87, 2023.

Detailed assessment of hypothalamic damage in craniopharyngioma patients with obesity.

BACKGROUND/OBJECTIVES: Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor craniopharyngioma (CP). Attempts have been made to predict the risk of HO based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but none have included volumetry. We performed qualitative and quantitative volumetric analyses of HT damage. The results were explored in relation to feeding related peptides and body fat. SUBJECTS/METHODS: A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was performed at median 22 years after first operation; 41 CPs, median age 35 (range: 17-56), of whom 23 had HT damage, were compared to 32 controls. After exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome measures were the relation of metabolic parameters to HT volume and qualitative analyses of HT damage. RESULTS: Metabolic parameters scored persistently very high in vascular risk particularly among HT damaged patients. Patients had smaller HT volumes compared to controls 769 (35-1168) mm3 vs. 879 (775-1086) mm3; P < 0.001. HT volume correlated negatively with fat mass and leptin among CP patients (rs = -0.67; P < .001; rs = -0.53; P = 0.001), and explained 39% of the variation in fat mass. For every 100 mm3 increase in HT volume fat mass decreased by 2.7 kg (95% CI: 1.5-3.9; P < 0.001). Qualitative assessments revealed HT damage in three out of six patients with normal volumetry, but HT damage according to operation records. CONCLUSIONS: A decrease in HT volume was associated with an increase in fat mass and leptin. We present a method with a high inter-rater reliability (0.94) that can be applied by nonradiologists for the assessment of HT damage. The method may be valuable in the risk assessment of diseases involving the HT.

Preoperative Assessment of Craniopharyngioma Adherence: Magnetic Resonance Imaging Findings Correlated with the Severity of Tumor Attachment to the Hypothalamus.

BACKGROUND AND OBJECTIVE: Craniopharyngioma (CP) adherence represents a heterogeneous pathologic feature that critically influences the potentially safe and radical resection. The aim of this study was to define the magnetic resonance imaging (MRI) predictors of CP adherence severity. METHODS: This study retrospectively investigated a cohort of 200 surgically treated CPs with their corresponding preoperative conventional MRI scans. MRI findings related to the distortions of anatomic structures along the sella turcica-third ventricle axis caused by CPs, in addition to the tumor's shape and calcifications, were analyzed and correlated with the definitive type of CP adherence observed during the surgical procedures. RESULTS: CP adherence is defined by 3 components, as follows: 1) the specific structures attached to the tumor, 2) the adhesion's extent, and 3) its strength. Combination of these 3 components determines 5 hierarchical levels of adherence severity with gradually increasing surgical risk of hypothalamic injury. Multivariate analysis identified 4 radiologic variables that allowed a correct overall prediction of the levels of CP adherence severity in 81.5% of cases: 1) the position of the hypothalamus in relation to the tumor-the most discriminant factor; 2) the type of pituitary stalk distortion; 3) the tumor shape; and 4) the presence of calcifications. A binary logistic regression model including the first 3 radiologic variables correctly identified the CPs showing the highest level of adherence severity (severe/critical) in almost 90% of cases. CONCLUSIONS: A position of the hypothalamus around the middle portion of the tumor, an amputated or infiltrated appearance of the pituitary stalk, and the elliptical shape of the tumor are reliable predictors of strong and extensive CP adhesions to the hypothalamus.

Management of craniopharyngioma: the Liverpool experience following the introduction of the CCLG guidelines. Introducing a new risk assessment grading system.

PURPOSE: The Children's Cancer Leukaemia Group (CCLG) proposed a management pathway for craniopharyngioma that advocated limited surgery followed by upfront radiotherapy (RT) for large tumours with hypothalamic involvement and a radical resection only for smaller tumours without hypothalamic involvement. This strategy is not proven to provide optimum care or to be risk-free. The aim of this study is to review our experience of the management of craniopharyngioma diagnosed since the introduction of the CCLG guidelines in 2005. METHODS: All children diagnosed with craniopharyngioma at Alder Hey Children's Hospital NHS Foundation Trust in the period between 1 January 2005 and 30 June 2011 were included. Management was based on the presence of hypothalamic syndrome, hydrocephalus, tumour size and radiological Paris grading system. Endoscopic drainage of tumour cyst was performed prior to formalising risk grade and surgical strategy. Definitive surgery was performed in 4-6 weeks time. In this respect, we developed a grading criteria. RESULTS: Twenty patients were included. Ten of the children underwent endoscopic cyst drainage prior to definitive surgery. The results of the subsequent surgical excision were complete resection, near total resection or subtotal resection in 30, 25 and 45 % patients, respectively. There was no surgical-related mortality and no new neurological deficits. Nine patients underwent RT at some stage. CONCLUSIONS: In this study, we tried to develop an advanced model for the management of craniopharyngioma with a new risk grading system. This may have a direct impact on the surgical strategy and outcome and could be able to improve morbidity.

Reduced energy expenditure and impaired feeding-related signals but not high energy intake reinforces hypothalamic obesity in adults with childhood onset craniopharyngioma.

CONTEXT: Obesity is a frequent manifestation of hypothalamic damage from a craniopharyngioma (CP). It is not yet clarified whether the obesity is due to alterations in energy expenditure, i.e. basal metabolic rate (BMR) and physical activity, or to increased energy intake (EI). OBJECTIVE: The aim was to investigate whether energy expenditure and EI differed between childhood onset CP patients and matched population controls and whether these measures were related to hypothalamic damage, as tumor growth into the third ventricle (TGTV). DESIGN AND METHODS: Forty-two CP patients (20 women) aged 28 yr (range, 17-57 yr) operated between 1958 and 2000 in the South Medical Region of Sweden (population, 2.5 million) were studied. Body composition, satiety hormones, BMR (indirect calorimetry), physical activity, EI, and attitudes toward eating were assessed. Comparisons were made with matched controls and between patients with (n=25) and without (n=17) TGTV. RESULTS: After adjustment, patients had lower BMR compared to controls (-90 kcal/24 h; P=0.02) and also had lower EI (1778 vs. 2094 kcal/24 h; P=0.008), and the EI/BMR ratio was significantly lower in TGTV patients. Similar dietary macronutrient composition was found, and only significantly higher scales in restricting food intake were recorded in patients. Ghrelin levels were significantly lower in patients, whereas serum insulin and leptin levels were higher (P<0.001), and both ghrelin and insulin correlated significantly to tumor growth. Lower levels of physical activity (P<0.01) were recorded in patients. CONCLUSIONS: The major mechanisms that reinforced obesity were hypothalamic damage causing disrupted or impaired sensitivity to feeding-related signals for leptin, insulin, and ghrelin, and reductions in both BMR and physical activity.

Comparative immunohistochemical assessment of craniopharyngioma and related lesions.

Craniopharyngiomas (CP), Rathke's cleft cysts (RCC), and sellar xanthogranulomas (XG) are closely related lesions. As expression of cytokeratins 8 (CK8) and 20 (CK20) was reported in RCC but not in CP, the present study investigates the reproducibility of immunohistochemical distinction between CP and RCC, attempting to identify the relationship of XG to these lesions. A comparative study of 55 patient specimens (25 CP, 28 RCC, and 2 XG) was analyzed for the histological features of xanthomatous changes and squamous metaplasia, and expression of CK8 and CK20. In the 25 CP cases, xanthomatous changes were seen in 5 (20%), with CK8 reactivity demonstrated in all 25 cases. A prominent xanthomatous component was identified in 13 of 28 RCC (46%), and squamous metaplasia was seen in 11 (39%), 9 of which also contained xanthomatous features. CK8 reactivity was demonstrated in all 28 RCC cases, whereas CK20 was seen only in 9 cases (32%). Of the two cases diagnosed as XG, none contained epithelium, and immunohistochemistry for cytokeratins was not observed. Overall, differential expression of cytokeratins cannot reliably distinguish CP from RCC. Furthermore, expression of CK20 in RCC is generally seen within a background of prominent squamous metaplasia and reactive xanthomatous changes.

Two tumors detected by thyroid assessment in two children.

OBJECTIVE: To describe the early detection of two tumors in two children by recognition of unusual features in initial thyroid assessments. METHODS: We present the clinical findings and results of laboratory studies in two children. In addition, we describe RET proto-oncogene studies in one of them. RESULTS: A 14.5-year-old boy was referred for assessment because of short stature in conjunction with lack of physical growth and development. His physical examination was remarkable for height at the 50th percentile (height age, 11.5 years), weight at the 50th percentile (weight age, 13 years), and prepubertal male status. Pertinent laboratory findings were a normal thyroid-stimulating hormone (TSH) level but low free thyroxine (FT4) index. These findings prompted an immediate magnetic resonance imaging study of the head. A parasellar tumor was detected and removed; histopathologic examination revealed that it was a craniopharyngioma. The patient requires lifelong multihormonal therapy for his panhypopituitarism and has responded with physical growth. Our second patient, a 7.5-year-old girl, was referred because of a painless left thyroid nodule of 4 months' duration. Her physical examination was remarkable for (1) upper lip swelling, (2) intermittent rash, and (3) a goiter with painless mobile left and right nodules. Normal levels of TSH and FT4, serum calcitonin of 6,192 pg/mL, and a fine-needle biopsy specimen that stained strongly for calcitonin were obtained at her first clinic visit. A total thyroidectomy was performed and confirmed the presence of medullary thyroid carcinoma. Genetic studies showed that she was positive for the RET multiple endocrine neoplasia IIB mutation. After 4 years of follow-up, the patient had serum calcitonin levels that remained low (<2.2 pg/mL). CONCLUSION: Attention to thyroid physical findings and laboratory studies can promptly lead to correct diagnoses and management of some rare and life-threatening tumors in children.

Proliferative assessment of craniopharyngioma and epidermoid by nucleolar organizer region staining.

The histologic distinction between craniopharyngioma and epidermoid is equivocal. Eight craniopharyngiomas and ten epidermoids (including three dermoids) as well as nine rat (Wistar) abdominal skins that acted as control were investigated by a silver colloid method for nucleolar organizer regions (Ag-NORs). The mean number of Ag-NORs in at least 200 cells of both basal (columnar) epithelial cells and suprabasal (prickle) cells was evaluated. It was found that the mean number of Ag-NORs in basal cells of epidermoid and rat skin was significantly greater than that in suprabasal cells (P < 0.001 in nine of ten epidermoids and in all rat skins). On the other hand, of eight craniopharyngiomas, the mean Ag-NOR number in basal cells was not significantly different from that in suprabasal cells in five cases, and, further, the former was significantly smaller than the latter in the other three cases (P < 0.01 in two and P < 0.05 in one). These findings suggest that a stepwise maturation of the epithelial cells like that in mammalian skin epidermis exists in epidermoids but not in craniopharyngiomas. In craniopharyngiomas, the maturation of the epithelial cells seems to be considerably limited or lost from the aspect of proliferative potential as assessed by Ag-NOR score, which indicates neoplastic growth of craniopharyngiomas. Ag-NOR staining may thus be a useful method to distinguish craniopharyngioma from epidermoid.