This tumor of the brain is seen in children and teenagers. It is derived from remnants of the structures that give rise to pituitary gland, Rathke's pouch. It commonly presents with symptoms related to the mass effect of the tumor with headaches and visual field defects. Hormonal deficiencies may result as the tumor interrupts the pituitary stalk or destroys the hypothalamus. Syndromes ranging from dwarfism in children to sexual dysfunction in adults may occur. Diabetes insipidus may occur in 25% of patients.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE 1-13% of intracranial neoplasms
Most frequent sellar tumor of childhood representing 10% of CNS tumors in children
AGE RANGE-MEDIAN Peak incidence from 5-20 years
Second smaller peak at 6th decade
SEX (M:F) Males slightly favored
DISEASE ASSOCIATIONS CHARACTERIZATION BARDET-BIEDL SYNDROME
Craniopharyngioma and Bardet-Biedl syndrome. A case report.
Erel CT, Oral E, Senturk LM, Aksu MF.
Department of Obstetrics and Gynecology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey.
J Reprod Med 2001 May;46(5):501-3 Abstract quote
BACKGROUND: Bardet-Biedl syndrome is a rare disorder and associated with a variety of anomalies.
CASE: An 18-year-old woman was referred with primary amenorrhea. Following physical, ophthalmologic, psychiatric, hormonal and radiologic examinations, the diagnosis of both craniopharyngioma and Bardet-Biedl syndrome was established.
CONCLUSION: Although the pathogenesis of hypogonadism in a woman with Bardet-Biedl syndrome remains unclear, cranial structures, especially the hypothalamus and pituitary gland, should be investigated to reveal any possible abnormalities.
Craniopharyngioma presenting during pregnancy 4 years after a normal magnetic resonance imaging scan: case report.
Magge SN, Brunt M, Scott RM.
Harvard Medical School, Boston, Massachusetts, USA.
Neurosurgery 2001 Oct;49(4):1014-6; conclusion 1016-7 Abstract quote
OBJECTIVE AND IMPORTANCE: Craniopharyngiomas, epithelial tumors of the hypothalamic and pituitary region, are thought to have congenital origins. It has been postulated that hormonal influences may stimulate growth in adults. This report describes a case and reviews the literature.
CLINICAL PRESENTATION: The case is discussed of a 39-year-old woman who experienced symptoms from a craniopharyngioma diagnosed during a pregnancy that resulted from in vitro fertilization. A magnetic resonance imaging scan performed 4 years previously had disclosed nothing abnormal.
INTERVENTION: The patient underwent a right frontotemporal craniotomy with total resection of the suprasellar tumor, which was dissected from the pituitary stalk.
CONCLUSION: This case suggests a possible link in the adult patient between the growth of this supposedly congenital tumor and hormonal stimulation.
PATHOGENESIS CHARACTERIZATION Thought to be derived from Rathke's pouch CLONALITY
Clonal composition of human adamantinomatous craniopharyngiomas and somatic mutation analyses of the patched (PTCH), Gsalpha and Gi2alpha genes.
Sarubi JC, Bei H, Adams EF, Boson WL, Friedman E, Brandao K, Kalapothakis E, Miranda D, Valle FL, Sarquis MS, De Marco L.
Departamento de Farmacologia, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
Neurosci Lett 2001 Sep 7;310(1):5-8 Abstract quote
Craniopharyngioma is the most common childhood tumor and thought to arise from embryonic remnants of Rathke's pouch. The paucity of published data on the molecular basis of these tumors prompted us to examine 22 adamantinomatous craniopharyngiomas looking for genetic abnormalities.
Using the X-linked polymorphic androgen receptor gene as a tool for X-chromosome inactivating analysis, we found that a subset of craniopharyngiomas are monoclonal and therefore are probably due to acquired somatic genetic defects. Thus, we investigated these tumours for mutations within three candidate genes, Gsalpha, Gi2alpha and patched (PTCH). Using single stranded conformational polymorphism (SSCP), denaturing gradient gel electrophoresis and direct sequencing, the presence of somatic mutations in these genes could not be demonstrated in any tumor.
Our data indicate that a subset of craniopharyngiomas are monoclonal and the mutations in the PTCH, Gsalpha, and Gi2alpha contribute little if any to craniopharyngioma development.
- Expression of Hard a-Keratins in Pilomatrixoma, Craniopharyngioma, and Calcifying Odontogenic Cyst.
Kusama K, Katayama Y, Oba K, Ishige T, Kebusa Y, Okazawa J, Fukushima T, Yoshino A.
Department of Oral Pathology, Meikai University School of Dentistry, Saitama, Japan.
Am J Clin Pathol. 2005 Mar;123(3):376-81. Abstract quote
To examine the properties of shadow and ghost cells, 3 kinds of antibodies were raised against human hair proteins and their immunoreactivity was examined in tumors expressing those cells: pilomatrixoma, 14 cases; craniopharyngioma, 17 cases; and calcifying odontogenic cyst (COC), 14 cases. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analyses demonstrated that 2 polyclonal antibodies, PA-HP1 and PA-HP 2, reacted strongly with type I acidic and type II neutral/basic hard a-keratins. The other monoclonal antibody, MA-HP1, reacted with type II neutral/basic hard a-keratins. Immunohistochemical examination revealed that all 3 antibodies reacted only with the hair shaft in sections of normal skin and dermoid cyst.
In all pilomatrixoma cases, 3 antibodies reacted with the cytoplasm of transitional and shadow cells but not with that of basophilic cells. Positive reactions were found only in shadow cells of all 13 adamantinomatous craniopharyngiomas. In all COCs, the antibodies reacted only with ghost cells, not with other epithelial components.
Immunoreactivity for phosphothreonine, detected in hard a-keratins, also was found in transitional, shadow, and ghost cells. The appearance of shadow or ghost cells might represent differentiation into hair in these 3 kinds of tumors.
CHARACTERIZATION CT exam Enlarged or eroded sella turcica in 50% of cases
Suprasellar calcifcation in 50% of these cases
Cysts in 85% of cases
Atypical magnetic resonance imaging findings of craniopharyngioma.
Wang YX, Jiang H, He GX.
Department of Radiology, Rui Jin Hospital, Shanghai Second Medical University, Shanghai, The People's Republic of China.
Australas Radiol 2001 Feb;45(1):52-7 Abstract quote
Three cases of craniopharyngiomas with atypical MRI findings are reported.
The first patient had a nasopharyngeal craniopharyngioma. Its unusual location made diagnosis difficult. The second patient had a massive craniopharyngioma with extensive cystic expansion, involving the anterior, middle and posterior cranial fossae, and extending into the foramen magnum. The tumour of the third patient involved the suprasellar region with a large extension into the third ventricle, and demonstrated a predominantly high signal intensity on all T1-weighted, proton-weighted and T2-weighted images.
These patients further stressed the complexity of MRI findings in craniopharyngiomas.
GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION General
Majority are suprasellar with 15% intrasellar
Most usually >1 cm
Well circumscribed tumors but may infiltrate into the brain
Cross sections reveal a crank case or black sludge cystic fluid with cholesterol crystals and calcifications
Giant cystic craniopharyngiomas with extension into the posterior fossa.
Buhl R, Lang EW, Barth H, Mehdorn HM.
Neurochirurgische Klinik, Christian-Albrechts-Universitat, Kiel, Germany.
Childs Nerv Syst 2000 Mar;16(3):138-42 Abstract quote
Between 1991 and 1998, 24 patients underwent surgery for a craniopharyngioma in our department. This group included two patients who had tumors with extensive growth along the midline, and along the posterior fossa in particular. In both cases suprasellar calcifications were typical features on magnetic resonance imaging (MRI) and computed tomography (CT).
A 7-year-old boy presented with a 6-month history of headache, nausea, and progressive unilateral hearing loss. With a suboccipital approach it was possible to remove the main part of the tumor. In a 13-year-old boy headache and visual deterioration led to the diagnosis of a craniopharyngioma, which was removed with a pterional approach.
For the neuroimaging work-up in such cases of atypically growing craniopharyngiomas MRI is the method of choice. Additional CT scanning is recommended, which provides valuable information about bony changes at the skull base due to space-occupying growth. CT substantiates the differential diagnosis if typical calcifications are seen.
Suprasellar and infrasellar craniopharyngioma with a persistent craniopharyngeal canal: case report and review of the literature.
2nd Department of Diagnostic Radiology, Chang Gung Memorial Hospital and University, Taipei, Taiwan.
Neuroradiology 2001 Sep;43(9):760-2 Abstract quote
Craniopharyngiomas are usually confined to the sellar and suprasellar regions; infrasellar craniopharyngioma is rare. From an embryological point of view, this unusual localisation can be explained by Erdheim's theory that these tumours can arise anywhere along the craniopharyngeal canal (CPC). However, there has been no proof of this theory, because the CPC is usually obliterated during the 12th week of gestation.
I present a case of supra- and infrasellar craniopharyngiomas with a persistent CPC. Imaging demonstrated an intimate relationship between the infrasellar tumour and the CPC, supporting Erdheim's view.
HISTOLOGICAL TYPES CHARACTERIZATION General
Cords or islands of epithelial cells in loose fibrous stroma with intervening cysts
Epithelium has palisaded outer layer with keratinization admixed with cholesterol clefts and midzone of stellate epithelial cells
Calcification is common
Adamantinomatous type Predominance of stellate components resembling dental ameloblastic organ, similar to adamantinomas MELANOTIC
Melanotic craniopharyngioma: a report of two cases.
Harris BT, Horoupian DS, Tse V, Herrick MK.
Department of Pathology, Neuropathology Rm. R241, 300 Pasteur Drive, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
Acta Neuropathol (Berl) 1999 Oct;98(4):433-6 Abstract quote
We report a 74-year-old woman and a 50-year-old woman with similar histories of headache and visual disturbance who were found to have adamantinomatous craniopharyngiomas which contained melanin pigment.
This finding was confirmed by the Masson Fontana method and ultrastructural studies. These are only the second and third cases reported describing melanin pigment within a craniopharyngioma.
The finding of melanin in craniopharyngiomas attests to their similarities with odontogenic tumors of the jaw, which can also contain melanin pigment and also supports the hypothesis that the histogenesis of these neoplasms derives from the vestiges of Rathke's pouch epithelium.
Papillary type Rare in children and associated with better prognosis
Solid or cystic growth of pseudopapillary squamous epithelium lacking palisading, fibrosis, and cholesterol accumulation
- Nuclear beta-Catenin Accumulation as Reliable Marker for the Differentiation Between Cystic Craniopharyngiomas and Rathke Cleft Cysts: A Clinico-Pathologic Approach.
Departments of *Neurosurgery double daggerNeuropathology, University of Erlangen-Nuremberg, Erlangen, Germany daggerDepartment of Pathology, Marienkrankenhaus, Hamburg, Germany.
- Am J Surg Pathol. 2006 Dec;30(12):1595-1603. Abstract quote
Clinical and histopathologic differentiation of cystic lesions from the sellar region, that is, craniopharyngiomas (CPs) and Rathke cleft cysts (RCCs), is challenging and has paramount importance with respect to variable clinical manifestation and adapted surgical treatment strategies in both entities.
Here, we retrospectively evaluated clinico-pathologic findings in 81 patients presenting with a cystic tumor located in the sellar region. All patients underwent transsphenoidal or transcranial resections. Microscopic inspection of surgical specimens identified CP in 51 patients, and RCC in 30 patients. Amongst the panel of immunohistochemical marker proteins used for histopathologic analysis, nuclear accumulation of beta-catenin was detectable only in CP.
On the basis of the histopathologic and immunohistochemical analysis, clinical presentation (sex, age, ophthalmologic, and endocrinologic deficits), imaging (tumor location, size, and calcification), as well as a description of cyst contents obtained during operation were retrospectively evaluated.
In purely cystic CPs, an isointense signal was more frequent in T1-weighted magnetic resonance images and calcification of the tumor capsule in computed tomography scans. In addition, the size of RCC was smaller and this tumor entity was more often located within the sella. Aberrant (nuclear) immunohistochemical staining for beta-catenin appeared, however, as most reliable factor for the differentiation between purely cystic CPs and RCCs, whereas tumor location, tumor size, and calcification of the tumor capsule were less consistent parameters.
The data are compatible with distinct pathogenic pathways associated with these related histopathologic entities.
Immunohistochemical localisation of cytokeratins in craniopharyngioma.
Kurosaki M, Saeger W, Ludecke DK.
Division of Neurosurgery, Institute of Neurological Sciences, Tottori University School of Medicine, Yonago, Japan.
Acta Neurochir (Wien) 2001;143(2):147-51 Abstract quote
BACKGROUND: Although craniopharyngiomas have been examined in several microscopical studies to date, immunohistochemical analysis has not been sufficient.
METHOD: In addition to the routine haematoxylin and eosin staining, 38 cases of intra- and/or supra-sellar craniopharyngioma, including 34 adamatinomatous and 4 squamous papillary types, were studied using immunohistochemistry for expression of four types of cytokeratin.
FINDINGS: Histological examination found epithelial cells in 26 of 38 (68.40%) cases. However, cytokeratins were demonstrated in 35 of 38 (92.1%) cases. The remaining 3 cases without demonstration of epithelial cell nests were supposed to be adamantinomatous craniopharyngiomas based on the findings in the stroma. In 31 of 34 adamantinomatous craniopharyngioma cases, the epithelium was detected by immunostaining for cytokeratins. The epithlieum expressed 56 kDa (KL-1) and 40 kDa (cytokeratin 19) cytokeratins with similar staining patterns and intensities. The staining intensity of 54 kDa cytokeratin (cytokeratin 7) was similar to that of the high molecular weight cytokeratin (keratin M-903). However, in many cases (15 of 27), immunoreactivity of cytokeratin 7 was not demonstrated in an outer palisaded basal layer. In all 4 squamous papillary craniopharyngiomas, moderate staining with cytokeratin 7 appeared in the superficial layer, whereas basal or mid-zone epithelial cells were negative for cytokeratin 7. The basal layer stained negatively for KL-1, as well as cytokeratin 7.
INTERPRETATION: Immunostaining for cytokeratin is valuable in the investigation of craniopharyngioma, especially when specimens contain only a small or questionable part of epithelium. Most notably, KL-1 or cytokeratin 7 stainings are suitable for analyzing these tumours, with special reference to histological subtypes.
Differential expression of cytokeratins 8 and 20 distinguishes craniopharyngioma from rathke cleft cyst.
Xin W, Rubin MA, McKeever PE.
Departments of Pathology (Drs Xin, Rubin, and McKeever) and Urology (Dr Rubin), and the Comprehensive Cancer Center, University of Michigan Medical Center, Ann Arbor.
Arch Pathol Lab Med 2002 Oct;126(10):1174-8 Abstract quote
Background.-Craniopharyngiomas are epithelial neoplasms usually located in the sellar and suprasellar regions. Distinguishing craniopharyngioma from Rathke cleft cyst is sometimes difficult, and the distinction is clinically significant because Rathke cleft cysts have a better prognosis than craniopharyngiomas.
Design.-We retrieved 10 cases with a primary diagnosis of craniopharyngioma and 5 cases with a diagnosis of Rathke cleft cyst for analysis. Five cases of normal pars intermedia of pituitary glands from autopsy served as controls. We evaluated the expression patterns of a broad range of low- to intermediate-molecular weight cytokeratins (CK7, CK8, CK10, CK17, CK18, CK19, and CK20) and high-molecular weight cytokeratins (K903: a combination of CK1, CK5, CK10, and CK14; and CK5/6) in these cases.
Results.-Craniopharyngiomas had a cytokeratin expression pattern distinct from that of Rathke cleft cysts and pituitary gland pars intermedia: craniopharyngiomas did not express cytokeratins 8 and 20, whereas Rathke cleft cysts and pars intermedia of pituitary glands both expressed cytokeratins 8 and 20.
Conclusion.-The differential expression of cytokeratins distinguishes between craniopharyngioma and Rathke cleft cyst, and this difference could be useful for identifying craniopharyngioma in difficult cases in which only a small biopsy is available. The different cytokeratin profiles of craniopharyngioma and Rathke cleft cyst suggest that these lesions do not come from the same origin, or that they come from a different developmental stage of the pouch epithelium.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES SINONASAL TERATO-CARCINOSARCOMA
Sinonasal teratocarcinosarcoma ("mixed olfactory neuroblastoma-craniopharyngioma") presenting with syndrome of inappropriate secretion of antidiuretic hormone.
Kleinschmidt-DeMasters BK, Pflaumer SM, Mulgrew TD, Lillehei KO.
Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA.
Clin Neuropathol 2000 Mar-Apr;19(2):63-9 Abstract quote
Sinonasal teratocarcinosarcoma (SNTC) is a rare, aggressive, histologically heterogeneous neoplasm of the paranasal sinuses and nasopharnyx of adults that is composed of variably benign or malignant neuroepithelial, epithelial, and mesenchymal elements. Occasional cases show intracranial extension and may be operated on by neurosurgeons and encountered by neuropathologists who may not be familiar with the entity. STNCs have not previously been associated with functional hypersecretory status.
We report a 59-year-old male who presented with headache and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and was subsequently found to have a bulky tumor of the frontal and ethmoid sinuses with focal dural invasion. The tumor was predominantly composed of olfactory neuroblastoma areas (90% of tumor) admixed with unusually well-developed craniopharyngioma-like mature squamous epithelium and ghost cells ( 10% of tumor). Scattered neuroblastoma tumor cells showed strong immunoreactivity with antibodies to arginine vasopressin, supporting ectopic hormone secretion by the tumor.
While the coexistence of neuroectodermal and oral ectodermal-like differentiation in SNTCs is characteristic, in our case it was developed to an extreme functional and morphologic degree and was unassociated with other mesenchymal or epithelial elements often found in these complex tumors. SNTCs with limited differentiation have prompted controversy in classification.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS
Untreated, these tumors are invasive and may extend into the hypothalamus and third ventricle resulting in obstructive hydrocephalus
10-40% recurrence rate usually because of incomplete surgical removal
One case report of a malignant transformation to squamous cell carcinoma after repeated recurrences over 35 years and 8 years post radiotherapy
Craniopharyngioma: the St. Jude Children's Research Hospital experience 1984-2001.
Merchant TE, Kiehna EN, Sanford RA, Mulhern RK, Thompson SJ, Wilson MW, Lustig RH, Kun LE.
Department of Radiation Oncology, St. Jude Children's Research Hospital, 332 N Lauderdale Street, Memphis, TN 38105-2794, USA.
Int J Radiat Oncol Biol Phys 2002 Jul 1;53(3):533-42 Abstract quote
PURPOSE: To review our institution's experience in the treatment of craniopharyngioma and assess the merits of initial therapy with limited surgery and irradiation.
METHODS AND MATERIALS: The data of 30 patients (median age 8.6 years) with a diagnosis of craniopharyngioma between April 1984 and September 1997 were reviewed. Their course of treatment, neurologic, endocrine, and cognitive function, and quality of life at last follow-up were compared.
RESULTS: Fifteen patients were initially treated with surgery (8 required irradiation after relapse) and 15 with limited surgery and irradiation (2 required additional treatment for tumor progression). Only 1 patient died of tumor progression. The surgery group lost a mean of 9.8 points in full-scale IQ, and the combined-modality group lost only 1.25 points (p <0.063). Patients in the surgery group who had relapses (n = 9) lost a mean of 13.1 points (p <0.067). A loss of 10 points was considered clinically significant. The surgery group also had more frequent neurologic, ophthalmic, and endocrine complications. The mean Health Utility Index (a functional quality-of-life index) was higher for the combined-modality group (0.85) than for the surgery group (0.71; p <0.063, one-sided t test).
CONCLUSIONS: The acute neurologic, cognitive, and endocrine effects of surgery often affect long-term function and quality of life. Our experience suggests that limited surgery and radiotherapy cause lesser or comparable sequelae. Diabetes insipidus was the only endocrine deficiency that differed substantially in frequency between the two groups. Newer radiation planning and delivery techniques may make a combined-modality approach a good initial option for most patients.
Long term results of multimodality treatment of craniopharyngioma in children.
Vernet O, Montes JL, Farmer JP, Blundell JE, Bertrand G, Freeman CR.
Departments of Neurosurgery, Radiation Oncology, The Montreal Children's Hospital, Montreal Neurological Institute (GB), McGill University, Montreal, Quebec, Canada
J Clin Neurosci 1999 May;6(3):199-203 Abstract quote
The management of craniopharyngioma has been controversial for years.
We review our 20 year experience in the treatment of paediatric craniopharyngioma. Twenty-five patients were treated for craniopharyngioma at The Montreal Children's Hospital from 1972 to 1991. They included 15 males and 10 females whose median age was 10 years.
The initial clinical manifestations were remarkable for a predominance of symptoms and signs related to intracranial hypertension, followed in frequency by visual and endocrinological deficits. Radiologically, there were five cystic craniopharyngiomas, one solid and 19 mixed.
Several therapeutic approaches were used including stereotactic drainage followed by radiotherapy or radiosurgery (three cases), transsphenoidal removal (six cases) and subfrontal and/or pterional craniotomy for total (three cases) or partial (13 cases) removal, followed by radiotherapy in 10 cases.
The follow up period averaged 11 years. Eight patients recurred, three after total and three after partial removal; none of these six patients had received radiotherapy. Two cases treated by stereotactic drainage recurred, one received adjuvant radiosurgery and the other conventional radiotherapy. Morbidity was lower, and quality of survival better, with more conservative approaches.
More conservative approaches in the management of craniopharyngioma are reasonable alternatives for treatment. Similar rates of disease control are observed with less morbidity and better quality of survival.
Long-term outcomes for surgically resected craniopharyngiomas.
Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota 55905, USA.
Neurosurgery 2000 Feb;46(2):291-302; discussion 302-5 Abstract quote
OBJECTIVE: This retrospective study critically analyzed the long-term functional outcomes and tumor recurrence rates for surgically treated craniopharyngiomas.
METHODS: This study used an outcome classification system that included functioning vision, independent versus dependent living, Karnofsky Performance Scale scores, academic levels, work status, and psychological status. Tumor recurrence rates were analyzed with respect to the extent of surgical resection and adjunctive radiotherapy.
RESULTS: For 121 patients, with a mean follow-up period of 10 years, the overall "good outcome" rate was 60.3%. Factors associated with poor outcomes included lethargy at presentation, visual deterioration, papilledema, tumor calcification, hydrocephalus, and tumor adhesiveness at surgery. Gross total resection was associated with good outcomes (P = 0.017) and decreased risk of recurrence (P = 0.024). Subtotal resection was associated with increased risk of tumor recurrence (P = 0.0235). The highest risk of recurrence was in the subtotal resection/no radiation group (P = 0.0001). There were no differences in outcomes or recurrence rates between pediatric and adult patients. There were also no differences in outcomes or recurrence rates between papillary and adamantinous tumors. Approximately one-third of patients exhibited morbid obesity, and permanent diabetes insipidus was observed for 25 patients.
CONCLUSION: A rigorous evaluation of outcomes for tumors such as craniopharyngiomas must consider not only the extent of resection, as judged by postoperative imaging, but also the long-term physical, intellectual, and psychological functioning of the patients.
Hormonal factors influencing weight and growth pattern in craniopharyngioma.
Pinto G, Bussieres L, Recasens C, Souberbielle JC, Zerah M, Brauner R.
Department of Pediatric Endocrinology, Universite Rene-Descartes and Hopital Necker-Enfants Malades, Paris, France.
Horm Res 2000;53(4):163-9 Abstract quote
Patients operated on for craniopharyngioma frequently suffer from hyperphagia and are obese, but their statural growth is normal despite growth hormone (GH) deficiency.
We have evaluated the hormonal factors influencing changes in weight and growth in 17 children before and 1, 3-6, 12, and/or 24 months after surgical resection of a craniopharyngioma performed at 7.7 +/- (SE) 1 years of age.
Of these, 15 patients had a GH deficiency before surgery, and all had complete pituitary deficiency after it. The plasma fasting insulin concentrations before surgery were positively correlated with body mass index (BMI, kg/m(2); p < 0.05), plasma insulin-like growth factors (IGFI, p = 0.03, and IGFII, p = 0.04), and leptin (p = 0.03). They increased significantly 1 month after surgery and continued to increase thereafter, whereas leptin increased significantly only 3-6 months after surgery, paralleling changes in BMI. The plasma fasting insulin concentrations before surgery were also positively correlated with the weight changes (12.3 +/- 2.3 kg, p < 0.01) during the 12 months after surgery, but not with changes in BMI SDS (3.1 +/- 0.5, p = 0.07). Both expressions of weight change were correlated with the concomitant growth rates (4.8 +/- 0.7 cm, p < 0.01).
IGFI was above the 10th percentile for children with idiopathic short stature in 10 of 15 patients with craniopharyngioma-induced GH deficiency and IGF-binding protein 3 in 14 of 15 patients.
Craniopharyngioma itself modified the control of insulin secretion, and surgery increased the insulin secretion which continued in the same way in a given patient after surgery. The increased insulin secretion in turn increases weight and keeps IGFI nearly normal. This may explain the normal growth rate despite the complete lack of GH.
Endocrine sequelae of childhood craniopharyngioma.
Bin-Abbas B, Mawlawi H, Sakati N, Khafaja Y, Chaudhary MA, Al-Ashwal A.
Department of Pediatrics, King Faisal Specialist Hospital and Research Hospital, Riyadh, Saudi Arabia.
J Pediatr Endocrinol Metab 2001 Jul-Aug;14(7):869-74 Abstract quote
The endocrine sequelae of 62 children with craniopharyngioma were studied retrospectively. These patients were followed for a median duration of 3 years (range 1 to 10 years). Eighteen patients had a long-term follow-up for more than 5 years (range 5 to 10 years). Complete surgical resection was achieved in 30 patients and 32 patients had residual tumor. Twenty-five patients had recurrence or progression of the residual tumor and were treated with radiotherapy.
Presenting complaints suggestive of endocrinopathy were infrequent. The most common presenting symptoms were headache, nausea and vomiting, followed by growth failure. Pre-operatively, growth hormone deficiency was the most commonly encountered pituitary hormonal deficiency; however postoperatively, most children had diabetes insipidus. Multiple pituitary hormonal deficiencies were more frequently observed in children treated with extensive radical surgery than in those treated with conservative surgery and radiotherapy.
The endocrine morbidity associated with craniopharyngioma and its different management modalities remains high; however, it is manageable with appropriate hormonal replacement therapy.
Proliferative activity in craniopharyngiomas: clinicopathological correlations in adults and children.
Raghavan R, Dickey WT Jr, Margraf LR, White CL 3rd, Coimbra C, Hynan LS, Rushing EJ.
Neuropathology Laboratory, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9073,
Surg Neurol 2000 Sep;54(3):241-7; discussion 248 Abstract quote
BACKGROUND: Craniopharyngiomas are slow-growing, locally invasive intracranial tumors that can generate considerable morbidity, and recurrences are often difficult to manage. Because reliable morphologic criteria for accurately predicting the clinical outcome of these tumors are lacking, we evaluated the growth potential of craniopharyngiomas by measuring their proliferative activity based on MIB-1 immunostaining for the Ki-67 antigen, which is expressed during all phases of the cell cycle except G(0.)
METHODS: Paraffin sections from 37 cases of craniopharyngiomas were immunostained with the monoclonal antibody MIB-1, and a labeling index was derived in each case from an the with the highest labeling.
RESULTS: MIB-1 immunoreactivity was mainly confined to the peripheral palisaded epithelium of craniopharyngiomas. In adult craniopharyngiomas, MIB-1 labeling indices (MIB-LI) varied from 0.1% to 34.6% (mean 8.9%; SD 9. 8), and in pediatric tumors the indices ranged from 1.8% to 15.0% (mean 6.3%; SD 3.7). MIB-LI was not found to be an independent predictor of recurrence, although in all the pediatric cases that recurred, MIB-LI in the second specimen was greater.
CONCLUSIONS: The actively proliferating compartment in craniopharyngiomas seems to be the peripheral palisaded epithelium. Low MIB-LI observed in the majority of tumors is in concordance with the slow growth and low-grade invasiveness associated with craniopharyngiomas. However, unlike other intracranial neoplasms, where Ki-67 labeling indices have been useful in predicting tumor behavior, a clear relationship could not be demonstrated between MIB-1 immunoreactivity, morphological features and clinical outcomes in adults or children with craniopharyngiomas.
Radical excision of pediatric craniopharyngioma: recurrence pattern and prognostic factors.
Kim SK, Wang KC, Shin SH, Choe G, Chi JG, Cho BK.
Division of Pediatric Neurosurgery, Cancer Research Institute, Seoul National University Children's Hospital, Korea.
Childs Nerv Syst 2001 Sep;17(9):531-6; discussion 537 Abstract quote
The purpose of our study was to investigate the pattern of recurrence and the prognostic factors for recurrence of pediatric craniopharyngiomas after radical excision.
A series of 36 patients with craniopharyngiomas (21 boys and 15 girls; age range 1-15 years; mean 7.3 years) were reviewed. All patients had undergone radical excision without radiotherapy. The mean follow-up period was 52 months (range 1-149 months). Tumors recurred in 14 patients within 83 months (mean 31.4 months). The overall 5-year recurrence-free survival rate was 55%. Regular neuroimaging follow-up detected tumor recurrence while the lesions were still small before symptoms developed (P<0.05).
At the first surgical procedure, the optic nerve/chiasm (n=23) was the most common adhesion site. The most frequent sites of recurrence were the optic nerve/chiasm (n=6) and the pituitary fossa (n=6). Tumor location was the single significant clinical predictor of recurrence. The 5-year recurrence-free survival rate was 39% for those who had an intrasellar tumor component and 81% for those who did not (P<0.05). The Ki-67 labeling indices (LIs) of primary tumors did not have prognostic value for recurrence. Recurrent tumors tended to have higher Ki-67 LIs than their primary counterparts.
On the basis of this study, we concluded that craniopharyngiomas with intrasellar components should be followed cautiously and the necessity for regular follow-up should be emphasized, even when the tumor is "totally" resected.
TREATMENT Surgery often followed by postoperative irradiation INTERFERON
Phase II evaluation of interferon-alpha-2a for progressive or recurrent craniopharyngiomas.
Jakacki RI, Cohen BH, Jamison C, Mathews VP, Arenson E, Longee DC, Hilden J, Cornelius A, Needle M, Heilman D, Boaz JC, Luerssen TG.
Indiana University, Indianapolis, USA.
J Neurosurg 2000 Feb;92(2):255-60 Abstract quote
OBJECT: Craniopharyngiomas originate from the same cells as squamous cell skin carcinoma, which can be treated successfully with interferon-alpha (IFNalpha)-2a. The authors evaluated the activity and toxicity of systemic IFN in young patients with craniopharyngiomas.
METHODS: Fifteen patients between the ages of 4.2 and 19.8 years who had progressive or recurrent craniopharyngiomas were enrolled in this study. Nine of these patients had never received external-beam radiation therapy. Therapy consisted of 8,000,000 U/m2 IFNalpha-2a administered daily for 16 weeks (induction phase) followed by the same dose three times per week for an additional 32 weeks (maintenance phase). Of the 12 patients who could be evaluated, radiological studies demonstrated a response to treatment in three with predominantly cystic tumors (one minor response, one partial response, and one complete response); one of these patients also showed improvement in visual fields. The size of the cystic component of the tumors often increased temporarily during the first several months of therapy. Three patients met the criteria for progressive disease during therapy. The median time to progression was 25 months. The need for radiation therapy in patients treated with IFN was delayed for 18 to 35 months (median 25 months) in six patients. All patients developed transient flulike symptoms shortly after receiving the first dose of IFN. Other toxicities (predominantly hepatic, neurological, and cutaneous) were seen in nine (60%) of the 15 patients during the first 8 weeks of treatment but resolved after temporary discontinuation and/or dose reduction.
CONCLUSIONS: Interferon-alpha-2a is active against some childhood craniopharyngiomas; its toxicity precludes administration of high daily doses, and the optimum dose level and schedule remain to be defined.
The role of radiation therapy in the management of craniopharyngioma: a 25-year experience and review of the literature.
Habrand JL, Ganry O, Couanet D, Rouxel V, Levy-Piedbois C, Pierre-Kahn A, Kalifa C.
Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France
Int J Radiat Oncol Biol Phys 1999 May 1;44(2):255-63 Abstract quote
PURPOSE: To review the outcome and quality of life at 5 years and more of 37 children treated with radiation therapy combined or not with surgical resection for a craniopharyngioma in a single institution.
METHODS AND MATERIALS: From January 1969 through December 1992, 37 children received external therapy at the Institut Gustave Roussy (Villejuif, France). Age ranged between 1 and 15 years (mean 7.4), M/F sex ratio was 0.76. In approximately one-half of the cases (18/37), radiation therapy was applied in conjunction with a surgical resection, and in almost one-half of the cases (18/37) as part of a salvage program following local failure. Total dose ranged between 45 and 56 Gy (median 50) given with a conventional fractionation in most children. Survival (S), event-free survival (EFS) were computerized according to the Kaplan-Meier method and prognostic factors for local failure and functional status analyzed. Functional outcome was evaluated according to the Wen score in 4 grades (gr 1: normal with/without hormonal replacement, gr 4: totally dependent, gr 2 and 3: intermediate disabilities).
RESULTS: At the time of analysis, 24 children (65%) were alive with NED, 4 (11%) alive after failure, and 9 (24%) dead of various causes. Following therapy, S and EFS regularly degraded and didn't seem to reach a plateau before 9 years (5 and 10 year S and EFS, respectively, 91, 65, and 78 and 56.5%). This was due to the occurrence of late failures (5 and 8.5 years) and late lethal complications (1 in-field glioblastoma multiforme at 9 years). A significant gain on EFS followed the introduction of modern imaging (p = 0.03), the association of surgical resection with RT (p = 0.01) and of higher doses of radiation superior or equal to 55 Gy (p = 0.05); a similar gain on S was observed in patients with a good initial performance status (p = 0.05). It is remarkable that surgical salvage of local failures following RT could induce prolonged remission in 4 children. Functional outcome was impaired in all but 5 children out of 35 fully evaluable (86%) and related with the initial symptomatology and/or therapy. Endocrinological, visual, neurological functions were affected in 97, 34, and 40%, respectively. It appeared correlated with the initial performance status (p = 0.02) and possibly with a younger age at treatment (p = 0.07).
CONCLUSIONS: Long-term follow-up beyond 5 years is warranted in craniopharyngioma to assess tumor control and functional outcome after radiation therapy. Although this therapeutical modality provides a high cure rate alone or in combination with surgery and even though at the time of failure, further strategies should aim to limit the severe toxicity (i.e., Wen gr 3 + 4) that was observed in more than one-third of our patients.
Gamma knife radiosurgery for craniopharyngiomas.
Chung WY, Pan DH, Shiau CY, Guo WY, Wang LW.
Department of Neurosurgery, Cancer Center, Taipei Veterans General Hospital and National Yang-Ming University, Taiwan, Republic of China.
J Neurosurg 2000 Dec;93 Suppl 3:47-56 Abstract quote
OBJECT: The goal of this study was to elucidate the role of gamma knife radiosurgery (GKS) and adjuvant stereotactic procedures by assessing the outcome of 31 consecutive patients harboring craniopharyngiomas treated between March 1993 and December 1999.
METHODS: There were 31 consecutive patients with craniopharyngiomas: 18 were men and 13 were women. The mean age was 32 years (range 3-69 years). The mean tumor volume was 9 cm3 (range 0.3-28 cm3). The prescription dose to the tumor margin varied from 9.5 to 16 Gy. The visual pathways received 8 Gy or less. Three patients underwent stereotactic aspiration to decompress the cystic component before GKS. The tumor response was classified by percentage reduction of tumor volume as calculated based on magnetic resonance imaging studies. Clinical outcome was evaluated according to improvement and dependence on replacement therapy. An initial postoperative volume increase with enlargement of a cystic component was found in three patients. They were treated by adjuvant stereotactic aspiration and/or Ommaya reservoir implantation. Tumor control was achieved in 87% of patients and 84% had fair to excellent clinical outcome in an average follow-up period of 36 months. Treatment failure due to uncontrolled tumor progression was seen in four patients at 26, 33, 49, and 55 months, respectively, after GKS. Only one patient was found to have a mildly restricted visual field; no additional endocrinological impairment or neurological deterioration could be attributed to the treatment. There was no treatment-related mortality.
CONCLUSIONS: Multimodality management of patients with craniopharyngiomas seemed to provide a better quality of patient survival and greater long-term tumor control. It is suggested that GKS accompanied by adjuvant stereotactic procedures should be used as an alternative in treating recurrent or residual craniopharyngiomas if further microsurgical excision cannot promise a cure.
Combined treatment with stereotactic intracavitary irradiation and gamma knife surgery for craniopharyngiomas.
Yu X, Liu Z, Li S.
Neurosurgical Department, Navy General Hospital, Beijing, China.
Stereotact Funct Neurosurg 2000 Dec;75(2-3):117-22 Abstract quote
Object: To evaluate the effectiveness of the combined treatment of stereotactic intracavitary irradiation and Gamma Knife surgery on craniopharyngiomas. Patients and
Methods: Combined treatment with stereotactic instillation of radioisotopes and Gamma Knife surgery was performed on 46 patients with craniopharyngioma between October 1996 and June 1999. There were 13 solid tumors and 33 mixed solid and cystic tumors.
Results: 38 patients (10 solid and 28 mixed) were followed up from 6 months to two years. The tumor control rate was 90% in solid tumors, 85.7% in mixed tumors, 92.1% in the solid segment and 89.5% in total.
Conclusions: Gamma Knife surgery plays an important role in the treatment of the solid component of craniopharyngiomas and the combination of treatment is a simple, safe and effective method for treatment of craniopharyngiomas, especially for the recurrent mixed solid and cystic tumors.
Stereotactic radiosurgery of residual or recurrent craniopharyngioma, after surgery, with or without radiation therapy.
Chiou SM, Lunsford LD, Niranjan A, Kondziolka D, Flickinger JC.
Department of Neurological Surgery and Radiation Oncology, Center for Image-Guided Neurosurgery, University of Pittsburgh Medical Center, PA 15213-2582, USA.
Neuro-oncol 2001 Jul;3(3):159-66 Abstract quote
This study evaluated the role of stereotactic radiosurgery in the multimodality management of craniopharyngioma patients whose prior therapies failed.
Ten consecutive patients (3 males and 7 females) had radiosurgery for craniopharyngioma during a 10-year interval. Their ages ranged from 9 to 64 years (median, 14.5 years). The median interval between diagnosis and radiosurgery was 46.5 months. In total, 12 stereotactic radiosurgical procedures were performed to control the solid component of the tumor (2 intrasellar and 10 suprasellar tumors).
The median tumor volume was 1.35 cm3. One to 9 isocenters with different beam diameters were used; the median marginal dose was 16.4 Gy; and the dose to the optic apparatus was limited to less than 8 Gy. Clinical and imaging follow-up data were obtained at a median of 63 months (range, 13-150 months) from radiosurgery.
Overall, 7 of 12 tumors became smaller or vanished within a median of 8.5 months. Prior visual defects objectively improved in 6 patients. One patient with prior visual defect deteriorated further and lost vision 9 months after radiosurgery. Multimodality therapy is often necessary for patients with refractory solid and cystic craniopharyngiomas.
Stereotactic radiosurgery is a reasonable option in select patients with small recurrent or residual craniopharyngioma.
Changes in Cyst Volume following Intraoperative MRI-Guided Ommaya Reservoir Placement for Cystic Craniopharyngioma.
Vitaz TW, Hushek S, Shields CB, Moriarty T.
Department of Neurological Surgery, University of Louisville School of Medicine and Norton Healthcare Intraoperative MRI Center, Louisville, Ky., USA.
Pediatr Neurosurg 2001 Nov;35(5):230-4 Abstract quote
Introduction: Intracavitary treatment of solitary cystic craniopharyngiomas with (32)P is an emerging treatment option, especially for pediatric patients. We have treated two patients with solitary cystic craniopharyngiomas using intraoperative MRI (iMRI)-guided catheter placement.
Methods: The optical tracking system of the General Electric Signa SP iMRI system was utilized for preoperative planning and intraoperative catheter tracking during insertion. Intraoperative volumetric imaging was then used to confirm final catheter position. Patients were brought back to the iMRI suite approximately 8 weeks later and diluted gadolinium was injected with further MRI to confirm the absence of communication between the cyst lumen and surrounding CSF spaces and for volumetric analysis.
Results: Intraoperative imaging illustrated deformation and changes in the cyst wall during catheter placement and cyst aspiration and confirmed final catheter placement. Images acquired 8 weeks following catheter placement prior to the instillation of (32)P showed decreases in cyst volume of 40 and 85%.
Conclusion: iMRI-guided catheter placement for cystic craniopharyngiomas helps to assure successful catheter placement. Significant decreases in cyst volume occur in the interval between catheter placement and (32)P administration and must be accounted for to prevent overdosing of the radioisotope.
COMPLICATIONS OF TREATMENT
Malignant glioma as a secondary malignant neoplasm after radiation therapy for craniopharyngioma: report of a case and review of reported cases.
Kranzinger M, Jones N, Rittinger O, Pilz P, Piotrowski WP, Manzl M, Galvan G, Kogelnik HD.
Institut fur Radiotherapie und Radio-Onkologie, St.-Johannes-Spital, Landeskliniken Salzburg, Salzburg.
Onkologie 2001 Feb;24(1):66-72 Abstract quote
BACKGROUND: The development of a secondary neoplasm in childhood cancer survivors attains growing importance due to the reported excellent survival and therefore the long exposure to potentially carcinogenic effects of treatment.
CASE REPORT: We report a 14-year-old girl in whom a large craniopharyngioma (CP) was diagnosed. After surgery, radiation therapy (RT) was given for residual tumour. Discrete progression necessitated further surgery, resulting in permanent tumour control. Soon after the second surgery hypothalamic-pituitary dysfunction developed together with obesity. Supportive hormone therapy was initiated. Growth hormone (GH) therapy was also given for 15 months. Four years after the diagnosis, a cerebropontine anaplastic astrocytoma WHO grade III was detected, with the main lesion being at the dorsal edge of the irradiated area. The girl died 1 month later from this secondary presumably radiation-induced tumour. Only recently a second child with RT for a CP was diagnosed with malignant glioma in our hospital.
CASE REPORTS IN THE LITERATURE: 12 other cases of malignant glioma have been reported after RT for CP. Including our present cases, the mean latency period was 10.7 years (median 9.6 years). However, the shortest latency periods were found in patients who had received GH therapy. In numerous cases, the secondary tumour was seen at the edge of the irradiated volume, and not in the region with the highest absorbed dose.
CONCLUSIONS: Therapy-induced secondary gliomas after treatment of CP or other intracranial tumours are rare but dramatic late events with a very poor prognosis. Including our own 2 patients, we reviewed 14 cases of CP with occurrence of a secondary, probably radiation-induced malignant glioma. The short latency periods for patients treated with GH is remarkable. We therefore suspect that GH therapy may accelerate the development of a secondary brain tumour. We are reluctant to recommend GH therapy in conventionally irradiated CP patients. In order to seriously answer the questions about therapy-induced secondary neoplasms, a life-long follow-up is mandatory for all patients who are survivors of childhood cancer.
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Crank Case Oil-Gross descriptive term sometimes used to describe the dark oily appearance of the cystic contents of the tumor.
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