Differential Expression of Stem Cell Markers in Human Adamantinomatous Craniopharyngioma and Pituitary Adenoma

Background/Aims: Although craniopharyngioma (CP) is histologically benign, it is a pituitary tumour that grows rapidly and often recurs. Adamantinomatous CP (ACP) was associated with an activating mutation in ß-catenin, and it has been postulated that pituitary stem cells might play a role in oncogenesis in human ACP. Stem cells have also been identified in pituitary adenoma. Our aim was to characterize the expression pattern of ABCG2, CD44, DLL4, NANOG, NOTCH2, POU5F1/OCT4, SOX2, and SOX9 stem cell markers in human ACP and pituitary adenoma. Methods and Results: We studied 33 patients (9 ACP and 24 adenoma) using real-time quantitative PCR (RT-qPCR) and immunohistochemistry. SOX9 was up-regulated in ACP, exhibiting positive immunostaining in the epithelium and stroma, with the highest expression in patients with recurrence. CD44 was overexpressed in ACP as confirmed by immunohistochemistry. SOX2 did not significantly differ among the tumour types. The RT-qPCR array showed an increased expression of MKI67,OCT4/POU5F1, and DLL4 in all tumours. NANOG was decreased in ACP. ABCG2 was down-regulated in most of the tumours. NOTCH2 was significantly decreased in the adenomas. Conclusion: Our results confirm the presence of stem cell markers in human pituitary tumours as well as the different expression patterns of ACP and adenoma. These findings suggest that ACP may originate from a more undifferentiated cell cluster. Additionally, SOX9 immunodetection in the stroma and the highest expression levels related to the relapse of patients suggest a contribution to the aggressive behaviour and high recurrence of this tumour type.

The Extended Pterional Approach and Microsurgery Resection for Craniopharyngiomas, Operative Nuances and Results: A Series of 29 Patients

Objective The aim of this paper is to observe if the extended pterional approach for the removal of craniopharyngiomas is safe and effective. The mortality, morbidity, and recurrence rates are presented and discussed. Method This is a retrospective analysis of 29 craniopharyngioma patients who underwent surgery between January 1988 and December 2014 at the Department of Neurosurgery of the Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil. The charts, operative reports and imaging studies were reviewed. Results We identified 17 males (58.6%) and 12 females (41.3%) ranging in age from 0.6 to 84 years (mean 57.4 years). Thirteen (44.8%) patients were infants or adolescents. Surgical mortality occurred in one patient (3.4%). Gross total tumor removal was achieved in 15 (51.7%) patients. The median follow-up time was 7.1 years. Conclusion The extended pterional approach provides adequate access to craniopharyngiomas, and the majority of lesions could be totally removed, with a low mortality rate, but the best treatment for craniopharyngiomas remains controversial.

Objetivo Observar se a craniotomia pterional estendida é uma técnica segura e efetiva. Método É um estudo retrospectivo de 29 pacientes com craniofaringiomas que foram submetidos a craniotomia pterional estendida entre 1988 e 2014. As imagens e os prontuários foram analisados. Resultados Esse grupo é composto por 17 homens (58,6%) e 12 mulheres (41,3%), e a idade variou de 0,6 a 84 anos (media 57,4 anos). Treze (44,8%) pacientes eram crianças ou adolescentes. A remoção total da lesão ocorreu em 15 (51,7%) indivíduos. A mortalidade cirúrgica: um paciente (3,4%). O follow-up médio é de 7,1 anos. Conclusão A craniotomia pterional estendida permitiu a remoção total da lesão na maioria dos pacientes, com baixa mortalidade, porém o melhor tratamento para o craniofaringioma ainda gera muita controvérsia.

Cystic craniopharyngioma: intratumoral chemotherapy with alpha interferon / Craniofaringioma cístico: quimioterapia intratumoral com interferon alfa

OBJECTIVE: To assess whether the cystic craniopharyngiomas can be controlled with the use of intratumoral applications of interferon alpha. METHOD: Nineteen patients with the diagnosis of cystic craniopharyngioma were treated with intratumoral chemotherapy with interferon alpha from January 2002 to April 2006. All patients underwent placement of an intracystic catheter connected to an Ommaya reservoir. Through this reservoir were made applications during chemotherapy cycles. Each cycle corresponded to application of 3,000,000 units of interferon alpha three times per week on alternate days totalizing 36,000,000 units. Response to treatment was evaluated by calculating the tumor volume on MRI control after one, three and six months after the end of each cycle. Patients who developed worsening of symptoms or who had insignificant reduction in tumor volume during follow-up underwent repeat cycle chemotherapy. RESULTS: Four patients received four cycles of chemotherapy, three patients received three cycles, six patients received two cycles and six patients received one. The lower percentage of reduction in tumor volume was 60 percent and the bigger reduction was 98.37 percent. Eleven patients had a reduction greater than 90 percent. Five patients had a tumor reduction between 75 and 90 percent and in three patients the tumors were reduced by less than 75 percent. No deaths occurred during treatment and side effects of interferon alpha were well tolerated. No treatment was discontinued. Follow-up after the last application ranged from one year and five months to three years and nine months. CONCLUSION: The intratumoral chemotherapy with interferon alpha decreases the volume of cystic craniopharyngiomas and so far can be considered a new therapeutic alternative.

OBJETIVO: Avaliar se os craniofaringiomas císticos podem ser controlados com aplicações intratumorais de interferon alfa. MÉTODO: De janeiro de 2002 a abril de 2006, 19 pacientes foram submetidos à colocação de um cateter intracístico conectado a reservatório de Ommaya para aplicações intratumorais de ciclos de 36.000.000 de unidades de interferon alfa. A resposta ao tratamento foi avaliada pelo cálculo do volume tumoral na ressonância magnética de controle ao término de cada ciclo. RESULTADOS: Os pacientes receberam de um a quatro ciclos de quimioterapia. Onze pacientes apresentaram uma redução do volume tumoral maior que 90 por cento; cinco pacientes apresentaram uma redução entre 75 por cento e 90 por cento e três pacientes uma redução menor de 75 por cento. Não houve óbitos durante o tratamento e os efeitos colaterais do inferferon alfa foram bem tolerados. Nenhum tratamento foi interrompido. CONCLUSÃO: A quimioterapia intratumoral com interferon alfa diminui o volume dos craniofaringeomas císticos e pode ser considerada uma nova alternativa terapêutica.

PROP1 and CTNNB1 expression in adamantinomatous craniopharyngiomas with or without β-catenin mutations

INTRODUCTION: Activating mutations in exon 3 of the β-catenin gene are involved in the pathogenesis of adamantinomatous craniopharyngiomas. Recently, the interaction between β-catenin and PROP1 has been shown to be responsible for pituitary cell lineage determination. We hypothesized that dysregulated PROP1 expression could also be involved in the pathogenesis of craniopharyngiomas OBJECTIVES: To determine whether dysregulated gene expression was responsible for tumor pathogenesis in adamantinomatous craniopharyngiomas, the β-catenin gene was screened for mutations, and the expression of the β-catenin gene and PROP1 was evaluated. β-catenin gene was amplified and sequenced from 14 samples of adamantinomatous craniopharyngiomas. PROP1 and β-catenin gene expression was assessed by real-time RT-PCR from 12 samples, and β-catenin immunohistochemistry was performed on 11 samples. RESULTS: Mutations in the β-catenin gene were identified in 64 percent of the adamantinomatous craniopharyngiomas samples. Evidence of β-catenin gene overexpression was found in 71 percent of the tumors with β-catenin mutations and in 40 percent of the tumors without mutations, and β-catenin immunohistochemistry revealed a nuclear staining pattern for each of the analyzed samples. PROP1 expression was undetectable in all of the tumor samples. CONCLUSION: We found evidence of β-catenin gene overexpression in the majority of adamantinomatous craniopharyngiomas, and we also detected a nuclear β-catenin staining pattern regardless of the presence of a bcatenin gene mutation. These results suggest that WNT signaling activation plays an important role in the pathogenesis of adamantinomatous craniopharyngiomas. Additionally, this study was the first to evaluate PROP1 expression in adamantinomatous craniopharyngiomas, and the absence of PROP1 expression indicates that this gene is not involved in the pathogenesis of this tumor, at least in this cohort.

Mixed germ cell tumor of the pituitary-hypothalamic region presenting as craniopharyngioma: case report and review of the literature / Tumor misto de células germinativas da região hipotálamo-hipofisária apresentando-se como craniofaringioma: relato de caso e revisão da literatura

Craniopharyngiomas and germ cell tumors (GCT) may affect the pituitary-hypothalamic region during childhood. Although different in origin, their clinical and radiological features may be similar. In this article we present a 5-year-old girl with clinical and radiological findings (computer tomography calcification) that were initially considered as craniopharyngioma. However clinical outcome, blood and cerebral spinal fluid tumoral markers, and results from anatomopathology and immunohistochemistry disclosed a mixed GCT. This case report highlights that some clinical features and radiological findings of pituitary-hypothalamic tumors may be misdiagnosed as craniopharyngioma mainly when there is a mature teratoma with cartilaginous tissue differentiation.

Craniofaringiomas e tumores mistos de células germinativas (TCG) podem acometer a região hipotálamo-hipofisária durante a infância. Embora tenham diferentes origens, as manifestações clínicas e achados radiológicos podem ser semelhantes. Nosso objetivo é relatar o caso de uma paciente de 5 anos de idade, cujas manifestações clínicas e achados radiológicos (presença de calcificações à tomografia computadorizada [TC]) foram inicialmente considerados como provável craniofaringioma. No entanto, a piora clínica progressiva, marcadores tumorais séricos e liquóricos elevados, assim como os resultados do estudo anatomopatológico e imunoistoquímico revelaram tratar-se de TCG. Este caso enfatiza que alguns achados clínicos e radiológicos de tumores da região hipotálamo-hipofisária podem ser erroneamente diagnosticados como craniofaringiomas, principalmente se houver presença de teratoma maduro com diferenciação em tecido cartilaginoso.

Ocular manifestations of suprasellar tumors.

OBJECTIVE: To determine ocular manifestations of suprasellar tumors and to identify the pre-operative factors that might influence final visual outcomes. MATERIAL AND METHOD: Medical records of 69 patients with a diagnosis of suprasellar tumor at Srinagarind Hospital between January 1995 and December 2005 were retrospectively reviewed. RESULTS: The present study focused on 69 patients (39% men and 61% women) with averaged 37.74 years of age (range, 6 to 75). The duration of symptoms was between 4 days and 5 years (average, 7.7 months). The ocular manifestations included visual loss in 59 (86%), eye pain in six (9%), diplopia in three (4%), and ptosis in one (1%) patient. The respective definite diagnosis were pituitary adenoma, suprasellar meningioma, and craniopharyngioma in 33 (48%), 19 (28%), and 17 (25%) patients. According to the pre-operative visual acuity in the worse eye, seven (10%), seven (10%), and 55 (80%) patients were stratified to Group I (VA 6/5 to 6/12), Group II (VA 6/18 to 6/36), and Group III (VA 6/60 to no vision), respectively. Post-operatively two (29%) patients in Group II and 14 (25%) in Group III had improved visual acuity. Three groups of visualfield defect were revealed, viz., Group A (normal visual field), Group B (typical field defect) and Group C (atypical field defect) in seven (10%), 49 (71%), and 13 (19%) patients, respectively. Positive relative afferent pupillary defect was detected in 31 patients (45%) and optic disc atrophy was detected in 26 patients (38%). CONCLUSION: Pituitary adenoma was the most frequent suprasellar tumor and visual loss was the most common ocular presentation. Bitemporal hemianopia frequently occurred in these patients, but was usually asymmetrical and unpredictable in its evolution.

Severe rhabdomyolysis due to adipsic hypernatremia after craniopharyngioma surgery

The association of diabetes insipidus and adipsia after craniopharyngioma surgery has high morbidity. Hypernatremia can be caused by adipsia and be aggravated by diabetes insipidus. Rhabdomyolysis rarely occurs. DASE REPORT: This is the first report of a diabetic patient with craniopharyngioma who developed diabetes insipidus and adipsia after surgery, evolving with severe hypernatremia that caused considerable rhabdomyolysis. CONCLUSION: The importance of the evaluation of muscle integrity when under hypernatremic states is pointed out. Although adipsia may have a simple solution through volunteer water ingestion, serious consequences such as repeated severe hypernatremia episodes and intense rhabdomyolysis with high morbidity could occur, if adipsia is not diagnosed.

A associação de diabetes insipidus e adipsia após cirurgia de craniofaringioma implica em alta morbidade. Hipernatremia pode desenvolver-se devido a adipsia e ser agravada por diabetes insipidus. Rabdomiólise raramente ocorre. DESCRIÇÃO DO CASO: Esta é a primeira descrição de paciente diabético com craniofaringioma que desenvolveu diabetes insipidus e adipsia após a cirurgia, evoluindo com hipernatremia grave e conseqüente rabdomiólise maciça. CONCLUSÃO: Ressalta-se a necessidade de avaliar a integridade muscular na vigência de estados hipernatrêmicos. Apesar de apresentar solução simples, como ingestão voluntária de água, pode haver sérias conseqüências se o diagnóstico de adipsia não é realizado, como episódios repetidos de hipernatremia grave com rabdomiólise intensa e elevada morbidade.

Abordaje transcalloso de craneofaringioma supraselar / Carniopharyngioma suprasellar transcallosal approach

El craniofaringioma es una neplasia epitelial benigna usualmente de origen supraselar, considerado un tumor hipofisiario de crecimiento lento, puede causar varios grados de hipopituitarismo. En este artículo se describe un caso manejado en el Hospital Dr. Patrocinio Peñuela Ruíz (IVSS) y se realiza una revisión bibliográfica acerca de la presentación, patología y tratamiento. Escolar masculino de 8 años, inicia enfermedad de 1 mes de evolución caracterizada por cefalea frontal de moderada intensidad, disminución de la agudeza visual, movimientos reiterativos a predominio de hemicuerpo derecho. En una primera intervención se coloca válvula de derivación ventrículo peritoneal por hidrocefalia obstructiva: al mes y medio se realizó exéresis completa del tumor mediante abordaje transcalloso. La evolución postoperatoria fue de difícil manejo por presentar alteraciones metabólicas e hidroelectrolíticas. En RMN se evidencia ausencia total del tumor. El trastorno hidroelectrol¡tico se mantuvo a pesar del tratamiento médico: 24 días después del acto quirúrgico, fallece por hipernatremia incohercible. La lesión apareció en nuestro paciente a los 8 años, como una tumoración de 6 por 4 cm. La clínica se presenta 1 mes antes de su ingreso, caracterizada por cefalea, trastornos visuales, movimientos repetitivos a predominio de hemicuerpo derecho sin alteraciones endocrinas al momento del diagnóstico. Mediante abordaje quirúrgico transcalloso se pudo resecar totalmente una tumoración que histopatológicamente determinó un adamantinoma. Sin embargo, el manejo multidisciplinario es condición sine cua non para terminar de lograr el éxito quirúrgico en cirugías tan d¡fíciles como la del paciente.

Infrasellar craniopharyngioma: case report

We report a case of infrasellar craniopharyngioma in a 34 year-old woman who presented with progressive headache and diplopia. Computed tomographic and magnetic resonance images showed a heterogeneous tumor originating from the sphenoid bone with ethmoid sinus and sella turcica extension. A sublabial rhinoseptal transsphenoidal surgery was performed. Craniopharyngiomas with infrasellar development are very rare. Infrasellar craniopharyngioma is uncommon, thirty-five cases has been reported in literature. The embryology, clinical features and radiographic investigation of these tumors are discussed

Suprasellar malignant mixed germ cell tumour presenting as craniopharyngioma.

A 15 year old boy presented with diminution in vision of both eyes, diabetes insipidus and hypopituitarism. MRI was suggestive of a large suprasellar and retrosellar craniopharyngioma with stretching of the optic chiasma. Histopathological findings on the first surgical specimen were interpreted as a craniopharyngioma. He was reoperated on account of clinical deterioration and increase in tumour size. Histological examination this time revealed derivatives of all three germ cell lineages along with areas of embryonal carcinoma, and yolk sac tumour besides squamous cysts, establishing the diagnosis of malignant mixed germ cell tumour. Serum and CSF were strongly positive for alpha foetoproteins.

Craniofaringiomas: achados clínicos, epidemiológicos e anatomopatológicos de 25 casos / Craniopharyngiomas: clinical, epidemiological and pathological findings of 25 cases

Relatamos os achados clínicos, epidemiológicos e anatomopatológicos de 25 casos de craniofaringiomas. Dos 25 pacientes analisados, 14 ocorreram em pacientes do sexo masculino e 11 em pacientes femininos. As idades variaram de 3 a 64 anos, com média de 30,52 anos. Quanto à localização, 12 casos foram supra-selares, 10 ocorreram em região selar, sendo que 8 apresentaram extensão supra-sela, dois localizaram-se em lobo frontal e 1 em região ponto-cerebelar. Os sinais e sintomas observados incluiram alterações visuais (72 por cento dos pacientes), cefaléia (68 por cento), vômitos (40 por cento) e edema de papila (24 por cento), com período de evolução variando de 18 dias a 60 meses, com média de 11,66 meses. Treze pacientes foram submetidos a ressecção cirúrgica parcial, 11 a exérese total e 1 a ressecção parcial associada a quimioterapia adjuvante. Evidenciou-se taxa de recidiva tumoral total de 48 por cento. Sete recidivas tumorais ocorreram nos pacientes submetidos apenas a exérese parcial, quatro nos pacientes submetidos a tumorectomia total e 1 no submetido a tratamento cirúrgico associado a quimioterapia. Estes achados aproximam-se dos encontrados na literatura, corroborando para a compreeensão do comportamento biológico deste tumor e apontando a extensão do tumor tecidual como único fator prognóstico para recidiva desta neoplasia.

AgNOR expression in CNS neoplasms.

Silver colloid staining of nucleolar organiser regions (AgNORs) is used for assessing the proliferative potential of tumours. The present study aimed at evaluating the AgNOR indices in normal and reactive CNS tissue, benign and malignant CNS neoplasms. The study group comprised of tissue from 22 controls and 100 cases (53 benign & 47 malignant neoplasms). The mean AgNOR index of controls was 0.95, benign neoplasms 1.25 and malignant neoplasms 2.12. A statistically significant difference was observed in controls and cases (p < 0.001) and between benign and malignant tumours (p = 0.002). Mean indices for low and high grade astrocytoma also significantly differed (p < 0.001). Using ROC curves cut off values were obtained for differentiation of neoplastic from non neoplastic (AgNOR index 1.10), benign from malignant (AgNOR index 1.75) and low grade (I & II) from anaplastic (Gr III & IV) Astrocytomas (AgNOR index 1.62). A spectrum of gradually increasing AgNOR indices from normal, reactive, benign to low and high grade malignancy indicates the usefulness of this simple technique as a proliferative marker.

Craneofaringioma. Estudio multicéntrico retrospectivo en cinco centros hospitalarios de la ciudad de Guayaquil

Se realizó un estudio multicéntrico retrospectivo en 5 hospitales de la ciudad de Guayaquil, desde 1984 a 1993 recopilándose 20 casos con los datos suficientes para el estudio- De los 20 casos, 12 fueron del sexo masculino (60 por ciento ) y 8 del sexo femenino (40 por ciento). El grupo de edad de mayor incidencia fue entre los 5 a 14 años con 12 casos (60 por ciento). El cuadro clínico más largo de evolución fue de 5 años en 2 casos (10 por ciento). el motivo de ingreso más frecuente fue la cefalea en 19 pacientes (95 por ciento). El síndrome neurológico que más se presentó fue el de hipertensión endocraneal que se presentó en todos los pacientes y dentro de éste la cefalea fue el síntoma más referido en los 19 casos. En todos los pacientes se realizó estudios radiológicos de cráneo siendo el hallazgo más frecuente las calcificaciones en 6 pacientes. El estudio por medio de tomografía computarizada (TC) demostró que el 50 por ciento de los tumores eran supreselar; en 9 casos del tumor fue mixto (45 por ciento), solo cinco tumores (25 por ciento) reportó calcificaciones, la prouección tumoral hacia el III ventrículo fue la más observada. La técnica quirúrgica más usada fue la subfrontal con 12 pacientes siendo el tipo de resección subtotal en 19 casos el más usado. Las complicaciones postquirúrgicas más observadas fue la diabetes insípida en 11 casos (55 por ciento) la mortalidad de la serie fue del 40 por ciento...

Análise retrospectiva da incidência de neoplasias supratentoriais da linha mediana em crianças e jovens: craniofaringeomas, neoplasias da hipótese e pineal / Retrospective analysis of the incidence of supratentorial neoplasms in the median line in children and young patients: craniopharyngiomas, hypophyseal and pineal neoplasms

Analisamos, retrospectivamente, 1.632 casos de neoplasias intracranianas, em um período de 50 anos (1931-1981), do Departamento de Patologia da Faculdade de Medicina da USP, 592 casos (36,2%) eram de indivíduos de 0 a 20 anos, grupo escolhido para este estudo. O total de craniofaringeomas nessa faixa etária foi de 21 casos (3,5%); de neoplasias de hipófise, oito (1,35%); de neoplasias da pineal, quatro (0,6%). Infiltraçöes em hipófise e pineal corresponderam a 24 casos (4,0%); näo houve nenhum caso de metástases. Descriçäo e importância destes achados e comparaçäo com os de outros autores é relatada

Empleo de Yttrium 90 coloidal en el tratamiento de craneofaringiomas quísticos. Presentación de técnicas y casos clínicos. Evaluación de resultados / Use of Yttrium 90 in the treatment of cystic craniopharyngiomas. Presentation of technichs and clinical cases. Evaluation of results

El craneofaringioma representa el 9