VEGF, VEGF165b and EG-VEGF expression is specifically related with hormone profile in pituitary adenomas.

Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.

Characterizing Indeterminate Renal Masses with Molecular Imaging: the Role of 99mTc-MIBI SPECT/CT.

PURPOSE OF REVIEW: The majority of enhancing renal masses cannot be characterized through imaging as malignant or benign; however, such characterization could save patients from unnecessary surgery and/or biopsy and associated morbidity. Herein, we review the recent literature on the emerging use of 99mTc-MIBI SPECT/CT in preoperative differentiation of enhancing renal masses. RECENT FINDINGS: Recent reports have shown that 99mTc-MIBI SPECT/CT imaging can differentiate mitochondrial-rich, benign, or indolent renal masses from renal cell carcinoma. These studies demonstrate good correlation between a positive 99mTc-MIBI SPECT/CT scan and a pathologically proven diagnosis of renal oncocytoma and hybrid oncocytic/chromophobe tumor. In addition, there is excellent correlation between a negative scan and a diagnosis of clear cell subtype of renal cell carcinoma. Preoperative 99mTc-MIBI SPECT/CT offers a non-invasive method for differentiating renal lesions with low aggressiveness from other RCCs, in particular, clear cell renal cell carcinoma.

Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma: A Case Report and Literature Review.

We describe a very rare case of nonfunctional pituitary adenoma (NFPA) that exhibited corticotrophic activity after resection and radiotherapy. The possible mechanisms of the transformation from NFPA to Cushing disease (CD) are discussed.A 43-year-old man presented with impaired vision, bilateral frontal headaches, and hyposexuality. He had no symptoms suggestive of hypercortisolism, and 8 am plasma cortisol concentration was 67.88 ng/mL. Brain imaging revealed a 15 × 15 × 21-mm sellar mass suggestive of a macroadenoma. The tumor was resected by transsphenoidal surgery and identified by immunohistochemical analysis as a chromophobic adenoma that did not stain for pituitary hormones. The patient was treated with prednisone and levothyroxine replacement therapy. After a third recurrence, the patient presented with clinical features and physical signs of Cushing syndrome. Plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations were elevated, and there was a loss of circadian rhythms. Inferior petrosal sinus sampling after desmopressin showed the central-peripheral ACTH ratio was greater than 3:1. A repeat transsphenoidal resection was undertaken. Immunohistochemistry revealed ACTH positivity. Three months following surgery, imaging showed little residual tumor, but plasma ACTH remained elevated. He was referred for postoperative Gamma Knife radiotherapy.The immunological activity and biological features of the hormones secreted from a pituitary adenoma vary with time. Because long-term outcomes are unpredictable, postoperative follow-up is essential to detect postoperative transformation from NFPA to CD.

Presentación de caso: Carcinoma Renal cromófobo. Hallazgos Imagenológicos.

Historia: Paciente masculino de 45 años de edad que acude al cuerpo de guardia por trastornos dispépticos de varios días de evolución con examen físico y de laboratorio negativos de cuadro abdominal agudo al que se indica un ultrasonido abdominal. Resultados: el ultrasonido y la TAC fueron sugestivas de una lesión ocupativa renal bien circunscrita sin adenopatías regionales o metástasis a otros órganos, lo cual motivo una intervención quirúrgica. Conclusiones: El carcinoma renal cromófobo es una entidad poco frecuente, casi siempre es asintomático y son detectados de forma incidental, presentan un buen pronóstico y tasa de supervivencia que supera el 90% a los 5 años, debe tenerse en cuenta como diagnóstico diferencial en una lesión ocupativa renal, siendo importante los hallazgos imagenologicos en el diagnostico preoperatorio.

Charlson score as a single pertinent criterion to select candidates for active surveillance among patients with small renal masses.

PURPOSE: The aim of the study was to assess the outcome after nephron-sparing surgery (NSS) of patients with small renal masses (SRMs) who would have been eligible for active surveillance (AS). METHODS: Data were collected retrospectively for 758 patients who underwent NSS over a 5-year period. Outcomes were assessed in two groups of patients who were eligible for AS according to different criteria. Group 1 criteria were as follows: age >75 years, renal mass ≤4 cm, significant comorbidities [Charlson Comorbidity Index (CCI) >2]. Group 2 criteria were as follows: any SRM ≤ 4 cm regardless of age, severe comorbidities with a 10-year mortality risk >50 % (CCI > 4). The two groups were not compared statistically because some patients were included in both. RESULTS: Fifty-five patients (7.3 %) were included in Group 1 and 62 (8.2 %) in Group 2. There was a significant proportion of benign tumours in Group 1 (N = 6; 11 %) and Group 2 (N = 6; 10 %). Six (11 %) positive margins were observed in Group 1 and 8 (13 %) in Group 2. The 2- and 5-year recurrence-free survival rates were 100 and 77.4 %, respectively, in Group 1, and 88.5 and 79.6 % in Group 2. The 2- and 5-year overall survival rates were 100 and 74.7 % in Group 1, and 96.7 and 78.1 % in Group 2. CONCLUSIONS: The majority of patients with SRMs who would have been eligible for AS had no recurrence after initial tumour removal. In these patients, a CCI > 4 appeared to be a pertinent criterion to identify those patients less likely to benefit from immediate surgery.

Reproducibilidad interobservador de un sistema de grado para el carcinoma de células renales tipo cromófobo / Interobserver Reproducibility of a Grading System for Chromophobe Renal Cell Carcinoma

Objetivos: Valorar la reproducibilidad interobservador y evaluar el sistema de gradación propuesto por Paner et al. para el carcinoma de células renales cromófobo. Material y métodos: Tras seleccionar 23 casos de carcinoma renal de tipo cromófobo de los hospitales Xeral-Cíes, Meixoeiro y POVISA de Vigo de los últimos 15 años se ha realizado una sesión informativa de los criterios del sistema de gradación de Paner et al. Posteriormente los patólogos observadores han aplicado dicho sistema a cada caso, valorando una laminilla seleccionada. Se ha calculado el índice Kappa de reproducibilidad interobservador, ponderado según la escala de Landis y Koch. Resultados: La distribución de grados en la mayoría de los 6 observadores participantes es similar, con predominio del grado 1 en 4 de los mismos. Los 2 observadores restantes consideraron una mayoría relativa de casos como grado 2. Los valores de Kappa oscilan entre 0,136 y 0,674, observándose un predominio de valores indicadores de reproducibilidad discreta-moderada (0,21-0,60). El mayor valor de Kappa (0,674) se ha dado entre un observador novel y el patólogo más experto. Entre los 2 observadores más veteranos se ha obtenido el índice más bajo (0,136). Conclusiones: La reproducibilidad interobservador en nuestros centros para el grado propuesto por Paner et al. es discreta-moderada. La asignación de los grados 1 y 2 no es homogénea entre los 6 observadores participantes. En espera de la existencia de una gradación consensuada por las sociedades científicas, creemos prudente no utilizar ningún sistema de gradación en los carcinomas de células renales de tipo cromófobo (AU)

Objectives: To evaluate interobserver reproducibility of a grading system proposed by Paner et al. for chromophobe renal cell carcinoma. Material and methods: After selecting 23 cases of chromophobe renal cell carcinoma from the Xeral-Cíes Hospital, Meixoeiro Hospital and POVISA Hospital from the last 15 years, an informative meeting on the Paner et al. grading system criteria was held. After, the participating pathologists applied the system to each case, evaluating one slide selected. Kappa index for interobserver reproducibility was calculated, and it was classified according to the Landis and Koch scale. Results: The grading distribution was similar for most of the 6 participating observers, with grade 1 predominance. The remaining 2 observers considered a relatively higher proportion of grade 2. Kappa index values ranged from 0.136 to 0.674, with a discrete-moderate reproducibility index predominance (0.21-0.60). Highest Kappa value (0.674) was obtained between the most novel and the most expert interobservers. The lowest Kappa value was obtained among the most veteran pathologists (0.136). Conclusions: Interobserver reproducibility for chromophobe renal cell carcinoma is discrete-moderate in our institutions when the novel grade proposed by Paner et al. is used. Labeling of grades 1 and 2 is not homogeneous among 6 participating observers. While awaiting a grading consensus on a new classification by the scientific societies, we consider that the routine use of a grading system for chromophobe renal cell carcinoma should not be used (AU)

Somatotroph pituitary tumors in budgerigars (Melopsittacus undulatus).

A series of 11 pituitary tumors in budgerigars were classified on the basis of their clinical, gross, microscopic, and immunohistochemical characteristics. Affected birds were young to middle-aged. Clinically, neurologic signs--including difficulties flying, ataxia, and blindness--were most commonly reported. Additional clinical signs included weight loss, abnormal feathers or molting, increased respiratory efforts, and exophthalmos. Nine birds were diagnosed with chromophobic pituitary adenomas, and 2 birds had chromophobic pituitary carcinomas. Only 1 tumor was delimited to the pituitary gland; the other 10 variably invaded the brain, skull, and retrobulbar space. Distant metastases were identified in 2 birds. All tumors were immunohistochemically strongly positive for growth hormone, consistent with the diagnosis of somatotroph tumors. The common occurrence and early onset may suggest a genetic predisposition of budgerigars to develop somatotroph pituitary tumors with a high incidence of local invasion and with metastatic potential.

Clipless and sutureless laparoscopic adrenalectomy carried out with the LigaSure device in 32 patients.

BACKGROUND: Laparoscopic adrenalectomy has become the standard procedure for treating patents with adrenal masses. The purpose of this study was to evaluate the use of the LigaSure vessel closure system during laparoscopic adrenalectomy. METHODS: The LigaSure device was used in 32 patients undergoing laparoscopic adrenalectomy for adrenal masses. Adrenalectomy was carried out without the use of clips or sutures for vessel closure. In 1 patient the adrenal tumor had invaded the ipsilateral kidney, so laparoscopic nephrectomy was also carried out during the same operation. In another patient, a renal cell carcinoma in the left kidney had metastasized to the right adrenal gland. Both the kidney and the contralateral adrenal gland were removed laparoscopically during the same operation. RESULTS: Adrenal masses had a mean greatest diameter of 3.48 cm (range 2 to 11 cm). Mean operative time was 83.2 minutes (range 30 to 190 min). Mean blood loss was 36.2 mL (range 10 to 140 mL). No conversions to open surgery were necessary. No patients experienced major bleeding intraoperatively or postoperatively. Adrenal tumor types included adrenocortical adenoma (16 patients), pheochromocytoma (13 patients), malignant pheochromocytoma (1 patient), chromophobic carcinoma (1 patient), and metastasis from a renal cell carcinoma (1 patient). CONCLUSIONS: For vessel closure during laparoscopic adrenalectomy, the LigaSure device seems to be safe and effective. For patients with conditions such as renal cell carcinoma combined with metastasis to the contralateral adrenal gland, nephrectomy, and contralateral adrenalectomy can be carried out during the same laparoscopic operation.

Gonadotrofinomas: análisis multicéntrico y retrospectivo de 66 pacientes / Gonadotrophinomas: multicenter and retrospective analysis of 66 patients

Objetivo: Analizar la presentación clínica, radiológica, bioquímica y el comportamiento posquirúrgico de una cohorte de pacientes portadores de gonadotrofinomas. Pacientes y Métodos: Se evaluaron pacientes con gonadotrofinomas estudiados en nueve centros endocrinológicos de la ciudad de Bs.As. durante el período 1983 a 2003. El criterio de inclusión fue la inmunohistoquímica (IH) positiva para hormona luteinizante (LH), folículoestimulante (FSH) y/o alfa subunidad (ASU). Los adenomas plurihormonales fueron excluidos. Resultados: Fueron analizados 66 pacientes de 51,8 ± 12,1 (X +/- DS) años (39 varones). Los síntomas mas frecuentemente observados fueron las alteraciones visuales (72,8%), seguidas por el hipogonadismo y las cefaleas. El 10,6% se diagnosticaron en forma incidental. El 98,5% fueron macroadenomas, 56,9% de los cuales correspondieron a un estadio Hardy (EH) 3 y 29,6% a un EH 4. El tiempo de seguimiento fue de 47,8 meses (r: 5-168). El hipogonadismo definido bioquímicamente se presentó en el 82,4% de los pacientes. En su mayoría presentaban niveles bajos o inapropiadamente normales de gonadotrofinas, pero 4 mujeres y 3 varones presentaron niveles séricos elevados y disociados de FSH y LH. La hiperprolactinemia por desconexión fue observada en 45,2% de la población (X: 65.6 ng/ml r: 30-172). El hipopituitarismo se detectó en 25,7% de los casos. La cirugía fue transeptoesfenoidal (TSE) en 80%; una segunda operación fue realizada en el 28% de la población. La IH fue positiva por orden de frecuencia para LH, FSH y ASU o las 3 combinaciones. La evolución posquirúrgica evidenció mejoría en el campo visual (CV) en el 41%. La presencia de restos tumorales y/o recidiva fue del 84%. Se indicó radioterapia en 37% y la sustitución hormonal fue necesaria en el 65% de los pacientes.

The aim of our study was to describe the clinical-biochemical and radiologic presentation and the post surgery outcome in a cohort of patients with gonadotrophinomas. Patients were selected from nine Endocrinology Units of the city of Buenos Aires from 1983 at 2003. The inclusion criteria was defined by nonfunctinoning pituitary adenomas with positive innmunohistochemical (IH) for luteinizing hormone (LH), follicle-stimulating hormone (FSH) and/or alpha subunit (ASU). Innmunohistochemically plurihormonal adenomas were excluded. Sixty six patients were analyzed, aged 51,8 ± 12,1 (X +/- DS) years; (39 men). More prevalent symptoms were visual alterations (72,8%), hypogonadism and headaches. Eleven percent was diagnosed as incidentalomas. Ninety eight percent were macroadenomas, 56,9% was Hardy stage (HS) 3 and 29,6% was HS 4. The patients were followed up for 47,8 months (r: 5-168). Hypogonadism was biochemically found in 82,4%. The majority showed low or inappropriately normal levels of gonadotrophins except for 4 women and 3 men that had high and dissociated levels. Hyperprolactinemia was observed in 45,2% and was interpreted as an interference with normal dopamine inhibition of prolactin secretion (X+/-DS: 65.6+/- ng/ml, r: 30-172). Hypopituitarism was found in 25,7% of the patients. Transsphenoidal surgery was carried out in 80% and in 28% a second surgery was needed. The IH was positive for LH, FSH and ASU in this order of frequency or its combinations. Tumor persistency and/or recurrency were found in 84% of the patients. Forty one percent showed improvement of visual defects. Radiotherapy was indicated in 37% and hormonal replacement was needed in 65% of the patients.

Expresión de MLH1, MSH2 y MSH6 en oncocitomas ycarcinomas de células cromófobas renales / MLH1, MSH2 and MSH6 expression in renal oncocytomas and chromophobe cell carcinomas

Objetivos: La alteraciones de los genes reparadores deADN llevan a la inestabilidad de microsatélites y caracterizanal adenocarcinoma familiar de colon no asociado a poliposisy al resto de tumores que se han descrito asociados aeste síndrome. Asimismo, aunque se han visto alterados enun número variable de casos de cáncer esporádico, han sidomuy raramente evaluados en los carcinomas de células renales.Material y métodos: Se han seleccionado 7 oncocitomasrenales y 7 carcinomas renales de células cromófobasmediante criterios histológicos e inmunohistoquímicos convencionales,para el estudio de los genes reparadores deADN mediante la expresión inmunohistoquímica de las proteínasMLH1, MSH2, y MSH6. Resultados: Existe un predominioclaro del sexo masculino, tanto entre los oncocitomas(2F/5M) como entre los carcinomas (3F/4M), con edadesmedias de presentación de 66,8 y 63,4 añosrespectivamente. Entre los oncocitomas renales se ha detectadopositividad para CK20 (4 casos) y CD15 (4 casos),negatividad para CK7 en todos los casos, y pérdida de laexpresión proteica de MLH1 en 1 caso, de MSH2 en 2casos, y de MSH6 en 1 caso. En los carcinomas de célulascromófobas se ha observado positividad para CK7 y negatividadpara CK20 y CD15 en todos los casos, y pérdida de laexpresión de MSH2 en 2 casos y de MSH6 en 3. Conclusiones:El patrón de expresión de las proteínas MLH1,MSH2 y MSH6 en oncocitomas y en carcinomas renales decélulas cromófobas es similar, apoyando la teoría vigente deun mismo origen para ambas entidades en la nefrona distal (AU)

Objectives: Mismatch repair gene disorders lead tomicrosatellite instability and characterise the nonpolyposishereditary colonic adenocarcinoma syndrome. Aside fromthat, the syndrome includes other carcinomas in differentlocations. Mismatch repair gene mutations have been alsodescribed in some sporadic carcinomas of diverse topographies,but only very occasionally in renal cortical carcinomas.Material and methods: Seven renal oncocytomas and7 chromophobe cell carcinomas have been selected followingconventional histological and immunohistochemicalmethods for the analysis of MLH1, MSH2 and MSH6 proteins.Results: There is a male predominance, both inoncocytomas and in carcinomas, with average ages of presentationof 66.8 and 63.4 years, respectively. Among theoncocytoma group, a positive immunostaining for CK20and CD15 has been seen in 4 cases each. Loss of MLH1expression has been detected in one case, loss of MSH2 in2, and loss of MSH6 in one. Among the chromophobe cellcarcinomas, CK7 was positive and CK20 and CD15 negativein all cases. Loss of MSH2 expression has been observedin 2 cases and loss of MSH6 in 3. Conclusions: The patternof MLH1, MSH2 and MSH6 expression is analogous inrenal oncocytomas and chromophobe cell carcinomas thussupporting the nowadays accepted theory of a similar originin the distal nephron for both pathological entities (AU)

Origin of renal cell carcinomas.

Cancer is a heritable disorder of somatic cells: environment and heredity are both important in the carcinogenic process. The primal force is the "two hits" of Knudson's hypothesis, which has proved true for many tumours, including renal cell carcinoma. Knudson et al. [1, 2] recognised that familial forms of cancer might hold the key to the identification of important regulatory elements known as tumour-suppressor genes. Their observations (i.e., that retinoblastoma tend to be multifocal in familial cases and unifocal in sporadic presentation) led them to propose a two-hit theory of carcinogenesis. Furthermore, Knudson postulated that patients with the familial form of the cancer would be born with one mutant allele and that all cells in that organ or tissue would be at risk, accounting for early onset and the multifocal nature of the disease. In contrast, sporadic tumours would develop only if a mutation occurred in both alleles within the same cell, and, as each event would be expected to occur with low frequency, most tumours would develop late in life and in a unifocal manner [3, 4]. The kidney is affected in a variety of inherited cancer syndromes. For most of them, both the oncogene/tumour-suppressor gene involved and the respective germline mutations have been identified. Each of the inherited syndromes predisposes to distinct types of renal carcinoma. Families with hereditary predisposition to cancer continue to provide a unique opportunity for the identification and characterisation of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal cell carcinoma, and genes associated with five of these syndromes have been already identified: VHL, MET, FH, BHD and HRPT2. Few cancers have as many different types of genetic predisposition as renal cancer, although to date only a small proportion of renal cell cancers can be explained by genetic predisposition.

Pathologic features of renal cortical tumors.

Our better understanding of the morphologic spectrum of renal cortical tumors has resulted in a clinically more relevant classification of these tumor types. We now recognize that "granular cell" and "sarcomatoid" renal cell carcinoma are only nonspecific descriptors, and that such features are seen in a variety of types of renal tumors. The authors believe that the recently gained knowledge about molecular-driven antigen expression will play an important role in the characterization, development, and evaluation of targeted therapies in kidney cancer in the coming years.

Contemporary radiologic imaging of renal cortical tumors.

Contemporary radiologic imaging has resulted in an increasing number of smaller renal cortical tumors being identified. The ability of imaging to classify these tumors is limited, although certain features may help classify the renal cortical neoplasm. The important role of radiologic imaging in tumor detection, characterization, staging, and follow-up of patients who have renal cortical tumors is reviewed in this article.

Origin of renal cell carcinomas

Cancer is a heritable disorder of somatic cells: environment and heredity are both important in the carcinogenic process. The primal force is the "two hits" of Knudson's hypothesis, which has proved true for many tumours, including renal cell carcinoma. Knudson et al. [1, 2] recognised that familial forms of cancer might hold the key to the identification of important regulatory elements known as tumour-suppressor genes. Their observations (i.e., that retinoblastoma tend to be multifocal in familial cases and unifocal in sporadic presentation) led them to propose a two-hit theory of carcinogenesis. Furthermore, Knudson postulated that patients with the familial form of the cancer would be born with one mutant allele and that all cells in that organ or tissue would be at risk, accounting for early onset and the multifocal nature of the disease. In contrast, sporadic tumours would develop only if a mutation occurred in both alleles within the same cell, and, as each event would be expected to occur with low frequency, most tumours would develop late in life and in a unifocal manner [3, 4]. The kidney is affected in a variety of inherited cancer syndromes. For most of them, both the oncogene/tumour-suppressor gene involved and the respective germline mutations have been identified. Each of the inherited syndromes predisposes to distinct types of renal carcinoma. Families with hereditary predisposition to cancer continue to provide a unique opportunity for the identification and characterisation of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal cell carcinoma, and genes associated with five of these syndromes have been already identified: VHL, MET, FH, BHD and HRPT2. Few cancers have as many different types of genetic predisposition as renal cancer, although to date only a small proportion of renal cell cancers can be explained by genetic predisposition (AU)

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Genética molecular del cáncer renal: utilidad en pronóstico y posibilidades terapéuticas / Molecular genetics of renal cancer: usefulness in prognosis and therapeutic possibilities

El cáncer renal tiene una incidencia del 3% del total de las neoplasias en adultos, y puede ser tanto de origen hereditario como esporádico. Histológicamente se clasifica en 5 tipos principales. Las técnicas actuales de citogenética y biología molecular han permitido conocer con más detalle algunos de los sucesos genéticos iniciales que causa la patogenia de los tipos mayoritarios como, por ejemplo, que un defecto en el cromosoma 3p está implicado en el desarrollo del carcinoma de células claras (ccRCC) o que en un 13% de los RCC de tipo papilar está mutado el gen c-MET (cromosoma 7), y en el resto de cánceres de este tipo existe duplicación de este mismo cromosoma, o que, en los oncocitomas la pérdida de los cromosomas 1 y/o 14 podría representar el suceso inicial. Aparte de estos defectos, el conocimiento de otros genes y alteraciones cromosómicas implicados, junto con otros factores, permite definir de manera aproximada el pronóstico en cada caso. Debido a que este tipo de cáncer desarrolla metástasis rápidamente, las terapias actuales, como la cirugía y el uso de interleucina (IL) 2, son poco eficaces y sólo consiguen alargar en unos meses la supervivencia del paciente. Aunque se están ensayando nuevas terapias, es necesario un conocimiento más profundo de los procesos moleculares implicados para obtener el éxito deseado tanto en el diagnóstico precoz como en el pronóstico y el tratamiento de la enfermedad(AU)

Renal cancer has a 3% incidence of all neoplasms in adults and it can be of hereditary or sporadic origin. Histologically, it is classified into 5 main types. The current cytogenetic and molecular biology techniques allow some of the initial genetic events responsible for the main types of pathogenesis to be studied in more detail, such as the implication of a defect in chromosome 3p in the development of clear cell renal cell carcinoma (ccRCC), or the presence of the mutated c-MET gene (chromosome 7) in 13% of papillary RCCs and the presence of the same chromosome duplication in the rest of these types of cancer, or the loss of chromosomes 1 and/or 14 which could represent the initial event in oncocytomas. Apart from these defects, knowledge other genes involved and chromosomic defects, as well as other factors, may enable an approximate prognosis to be made in each case. As the metastatic process in this cancer type develops very early, the current therapies, such as surgery and the use of IL-2, are not very effective and they only manage to extend patient survival by a few months. Although newer therapies are being assessed, a deeper knowledge about the molecular processes involved is necessary to obtain the desirable success both in the early diagnosis, as well as the prognosis and treatment of the disease(AU)

[Differential diagnosis in visual field defects of glaucoma patients]. / Differenzialdiagnose bei glaukomatösen Gesichtsfeldausfällen.

In both cases optic disc neuropathy with perimetry defects and loss of vision is caused by a cerebral tumour. The progression of optic damage was stopped by resection of the tumor in both patients. We recommend the performance of a radiological examination in patients with visual field defects if the intraocular pressure is normal and thus glaucoma may not be the cause of the defects.

Non-functioning pituitary adenomas infrequently harbor G-protein gene mutations.

BACKGROUND: Mutations of the genes encoding the alpha subunit of the stimulatory G protein (Gs) and of the inhibiting Gi2 protein (GNAS1 and GNAI2 genes, respectively) have been described in various endocrine neoplasias, including pituitary tumors. AIM: To search for mutations of GNAS1 and GNAI2 in a continuous series of non-functioning pituitary adenoma (NFPA) patients neurosurgically treated. SUBJECTS AND METHODS: The surgical samples of 22 patients who have been defined and characterized on a clinical, biochemical, histological, and immunohistochemical point of view have been processed for investigating the presence of the above mutations by PCR amplification of the hot spots exons 8 and 9 of GNAS1, and exons 5 and 6 of GNAI2, followed by direct sequencing. Moreover, the promoter region of GNAI2, in order to assess the prevalence of single nucleotide polymorphisms (SNP), was investigated in the same series. RESULTS: A CGT>TGT mutation at codon 201 of GNAS1 gene in a single case of NFPA was found, but no mutation of GNAI2A was demonstrated. CONCLUSIONS: This finding suggests and confirms that G-protein mutations are rare and not crucial in NFPA development. Additionally, we found a silent SNP at codon 318 in the promoter of the Gi2alpha gene in one out of the 22 NFPA.

Expression of adrenocorticotropic hormone, prolactin and transcriptional factors in clinically nonfunctioning pituitary adenoma.

We describe here a case of a clinically nonfunctioning pituitary adenoma, but with expression of ACTH and PRL. A 42-year-old woman was referred to our department for further evaluation of pituitary tumor. She had no acromegaloid features, and no typical Cushingoid features. She had no galactorrhea, and had regular menses. GH, IGF-I, LH, FSH, TSH, ACTH and cortisol levels in blood were all within the normal ranges, while PRL levels were mildly elevated. Both ACTH and cortisol levels were adequately increased in response to CRH, and both were suppressed by a small dose of dexamethasone. Plasma ACTH and cortisol levels were decreased at night, suggesting the circadian rhythms for plasma ACTH levels were undisturbed. Based on these findings we did not clinically suspect ACTH-producing tumor, however immunohistochemistry revealed ACTH immunoreactivity in the pituitary adenoma. Therefore, the tumor was considered a silent corticotroph adenoma. PRL was co-expressed in a significant subpopulation of ACTH-immunoreactive tumor cells. Ptx1, Neuro D1, and T pit were densely expressed and Pit-1 was sparsely expressed in the nuclei of adenoma cells. It is therefore possible that a tumor originating in an immature or uncommited adenohypophysial stem cell may later differentiate into different cell types due to a combination of certain specific transcriptional factors.