Estudo da Beta-catenina em tumores adrenocorticais humanos / Study of beta-catenin in human adrenocortical tumors

Introdução: A incidência de tumores adrenocorticais em crianças é particularmente elevada nas regiões sudeste e sul do Brasil, correlacionandose com a ocorrência da mutação germinativa p.R337H do supressor tumoral p53, entretanto, o carcinoma adrenocortical é uma neoplasia endócrina maligna rara em todo o mundo com uma incidência aproximada de 0,5 - 2 casos por milhão por ano. Esta condição é uma doença heterogênea, apresentando frequentemente comportamento clínico agressivo e letal. A cascata de sinalização Wnt é uma via importante de transdução de sinal em cânceres humanos e tem sido implicada na tumorigênese adrenocortical. A atividade desta via de sinalização é dependente da quantidade de beta-catenina citoplasmática e nuclear. Mutações ativadoras no gene da beta-catenina (CTNNB1) foram relatadas em diversas neoplasias humanas. Estudos demonstraram que mutações no gene CTNNB1 são os defeitos genéticos mais frequentemente encontrados em adenomas e em carcinomas adrenocorticais. O estudo destas mutações demonstrou que as alterações no gene CTNNB1 localizam-se principalmente exon 3, que codifica a porção amino terminal da beta- catenina. Objetivos: determinar a ocorrência e a frequência das mutações somáticas no exon 3 do gene CTNNB1. Adicionalmente, determinar a imunorreatividade de beta-catenina e de p53 em tumores adrenocorticais benignos e malignos de crianças e adultos. Correlacionar os resultados da análise de mutações gênicas e os dados de imunorreatividade com as características hormonais, a mutação p.R337H do p53, o diagnóstico histológico e a evolução dos tumores adrenocorticais de crianças e adultos. Métodos: Neste estudo, a análise de imunohistoquímica para beta-catenina e p53 foi realizada em 103 tumores adrenocorticais benignos e malignos (40 crianças e 63 adultos), estando as amostras histológicas alocadas em micromatriz tecidual (TMA). A pesquisa de mutações no exon 3 do gene CTNNB1 foi determinada por seqüenciamento automático em 64 tumores...

Introduction: The incidence of adrenocortical tumors in children is particularly high in the southeastern and southern regions of Brazil, correlating with the occurrence of p.R337H p53 tumor suppressor germline mutation. However, adrenocortical carcinoma is a worldwide rare endocrine malignancy with an approximate incidence of 0.5 to 2 cases per million per year. This condition is a heterogeneous disease and is often lethal. The Wnt signaling pathway is an important signal transduction pathway in human cancers and has been implicated in adrenocortical tumorigenesis. The activity of this signaling pathway is dependent on the amount of nuclear and cytoplasmic beta-catenin. Activating mutations of ?-catenin (CTNNB1) gene have been reported in several human malignancies. Studies have shown that CTNNB1 mutations are the most common genetic defect found in adrenocortical adenomas and carcinomas. The study of these mutations demonstrated that the changes in CTNNB1 gene are mainly located in exon 3, which encodes the amino terminal portion of the beta- catenin. Objectives: to determine the occurrence and frequency of CTNNB1 somatic mutations and the abnormal beta-catenin and p53 accumulation in benign and malignant adrenocortical tumors in both children and adults. We also evaluated the correlation of the gene mutations analysis and immunohistochemistry data with the hormonal characteristics, the p.R337H germline mutation, the histological diagnosis and the prognosis of adrenocortical tumors in children and adults. Methods: In this study, immunohistochemistry for beta-catenin and p53 was performed in 103 benign and malignant (40 children and 63 adults) adrenocortical tumors. The histological samples were allocated in a tissue microarray (TMA). The study of the CTNNB1 gene was performed by direct sequencing of 64 adrenocortical tumors. Results: The beta-catenin abnormal accumulation was similar in benign and malignant adrenocortical tumors of children and adults (15...(au)

A Case Report of Bilateral Adrenocortical Carcinoma Complicated by Adrenal Insufficiency

Adrenocortical carcinoma is often functional and presents with signs and symptoms of adrenal steroid hormone excess. Adrenal insufficiency secondary to bilateral adrenocortical carcinoma is a particularly rare complication. We recently encountered a case of bilateral adrenocortical carcinoma complicated by adrenal insufficiency. A 52-year-old male was transferred to this hospital complaining of general weakness and weight loss. A bilateral adrenal mass was detected on abdomen CT. Plasma cortisol and aldosterone failed to rise during the rapid ACTH stimulation test. The CT-guided adrenal biopsy revealed findings consistent with adrenocortical carcinoma. Left hemiparesis was developed and brain metastasis was detected via brain MRI. Despite the application of gamma knife surgery and chemotherapy, the disease progressed and the patient died.

Adrenocortical Oncocytoma: A Case Report

Adrenocortical oncocytomas have rarely been reported on in the medical literature, and most of them have been nonfunctional and benign. We report here on a case of a 43-year-old man with a left abdominal mass. The patient showed no signs of hypertension or hormonal imbalance. The abdominal CT scans showed a huge mass that measured 11 cm in diameter, and it was located at the left adrenal area. Grossly, the tumor was well encapsulated and homogenous with central necrosis. Microscopically, the tumor was composed of oncocytes with abundant granular cytoplasm. Immunohistochemically, these cells were diffusely positive for cytokeratin and focally positive for synaptophysin and NSE. The ultrastructural studies showed numerous mitochondria in the cytoplasm. We will discuss the criteria that indicates malignancy as presented by Weiss et al. and we summarize the difference between conventional and oncocytic adrenocortical neoplasm. This case showed some features of malignancy based on the criteria presented by Weiss et al.

Adrenocortical Oncocytoma / 대한비뇨기과학회지

An adrenocortical oncocytoma is very rare and unusual disease. Only 22 and 2 cases have been reported in the foreign and Korean literatures, respectively. Herein, the case of a left adrenocortical oncocytoma, observed by ultrasonography during a periodic medical examination of a 32 year old male patient is reported.

Pediatric Adrenal Cortical Neoplasm with Histologic Malignancy: A Case Report with Review of Literature

Adrenal cortical neoplasm, especially carcinoma, is extremely rare in pediatric patients. We describe here a rare pediatric case of adrenal cortical neoplasm. A 2-year-old girl presented with an enlarged clitoris. The other physical findings and laboratory tests were nonspecific. The magnetic resonance imaging showed a 4 cm-sized heterogeneously enhancing soft tissue mass with calcification in the left adrenal gland. The mass was removed by laparoscopic operation. Grossly, several fragments of reddish tan soft tissue were present, and they weighed 19 gm in total. Microscopically, there were capsular invasion, diffuse/solid growth pattern with focal necrosis, high cellularity, cytoplasmic eosinophilia, marked nuclear pleomorphism, high N/C ratio, prominent nucleoli, atypical mitotic figures and calcifications, which all suggested adrenal cortical neoplasm of histologic malignancy. On immunohistochemistrical staining, there were positive reactivities to pancytokeratin, cytokeratin 7/20, CEA, inhibin and p53. The Ki-67 labeling index was about 6%. All these findings were indicative of adrenal cortical neoplasm of histologic malignancy.

A case of gastric diverticulum simulating an adrenal incidentaloma / 대한내과학회지

Adrenal incidentalomas are increasingly diagnosed with the widespread escalation in the use of high-tech imaging modalities and marked improvements in image resolution. However, several conditions can simulate a left adrenal mass as a result of the proximity of the left adrenal gland to the gastric fundus, spleen, first loops of the jejunum, and tail of the pancreas. We report a patient with a diverticulum of the gastric cardia that simulated a left adrenal mass. To the best of our knowledge, this is the first report of such a case in Korean literature. Typical radiologic findings and clinical course are presented with reviews of the literature.

A Typical Korean Case Of Carney Complex

Carney complex is a multiple neoplasia syndrome, inherited in an autosomal dominant manner, that is characterized by lentigines, cardiac myxoma, and numerous endocrine and other tumors, including primary pigmented nodular adrenocortical disease. Here, we describe a typical case of Carney complex in a 27- year-old female who exhibited spotty skin pigmentation on the lips, oral mucosa, fingers, and toes and several manifestations of Cushing's syndrome due to primary pigmented nodular adrenocortical disease. She also had pituitary adenoma, breast tumor and thyroid nodule. Only a few cases of this disorder have been reported in the Korean literature. All of them, however, had only two components of Carney complex: composed of skin pigmentation and primary pigmented nodular adrenocortical disease. Therefore, the present case seems to be the first true case of Carney complex reported in Korea.

THE EXPRESSION OF TELOMERASE IN ADRENAL CORTICAL TUMORS AND ITS CLINICAL SIGNIFICANCE / 解放军医学杂志

To study the telomerase expression in adrenal cortical tumors and its clinical signinificance. Telomerase expression was estimated in 8 cases of adrenal cortical carcinoma, 20 cases of adrenal cortical adenoma, 24 tissues adjacent to cancer, and 4 specimens of normal adrenal tissue by the PCR based telomeric repeat amplification protocol. Telomerase was found to be expressed positively in 7(87 5%) of 8 adrenal cortical carcinoma samples and 1(4 2%) of 24 tissues adjacent to tumor, while it was not expressed in all the 20 samples of adrenal cortical adenoma and normal adrenal tissue. The expression of telomerase in adrenal cortical tumors clearly demonstrated the malignant behavior of the tumor cells. Demonstration of telomerase expression appears to be a useful tool for the diagnosis of malignant adrenal cortical tumors.