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Autops. Case Rep ; 11: e2021259, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249015


Androgen secreting adrenocortical carcinoma (ACC) is a very rare disease with a poor prognosis. Approximately 80% of tumors are functional, most commonly secreting glucocorticoids. We herewith report a case of a huge functional ACC of the right adrenal gland in a 33-year-old female who presented with complaints of hirsutism, amenorrhea and an abdominal lump. On abdominal examination a large lump was palpable in the right hypochondrium reaching up to the umbilicus. Contrast-enhance computed tomography (CECT) revealed a mass in the right suprarenal region. The tumor measured 29 cm × 20 cm × 12 cm and weighed 7.8 kg, the largest reported case of ACC in the world to the best of our knowledge.

Humans , Female , Adult , Adrenal Glands/pathology , Adrenocortical Carcinoma/pathology , Adrenal Cortex Neoplasms/pathology , Rare Diseases
Article in English | WPRIM | ID: wpr-816620


BACKGROUND: Adrenal cortical carcinoma (ACC) is a rare cancer with a variable prognosis. Several prognostic factors of ACC have been previously reported, but a proteomic analysis has not yet been performed. This study aimed to investigate prognostic biomarkers for ACC using a proteomic approach.METHODS: We used reverse-phase protein array data from The Cancer Proteome Atlas, and identified differentially expressed proteins in metastatic ACCs. Multivariate Cox regression analysis adjusted by age and staging was used for survival analysis, and the C-index and category-free net reclassification improvement (cfNRI) were utilized to evaluate additive prognostic value.RESULTS: In 46 patients with ACC, cyclin B1, transferrin receptor (TfR1), and fibronectin were significantly overexpressed in patients with distant metastasis. In multivariate models, high expression of cyclin B1 and TfR1 was significantly associated with mortality (hazard ratio [HR], 6.13; 95% confidence interval [CI], 1.02 to 36.7; and HR, 6.59; 95% CI, 1.14 to 38.2; respectively), whereas high fibronectin expression was not (HR, 3.92; 95% CI, 0.75 to 20.4). Combinations of high cyclin B1/high TfR1, high cyclin B1/high fibronectin, and high TfR1/high fibronectin were strongly associated with mortality ([HR, 13.72; 95% CI, 1.89 to 99.66], [HR, 9.22; 95% CI, 1.34 to 63.55], and [HR, 18.59; 95% CI, 2.54 to 135.88], respectively). In reclassification analyses, cyclin B1, TfR1, fibronectin, and combinations thereof improved the prognostic performance (C-index, 0.78 to 0.82–0.86; cfNRI, all P values <0.05).CONCLUSION: In ACC patients, the overexpression of cyclin B1, TfR1, and fibronectin and combinations thereof were associated with poor prognosis.

Adrenocortical Carcinoma , Biomarkers , Cyclin B1 , Cyclins , Fibronectins , Humans , Mortality , Neoplasm Metastasis , Prognosis , Protein Array Analysis , Proteome , Proteomics , Receptors, Transferrin , Transferrin
Int. braz. j. urol ; 45(3): 514-522, May-June 2019. tab
Article in English | LILACS | ID: biblio-1012319


ABSTRACT Purpose: To investigate risk factors for complications in patients undergoing adrenalectomy. Materials and Methods: A retrospective search of our institutional database was performed of patients who underwent adrenalectomy, between 2014 and 2018. Clinical parameters and adrenal disorder characteristics were assessed and correlated to intra and post-operative course. Complications were analyzed within 30-days after surgery. A logistic regression was performed in order to identify independent predictors of morbidity in patients after adrenalectomy. Results: The files of 154 patients were reviewed. Median age and Body Mass Index (BMI) were 52-years and 27.8kg/m2, respectively. Mean tumor size was 4.9±4cm. Median surgery duration and estimated blood loss were 140min and 50mL, respectively. There were six conversions to open surgery. Minor and major post-operative complications occurred in 17.5% and 8.4% of the patients. Intra-operative complications occurred in 26.6% of the patients. Four patients died. Mean hospitalization duration was 4-days (Interquartile Range: 3-8). Patients age (p=0.004), comorbidities (p=0.003) and pathological diagnosis (p=0.003) were independent predictors of post-operative complications. Tumor size (p<0.001) and BMI (p=0.009) were independent predictors of intra-operative complications. Pathological diagnosis (p<0.001) and Charlson score (p=0.013) were independent predictors of death. Conclusion: Diligent care is needed with older patients, with multiple comorbidities and harboring unfavorable adrenal disorders (adrenocortical carcinoma and pheocromocytoma), who have greater risk of post-operative complications. Patients with elevated BMI and larger tumors have higher risk of intra, but not of post-operative complications.

Humans , Male , Female , Adult , Aged , Postoperative Complications/etiology , Adrenal Gland Diseases/surgery , Adrenalectomy/adverse effects , Intraoperative Complications/etiology , Time Factors , Logistic Models , Retrospective Studies , Risk Factors , Analysis of Variance , Treatment Outcome , Adrenal Cortex Neoplasms/surgery , Adrenal Cortex Neoplasms/complications , Adrenal Cortex Neoplasms/pathology , Adrenal Gland Diseases/complications , Adrenal Gland Diseases/pathology , Adrenocortical Carcinoma/complications , Adrenocortical Carcinoma/pathology , Adrenocortical Carcinoma/blood , Statistics, Nonparametric , Tumor Burden , Middle Aged
Article in English | WPRIM | ID: wpr-785295


Adrenocortical carcinoma is a rare type of endocrine malignancy with an annual incidence of approximately 1–2 cases per million. The majority of these tumors secrete cortisol, and a few secrete aldosterone or androgen. Estrogen-secreting adrenocortical carcinomas are extremely rare, irrespective of the secretion status of other adrenocortical hormones. Here, we report the case of a 53-year-old man with a cortisol and estrogen-secreting adrenocortical carcinoma. The patient presented with gynecomastia and abdominal discomfort. Radiological assessment revealed a tumor measuring 21×15.3×12 cm localized to the retroperitoneum. A hormonal evaluation revealed increased levels of estradiol, dehydroepiandrosterone sulfate, and cortisol. The patient underwent a right adrenalectomy, and the pathological examination revealed an adrenocortical carcinoma with a Weiss' score of 6. After surgery, he was treated with adjuvant radiotherapy. Twenty-one months after treatment, the patient remains alive with no evidence of recurrence.

Adrenal Gland Neoplasms , Adrenalectomy , Adrenocortical Carcinoma , Aldosterone , Dehydroepiandrosterone Sulfate , Estradiol , Gynecomastia , Humans , Hydrocortisone , Incidence , Male , Middle Aged , Radiotherapy, Adjuvant , Recurrence
Rev. argent. radiol ; 82(3): 124-130, set. 2018. ilus
Article in Spanish | LILACS | ID: biblio-977273


Los síndromes de neoplasia endocrina múltiple (MEN), incluyen una serie de enfermedades con alteraciones genéticas que se caracterizan por la presencia de tumores que afectan a dos o más glándulas endocrinas. Son síndromes con una herencia autosómica dominante e incluyen tres patrones: MEN 1 (síndrome de Wermer), MEN 2 (que incluye MEN 2A o síndrome de Sipple y MEN 2B o síndrome de Wagenmann-Froboese) y MEN 4. Los adenomas paratiroideos y el carcinoma medular tiroideo, son los tumores más frecuentes del MEN tipo 1 y 2 respectivamente. Esos síndromes son más comunes en pacientes jóvenes, con patología de afectación bilateral, múltiple o multifocal y, sobre todo, en pacientes con antecedentes familiares. Es necesario el trabajo en equipo de endocrinólogos, cirujanos, oncólogos y radiólogos para optimizar el tratamiento de esos pacientes.

Multiple endocrine neoplasia (MEN) encompasses a serial of familial genetically disorders in wich tumors simultaneusly occur in two or more endocrine organs. MEN síndromes are autosomal-dominant disorders categorized into three main patterns: MEN 1 (Wermer syndrome), MEN 2 (includes MEN 2A o Sipple syndrome and MEN 2B o Wagenmann-Froboese syndrome) and MEN 4. Parathyroid adenomas and medullary thyroid carcinoma are the most frecuent tumors in MEN 1 and MEN 2 respectively. These entities will be suspected in younger patients, bilateral, multiple or multifocal disease and, specially, in patients with family background. Cooperation between endocrinologist, surgeons, oncologists and radiologists is pivotal for optimizing patient treatment.

Humans , Multiple Endocrine Neoplasia/diagnostic imaging , Multiple Endocrine Neoplasia Type 2b/diagnostic imaging , Multiple Endocrine Neoplasia Type 2a/diagnostic imaging , Multiple Endocrine Neoplasia Type 1/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Parathyroid Neoplasms/diagnostic imaging , Pituitary Diseases/complications , Pituitary Diseases/diagnostic imaging , Multiple Endocrine Neoplasia/complications , Thyroid Neoplasms/diagnostic imaging , Adrenal Cortex Neoplasms/diagnostic imaging , Adrenocortical Carcinoma/diagnostic imaging , Hyperparathyroidism, Primary/diagnostic imaging
Clinics ; 73(supl.1): e756s, 2018. tab
Article in English | LILACS | ID: biblio-974949


Malignancy must be considered in the management of adrenal lesions, including those incidentally identified on imaging studies. Adrenocortical carcinomas (ACCs) are rare tumors with an estimated annual incidence of 0.7-2 cases per year and a worldwide prevalence of 4-12 cases per million/year. However, a much higher incidence of these tumors (>15 times) has been demonstrated in south and southeastern Brazil. Most ACCs cause hypersecretion of steroids including glucocorticoids and androgens. ACC patients have a very poor prognosis with a 5-year overall survival (OS) below 30% in most series. Pheochromocytoma or paraganglioma (PPGL) is a metabolically active tumor originating from the chromaffin cells of the adrenal medulla. The incidence of PPGL is 0.2 to 0.9 cases per 100,000 individuals per year. Pheochromocytomas are present in approximately 4-7% of patients with adrenal incidentalomas. Classically, PPGL manifests as paroxysmal attacks of the following 4 symptoms: headaches, diaphoresis, palpitations, and severe hypertensive episodes. The diagnosis of malignant PPGL relies on the presence of local invasion or metastasis. In this review, we present the clinical and biochemical characteristics and pathogenesis of malignant primary lesions that affect the cortex and medulla of human adrenal glands.

Humans , Paraganglioma/therapy , Pheochromocytoma/therapy , Adrenal Cortex Neoplasms/therapy , Adrenal Gland Neoplasms/therapy , Adrenocortical Carcinoma/therapy , Paraganglioma/diagnosis , Paraganglioma/pathology , Pheochromocytoma/diagnosis , Pheochromocytoma/pathology , Adrenal Cortex Neoplasms/diagnosis , Adrenal Cortex Neoplasms/pathology , Adrenal Gland Neoplasms/diagnosis , Adrenal Gland Neoplasms/pathology , Adrenocortical Carcinoma/diagnosis , Adrenocortical Carcinoma/pathology , Antineoplastic Agents, Hormonal/therapeutic use , Mitotane/therapeutic use
Rev. inf. cient ; 97(1): i:166-f:174, 2018. ilus
Article in Spanish | LILACS, CUMED | ID: biblio-995975


Se realizó un estudio clínico anatomopatológico sobre la base de la metodología cualitativa para la descripción de un caso de carcinoma de la corteza suprarrenal en el Hospital General Docente "Dr Agostinho Neto" de Guantánamo en el año 2015. Se describió el caso de un paciente con antecedentes de buena salud, que acude por presentar molestia dolorosa de intensidad gravativa en región posterior izquierda lumboabdominal, se indica chequeo general y mediante la ecografía se diagnostica tumoración suprarrenal izquierda se realizó supraadrenelectomia. El resultado histopatológico señala carcinoma de la corteza suprarrenal(AU)

A pathological clinical study was carried out based on the qualitative methodology for the description of a case of carcinoma of the adrenal cortex at Guantanamo General Teaching Hospital in 2015. A case of a patient with a history of good health, but presenting painful discomfort of gravel intensity in the left posterior lumbo-abdominal region is presented besides general check by ultrasound were indicated. Left adrenal tumor is diagnosed and supra adrenelectomy is performed. Histopathologic results indicate carcinoma of the adrenal cortex(AU)

Humans , Male , Diagnostic Imaging , Adrenocortical Carcinoma/pathology
São Paulo; s.n; s.n; 2018. 165 p. ilus, tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-911612


O FGF2 (Fibroblast Growth Factor 2) é um clássico fator peptídico de crescimento que ativa vias intracelulares de sinalização molecular promovendo a transição G0 → G1 e o comprometimento com o ciclo celular. Não surpreendentemente, seus papéis pró-tumoral e angiogênico estão bem caracterizados e estabelecidos na literatura. No entanto, um crescente corpo de evidências tem indicado que o FGF2 também pode exercer efeitos anti-tumorais in vitro e in vivo, em modelos murinos e também humanos. Neste contexto, nosso grupo publicou em 2008 que o FGF2 exerce um efeito antiproliferativo seletivo em células murinas malignas dependentes de alta atividade de K-Ras e H-Ras. Os genes ras compõem a família de oncogenes mais frequentemente mutada em tumores malignos humanos, alcançando aproximadamente 30% de todos os casos. O desenvolvimento de terapias contra tumores dependentes de Ras fracassou, apesar dos intensos esforços e investimentos desde a descoberta em 1982 de suas mutações ativadoras em múltiplos cânceres. O objetivo deste trabalho foi desvendar os mecanismos moleculares pelo quais o FGF2 inibe irreversivelmente a proliferação de células malignas dependentes da atividade de Ras, empregando como modelos experimentais a linhagem murina Y1 de células adrenocorticais, e 4 linhagens humanas derivadas de sarcomas de Ewing. Identificamos que o efeito citotóxico do FGF2 não se processa por um mecanismo novo e independente das viasproliferativas classicamente ativadas por fatores peptídicos de crescimento. Ao contrário, seu efeito tóxico é resultado de sinalização mitogênica exagerada decorrente de estimulação sustentada por FGF2. A ativação da via de MAPK, principal sinalização mitogênica intracelular, a níveis elevados e sustentados provoca estresse mitogênico, que se propaga para a fase S na forma de estresse replicativo. Nesta situação, a célula passa a depender exageradamente da sinalização protetora de ATR, de modo que a combinação de estimulação com FGF2 e inibição de ATR foi altamente letal para as células malignas dependentes de Ras empregadas neste trabalho. Também analisamos as bases moleculares de resistência a FGF2 exibida por células Y1 anteriormente selecionadas para resistir ao efeito tóxico do FGF2 (Y1FRs). Descobrimos que a pressão seletiva do FGF2 não teve efeito na expressão de seus receptores, mas provocou a eliminação de um dos dois cromossomos que portam a amplificação gênica de ras nesta linhagem, enquanto o segundo cromossomo foi mantido por ser a única fonte de genes ribossomais ativos. Suas cópias de ras, no entanto, mostraram-se transcricionalmente silenciadas. Além disso, as sublinhagens Y1FRs não expressam o principal RasGEF, GRP4, encontrado nas células parentais Y1, o que pode ter influenciado o surgimento do fenótipo resistente ao FGF2. As linhagens resistentes mostraram grande redução no número de cromossomos e aumento da frequência de fusões entre cromossomos não homólogos em relação às células parentais

FGF2 (Fibroblast Growth Factor 2) is a classic peptide growth factor that activates intracellular molecular signaling pathways promoting the G0 → G1 transition and cell cycle commitment. Not surprisingly, its pro-tumor and angiogenic roles are well characterized and established in the literature. However, a growing body of evidence has indicated that FGF2 may also exert anti-tumor effects in vitro and in vivo in murine and human models. In this context, our group reported in 2008 that FGF2 exerts a selective antiproliferative effect in murine cells dependent on high activity of K-Ras and H-Ras. Ras genes make up the most frequently mutated oncogene family in human malignant tumors, reaching approximately 30% of all cases. The development of therapies against Ras-dependent tumors has failed despite intense efforts and investments since the discovery in 1982 of its activating mutations in multiple cancers. The objective of this work was to uncover the molecular mechanisms by which FGF2 irreversibly inhibits the proliferation of malignant cells dependent on Ras activity, using as experimental models the Y1 murine lineage of adrenocortical malignant cells and 4 human lineages derived from Ewing sarcomas. We showed that the cytotoxic effect of FGF2 did not involve novel cell cycle regulatory pathways; instead, this cytotoxic effect is a result of sustainedhyper mitogenic stimulation by FGF2. Activation of the KRas/MAPK pathway, the major intracellular mitogenic signaling, at high and sustained levels provokes mitogenic stress, which is propagated to S phase as replicative stress. In this situation, the cell dependence on the ATR protective signaling is enhanced, so that the combination of stimulation with FGF2 and inhibition of ATR was highly lethal for the Ras dependent malignant cells employed in this work. We also analyzed the molecular basis of FGF2 resistance exhibited by Y1 cells previously selected for resistance to FGF2. We found that the selective pressure of FGF2 had no effect on the expression of its receptors but promoted the elimination of one of the two marker chromosomes that carry the K-ras amplified copies, while the second chromosome was maintained because it is the only source of active ribosomal genes; however, its K-ras amplified copies were transcriptionally silenced. In addition, the Y1FRs sublines did not express the main RasGEF, GRP4, found in the parental Y1 cells, which might have played a role in the emergence of the FGF2-resistant phenotype. The resistant Y1FRs sublines showed a large reduction in chromosome numbers and increased frequency of fusions between non-homologous chromosomes in relation to parental cells

Fibroblast Growth Factor 2/adverse effects , Fibroblast Growth Factor 2/analysis , Genes, ras/genetics , Adrenocortical Carcinoma/classification , Molecular Mechanisms of Pharmacological Action , Synthetic Lethal Mutations
São Paulo; s.n; 2018. 127 p. ilus, tab, quadros.
Thesis in Portuguese | LILACS, Inca | ID: biblio-1015262


A Síndrome de Li Fraumeni (LFS) tem caráter autossômico dominante associada ao risco aumentado de câncer hereditário. Embora rara no mundo, no Brasil é frequente devido à ocorrência de uma mutação fundadora, a p.R337H TP53. A ocorrência de câncer e a idade de acometimento são variáveis mesmo em portadores da mesma mutação. Pacientes com mutações no gene TP53 podem desenvolver um amplo espectro de tumores, incluindo o carcinoma adrenocortical (ADR). Os mecanismos moleculares envolvidos na carcinogênese adrenocortical assim como os dados epidemiológicos associados a estes tumores são pouco explorados em literatura. Neste estudo, foram coletados e analisados os dados epidemiológicos dos ADR incluindo os efeitos de idade, período e coorte utilizando o banco de dados SEER, o qual reúne dados de 18 registros de câncer de base populacional dos EUA. Foi avaliado o perfil de alterações genômicas (CytoScan HD Array, Affymetrix) em ADR de pacientes com e sem a mutação p.R337H. Foi também comparado o perfil mutacional (sequenciamento do genoma) de três pacientes (tumor e tecido normal de 2 adultos e 1 criança) com ADR portadores da mutação TP53 p.R337H. Entre os casos de ADR diagnosticados nos EUA, aproximadamente 80% ocorreram após a quarta década de vida. Nas análises de sobrevida, houve diferença estatística (p<0,05) para gênero, com uma melhor sobrevida para as mulheres. Pacientes diagnosticados até os 19 anos e com doença localizada apresentaram uma sobrevida maior. A análise genômica em sete casos revelou 644 alterações. Os três casos positivos para a mutação p.R337H apresentaram 175 alterações genômicas (127 ganhos, 27 cnLOH e 21 perdas). Os quatros casos negativos para a mutação apresentaram 469 alterações (326 ganhos, 63 cnLOH e 80 perdas). Apesar do pequeno número amostral, os casos ADR positivos para a mutação TP53 p.R337H apresentaram um baixo nível de instabilidade genômica quando comparados com os casos não mutados. A análise de sequenciamento do genoma revelou alterações em genes previamente associados o ADR (como TP53, CTNNB1 e ATRX). Foram identificadas alterações em cinco genes com potencial associação ao desenvolvimento do ADR: HBB, MSR1, SH3TC2, LSS e ABCA4. Apesar do pequeno número amostral, foram identificados novos genes que podem estar associados ao ADR, no entanto esses achados deverão ser confirmados em estudos conduzidos em um grupo amostral maior (AU)

Li-Fraumeni syndrome (LFS) is an autosomal dominant disease with high risk to develop hereditary tumors. Although LFS is a worldwide rare disorder, in Brazil its incidence is higher due to the occurrence of a founder mutation, TP53 p.R337H. The cancer occurrence and age of onset are variable even considering patients with the same mutation. Patients carrying TP53 mutations can develop a large spectrum of tumors, including the adrenocortical carcinoma (ADR). The main molecular mechanisms and the epidemiological factors associated with these tumors are poorly explored in literature. In this study, epidemiological data of ADR were collected and analyzed, including the effects of age, period and cohort. The SEER database, which collects and publishes cancer incidence and survival data from 18 cancer registries from the USA, was used for this analysis. The genomic profile (CytoScan HD Array, Affymetrix) of ADR positive or negative for TP53 p.R337H was also investigated. Furthermore, the mutational profile (Whole Genome Sequencing- WGS) of three ADR patients (normal and tumor samples - 2 adults and 1 pediatric case), all of them positive for TP53 p.R337H mutation, were analyzed. Approximately 80% of the ADR cases diagnosed in the USA developed after the fourth decade of life. In the survival analyses, a statistical difference (p <0.05) was observed for gender, with women showing better survival. Patients diagnosed up to the age of 19 and with localized disease presented better survival. The genomic analysis of seven cases revealed 644 genomic alterations. The three TP53 p.R337H positive cases showed 175 genomic alterations (127 gains, 27 cnLOH and 21 losses). The four negative mutated cases presented 469 alterations (369 gains, 63 cnLOH and 80 losses). Despite the small set of samples, mutated cases presented lower level of chromosome instability compared to cases not carrying this mutation. The WGS analysis identified alterations in genes previously associated with ADR (as TP53, CTNNB1 and ATRX). In addition, five genes (HBB, MSR1, SH3TC2, LSS and ABCA4) potentially associated with the development of ADR were identified. This study revealed new genes that might be associated with ADR. However, further analysis are necessary in a larger number of samples to confirm our findings (AU)

Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Neoplastic Syndromes, Hereditary , Li-Fraumeni Syndrome , Adrenocortical Carcinoma , Whole Genome Sequencing
Yonsei Medical Journal ; : 501-510, 2018.
Article in English | WPRIM | ID: wpr-715391


PURPOSE: Previous studies on adrenal incidentalomas (AIs) are limited by their retrospective design, small numbers of patients, Western populations, or use of an outdated imaging technique. We investigated the characteristics of AIs in Korean patients and compared them with those reported in the largest retrospective study in Italy to discover the effects of improved imaging techniques and ethnicity differences. MATERIALS AND METHODS: This was a prospective, multicenter, cross-sectional observational study including 1005 Korean patients. Levels of plasma adrenocorticotrophic hormone, 24-h urinary free cortisol (UFC), serum cortisol after a 1 mg-dexamethasone suppression test, 24-h urinary fractionated metanephrine, and plasma aldosterone and plasma renin activity were measured. All AIs were characterized using computed tomography (CT). RESULTS: Compared with the results of the Italian study, AIs in Korean patients were observed more frequently in men and predominantly on the left side. Korean patients with AIs were slightly younger, and fewer patients underwent surgery. Most AIs were nonfunctional in both studies, while fewer subclinical hypercortisolism and more primary aldosteronism (PA) cases were detected in Korean patients. In our study, high UFC levels showed very low sensitivity, compared to those in the Italian study. In pheochromocytoma or PA cases, there were no hormonal differences between the studies. AIs in Korean patients were smaller, such that a lower cutoff size for detecting adrenocortical carcinoma (ACC) could be warranted. CONCLUSION: Recent advances in CT technology were leveraged to provide accurate characteristics of AIs and to detect smaller ACCs.

Adrenocortical Carcinoma , Adrenocorticotropic Hormone , Aldosterone , Cushing Syndrome , Humans , Hydrocortisone , Hyperaldosteronism , Italy , Korea , Male , Metanephrine , Observational Study , Pheochromocytoma , Plasma , Prospective Studies , Renin , Retrospective Studies
Article in English | WPRIM | ID: wpr-741197


We describe a case of a 61-year-old Korean man who was diagnosed with renal cell carcinoma that was discovered on abdominopelvic computed tomography obtained after the patient complained of back pain. A radical nephrectomy was performed, and the surgical specimen showed a relatively well-circumscribed and yellowish lobulated hard mass. Microscopically, the tumor showed sheets and nests of hypercellular pleomorphic cells with thick fibrous septation, frequent mitoses, and areas of adrenal cortical-like tissue. Immunohistochemical staining revealed that the tumor cells were positive for inhibin-α, vimentin, synaptophysin, and melan A. It also revealed that the tumor cells were negative for pan-cytokeratin, epithelial membrane antigen, paired box 8, α-methylacyl-coenzyme A racemase, CD10, cytokeratin 7, carbonic anhydrase 9, c-Kit, renal cell carcinoma, transcription factor E3, human melanoma black 45, desmin, smooth muscle actin, S-100, chromogranin A, CD34, anaplastic lymphoma kinase, and integrase interactor 1. Based on these histopathological and immunohistochemical findings, we diagnosed the tumor as intrarenal adrenocortical carcinoma arising in an adrenal rest. Several cases of intrarenal adrenocortical carcinoma have been reported, although they are very rare. Due to its poor prognosis and common recurrence or metastasis, clinicians and pathologists must be aware of this entity.

Actins , Adrenal Rest Tumor , Adrenocortical Carcinoma , Back Pain , Carbonic Anhydrases , Carcinoma, Renal Cell , Chromogranin A , Desmin , Humans , Integrases , Keratin-7 , Lymphoma , MART-1 Antigen , Melanoma , Middle Aged , Mitosis , Mucin-1 , Muscle, Smooth , Neoplasm Metastasis , Nephrectomy , Phosphotransferases , Prognosis , Recurrence , Synaptophysin , Transcription Factors , Vimentin
Int. braz. j. urol ; 43(5): 841-848, Sept.-Oct. 2017. tab, graf
Article in English | LILACS | ID: biblio-892887


ABSTRACT Purpose: To evaluate the role of ARDT after surgical resection of ACC. Materials and Methods: Records of patients from our institutional ACC database were retrospectively assessed. A paired comparison analysis was used to evaluate the oncological outcomes between patients treated with surgery followed by ARDT or surgery only (control). The endpoints were LRFS, RFS, and OS. A systematic review of the literature and meta-analysis was also performed to evaluate local recurrence of ACC when ARDT was used. Results: Ten patients were included in each Group. The median follow-up times were 32 months and 35 months for the ARDT and control Groups, respectively. The results for LRFS (p=0.11), RFS (p=0.92), and OS (p=0.47) were similar among subsets. The mean time to present with local recurrence was significantly longer in the ARDT group compared with the control Group (419±206 days vs. 181±86 days, respectively; p=0.03). ARDT was well tolerated by the patients; there were no reports of late toxicity. The meta-analysis, which included four retrospective series, revealed that ARDT had a protective effect on LRFS (HR=0.4; CI=0.17-0.94). Conclusions: ARDT may reduce the chance and prolong the time to ACC local recurrence. However, there were no benefits for disease recurrence control or overall survival for patients who underwent this complementary therapy.

Humans , Male , Female , Aged , Aged, 80 and over , Young Adult , Adrenal Cortex Neoplasms , Adrenocortical Carcinoma/radiotherapy , Case-Control Studies , Retrospective Studies , Follow-Up Studies , Adrenal Cortex Neoplasms/surgery , Adrenocortical Carcinoma/surgery , Adrenalectomy , Radiotherapy, Adjuvant/methods , Disease-Free Survival , Middle Aged
Kosin Medical Journal ; : 269-276, 2017.
Article in English | WPRIM | ID: wpr-60691


The incidence of malignant adrenal tumors, including primary adrenal lymphoma (PAL) and adrenocortical carcinoma (ACC), is rather low. Early differentiation between ACC and PAL is necessary because the therapeutic strategies for the two differ and the prognosis of each disease is poor. Unfortunately, there is no pathognomonic characteristic of PAL, so radiologists have difficulty in differentiating it from ACC. To our knowledge, there have been only two case reports on ACC that was evaluated and followed up using F-18 FDG PET/CT. The previously reported cases were simple, involving only the bilateral adrenal glands. Here, we report on a 52-year-old man diagnosed with PAL that radiologically mimicked ACC. He had findings of heterogeneous enhancement on CT, several adjacent lymphadenopathies with internal necrosis, and abutting hepatic and bilateral crural invasion. After pathological confirmation, we monitored his prognosis using F-18 FDG PET/CT after three cycles of rituximab-CHOP and again after six cycles of treatment.

Adrenal Glands , Adrenocortical Carcinoma , Follow-Up Studies , Humans , Incidence , Lymphoma , Lymphoma, B-Cell , Lymphoma, Non-Hodgkin , Middle Aged , Necrosis , Positron Emission Tomography Computed Tomography , Prognosis
Article in English | WPRIM | ID: wpr-25086


The aim of this study is to describe rare variants of adrenocortical carcinoma (ACC) and to compare the prognosis with that of conventional ACC. We retrospectively reviewed 8 cases of myxoid variant, 1 sarcomatoid variant, and 14 cases of conventional ACC, who underwent surgical resection at the Asan Medical Center between 1996 and 2014. An analysis of the clinicopathological characteristics, including the Weiss score, Ki-67 labeling index, and reticulin framework assessment is presented. The mean age of patients with myxoid/sarcomatoid ACC was 45 years; 4 out of 9 patients were women. Mean primary tumor size was 12.9 cm and the mean weight was 702.4 g. Seven patients presented in an advanced stage (stage III/IV); 8 of these eventually developed distant metastasis. The mean Weiss score was 5.0 points and the Ki-67 labeling index was 15.6%. The extent of myxoid or sarcomatoid change on histological examination ranged from 10% to 75% of the examined tumor areas; reticulin framework alteration was observed in all cases. Four patients showed venous tumor thrombus. Most of the clinicopathological parameters were not significantly different from those of conventional ACC. However, myxoid or sarcomatoid variant (hazard ratios [HR], 3.59; 95% confidence intervals [CI], 1.13–11.38; P = 0.030) and Ki-67 labeling index (HR, 3.97; 95% CI, 1.18–13.41; P = 0.030) were independent predictors of overall survival after adjusting for age and sex. Myxoid or sarcomatoid histological features or an increased Ki-67 labeling index may be associated with poor overall survival in patients with ACC.

Adrenocortical Carcinoma , Female , Humans , Neoplasm Metastasis , Prognosis , Reticulin , Retrospective Studies , Tertiary Care Centers , Tertiary Healthcare , Thrombosis
São Paulo; s.n; 2016. 158 p. ilust, tabelas, quadros.
Thesis in Portuguese | LILACS, Inca | ID: biblio-1178234


INTRODUÇÃO: a Síndrome de Li-Fraumeni (LFS; OMIM#151623) é uma síndrome rara de predisposição hereditária ao câncer, de caráter autossômico dominante e de alta penetrância, relacionada a mutações germinativas no gene TP53. Os tumores típicos da LFS são sarcomas de partes moles e ósseos, leucemias, tumores do sistema nervoso central (SNC), tumores adrenocorticais e tumores de mama. No entanto, há uma variação no espectro tumoral de acordo com o genótipo. No Brasil, há uma alta prevalência da mutação germinativa p.R337H (presente em 0.3% da população do Sul e Sudeste) devido a um efeito fundador. O conhecimento do real espectro tumoral da síndrome associada a esta mutação fundadora ainda é objeto de discussão. PACIENTES E MÉTODOS: foram avaliados dados clínicos, retrospectivamente, a partir de prontuários médicos, de 247 pacientes com LFS e LFS portadores de mutações germinativas no gene TP53, atendidos no Departamento de Oncogenética do A.C.Camargo Cancer Center de 2001 a 2015. As características dos tumores apresentados pelos pacientes portadores de mutação (espectro tumoral, idade do diagnóstico do primeiro tumor e dos tumores subsequentes, tipo histológico dos tumores) foram comparadas entre o grupo de portadores da mutação p.R337H e o grupo de pacientes com as demais mutações patogênicas no gene TP53. As taxas de frequência das mutações (p.R337H versus outras mutações), assim como sexo (masculino e feminino) foram correlacionados com o status de óbito, desenvolvimento ou não de câncer, a idade do diagnóstico do primeiro câncer, tempo do primeiro câncer até aparecimento do segundo câncer, através do teste qui-quadrado ou teste exato de Fisher. Foi aplicado o Teste T para amostras independentes. O estimador de Kaplan-Meier e o teste de log rank foram utilizados para avaliar a influência das variáveis nos tempos de sobrevida global, tempo de aparecimento do primeiro câncer e tempo do primeiro câncer até aparecimento do segundo câncer. RESULTADOS: de 247 portadores de LFS incluídos no estudo, 193 pacientes eram portadores da mutação p.R337H. Deste total de 193 portadores da mutação p.R337H, 101 pacientes apresentaram câncer (52.3%) e 23,8% dos pacientes com câncer tiveram dois ou mais tumores ao longo da vida; enquanto dos 54 pacientes portadores de outras mutações no gene TP53 (21.9% da população total), 39 pacientes tiveram câncer (72.2%), p=0.009. A idade média de diagnóstico do primeiro câncer nos portadores da mutação p.R337H foi de 30.8 anos, comparada a 28.9 anos nos portadores de outras mutações no gene TP53, p=0.604. nos portadores da mutação p.R337H, o primeiro tumor também ocorreu em idade mais precoce nas pacientes femininas (média de 34.7 anos versus 50.4 anos, p<0.001). Em relação ao espectro dos tumores p.R337H na nossa população, câncer de mama e sarcoma de partes moles foram os tumores mais frequentes, seguidos de carcinoma adrenocortical, perfazendo 70,5% dos tumores apresentados nesta população. Nos portadores de outras mutações no gene TP53 , câncer de mama, sarcoma de partes moles, tumor de sistema nervoso central e sarcoma ósseo corresponderam a 69.3% de todos os tumores observados. Nossos dados revelam uma alta frequência de carcinoma adrenocortical (21.5%), carcinoma papilífero de tireoide (6.8%), adenocarcinoma de pulmão (4.9%) e carcinoma renal (4.3%) nos portadores da mutação p.R337H. Interessantemente carcinoma colorretal foi observado apenas nos portadores de outras mutações não-p.R337H. O sarcoma de partes moles nos portadores p.R337H mais frequente foi o leiomiossarcoma e a idade média de diagnóstico foi 46.8 anos; nos portadores das outras mutações, rabdomiossarcoma e leiomiossarcoma foram os subtipos mais frequentes e a idade média do diagnóstico foi 24 anos (p=0.001). A idade média de diagnóstico de câncer de mama foi 42.8 anos nos portadores da mutação p.R337H e 37 anos nos portadores das demais mutações no gene TP53 (p=0.029). O câncer de mama nos portadores das outras mutações apresentavam hiperexpressão de HER2 em 62.5% dos casos, comparado a 19% nos tumores de mama das portadoras da mutação p.R337H. CONCLUSÕES: nossos dados mostram um espectro tumoral distinto para os portadores da LFS com a mutação p.R337H. Esses dados podem ajudar a estabelecer um programa de rastreamento para esses portadores diferente do preconizado para os portadores das demais mutações no gene TP53.

INTRODUCTION: Li Fraumeni syndrome (LFS, OMIM #151623) is a rare autosomal dominant genetic disorder inherited by germline TP53 mutations. Carriers have a high lifetime risk of developing multiple early-onset childhood and adult cancers, including soft tissue and bone sarcomas, central nervous system (CNS) tumors, adrenocortical tumors (ACT), breast cancer and leucemia. However, tumor spectrum may have difference according to genotype. In Brazil, it is observed a high prevalence of a founder germline mutation p.R337H (present in 0.3% of the population in South and Southeast). The exact tumor profile associated to p.R337H carriers is unknown. PATIENTS AND METHODS: we have analyzed medical records of a cohort of 247 germline TP53 mutation carriers, members of Brazilian families who fulfilled LFS/LFL clinical criteria, between 2001 and 2015 from the Oncogenetics Department at A.C.Camargo Cancer Center, Sao Paulo, Brazil. Clinical data were retrospectively evaluated and the tumor characteristics of carriers (tumor spectrum, age at diagnosis, histological subtype) were compared between p.R337H carriers and carriers of other mutations in TP53 gene. The mutation status (p.R337H and other mutations) and gender (male and female) were correlated with death rate, cancer risk, age at diagnosis of cancer, interval between the first and the second cancer diagnosis, using the chi-squared test or Fisher's exact test. The T test was used for independent samples analysis. The Kaplan-Meier and log rank test were used to evaluate the influence of variables on overall survival, time and cancer the first time until onset of the second cancer. RESULTS: the study evaluated 247 patients with LFS, 193 patients had the mutation p.R337H. Among 193 p.R337H carriers, 101 patients had cancer (52.3%) and 23.8% of cancer-affected carriers had two or more tumors lifetime; whereas from 54 non-p.R337H mutation carriers, 39 patients were cancer-affected (72.2%), p = 0.009. The mean age at diagnosis of first cancer in p.R337H carriers was 30.8 years old (yo) compared to 28.9 yo in non-p.R337H mutation carriers, p = 0.604. In p.R337H patients, the first tumor occurred at an earlier age in female patients (mean age at 34.7 yo vs. 50.4 yo, p <0.001). Regarding the tumor spectrum in p.R337H carriers, breast cancer and soft tissue sarcoma were the most frequent tumors, followed by adrenocortical carcinoma (70.5% of the total of tumors). In non-p.R337H mutation carriers, breast cancer, soft tissue sarcoma, central nervous system tumor and bone sarcoma accounted for 69.3% of all tumors observed. Our results showed a high frequency of adrenocortical carcinoma (21.5%), papillary thyroid carcinoma (6.8%), lung adenocarcinoma (4.9%) and renal cell carcinoma (4.3%) in p.R337H patients. Interestingly, colorectal carcinoma was observed only in nonp.R337H mutation patients. Leiomyosarcoma was the most frequent sarcoma subtype in p.R337H carriers and the mean age at diagnosis was 46.8 yo; in non-p.R337H mutation patients, rhabdomyosarcoma and leiomyosarcoma were the most frequent subtypes and the mean age at diagnosis was 24 yo (p = 0.001). The mean age at diagnosis of breast cancer was 42.8 yo in p.R337H patients and 37 yo in non-p.R337H mutation patients (p = 0.029). The breast cancer in non-p.R337H mutation patients showed overexpression of HER2 in 62.5% of cases, compared to 19% in breast tumors from p.R337H carriers. CONCLUSIONS: our clinical cohort revealed a different tumor spectrum associated with p.R337H TP53 mutation. The major limitation in our study was the relatively small sample of nonp.R337H mutation carriers to compare with p.R337H carriers. Notwithstanding, our findings offer insight into exploring a distinct cancer screening protocol for p.R337H mutation carriers in Brazil.

Humans , Male , Female , Adult , Middle Aged , Aged , Phenotype , Sarcoma , Breast Neoplasms , Genes, p53 , Li-Fraumeni Syndrome/genetics , Adrenocortical Carcinoma
Article in English | WPRIM | ID: wpr-162229


OBJECTIVES: Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. METHODS: Cortisol, aldosterone, testosterone, and 17β-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/17/19/21) and the hydroxysteroid dehydrogenases (3β-HSD2 and 17β-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. RESULTS: H295R cells exposed to EGb761 (10 and 100 μg/mL) showed a significant decrease in 17β-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and 17β-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/ Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. CONCLUSIONS: These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and 17β-HSD1, and lead to a decrease in 17β-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

Adrenocortical Carcinoma , Aldosterone , Anticarcinogenic Agents , Aromatase Inhibitors , Aromatase , Blotting, Western , Breast Neoplasms , Clinical Coding , Cytochrome P-450 Enzyme System , Estrogens , Exons , Ginkgo biloba , Humans , Hydrocortisone , Hydroxysteroid Dehydrogenases , In Vitro Techniques , Real-Time Polymerase Chain Reaction , Testosterone , Therapeutic Uses
Int. braz. j. urol ; 41(6): 1108-1115, Nov.-Dec. 2015. tab, graf
Article in English | LILACS | ID: lil-769753


Purpose: To analyze the association of marital status and survival of patients with ACC using a population-based database. Material and Methods: Patients with ACC were abstracted from the Surveillance Epidemiology and End Results (SEER) database from 1988-2010 (n=1271). Variables included marital status (married vs single/divorced/widowed (SDW)), gender, age, race, tumor (T) and node (N) classification, receipt of surgery, and SEER stage. Statistical analysis was performed using Cox proportional hazard models to generate hazard ratios and 95% confidence intervals. Results: There were 728 (57.3%) females and median age was 56 years (IQR 44-66). Patients who were alive were more frequently married (65.6% vs 61.6%, p=0.008), female (61.1% vs 58.0%, p=0.001), younger (median 51 vs 57 years, p=0.0001), submitted to adrenalectomy (88.6% vs 63.8%, p<0.0001), and more favorable SEER stage (localized-64.9% vs 29.9%; regional–25.1% vs 30.1%; distant 4.8% vs 31.5%, p<0.0001) compared to patients dead of disease (DOD). On multivariable analysis, factors significantly associated with all-cause mortality were SDW status (HR 1.28, 95% CI 1.091.51), age, non-operative management, and N+ disease. Risk factors for disease-specific mortality included SDW status (HR 1.30, 95% CI 1.07-1.56), age, non-operative management, T-classification, and N+ disease. Conclusions: Marital status is significantly associated with survival in patients with ACC. Our results suggest that the decreased survival seen among SDW individuals highlights an area for further research and needed intervention to reduce disparity.

Adult , Aged , Female , Humans , Male , Middle Aged , Adrenal Cortex Neoplasms/mortality , Adrenocortical Carcinoma/mortality , Marital Status/statistics & numerical data , Adrenal Cortex Neoplasms/psychology , Adrenocortical Carcinoma/psychology , Kaplan-Meier Estimate , Proportional Hazards Models , Risk Factors , SEER Program , Sex Distribution , United States/epidemiology