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CONTEXT: SDHB mutations are found in an increasing number of neoplasms, most notably in paragangliomas and pheochromocytomas (PPGLs). SDHB-PPGLs are slow-growing tumors, but â¼50% of them may develop metastasis. The molecular basis of metastasis in these tumors is a long-standing and unresolved problem. Thus, a better understanding of the biology of metastasis is needed. OBJECTIVE: This study aimed to identify gene methylation changes relevant for metastatic SDHB-PPGLs. DESIGN: We performed genome-wide profiling of DNA methylation in diverse clinical and genetic PPGL subtypes, and validated protocadherin γ-C3 (PCDHGC3) gene promoter methylation in metastatic SDHB-PPGLs. RESULTS: We define an epigenetic landscape specific for metastatic SDHB-PPGLs. DNA methylation levels were found significantly higher in metastatic SDHB-PPGLs than in SDHB-PPGLs without metastases. One such change included long-range de novo methylation of the PCDHA, PCDHB, and PCDHG gene clusters. High levels of PCDHGC3 promoter methylation were validated in primary metastatic SDHB-PPGLs, it was found amplified in the corresponding metastases, and it was significantly correlated with PCDHGC3 reduced expression. Interestingly, this epigenetic alteration could be detected in primary tumors that developed metastasis several years later. We also show that PCDHGC3 down regulation engages metastasis-initiating capabilities by promoting cell proliferation, migration, and invasion. CONCLUSIONS: Our data provide a map of the DNA methylome episignature specific to an SDHB-mutated cancer and establish PCDHGC3 as a putative suppressor gene and a potential biomarker to identify patients with SDHB-mutated cancer at high risk of metastasis who might benefit from future targeted therapies.
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Neoplasias de las Glándulas Suprarrenales/genética , Cadherinas/genética , Epigénesis Genética , Mutación , Paraganglioma/genética , Feocromocitoma/genética , Succinato Deshidrogenasa/genética , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/patología , Proteínas Relacionadas con las Cadherinas , Cadherinas/metabolismo , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Humanos , Masculino , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Paraganglioma/metabolismo , Paraganglioma/patología , Feocromocitoma/metabolismo , Feocromocitoma/patología , Succinato Deshidrogenasa/metabolismoRESUMEN
High-grade papillary urothelial carcinoma with subepithelial connective tissue invasion (T1HG) is an aggressive disease at high risk of progression after transurethral resection/Bacillus Calmette-Guerin standardized therapy. The European Organization for Research and Treatment of Cancer has identified T1HG bladder carcinoma that is single and ≤3 cm in the largest dimension at first diagnosis as a category in which the prognosis cannot be further stratified based on conventional criteria. This category may benefit from biomarker analysis as a valuable tool to determine the patient's outcome. To further the issue of biomarkers in predicting aggressiveness in single T1HG bladder carcinoma ≤3 cm in greatest dimension at first diagnosis, we have conducted a validation study of the biomarker risk score set previously reported by our group. The study set included immunohistochemical detection of galectin-3, CD44, E-cadherin (E-CAD), CD138, p16, survivin, HYAL-1, and topoisomerase-IIα in 92 randomly selected specimens at participating institutions. Topoisomerase-IIα expression was identified as a predictor of disease-free survival. p16, survivin, and E-CAD expression predicted progression-free survival, but p16 and E-CAD also predicted overall survival. The current study validates a panel of immunohistochemical markers with the potential of being implemented in practice and supports the use of biomarkers in predicting aggressiveness in patients with first diagnosis of single T1HG bladder carcinoma ≤3 cm in greatest dimension and therefore in identifying patients who need closer surveillance or earlier aggressive treatment.
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Antígenos de Neoplasias/análisis , Biomarcadores de Tumor/análisis , Cadherinas/análisis , Carcinoma Papilar/enzimología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , ADN-Topoisomerasas de Tipo II/análisis , Proteínas de Unión al ADN/análisis , Proteínas Inhibidoras de la Apoptosis/análisis , Neoplasias de la Vejiga Urinaria/enzimología , Anciano , Antígenos CD , Carcinoma Papilar/mortalidad , Carcinoma Papilar/patología , Carcinoma Papilar/terapia , Supervivencia sin Enfermedad , Europa (Continente) , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Clasificación del Tumor , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Reproducibilidad de los Resultados , Survivin , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
BACKGROUND: Adrenal gland involvement by metastatic melanoma can be found in up to 50% of patients with ocular or cutaneous melanomas. Since these tumors are not hormone secreting, they usually present with locally advanced disease. CASE: We report on the presence of a bilateral massive metastatic adrenal melanoma in an 80-year-old, symptomatic woman with the initial clinical diagnosis of adrenal hemorrhage/carcinoma. Histological assessment of the bilateral adrenalectomy showed a massive malignant melanoma in the adrenal glands, consistent with metastasis. Following that diagnosis, thorough studies revealed no ocular, mucocutaneous or primary tumor. The presence of melanoma in both adrenal glands favors metastatic melanoma over a primary adrenal melanoma. CONCLUSION: What makes this case rare is the unusually great size of the symptomatic bilateral malignant melanoma adrenal metastasis of occult primary with wide hemorrhagic and necrotic areas, which was probably responsible for the patient's acute symptoms. The search for the primary tumor may be exigent, and it might not even be present at the time of diagnosis. Confirmation at autopsy is advisable, however this may not always be feasible.
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Neoplasias de las Glándulas Suprarrenales/secundario , Neoplasias de las Glándulas Suprarrenales/cirugía , Melanoma/secundario , Melanoma/cirugía , Neoplasias Primarias Desconocidas/cirugía , Anciano de 80 o más Años , Biopsia , Femenino , Humanos , Carga TumoralRESUMEN
We report the case of an urgent nephrectomy because of a pyonephrosis and sepsis due to an unsuspected sarcomatoid transitional cell carcinoma, an infrequent subtype with a bad oncological prognosis. We present a 58-year-old man assessed by internal medicine for a general syndrome and weakness many months previously. A pyonephrotic kidney was observed at abdominal computed tomography in the context of septic shock, without suspecting the underlying cause. The pathology report described a sarcomatoid transitional cell carcinoma. Sarcomatoid transitional cell carcinoma is an invasive and infrequent subtype of urothelial tumors. The symptoms are often the same as other renal masses; however, in this case, sepsis and pyonephrosis were the rare initial symptoms.
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We report the case of a left laparoscopic nephroureterectomy with the incidental discovery of a non-Hodgkin's lymphoma in one of the lymph nodes of the renal hilum. A laparoscopic nephroureterectomy was decided on for a 64-year-old man. Renal cell carcinoma in the kidney and one lymph node of the renal hilum with non-Hodgkin's lymphoma was found. Chemotherapy was not started for the lymphoma discovery. There are no signs of relapse after two years of follow up. Coexistence in the same patient is an extremely rare condition. We review the literature about this issue to clarify this association.
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This article reports the case of a 22-year-old woman with right renal angiomyolipoma (AML) and inferior vena cava thrombus. Laparoscopic right nephrectomy and thrombectomy were performed. To the authors' knowledge there have been only 46 reported cases of renal AML with endovascular extension and this is the first case to be completely removed by a laparoscopic approach. Laparoscopic management of this kind of tumour is feasible in spite of the vascular involvement. The centre's experience and enlargement of the tumour are key points for this approach.
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Angiomiolipoma/cirugía , Neoplasias Renales/cirugía , Laparoscopía/métodos , Nefrectomía/métodos , Trombosis/cirugía , Vena Cava Inferior , Angiomiolipoma/diagnóstico , Angiomiolipoma/epidemiología , Comorbilidad , Femenino , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/epidemiología , Trombectomía , Trombosis/diagnóstico , Trombosis/epidemiología , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To report a new case of secondary bladder amyloidosis, beinginvolvement of the urinary bladder by amyloidosis infrequent on the basis of very few references in the literature (we estimate the number of cases of secondary vesical amyloidosis reported to be around 30). METHODS/RESULTS: The case presented here corresponds to secondary bladder amyloidosis in a patient suffering from Still's disease, who began with hematuria and ended dying. CONCLUSION: Secondary bladder amyloidosis constitutes a very infrequent pathology, and we can distinguish between primary forms of bladder amyloidosis and systemic forms of amyloidosis that affect the urinary bladder (secondary bladder amyloidosis). It is associated in the majority of patients with rheumatoid arthritis that has evolved over a long period. Clinical diagnosis is difficult, and it is necessary to carry out differential diagnosis with bladder tumours. The pathological and immunohistochemical studies confirm the diagnosis.