Epigenetic Deregulation of Protocadherin PCDHGC3 in Pheochromocytomas/Paragangliomas Associated With SDHB Mutations.

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 ∼50% 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.

T1 high-grade bladder carcinoma outcome: the role of p16, topoisomerase-IIα, survivin, and E-cadherin.

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.

Pyonephrosis as a sign of sarcomatoid carcinoma of the renal pelvis.

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.

Massive bilateral adrenal metastatic melanoma of occult origin: a case report.

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.

Lymph node non-Hodgkin's lymphoma incidentally discovered during a nephrectomy for renal cell carcinoma.

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.

Laparoscopic management of right renal angiomyolipoma with involvement of the inferior vena cava: case report and review of the literature.

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.

Secondary bladder amyloidosis: a new case report.

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.

Un nuevo caso de amiloidosis vesical secundaria / Secondary bladder amyloidosis: a new case report

OBJETIVO: Dar a conocer un nuevo caso de amiloidosis vesical secundaria, siendo la afectación vesical en la amiloidosis un hecho poco frecuente, en base a la escasez de referencias en la literatura (estimamos que el número de casos de amiloidosis vesical secundaria descritos se aproxima a 30). MÉTODO/RESULTADO: El caso que presentamos corresponde a una amiloidosis vesical secundaria en un paciente afecto de Enfermedad de Still, que debutó con hematuria y presentó evolución fatal. CONCLUSIÓN: La amiloidosis vesical secundaria constituye una entidad patológica muy infrecuente, pudiendo distinguir entre formas primarias de amiloidosis vesical y formas de amiloidosis sistémica con afectación vesical (amiloidosis vesical secundaria). Se asocia en la mayor parte de los pacientes a artritis reumatoide de larga evolución. El diagnostico clínico es difícil, siendo necesario el diagnóstico diferencial con los tumores vesicales. El estudio patológico e inmunohistoquímico, confirma el diagnóstico (AU)

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 (AU)