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Find video protocols related to scientific articles indexed in Pubmed.
Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of the Kidney: A Retrospective Detailed Study of Radiologic, Pathologic and Clinical Outcomes.
BJU Int.
PUBLISHED: 11-10-2014
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To characterize the clinical, radiologic and histologic features of Mucinous Tubular and Spindle Cell Carcinoma (MTSCC), as well as oncologic outcomes.
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Preoperative Predictors of Pathologic Lymph Node Metastasis in Patients with Renal Cell Carcinoma Undergoing RPLND.
J. Urol.
PUBLISHED: 10-22-2014
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Patients with locally advanced renal cell carcinoma (RCC) represent a subset of patients who may benefit from retroperitoneal lymph node dissection (RPLND). We aimed to identify preoperative clinical predictors of positive lymph nodes in patients with RCC without distant metastasis who underwent RPLND.
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The somatic genomic landscape of chromophobe renal cell carcinoma.
Cancer Cell
PUBLISHED: 08-21-2014
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We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.
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Glandular neoplasms of the urachus: a report of 55 cases emphasizing mucinous cystic tumors with proposed classification.
Am. J. Surg. Pathol.
PUBLISHED: 07-16-2014
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Published experience remains limited for glandular neoplasms of the urachus, especially mucinous cystic tumors. We reviewed 55 glandular urachal neoplasms to evaluate their clinical features and histopathologic spectrum and to devise a classification system for the mucinous cystic forms. Within the 55 cases studied, we observed 2 groups with differing clinical, gross, and histopathologic features. The first group, invasive, noncystic adenocarcinomas (n=24), had clinicopathologic features in accord with the known spectrum of urachal adenocarcinoma (mean age 50 y, female:male ratio 1.7, with recurrence or death from disease in 9/16 cases over a 45 mo mean follow-up). The second group, mucinous cystic tumors (n=31), morphologically resembled mucinous cystic tumors of the ovary and appeared classifiable by the same approach (mean age 47 y, female:male ratio 1.4) and included mucinous cystadenoma (n=4), mucinous cystic tumor of low malignant potential (n=22, including 2 cases with intraepithelial carcinoma), and mucinous cystadenocarcinoma with microscopic (n=4) or frank invasion (n=1). Follow-up information was available for 13 patients with mucinous cystic tumors (mean 41 mo); we observed no local recurrence or distant metastasis. This experience suggests that there is a distinct group of glandular, cystic tumors of the urachus that is classifiable in a manner similar to ovarian neoplasms and that has a favorable prognosis after complete excision. As with cystic neoplasms of other organs, rigorous sampling is recommended to identify potentially small foci of carcinoma that could be missed by inadequate sampling. Accordingly, classification based on methods other than complete surgical excision may be hazardous.
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Clear cell papillary renal cell carcinoma in patients with von Hippel-Lindau syndrome--clinicopathological features and comparative genomic analysis of 3 cases.
Hum. Pathol.
PUBLISHED: 04-25-2014
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Clear cell papillary renal cell carcinoma (CCPRCC) is a renal neoplasm that has recently received widespread recognition in the literature. There have been several reports of this tumor arising in a sporadic setting and in patients with end-stage renal disease; however, there is limited information available about the clinical, pathologic, and genetic characteristics of this tumor in the setting of von Hippel-Lindau (VHL) disease. We herein report a series of 3 patients who developed CCPRCC in this unique clinical setting. The histology and immunohistochemical profile for all 3 cases was similar to that which has been previously reported for CCPRCC. All tumors were diffusely and strongly positive for cytokeratin 7, negative for ?-methyl-CoA-racemase, and showed at least focal staining for CD10. Comparative genomic analysis was performed on tumors from all 3 patients. One tumor demonstrated monosomy 3, and the other 2 tumors showed normal chromosomal content. All 3 patients were alive without evidence of disease progression 5, 3, and 3 years after surgery. CCPRCC represents a distinct tumor type that may occur in the setting of VHL disease and should be considered in the differential diagnosis of extensively cystic renal tumors arising in this clinical setting. Molecular analysis in our series of cases suggests that CCPRCC does indeed represent a unique histologic subtype and must be distinguished from clear cell renal cell carcinoma due to different biological potentials. Ancillary studies for accurate classification are recommended due to significant morphologic overlap with clear cell renal cell carcinoma.
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Primary intra-renal desmoplastic small round cell tumor: Expanding the histologic spectrum, with special emphasis on the differential diagnostic considerations.
Pathol. Res. Pract.
PUBLISHED: 03-17-2014
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Intra-abdominal desmoplastic small round cell tumor (DSRCT) is a rare, aggressive tumor affecting adolescent and young males. DSRCT presenting as a primary renal mass in the absence of visceral or serosal involvement is extremely rare. Herein, we present the pathologic and molecular findings in the case of a young man who presented with a large renal mass without any visceral or serosal involvement. Noticeably, the tumor lacked prominent desmoplastic stroma and only focally expressed cytokeratin, both of which are considered characteristic histologic features for this tumor. Fluorescence in situ hybridization studies using an EWSR1 break-apart probe confirmed the presence of a rearrangement involving the EWSR1 locus and RT-PCR demonstrated the presence of an EWSR1-WT1 fusion transcript associated with the t(11;22) rearrangement, which supported a diagnosis of DSRCT. We also discuss the differential diagnostic considerations faced by the pathologist in the workup of small round cell neoplasms of the kidney.
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Collision tumor of the kidney composed of clear cell carcinoma and collecting duct carcinoma: report of a case with unusual morphology and clinical follow-up.
Chin J Cancer
PUBLISHED: 03-04-2014
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We report the case of a 67-year-old female who presented with a large renal mass. Gross examination of the nephrectomy specimen demonstrated a 6-cm renal mass that invaded into the renal sinus and perinephric fat. Histologic examination revealed two distinct tumor types. The first type was a conventional (clear cell) renal cell carcinoma that was of low nuclear grade and comprised the minority of the overall tumor. The second type was a high-grade collecting duct carcinoma with glandular/tubular differentiation and composed the majority of the tumor. Immunohistochemical studies demonstrated distinctive patterns of the two tumor types, thus confirming two distinct lineages. Five months postoperatively, the patient developed metastasis to the lungs and right hilar lymph node region. A fine needle aspiration of a lung nodule demonstrated a metastatic, poorly differentiated carcinoma, similar to the collecting duct carcinoma component in the kidney. Collision tumors of the kidney are rare with fewer than 10 cases reported in the literature. Our report further expands the spectrum of this rare phenomenon.
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ClearCode34: A prognostic risk predictor for localized clear cell renal cell carcinoma.
Eur. Urol.
PUBLISHED: 02-13-2014
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Gene expression signatures have proven to be useful tools in many cancers to identify distinct subtypes of disease based on molecular features that drive pathogenesis, and to aid in predicting clinical outcomes. However, there are no current signatures for kidney cancer that are applicable in a clinical setting.
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Phase 2 Trial of Neoadjuvant Axitinib in Patients with Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma.
Eur. Urol.
PUBLISHED: 01-28-2014
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Previous studies have shown a modest impact of tyrosine kinase inhibitors on primary renal tumors. Those studies were mostly retrospective or heterogeneous in their eligibility criteria with regard to histology, disease stage, duration of therapy, and time off therapy prior to surgery.
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Partial Nephrectomy in the Setting of Metastatic Renal Cell Carcinoma.
J. Urol.
PUBLISHED: 01-13-2014
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Cytoreductive nephrectomy remains the standard of care for appropriately selected patients with metastatic renal cell carcinoma. Although the role of partial nephrectomy is well accepted in patients with localized disease, limited data are available on partial nephrectomy in the metastatic setting. We identified the indications for and outcomes of partial nephrectomy in the setting of metastatic renal cell carcinoma with particular attention to partial nephrectomy subgroups.
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Cadherin-11 in renal cell carcinoma bone metastasis.
PLoS ONE
PUBLISHED: 01-01-2014
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Bone is one of the common sites of metastases from renal cell carcinoma (RCC), however the mechanism by which RCC preferentially metastasize to bone is poorly understood. Homing/retention of RCC cells to bone and subsequent proliferation are necessary steps for RCC cells to colonize bone. To explore possible mechanisms by which these processes occur, we used an in vivo metastasis model in which 786-O RCC cells were injected into SCID mice intracardially, and organotropic cell lines from bone, liver, and lymph node were selected. The expression of molecules affecting cell adhesion, angiogenesis, and osteolysis were then examined in these selected cells. Cadherin-11, a mesenchymal cadherin mainly expressed in osteoblasts, was significantly increased on the cell surface in bone metastasis-derived 786-O cells (Bo-786-O) compared to parental, liver, or lymph node-derived cells. In contrast, the homing receptor CXCR4 was equivalently expressed in cells derived from all organs. No significant difference was observed in the expression of angiogenic factors, including HIF-1?, VEGF, angiopoeitin-1, Tie2, c-MET, and osteolytic factors, including PTHrP, IL-6 and RANKL. While the parental and Bo-786-O cells have similar proliferation rates, Bo-786-O cells showed an increase in migration compared to the parental 786-O cells. Knockdown of Cadherin-11 using shRNA reduced the rate of migration in Bo-786-O cells, suggesting that Cadherin-11 contributes to the increased migration observed in bone-derived cells. Immunohistochemical analysis of cadherin-11 expression in a human renal carcinoma tissue array showed that the number of human specimens with positive cadherin-11 activity was significantly higher in tumors that metastasized to bone than that in primary tumors. Together, these results suggest that Cadherin-11 may play a role in RCC bone metastasis.
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Phase II trial of pemetrexed plus gemcitabine in patients with locally advanced and metastatic nonclear cell renal cell carcinoma.
Am. J. Clin. Oncol.
PUBLISHED: 11-15-2013
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To determine the clinical activity and safety of the combination of pemetrexed and gemcitabine in advanced nonclear cell renal cell carcinoma (nccRCC).
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Handling and staging of renal cell carcinoma: the International Society of Urological Pathology Consensus (ISUP) conference recommendations.
Am. J. Surg. Pathol.
PUBLISHED: 09-13-2013
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The International Society of Urologic Pathology 2012 Consensus Conference on renal cancer, through working group 3, focused on the issues of staging and specimen handling of renal tumors. The conference was preceded by an online survey of the International Society of Urologic Pathology members, and the results of this were used to inform the focus of conference discussion. On formal voting a ?65% majority was considered a consensus agreement. For specimen handling it was agreed that with radical nephrectomy specimens the initial cut should be made along the long axis and that both radical and partial nephrectomy specimens should be inked. It was recommended that sampling of renal tumors should follow a general guideline of sampling 1 block/cm with a minimum of 3 blocks (subject to modification as needed in individual cases). When measuring a renal tumor, the length of a renal vein/caval thrombus should not be part of the measurement of the main tumor mass. In cases with multiple tumors, sampling should include at a minimum the 5 largest tumors. There was a consensus that perinephric fat invasion should be determined by examining multiple perpendicular sections of the tumor/perinephric fat interface and by sampling areas suspicious for invasion. Perinephric fat invasion was defined as either the tumor touching the fat or extending as irregular tongues into the perinephric tissue, with or without desmoplasia. It was agreed upon that renal sinus invasion is present when the tumor is in direct contact with the sinus fat or the loose connective tissue of the sinus, clearly beyond the renal parenchyma, or if there is involvement of any endothelium-lined spaces within the renal sinus, regardless of the size. When invasion of the renal sinus is uncertain, it was recommended that at least 3 blocks of the tumor-renal sinus interface should be submitted. If invasion is grossly evident, or obviously not present (small peripheral tumor), it was agreed that only 1 block was needed to confirm the gross impression. Other recommendations were that the renal vein margin be considered positive only when there is adherent tumor visible microscopically at the actual margin. When a specimen is submitted separately as "caval thrombus," the recommended sampling strategy is to take 2 or more sections to look for the adherent caval wall tissue. It was also recommended that uninvolved renal parenchyma be sampled by including normal parenchyma with tumor and normal parenchyma distant from the tumor. There was consensus that radical nephrectomy specimens should be examined for the purpose of identifying lymph nodes by dissection/palpation of the fat in the hilar area only; however, it was acknowledged that lymph nodes are found in <10% of radical nephrectomy specimens.
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Genomic heterogeneity of translocation renal cell carcinoma.
Clin. Cancer Res.
PUBLISHED: 07-01-2013
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Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney cancer involving the TFEB/TFE3 genes. We aimed to investigate the genomic and epigenetic features of this entity.
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Tumor-specific isoform switch of the fibroblast growth factor receptor 2 underlies the mesenchymal and malignant phenotypes of clear cell renal cell carcinomas.
Clin. Cancer Res.
PUBLISHED: 02-26-2013
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We aim to identify tumor-specific alternative splicing events having potential applications in the early detection, diagnosis, prognosis, and therapy for cancers.
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Epidemiology and sites of involvement of invasive fungal infections in patients with haematological malignancies: a 20-year autopsy study.
Mycoses
PUBLISHED: 01-11-2013
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Autopsy studies remain an essential tool for understanding the patterns of fungal disease not detected ante mortem with current diagnostic approaches. We collected data concerning the microbiological trends, patient clinical characteristics and sites of involvement for invasive fungal infections (IFIs) identified at autopsy in a single large cancer treatment centre over a 20-year period (1989-2008). The autopsy rate and IFI prevalence both declined significantly during the study period. The prevalence of Aspergillus spp. decreased significantly from the first 15 years of the study (from 0.12 to 0.14 cases per 100 autopsies to 0.07 in 2004-2008; P = 0.04), with only Mucorales accounting for a greater proportion of IFIs over the duration of the study period (0.06 to 0.2 cases per 100 autopsies, P = 0.04). After 2003, moulds accounted for the majority of infections identified at autopsy in the spleen, kidney, heart and gastrointestinal tract. Despite a trend of decreasing prevalence from 1989 to 2004, invasive candidiasis increased in prevalence during later periods 2004-2008 (0.02-0.05 per 100 autopsies) with decreasing kidney, heart and spleen involvement. Despite a declining autopsy rate, these data suggest a decreasing prevalence overall of IFIs with changing patterns of dissemination in patients with haematological malignancies.
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Role of inflammatory related gene expression in clear cell renal cell carcinoma development and clinical outcomes.
J. Urol.
PUBLISHED: 09-23-2011
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Renal cell carcinoma is the eighth most common cancer in the United States and clear cell renal carcinoma is the most common type. Many signaling pathways are implicated in clear cell renal carcinoma development, including the inflammation pathway. However, less is known about how gene expression variation in this pathway influences clear cell renal carcinoma development and clinical outcomes.
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Early primary tumor size reduction is an independent predictor of improved overall survival in metastatic renal cell carcinoma patients treated with sunitinib.
Eur. Urol.
PUBLISHED: 04-11-2011
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In metastatic renal cell carcinoma (mRCC) patients treated with targeted agents and their primary tumor (PT) in situ, early PT decrease in size correlates with improved overall PT response, but the effect on overall survival (OS) is unknown.
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Small cell carcinoma of the kidney: a clinicopathologic study of 14 cases.
Hum. Pathol.
PUBLISHED: 01-20-2011
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Small cell carcinoma of the kidney is distinctively rare. We searched pathology files in 2 institutions and found 14 cases of renal small cell carcinoma. The patients mean age at diagnosis was 59 years (range, 22-75 years); 8 were women, and 6 were men. Patients usually presented with hematuria (n = 6) and abdominal pain (n = 5). The mean tumor size was 7.1 cm (range, 3.5-14.0 cm). The small cell carcinoma was pure in 9 cases and mixed with high-grade urothelial carcinoma in 5 cases. None was associated with any type of renal cell carcinoma. Tumor necrosis was present in all cases, and lymphovascular invasion was identified in 6 cases. The tumor invaded the perinephric adipose tissue in 13 cases and was confined to the kidney in only 1 case. Lymph node metastases were identified in all patients who underwent lymph node dissection (5/5). On immunostains, the small cell carcinoma cells were positive for pancytokeratin (11/12), chromogranin (6/9), and synaptophysin (8/9). Follow-up data were available for 13 patients, and 11 died of small cell carcinoma at a mean of 15 months (range, 4-31 months) after diagnosis. Of the 2 surviving patients, 1 was alive at 5 months after diagnosis, and the other, whose disease was confined to the kidney, was alive with no evidence of disease at 137 months. In summary, renal small cell carcinoma is a highly aggressive disease that often presents at an advanced stage with widespread metastases. Patients usually have a poor clinical outcome despite multimodal therapy. The frequent coexistence of small cell carcinoma with urothelial carcinoma suggests that renal small cell carcinomas may evolve from a preexisting urothelial carcinoma.
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Can a durable disease-free survival be achieved with surgical resection in patients with pathological node positive renal cell carcinoma?
J. Urol.
PUBLISHED: 01-14-2011
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Patients with isolated regional nodal metastases from renal cell carcinoma are a distinct cohort for which resection of involved lymph nodes may be therapeutic. We assessed the outcomes of patients treated at our institution with pathological node positive renal cell carcinoma without concomitant metastatic disease (T(any)N+M0).
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Mesenchymal neoplasms of the kidney in adults: imaging spectrum with radiologic-pathologic correlation.
Radiographics
PUBLISHED: 11-13-2010
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Mesenchymal neoplasms of the kidney in adults cover a wide spectrum with characteristic ontogeny and histologic findings and variable biologic profiles and imaging findings. Benign mesenchymal renal tumors include angiomyolipoma, leiomyoma, hemangioma, lymphangioma, juxtaglomerular cell tumor, renomedullary interstitial cell tumor (medullary fibroma), lipoma, solitary fibrous tumor, and schwannoma. Malignant renal tumors of mesenchymal origin include leiomyosarcoma, rhabdomyosarcoma, angiosarcoma, osteosarcoma, synovial sarcoma, fibrosarcoma, malignant fibrous histiocytoma, and solitary fibrous tumor. Cross-sectional imaging findings for mesenchymal renal tumors in adults are varied. Although angiomyolipomas and lipomas show macroscopic fat, lymphangiomas are cystic in appearance. Renal hemangioma may show phleboliths and a characteristic enhancement pattern. Leiomyoma typically arises from the capsule and causes buckling of the renal cortex. Although osteosarcoma may demonstrate characteristic dense ossification, most renal sarcomas demonstrate imaging features that are indistinguishable from the more common renal cell carcinoma. Although some renal mesenchymal tumors have typical imaging findings, biopsy is warranted to establish a definitive diagnosis. Awareness of the various mesenchymal renal tumors and familiarity with their imaging findings permit optimal patient management.
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Development and characterization of clinically relevant tumor models from patients with renal cell carcinoma.
Eur. Urol.
PUBLISHED: 11-07-2010
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Animal models are instrumental in understanding disease pathophysiology and mechanisms of therapy action and resistance in vivo.
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Genetic variations in microRNA-related genes are associated with survival and recurrence in patients with renal cell carcinoma.
Carcinogenesis
PUBLISHED: 08-23-2010
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We took a polygenic approach to evaluate the effects of 41 potentially functional single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs)-related genes on survival and recurrence among renal cell carcinoma (RCC) patients. During a median follow-up of 21.8 months, among 316 RCC patients, 64 died and 56 developed recurrence. In single-SNP analysis, we identified seven SNPs significantly associated with RCC survival and five SNPs with recurrence. The most significant associations were SNPs in GEMIN4 with the variant alleles of both rs7813 and rs910925 associated with 1.74-fold [95% confidence interval (CI) = 1.15-2.62] increased risk of death, whereas the variant allele of rs3744741 conferred a decreased risk of death [hazard ratio (HR) = 0.39; 95% CI = 0.19-0.77]. Several SNPs belonging to the pre-miRNA and were identified to be significantly associated with RCC recurrence. Haplotypes of DICER and DROSHA were also associated with altered patient survival and recurrence. More importantly, we observed cumulative effects of multiple SNPs on RCC survival. Compared with subjects carrying zero to two unfavorable genotypes, those carrying three to five and six and more unfavorable genotypes had an increased risk of death with a HR of 2.49 (95% CI = 1.24-5.00) and 6.66 (95% CI = 2.49-17.86), respectively, with significant dose-response trend (P for trend<0.001). As the first study of miRNA-related genetic polymorphisms on RCC clinical outcome, our results strongly suggested that miRNA-related SNPs may impact the recurrence and survival in RCC patients. Future investigation in larger populations and functional characterizations are necessary to validate these results.
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Interobserver reproducibility in the diagnosis of invasive micropapillary carcinoma of the urinary tract among urologic pathologists.
Am. J. Surg. Pathol.
PUBLISHED: 08-19-2010
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Invasive micropapillary carcinoma (IMPC) of the urinary tract is a well-described variant of the urothelial carcinoma with aggressive clinical behavior. Recent studies have proposed that patients with IMPC on transurethral resection should be treated with radical cystectomy regardless of the pathologic stage. Despite the potentially important therapeutic implications of this diagnosis, interobserver variation in the diagnosis of IMPC has not been studied. Sixty digital images, each from hematoxylin and eosin-stained slides, representing 30 invasive urothelial carcinomas (2 images per case), were distributed to 14 genitourinary subspecialists and each pathologist was requested to classify cases as IMPC or not. These cases included "classic" IMPC (n=10) and urothelial carcinoma with retraction and variably sized nests that might potentially be regarded as IMPC (n=20). The following 13 morphologic features were recorded as positive/negative for all cases independent of the reviewers diagnoses: columnar cells, elongate nests or processes, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial ring forms, intracytoplasmic vacuolization, multiple nests within the same lacunar space, back-to-back lacunar spaces, epithelial nest anastomosis/confluence, marked nuclear pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, and tumor nest size. In addition, a mean tumor nest size was calculated for each image based on the number of nuclei spanning the width of the nests. Interobserver reproducibility was assessed and the morphologic features were correlated with the classic IMPC and nonclassic/potential IMPC groups. In addition, the relationships between morphologic features, pathologists interpretations, and case type (classic IMPC vs. nonclassic/potential IMPC) were evaluated using unsupervised hierarchical clustering analysis. Interobserver reproducibility for a diagnosis of IMPC in the 30 study cases was moderate (kappa: 0.54). Although classification as IMPC among the 10 "classic" IMPC cases was relatively uniform (93% agreement), the classification in the subset of 20 invasive urothelial carcinomas with extensive retraction and varying sized tumor nests was more variable. Multiple nests within the same lacunar space had the highest association with a diagnosis of classic IMPC. These findings suggest that more study of IMPC is needed to identify the individual pathologic features that might potentially correlate with an aggressive outcome and response to intravesical therapy.
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Primary tumor response to targeted agents in patients with metastatic renal cell carcinoma.
Eur. Urol.
PUBLISHED: 08-16-2010
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The recent development of multiple targeted agents for metastatic renal cell carcinoma (mRCC) has changed the treatment paradigm; hence the benefit and optimal timing of cytoreductive nephrectomy is being reevaluated.
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Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma.
Cancer
PUBLISHED: 07-29-2010
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Adult "translocation" renal cell carcinoma (RCC), bearing transcription factor E3 (TFE3) gene fusions at Xp11.2, is a recently recognized, unique entity for which prognosis and therapy remain poorly understood. In the current study, the authors investigated the effect of vascular endothelial growth factor (VEGF)-targeted therapy in this distinct subtype of RCC.
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Intraluminal polypoid metastasis of renal cell carcinoma in gallbladder mimicking gallbladder polyp.
Arch. Pathol. Lab. Med.
PUBLISHED: 07-01-2010
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Metastatic renal cell carcinoma (RCC) in gallbladder is rare with only 18 cases published in the English literature.
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Can we better select patients with metastatic renal cell carcinoma for cytoreductive nephrectomy?
Cancer
PUBLISHED: 06-22-2010
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The benefits of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) should outweigh surgical morbidity. Even when the generally agreed upon selection criteria for CN are met, some patients do poorly after surgery. The objective of this study was to identify preoperative factors that were prognostic of outcome in patients who were being considered for CN.
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Identifying the risk of disease progression after surgery for localized renal cell carcinoma.
BJU Int.
PUBLISHED: 04-17-2010
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To identify factors in a large cohort of patients with pathologically localized renal cell carcinoma (RCC) that predicted disease progression after surgery, as RCC most commonly presents as a localized tumour which is treated with surgical excision.
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Warty-basaloid carcinoma: clinicopathological features of a distinctive penile neoplasm. Report of 45 cases.
Mod. Pathol.
PUBLISHED: 03-19-2010
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Most penile cancers are squamous cell carcinomas, but there are several subtypes with different clinicopathologic, viral, and outcome features. We are presenting 45 cases of a distinctive morphological variant of penile squamous cell carcinoma composed of mixed features of warty and basaloid carcinomas. This tumor was earlier recognized in a recent viral study and showed a high association with human papillomavirus infection. However, clinicopathologic features are not well known. In this multi-institutional study, patients mean age was 62 years. Most tumors (64%) invaded multiple anatomical compartments, including glans, coronal sulcus, and, especially, inner foreskin mucosa. Tumor size ranged from 2 to 12 cm (mean 5.5 cm). Three morphological patterns were recognized: (1) the most common, observed in two-thirds of the cases was that of a typical condylomatous tumor on surface and basaloid features in deep infiltrative nests; (2) in 15% of the cases, there were non-papillomatous invasive carcinoma nests with mixed basaloid and warty features; and (3) unusually, predominantly papillomatous. Invasion of penile erectile tissues was frequent, either corpus spongiosum or cavernosum (47% each). Tumors limited to lamina propria were rare. Most tumors were of high grade (89%). Vascular and perineural invasion were found in about one-half and one-quarter of cases, respectively. Associated penile intraepithelial neoplasia was identified in 19 cases and mostly showed basaloid, warty-basaloid, or warty features. Inguinal nodal metastases were found in 11/21 patients with groin dissections. Invasion of corpora cavernosa, high histological grade, and presence of vascular/perineural invasion were more prevalent in metastatic cases. In 21 patients followed, the cancer-specific mortality rate was 33% with a mean survival time of 2.8 years. Warty-basaloid carcinomas are morphologically distinctive human papillomavirus-related penile neoplasms that, such as basaloid carcinomas, are biologically more aggressive than typical warty carcinoma from which they should be distinguished.
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Percutaneous biopsy of primary tumor in metastatic renal cell carcinoma to predict high risk pathological features: comparison with nephrectomy assessment.
J. Urol.
PUBLISHED: 02-24-2010
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As treatment options evolve for metastatic renal cell carcinoma, there is a need for predictive information to help guide therapy. We assessed the accuracy of percutaneous primary tumor biopsy for metastatic renal cell carcinoma by comparing biopsy findings to final nephrectomy pathology in patients undergoing cytoreductive nephrectomy.
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The mammalian target of rapamycin pathway is widely activated without PTEN deletion in renal cell carcinoma metastases.
Cancer
PUBLISHED: 02-19-2010
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Inhibitors of the mammalian target of rapamycin (mTOR) are emerging as promising therapies for metastatic renal cell carcinoma (RCC). Because rational treatment strategies require understanding the activation status of the underlying signaling pathway being targeted at the desired stage of disease, the authors examined the activation status of different components of the mTOR pathway in RCC metastases and matched primary tumors.
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Mediastinal germ cell tumors with an angiosarcomatous component: a report of 12 cases.
Hum. Pathol.
PUBLISHED: 02-12-2010
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The development of an angiosarcomatous component in germ cell tumors is rare. Here we studied 12 cases of mediastinal germ cell tumors with an angiosarcomatous component. All patients were men with a mean age of 34 years (range, 24-49 years). No patient had a documented testicular germ cell tumor. The mean size of mediastinal tumors was 12.9 cm (range, 5.5-16.0 cm). Grossly, the tumors were cystic with variegated hemorrhagic, mucinous, and fleshy solid areas. Microscopically, all tumors were composed of germ cell tumor. The most common germ cell tumor component was teratoma (n = 10); and other germ cell tumor components included seminoma (n = 3), yolk sac tumor (n = 3), embryonal carcinoma (n = 2), and choriocarcinoma (n = 1). The angiosarcomatous component was present in primary mediastinal tumors (n = 6), metastasis (n = 3), or both primary mediastinal tumor and metastasis (n = 3). The angiosarcomatous component accounted for an average of 30% (range, 5%-95%) of the primary mediastinal tumor. In addition, other non-germ cell components, including rhabdomyosarcoma (n = 3), leiomyosarcoma (n = 1), and poorly differentiated carcinoma (n = 1), were also present in the tumors. Of the 10 patients with follow-up available, all patients developed metastasis (n = 8) or local recurrence (n = 2); 7 died of disease at a mean of 33 months (range, 21-75 months), and 3 patients were alive at a mean of 75 months (range, 5-120 months). Our findings suggest that the presence of an angiosarcomatous component in mediastinal germ cell tumor, even in a small amount, is associated with a poor clinical outcome.
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Thyroid-like follicular carcinoma of the kidney with metastases to the lungs and retroperitoneal lymph nodes.
Hum. Pathol.
PUBLISHED: 01-13-2010
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Thyroid-like follicular carcinoma of the kidney is an extremely rare variant of renal cell carcinoma. Most previously reported cases presented as incidental small tumors confined to the kidney. Here we report a unique case in which the patient presented with flank pain and hematuria. Imaging studies demonstrated a large tumor in the right kidney and metastases to the lungs and retroperitoneal lymph nodes. Both the renal tumor and the sampled lung metastasis were composed almost entirely of follicles with dense, colloid-like material resembling thyroid follicular carcinoma. However, no lesion was found in the thyroid gland; and the patients thyroid function test results were normal. The tumor cells were immunoreactive for PAX2 and PAX8 but lacked reactivity for thyroglobulin and thyroid transcription factor-1. To our knowledge, this is the first case of thyroid-like follicular carcinoma of the kidney to be initially associated with marked symptoms and widespread metastases, providing evidence that this rare variant of renal cell carcinoma can be clinically aggressive.
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Phase II presurgical feasibility study of bevacizumab in untreated patients with metastatic renal cell carcinoma.
J. Clin. Oncol.
PUBLISHED: 07-27-2009
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To assess safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC), and to explore the hypothesis that pretreatment of patients with antiangiogenic therapy will select patients who benefit most from cytoreductive nephrectomy.
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Comparison of subtypes of penile squamous cell carcinoma from high and low incidence geographical regions.
Int. J. Surg. Pathol.
PUBLISHED: 07-03-2009
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There is a worldwide geographical variation in the incidence of penile squamous cell carcinoma (PSCC); some subtypes are HPV-related (warty, basaloid) while others (keratinizing variants) are not. The aims of this study were to compare the distribution of different histological subtypes of PSCC from regions of low (Paraguay, 144 cases) and high (USA, 157 cases) incidence and to identify and compare tumors with and without warty and/or basaloid morphology. The distribution of subtypes in the Paraguayan and the American series was: usual, 49.3 and 46.5%; verrucous, 8.3 and 7.6%; papillary NOS, 7.6 and 5.7%; warty, 6.9 and 8.3%; basaloid, 4.2 and 7.0%; sarcomatoid, 0.7 and 0.6%; adenosquamous, 3.5 and 0.6%; and mixed, 19.4 and 23.6%, respectively. The distribution of mixed PSCC was: warty-basaloid, 50.0 and 59.5%; usual-verrucous, 21.4 and 21.6%; usual-warty, 14.3 and 8.1%; usual-basaloid, 7.1 and 0.0%; usual-papillary, 3.6 and 5.4%; and others, 3.6 and 5.4%, respectively. In conclusion, we found no geographical difference in the incidence of histological subtypes (p = 0.6501), mixed PSCC (p = 0.5937) or HPV-related tumors (p = 0.2505). Geographical variation may be the result of staging variation at clinical presentation or of pathological diagnosis. The identification of similar histological subtypes in both series validates this classification approach for penile cancer. The tendency for typical SCC to mix with verrucous and papillary carcinomas and of the basaloid to preferentially mix with benign condyloma and condylomatous (warty) carcinomas would support the hypothesis of the existence of an etiologically different dual population of penile tumors.
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Testicular germ cell tumors with sarcomatous components: an analysis of 33 cases.
Am. J. Surg. Pathol.
PUBLISHED: 06-30-2009
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The development of sarcomatous component (SC) in testicular germ cell tumor (GCT) is an uncommon phenomenon. We searched our surgical pathology files from 1985 to 2007 and identified 33 cases of testicular GCTs with SC. The average age of patients was 31 years. All patients underwent radical orchiectomy, which demonstrated a GCT in all patients except for 3 patients who had received neoadjuvant chemotherapy. All testicular GCTs contained a teratomatous component. The GCTs were pure teratomas in 3 cases, and were mixed GCTs in the other cases. The SC was observed in primary testicular tumor (n=19), in metastasis (n=11), or in both primary testicular tumor and metastasis (n=3). The average percentage of the SC in the primary testicular GCT was 32% (range: 5% to 99%). The most common histologic type of SC was rhabdomyosarcoma (n=24), followed by high-grade unclassified sarcoma (n=5), rhabdomyosarcoma admixed with high-grade unclassified sarcoma (n=2), angiosarcoma (n=1), and low-grade myxoid sarcoma (n=1). Clinical follow-up information was available for 27 patients. Of the 13 patients whose SC was limited to the testicular GCT, 2 patients died of GCT not otherwise specified at 37 and 68 months, respectively; and 11 patients were free of disease at a mean of 46 months. Of the 14 patients with a SC in the metastasis, 7 patients died of GCT not otherwise specified at a mean of 95 months, and 7 patients were free of disease at a mean of 104 months. These results suggest that patients with a SC confined to the primary testicular GCT may not have a higher risk of mortality than those at a comparable stage without a SC. However, patients with a SC in the metastasis have an increased risk of mortality.
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Genome-wide profiling of chromosomal alterations in renal cell carcinoma using high-density single nucleotide polymorphism arrays.
Int. J. Cancer
PUBLISHED: 06-13-2009
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The identification of genetic aberrations may help understand the mechanisms of tumorigenesis and has important implications in diagnosis, prognosis and treatment. We applied Illuminas 317K high-density single nucleotide polymorphism (SNP) arrays to profile chromosomal aberrations in clear cell renal cell carcinoma (ccRCC) from 80 patients and analyzed the association of LOH/amplification events with clinicopathological characteristics and telomere length. The most common loss of heterozygosity (LOH) were 3p (69 cases) including 38 whole 3p arm losses, 30 large fragment LOH (spanning 3p21-36), and 1 interstitial LOH (spanning 3p12-14, 3p21-22, 3p24.1-24.2 and 3p24.3), followed by chromosome losses at 8p12-pter, 6q23.3-27, 14q24.1-qter, 9q32-qter, 10q22.3-qter, 9p13.3-pter, 4q28.3-qter and 13q12.1-21.1. We also found several smallest overlapping regions of LOH that contained tumor suppressor genes. One smallest LOH in 8p12 had a size of 0.29 Mb and only contained one gene (NRG1). The most frequent chromosome gains were at 5q (32 cases), including 10 whole 5q amplification, 21 large amplifications encompassing 5q32-ter and 1 focal amplification in 5q35.3 (0.42 Mb). The other common chromosome gains were 1q25.1-qter, 7q21.13-qter, 8q24.12-qter and whole 7p arm. Significant associations of LOH at 9p, 9q, 14q and 18q were observed with higher nuclear grade. Significant associations with tumor stage were observed for LOH at 14q, 18p and 21q. Finally, we found that tumors with LOH at 2q, 6p, 6q, 9p, 9q and 17p had significantly shorter telomere length than those without LOH. This is the first study to use Illuminas SNP-CGH array that provides a close estimate of the size and frequency of chromosome LOH and amplifications of ccRCC. The identified regions and genes may become diagnostic and prognostic biomarkers as well as potential targets of therapy.
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Clear cell adenocarcinoma of the urinary bladder: a short review.
Arch. Pathol. Lab. Med.
PUBLISHED: 06-05-2009
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In this short review, we discuss clear cell adenocarcinoma of the urinary bladder, a rare tumor that primarily affects women. The histogenesis of this neoplasm is uncertain; in some tumors the clinicopathologic and histologic features are suggestive of a müllerian origin. Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. These tumors are positive for pancytokeratin, cytokeratin 7, and CA 125 immunohistochemical stains. Patients typically present with gross hematuria, dysuria, and discharge. The natural history is poorly understood and patient outcomes remain unclear. Currently, surgery is the treatment of choice. Nephrogenic adenoma is the most important differential diagnostic consideration, followed by metastatic clear cell carcinoma.
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Papillary renal cell carcinoma: radiologic-pathologic correlation and spectrum of disease.
Radiographics
PUBLISHED: 05-19-2009
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Papillary renal cell carcinoma (pRCC) is the second most common type of renal cell carcinoma (RCC). pRCC has unique imaging and clinical features that may allow differentiation from clear cell RCC (cRCC). There have been significant advances in our knowledge of the natural history and treatment of pRCC, with data suggesting that it may be best to manage pRCC differently from the other subtypes of RCC. At contrast material-enhanced computed tomography, pRCC enhances less than does cRCC in all phases of contrast-enhanced imaging. The difference in the degree of enhancement between pRCC and cRCC is due to differences in their intratumoral vascularity. In general, if a heterogeneous mass enhances to a degree similar to that manifested by the renal cortex, it is likely to be a cRCC. A mass that enhances to a lesser degree is likely to be a non-clear cell RCC. It is common for metastatic lesions from pRCC to show enhancement characteristics similar to those of the primary tumor and be hypovascular.
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Pleomorphic and dedifferentiated leiomyosarcoma: clinicopathologic and immunohistochemical study of 41 cases.
Hum. Pathol.
PUBLISHED: 05-14-2009
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In this article, we supplement the few published articles by describing the clinical and pathologic features of pleomorphic and dedifferentiated leiomyosarcoma from 41 patients (27 women and 14 men) with an age range of 25 to 75 years (mean, 56.5 years), representing the largest cohort reported to date. The typical leiomyosarcoma component accounted for <5% to 60% (mean, 15%) of the tumor. The pleomorphic sarcoma component was composed of polygonal cells in 57% of cases, spindle cells in 21%, a combination of polygonal, epithelioid, rhabdoid, and/or spindle cells in 18%, and predominantly epithelioid cells in 3%. The classical leiomyosarcoma component was positive for at least one myogenic immunohistochemical marker in 29 tumors tested; smooth muscle actin in 100% (27/27), calponin in 90% (9/10), muscle-specific actin in 90% (10/11), desmin in 86% (23/27), smooth muscle myosin heavy chain (SMMS-1) in 67% (4/6), and caldesmon in 57% (4/7). The pleomorphic sarcoma component was reactive for at least one muscle marker in 77% (23/30) of cases; smooth muscle actin in 63% (17/27), calponin in 60% (6/10), SMMS-1 in 60% (3/5), desmin in 59% (16/27), muscle-specific actin in 40% (4/10), and caldesmon in 29% (2/7). The classical leiomyosarcoma component was often strongly positive for myogenic markers, and the pleomorphic sarcoma component usually showed focal and less intense immunoreactivity. Based on staining for muscle markers in the pleomorphic component, twenty-three cases were designated as pleomorphic leiomyosarcoma, and 7 cases were designated as dedifferentiated leiomyosarcoma (negative for all muscle markers used). Eleven cases, in which tissue was not available for immunhistochemical stains, the question of pleomorphic versus dedifferentiated leiomyosarcoma could not be answered. The incidence of metastasis was 89% (32/36) and the mortality rate was 50% (18/36) at last follow-up (3-104 months; mean, 27.5 months).
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Plasmacytoid urothelial carcinoma: detailed analysis of morphology with clinicopathologic correlation in 17 cases.
Am. J. Surg. Pathol.
PUBLISHED: 03-26-2009
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The plasmacytoid variant of urothelial carcinoma is rare, of which less than 40 cases have been reported in the English language literature. Herein we report the largest series to date of 17 cases of urothelial carcinoma with plasmacytoid features and report the associated clinicopathologic findings. The architectural pattern of the tumor varied from cells arranged in cords and single cells (35%), small nests (17%), solid sheetlike growth (29%), and diffuse discohesive patternless architecture (23%). The plasmacytoid component varied from 15% to 100% of the specimen analyzed; in 12 cases the plasmacytoid component composed greater than 50% of the tumor. The individual tumor cells had striking morphologic overlap with plasma cells with an eccentrically placed nucleus and abundant amphophilic to eosinophilic cytoplasm. The nuclei were of low to intermediate nuclear grade with minimal nuclear pleomorphism. Thirteen of 17 cases (76%) were associated with conventional high-grade invasive urothelial carcinoma and 9 cases showed very focal intracytoplasmic vacuoles mimicking signet ring cells. One case also showed sarcomatoid dedifferentiation. The tumor cells were positive for cytokeratin 7 (94%) and cytokeratin 20 (31%); CD138 was positive in 94% of cases. All cases were invasive -- 7 into at least the lamina propria, 7 into at least the muscularis propria, and 3 into perivesical fat. Follow-up information was available in 16 cases (range: 2 wk to 43 mo; mean 10 mo; median 5.5 mo). Eleven patients died of disease and 5 patients were alive with disease. Plasmacytoid variant of urothelial carcinoma is an aggressive subtype associated with poor prognosis. In limited samples, it may be misdiagnosed as chronic cystitis or plasmacytoma, a pitfall further compounded by CD138 expression. Distinction from metastatic carcinoma from other primary sites such as stomach and breast is critical due to differing therapeutic implications.
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Predictors of oncological outcome after resection of locally recurrent renal cell carcinoma.
J. Urol.
PUBLISHED: 03-14-2009
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Local renal cell carcinoma recurrence is rare after radical nephrectomy with curative intent. We examined our experience to describe the natural history of isolated local recurrence and characterize important prognostic factors that predict the outcome in patients treated with aggressive resection.
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Association between lymph node density and disease specific survival in patients with penile cancer.
J. Urol.
PUBLISHED: 03-11-2009
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We assessed the value of lymph node density for predicting disease specific survival after lymphadenectomy for penile cancer.
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Randomized trial of adjuvant thalidomide versus observation in patients with completely resected high-risk renal cell carcinoma.
Urology
PUBLISHED: 03-06-2009
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To evaluate the effect of adjuvant thalidomide on recurrence-free survival (RFS) after nephrectomy for high-risk metastatic renal cell carcinoma (RCC).
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Squamous cell carcinoma of the urinary bladder: a clinicopathologic and immunohistochemical study of 16 cases.
Hum. Pathol.
PUBLISHED: 03-02-2009
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Squamous cell carcinoma is an uncommon histologic type in the urinary bladder. We searched our surgical pathology files and identified 16 cases of squamous cell carcinoma of the urinary bladder. The mean age of patients was 65.4 years (range, 41-77 years). All patients received transurethral resection of the bladder, which demonstrated pure squamous cell carcinomas. Seven patients had clinical evidence of tumor spreading out of the bladder (T4) and did not undergo radical cystectomy. The other 9 patients underwent cystectomy with pelvic lymph node dissection. The cystectomy specimens revealed tumors invading muscularis propria (T2) (n = 4) or perivesical soft tissue (T3) (n = 5). Two patients also had metastasis to lymph nodes. Immunohistochemical studies demonstrated that squamous cell carcinoma cells were positive for epidermal growth factor receptor (n = 16) and for p53 (n = 11). For the 9 patients who received cystectomy, 5 patients were alive at a mean of 92.8 months (range, 59-128 months) and 4 patients died of disease at a mean of 24.0 months (range, 6-58 months). For the 7 patients who did not receive cystectomy, 6 died at a mean of 5.7 months (range, 3-9 months), and no follow-up was available for the remaining patient. In conclusion, squamous cell carcinoma of the bladder frequently presents at an advanced stage and is associated with enhanced expression of EGFR and p53.
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Family history and risk of renal cell carcinoma: results from a case-control study and systematic meta-analysis.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 02-24-2009
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We conducted a case-control analysis, a family-based population analysis, and a meta-analysis to assess the role of family history of cancer and kidney cancer in association with the risk of renal cell carcinoma (RCC). A total of 325 cases and 329 controls were identified from an ongoing case-control study of RCC. Study variables were assessed through 45-minute structured face-to-face interviews. In the case-control analysis, a family history of any cancer (in first-degree relatives) was associated with a nonsignificant 1.2-fold increase in RCC risk [95% confidence interval (95% CI), 0.8-1.6]. The risk increased to 1.7 and became significant when the relative was a sibling (95% CI, 1.1-2.5). A family history of kidney cancer (kidney cancer in first-degree relatives) was associated with a 4.3-fold significantly increased risk of RCC (95% CI, 1.6-11.9). The cases reported a total of 2,536 first-degree relatives of which 21 (0.8%) had kidney cancer, and the controls reported a total of 2,333 first-degree relatives of which 5 (0.2%) had kidney cancer (P=0.003). In the family-based population analysis, a family history of kidney cancer was associated with a 2.8-fold increased risk of RCC (95% CI, 1.0-7.8). The meta-analysis further confirmed this significant association with a 2.2-fold increased risk of RCC (95% CI, 1.6-2.9). To our knowledge, this is the first study to use three analytic strategies to investigate the association between a family history of kidney cancer and risk of RCC, and the first systematic evaluation of the relative risk for developing RCC associated with family history.
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Micropapillary variant of urothelial carcinoma in the upper urinary tract: a clinicopathologic study of 11 cases.
Arch. Pathol. Lab. Med.
PUBLISHED: 01-07-2009
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Micropapillary urothelial carcinoma (MPUC) is a rare variant of urothelial carcinoma. Most studies of MPUC have focused on the urinary bladder, but MPUC of the upper urinary tract remains to be investigated.
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Cytoplasmic sequestration of p27 via AKT phosphorylation in renal cell carcinoma.
Clin. Cancer Res.
PUBLISHED: 01-02-2009
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p27 localization and expression has prognostic and predictive value in cancer. Little is known regarding expression patterns of p27 in renal cell carcinoma (RCC) or how p27 participates in disease progression or response to therapy.
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Development of accurate models for individualized prediction of survival after cytoreductive nephrectomy for metastatic renal cell carcinoma.
Eur. Urol.
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There is limited evidence to guide patient selection for cytoreductive nephrectomy (CN) following the diagnosis of metastatic renal cell carcinoma (mRCC).
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Contemporary approach to diagnosis and classification of renal cell carcinoma with mixed histologic features.
Chin J Cancer
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Renal cell carcinoma (RCC) is an important contributor to cancer-specific mortality worldwide. Targeted agents that inhibit key subtype-specific signaling pathways have improved survival times and have recently become part of the standard of care for this disease. Accurately diagnosing and classifying RCC on the basis of tumor histology is thus critical. RCC has been traditionally divided into clear-cell and non-clear-cell categories, with papillary RCC forming the most common subtype of non-clear-cell RCC. Renal neoplasms with overlapping histologies, such as tumors with mixed clear-cell and papillary features and hybrid renal oncocytic tumors, are increasingly seen in contemporary practice and present a diagnostic challenge with important therapeutic implications. In this review, we discuss the histologic, immunohisto-chemical, cytogenetic, and clinicopathologic aspects of these differential diagnoses and illustrate how the classification of RCC has evolved to integrate both the tumors microscopic appearance and its molecular fingerprint.
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Depressive symptoms and cortisol rhythmicity predict survival in patients with renal cell carcinoma: role of inflammatory signaling.
PLoS ONE
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Evidence has supported the association between psychological factors and cancer biology; however, findings are equivocal on the role of psychosocial factors in cancer progression. This study generates a hypothesis of mechanistic variables by examining the clinical effects of psychosocial factors and cortisol dysregulation in patients with metastatic renal cell carcinoma (RCC) and examines associated activation of transcription control pathways.
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A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma.
Eur. Urol.
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Sunitinib is a standard-of-care treatment in advanced clear cell renal cell carcinoma (ccRCC). Retrospective and expanded access data suggest sunitinib has activity in advanced non-clear cell renal cell carcinoma (nccRCC).
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Limitations of preoperative biopsy in patients with metastatic renal cell carcinoma: comparison to surgical pathology in 405 cases.
BJU Int.
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Study Type--Diagnostic (cohort) Level of Evidence: 2b. Whats known on the subject? and What does the study add? Although there have been many investigations of biopsy for small renal masses, there are scant data on the accuracy of biopsy in the setting of metastatic renal cell carcinoma (mRCC). We report a large series of biopsies and compare with nephrectomy pathology in patients with mRCC. The present study highlights the inaccuracy of biopsy in the setting of metastatic disease, which is related to sampling error because of heterogeneity within the tumour and among metastases. These limitations are important to realize when designing trials that depend on pathological findings from biopsy and not nephrectomy. In addition, we found that biopsy of primary tumours were more likely than biopsy of metastatic sites to be diagnostic of RCC. Future studies with multiquadrant biopsies of primary tumours could yield the most accurate pathological results for future studies.
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Expression of OCT3/4 in renal medullary carcinoma represents a potential diagnostic pitfall.
Am. J. Surg. Pathol.
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Renal medullary carcinoma (RMC) is a rare aggressive renal tumor that classically afflicts young black patients with sickle cell trait. The tumor shows overlapping pathologic and clinical characteristics with collecting duct carcinoma and urothelial carcinoma, which often results in a diagnostic conundrum. When the tumor presents in a metastatic site in the absence of a history of renal tumor, germ-cell tumor is often a primary diagnostic consideration, given the young age of most patients. OCT3/4 is an immunohistochemical marker that is routinely used in clinical practice and is widely considered to be a specific marker for germ-cell tumor. We studied the pathologic and immunohistochemical characteristics of 14 cases of RMC. Immunohistochemical staining for OCT3/4 staining was noted in 10/14 RMCs with strong nuclear staining in 8 cases and was absent in all cases of collecting duct carcinoma and urothelial carcinoma. OCT3/4 expression is not specific to germ-cell tumor and is seen in the majority of RMC cases. Caution must be exercised in interpreting the presence of OCT3/4 staining in a poorly differentiated neoplasm, especially at a metastatic site as a germ-cell tumor, as this may represent a potential diagnostic pitfall.
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Kinome expression profiling identifies IKBKE as a predictor of overall survival in clear cell renal cell carcinoma patients.
Carcinogenesis
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There are 516 known kinases in the human genome. Because of their important role maintaining proper cellular function, they are often misregulated during tumorigenesis and associated with clinical outcomes in cancer patients, including clear cell renal cell carcinoma (ccRCC). However, less is known about the global expression status of these genes in renal cell carcinoma and their association with clinical outcomes. We performed a systematic analysis of gene expression for 503 kinases in 93 tumor samples and adjacent normal tissues. Expression patterns for 41 kinases were able to clearly differentiate tumor and normal samples. Expression of I-kappa-B kinase epsilon (IKBKE) was associated with a 5.3-fold increased risk of dying [95% confidence interval (CI): 1.93-14.59, P-value: 0.0012]. Individuals with high IKBKE expression were at a significantly increased risk of death (hazard ratio: 3.34, 95% CI: 1.07-10.40, P-value: 0.038) resulting in a significantly reduced overall survival time compared with those with low IKBKE tumor expression (P-value: 0.049). These results for IKBKE were validated in a replication population consisting of 237 ccRCC patients (P-value: 0.0021). Furthermore, IKBKE was observed to be higher expressed in tumors compared with adjacent normal tissues (P-value < 10(-7)). IKBKE is a member of the nuclear factor-kappaB (NF-?B) signaling pathway and interestingly, gene expression patterns for other members of the NF-?B pathway were not associated with survival, suggesting that IKBKE gene expression may be an independent marker of variation in overall survival. Overall, these results support a novel role for IKBKE expression in modulating overall survival in ccRCC patients.
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Positive vascular wall margins have minimal impact on cancer outcomes in non-metastatic RCC patients with tumor thrombus.
BJU Int.
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? Despite resection of all visible tumor, RCC may be present within the vein wall of after nephrectomy with thrombectomy, but the significance of positive vein wall margins is unknown. ? The purpose of this study was to evaluate the impact of microscopically positive vascular margins on recurrence and cancer specific survival in RCC patients with venous thrombus PATIENTS AND METHODS: ? All records were reviewed from 1993-2009 at University of Texas MD Anderson Cancer Center of consecutive patients treated surgically for RCC with venous tumor thrombus. ? Patients with metastatic disease, positive soft tissue margins or gross residual disease at time of thrombectomy were excluded. ? Primary outcome measurements were local or systemic disease recurrence, and cancer specific survival. ? Univariate and multivariate analysis was used to evaluate whether microscopically positive vascular margins were associated with RCC recurrence or cancer specific survival after nephrectomy with thrombectomy.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.