Association Of Renal Cell Carcinoma Research Articles

Paraneoplastic Nephropathy with Peculiar Immunofluorescence Pattern: Report of a Rare Case

Abstract Introduction/Objective Hematolymphoid neoplasms are commonly associated with medical renal disease; however, association of renal cell carcinoma and nephrotic/nephritic syndrome is exceedingly rare. Paraneoplastic nephropathy in setting of renal cell carcinoma can manifest as membranous nephropathy, IgA nephropathy, or minimal change disease. The purpose of this report is to describe a rare case of clear cell renal cell carcinoma with associated membranous nephropathy with concurrent glomerular IgG and IgA deposition. Methods/Case Report A 68-year-old male presented with a penile mass. Diagnostic work up reveled an 11cm renal mass. Urinalysis demonstrated nephrotic range proteinuria (>5 g/d). Subsequently, the patient underwent nephrectomy and penectomy. Pathologic evaluation showed clear cell renal carcinoma with sarcomatoid component and metastasis to penis. Nonneoplastic kidney workup revealed membranous glomerulopathy, with 3+ granular IgG predominantly within glomerular capillaries and 2+ IgA and 1+ C3 in a similar pattern. Electron microscopy demonstrated numerous subepithelial and intramembranous immune deposits, and few small mesangial deposits. Concurrent membranous and IgA nephropathy has been reported, but the IgA in that case is typically mesangial. The peculiar pattern of IgG and IgA deposition in this case can be seen with membranous nephropathy secondary to lupus or neoplasia. Lupus was excluded based on patient’s history, serology, and absence of significant C1q staining. Therefore, the findings were consistent with membranous glomerulopathy secondary to patient’s cancer. Patient’s proteinuria improved after nephrectomy. He is alive and disease-free 10months after nephrectomy, with proteinuria in 0.1-0.6 g/d range. Results (if a Case Study enter NA) NA Conclusion This case highlights the importance of thorough evaluation of non-neoplastic kidney in nephrectomy specimens for cancer, thus guiding the type of surgical intervention. Non-orthodox presentation of immunoglobulin deposition may be the herald of neoplasia in select cases.

Gene expression profile analysis unravelled the systems level association of renal cell carcinoma with diabetic nephropathy and Matrix-metalloproteinase-9 as a potential therapeutic target

Type 2 diabetes (T2D) and cancer share many common risk factors. However, the potential biological link that connects the two at the molecular level is still unclear. The experimental evidence suggests that several genes and their pathways may be involved in developing cancerous conditions associated with diabetes. In this study, we identified the protein-protein interaction (PPI) networks and the hub protein(s) that interlink T2D and cancer using genome-scale differential gene expression profiles. Further, the PPI network of AMP-activated protein kinase (AMPK) in cancer was analyzed to explore novel insights into the molecular association between the two conditions. The densely connected regions were analyzed by constructing the backbone and subnetworks with key nodes and shortest pathways, respectively. The PPI network studies identified Matrix-metalloproteinase-9 (MMP-9) as a hub protein playing a vital role in glomerulonephritis tubular diseases and some genetic kidney diseases. MMP-9 was also associated with different growth factors, like tumor necrosis factor (TNF-α), transforming growth factor 1 (TGF-1), and pathways like chemokine signaling, NOD-like receptor signaling, etc. Further, the molecular docking and molecular dynamic simulation studies supported the druggability of MMP-9, suggesting it as a potential therapeutic target in treating renal cell carcinoma linked with diabetic kidney disease. Communicated by Ramaswamy H. Sarma

Association of renal cell carcinoma (RCC) metastatic to pancreas with a distinct molecular profile and immune cell population.

366 Background: RCC may metastasize to diverse sites, which confers variable prognosis and treatment response. Pancreatic metastases in RCC have been associated with indolent biology, low genomic instability and decreased inflammation, which may lead to worse responses to immunotherapy. To further investigate this phenomenon, we compared the genomic landscape and immunotherapy biomarkers of metastatic RCC patients with and without pancreatic metastases. Methods: We identified a cohort from the de-identified Tempus database, consisting of patients with metastatic RCC who received next generation sequencing via the Tempus|xT assay (DNA-seq of 648 genes at 500x coverage; whole-exome capture RNA-seq). Records were included if patients had RCC diagnosis and metastases to at least one of: pancreas, liver, brain, or lung (regardless of the presence of other metastases). RCC diagnosis and metastatic sites were determined from abstracted clinical notes received at the time of sequencing. If individuals had multiple xT results, the results from the most recent sample were included (irrespective of tissue site). We compared the prevalence of somatic gene alterations (using false discovery rate corrected q-values) and immunotherapy markers among records with vs without pancreatic metastases. Statistical significance was determined via Wilcoxon rank-sum tests or Chi-squared/Fisher’s exact tests. Results: 654 patients (median age 61, 30% female, 62% clear cell) with metastatic RCC were included. 58 harbored pancreatic metastases and 596 had metastases to sites other than pancreas (36 brain, 88 liver, 358 lung, 114 brain/liver/lung combinations). Females had a significantly higher representation in the group with pancreatic metastases (43% vs 29%, p = 0.02). The group with pancreatic metastases had significantly more PBRM1 alterations (52% vs 25%, q < 0.001), and trended towards more prevalent copy number loss of ALK (22% vs 10%, q = 0.06) and NTRK3 (16% vs 6%, q = 0.08) and less prevalent alterations in CDKN2A (3% vs 13%, q = 0.08), BAP1 (2% vs 13%, q = 0.06) and MTAP (0% vs 9%, q = 0.06). Individuals harboring pancreatic metastases had similar MSI status and TMB, but had lower rates of PD-L1 positivity, lower proportions of B-cells and higher proportion of NK cells in immune cell composition (Table). Conclusions: RCC patients with pancreatic metastases have a distinct molecular profile and lower rates of PD-L1 positivity, which suggests a unique disease biology and potential non-immunogenic phenotype. Further investigation and prospective validation is needed to determine immunotherapy outcomes in this population.[Table: see text]

The association of renal cell carcinoma with gastrointestinal stromal tumors.

Prior small studies have reported a possible association between renal cell carcinoma (RCC) and gastrointestinal stromal tumors (GISTs). In the largest known series, our objective was to describe the prevalence of RCC among patients with GISTs over 26 years at Memorial Sloan Kettering Cancer Center (MSKCC). We retrospectively reviewed MSKCC's prospectively maintained sarcoma and RCC databases and identified all patients with both RCC and GIST between 1980 and 2016. Demographic and clinicopathological characteristics were obtained. A total of 9/405 (2.2%) GIST patients were identified with RCC, with a mean follow-up of 9.2 (range 3.8-28.4) years. Five out of nine (55.6%) patients had RCC and GIST diagnosis within 6 months of each other. Mean RCC tumor size was 3.0 (range 1.8-8) cm and 8/9 (88.9%) patients were RCC stage 1. A total of 4/9 (44.4%) patients had papillary RCC (pRCC) histology, 5/9 (55.6%) had additional alternative malignancies, and 4/9 (44.4%) had primary small bowel GIST. Our series suggests a possible association of RCC with GISTs. In addition, we found a high frequency of pRCC histology, alternative malignancies, and small bowel GISTs in co-occurring RCC-GIST patients. Further investigation to identify genetic mutations, in this population, would assist in surveillance and treatment.

Small renal tumor with lymph nodal enlargement: A histopathological surprise

Renal cancer with lymph nodal mass on the investigation is clinically suggestive of an advanced tumor. Small renal cancers are not commonly associated with lymph nodal metastasis. Association of renal cell carcinoma with renal tuberculosis (TB) in the same kidney is also rare. We report here a case of small renal cancer with multiple hilar and paraaortic lymph nodes who underwent radical nephrectomy, and histopathology report showed renal and lymph nodal TB too.

Laparoscopic partial nephrectomy for renal cell carcinoma in a horseshoe kidney.

Horseshoe kidney has an incidence rate ranging from 1 in 400 to 1 in 1000, with a 2:1 ratio in men. It also has a predilection for chromosomal aneuploidies. From a pathophysiology standpoint, this anomaly occurs during the second to sixth week of gestation when the inferior portion of the metanephric blastema fuses to form an isthmus, commonly in the lower renal pole (90%). As a result of this fusion, the kidney may not bypass the inferior mesenteric artery and is impeded in its ascent. With an aberrant anatomical orientation and location, complications arise including hydronephrosis, renal calculi and a twofold risk of Wilms tumour. Despite these findings, the association of renal cell carcinoma (RCC) within a horseshoe kidney is extremely rare and fewer than 200 cases have been described. Therapeutically speaking, partial nephrectomies are the gold standard of treatment for renal tumours smaller than 4 cm in diameter, with a growing indication to accomplish this procedure by laparoscopic or robotic means. We report a case of an asymptomatic 58-year-old male with an incidental computed tomography scan finding of a 4-cm solid mass in the right moiety of a horseshoe kidney. He was treated by laparoscopic partial nephrectomy. There have only been 2 other reported cases to our knowledge on a laparoscopic partial nephrectomy in a horseshoe kidney for RCC. We believe that, in experienced hands, the laparoscopic approach may be used successfully for this clinical situation.

Risk Factors for Renal Cell Carcinoma in the VITAL Study

The incidence of renal cell carcinoma is increasing worldwide. Cited risk factors include obesity, smoking and hypertension but few others have been confirmed in prospective studies. We used a prospective cohort to validate established renal cell carcinoma risk factors and evaluate more controversial risk factors for incident renal cell carcinoma. A total of 77,260 residents of Washington 50 to 76 years old completed a questionnaire between 2000 and 2002 on demographic, lifestyle and health data. Incident renal cell carcinoma cases were determined by linkage to the regional cancer registry through December 31, 2009. Multivariate methods using covariates and cutoffs selected a priori were applied to analyze the association between renal cell carcinoma and previously studied factors related to lifestyle (body mass index, smoking and alcohol/fruit/vegetable consumption) and health (hypertension, diabetes, kidney disease and viral hepatitis). There were 249 incident cases of renal cell carcinoma. Independent renal cell carcinoma risk factors in the fully adjusted model were body mass index (35 or greater vs less than 25 kg/m2 HR 1.71, 95% CI 1.06-2.79), smoking (greater than 37.5 pack-years vs never HR 1.58, 95% CI 1.09-2.29), hypertension (HR 1.70, 95% CI 1.30-2.22), kidney disease (HR 2.58, 95% CI 1.21-5.50) and viral hepatitis (HR 1.80, 95% CI 1.03-3.14). Diabetes was associated with renal cell carcinoma (HR 1.83, 95% CI 1.26-2.65) in a base model adjusting for age and gender but not in the multivariate model. We found no association between alcohol, fruit or vegetable intake and renal cell carcinoma. We identified a significant association of renal cell carcinoma with obesity, smoking, hypertension, renal disease and viral hepatitis. Identifying risk factors offers an opportunity for targeted education and intervention.

Association of renal cell carcinoma and hematologic malignancy.

449 Background: An increased incidence of both RCC and HM occurring in the same patients has been reported. Also, a relationship between adenocarcinoma and HM has been previously suggested. Moreover, detailed family history in our patients with RCC suggested an increased incidence of HM in their family members. The purpose of this study is to characterize the HM in relatives of patients with RCC. Methods: Data from 700 patients with RCC seen by us from 2004 to the present were retrospectively evaluated through chart review. The patient, family history and pathology characteristics were collected to determine the frequency of HM in first and second-degree relatives of patients with RCC. Pedigrees were then constructed and subtypes of HM were characterized. Results: A family history of HM was observed in 74 relatives involving 59 families. Of these, 50/74 cases of HM were in first-degree relatives and 19/74 were in second-degree relatives. The most common HMs were lymphoma and leukemia: 24 non-Hodgkin’s lymphoma, 8 Hodgkin’s lymphoma, 8 lymphoma not further specified (NOS), 11 chronic lymphocytic leukemia, 1 chronic myeloid leukemia, 1 acute myeloid leukemia, 5 acute leukemia NOS and 4 leukemia NOS. Other HM observed were multiple myeloma in 2 patients, Waldenström’s macroglobulinemia, myelodysplastic syndrome, and myelofibrosis. Additionally, 2 relatives had blood cancers that were NOS. Of the 59 patients with RCC, 40 had clear cell histology, 4 papillary, 3 chromophobe, 1 sarcomatoid, 1 transitional and in 10, RCC histology was not recorded. Conclusions: HM is observed in patients with RCC with increased frequency compared with the SEER database. We now observed an increased frequency of HM in relatives of patients with RCC. The majority of HMs observed were B-cell malignancies, as we previously reported for HMs that occur in patients with breast cancer or RCC. The etiology of this association remains unclear, but suggests a common etiopathogenesis for RCC and B-cell tumors. Genetic mutations, hereditary immunological defects, and environmental factors may be involved. A larger study with statistical evaluation for confirmation is required. We plan to collect serum and tissue samples from patients and relatives for future molecular studies.

Association Of An Urothelial Carcinoma Of The Bladder And A Papillairy Carcinoma Of The Kidney: Common Carcinogenesis Or incidental finding?

The association between renal cell carcinomas and other cancers has been documented in the literature leading to the study of many possible etiopathogenic factors. We report two cases of an association between a high grade urothelial carcinoma of the bladder with a renal papillary carcinoma. These cases have been diagnosed among a retrospective study of 100 patients presenting renal cell carcinomas that were diagnosed between 1994 and 2003. The review of the English literature revealed a high incidence of the cancer of the bladder and the prostate in patients with renal cell carcinoma especially the papillary subtype. The etiopathogenesis of this association remains debated. It seems to be based on genetic alterations that haven’t been formally proved.Our study puts emphasis on the possible association of renal cell carcinoma with high grade tumours of the bladder. This finding may be incidental, so that, more clinical trials should be monitored.

Nitrate in public water supplies and the risk of renal cell carcinoma

Drinking water and dietary sources of nitrate and nitrite can react in vivo with amines and amides to form N-nitroso compounds (NOC), potent animal carcinogens. Nitrate is a widespread contaminant of drinking water supplies especially in agricultural areas. We conducted a population-based case-control study of renal cell carcinoma in 1986-1989 in Iowa, a state with elevated levels in many public water supplies. We collected a lifetime water source history, but due to limited monitoring data, most analyses focused on the subpopulation, who used Iowa public supplies with nitrate measurements (actual or imputed data) for > or = 70% of their person-years since 1960 (201 cases, 1,244 controls). We computed the average nitrate level and years using a public supply with nitrate levels >5 and >10 mg/l. Dietary nitrate and nitrite were estimated from a 55-item food frequency questionnaire. There was no association of renal cell carcinoma with the average nitrate level and years using public supplies >5 and >10 mg/l nitrate-nitrogen (10+ years >5 mg/l odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.66, 1.60). However, higher nitrate exposure was associated with an increased risk among subgroups with above the median red meat intake (10+ years >5 mg/l OR = 1.91, 95% CI 1.04-3.51) or below the median vitamin C intake (10+ years >5 mg/l OR = 1.90, 95% CI 1.01, 3.56), dietary factors that increase the endogenous formation of NOC. Exclusion of long-term Des Moines residents, a large proportion of the high exposure categories, attenuated the association. These findings deserve additional study in populations with high water nitrate intake and information on dietary intakes.

Tumor renal en riñón ectópico pelvico: Presentación de un caso

An uncommon association of renal cell carcinoma in a pelvic kidney is described, the literature is reviewed. A case of renal cell carcinoma in a pelvic kidney is presented, and the literature briefly reviewed, with special reference to six cases reported. Renal cell carcinoma in a pelvic kidney is uncommon, the paucity of previous reports of this association is surprising. Besides renal cell carcinoma is the most common malignant renal tumour in the adult and renal ectopy is relatively common more cases of this association would be expected. Renal cell carcinoma is the most common malignant renal tumour in the adult and renal ectopy is relatively common, the actual incidence among autopsy series is 1 in 900, it has been an uncommon association, with only six cases reported. The surgical approach to ectopic kidneys merits caution because of the uncertain vascular anatomy, and vascular studies may be indicated to avoid complications, the present case is important because it represent the most common urological cancers at our institution with an unusual presentation.

229: Association of Renal Cell Carcinoma with Breast Prostate and Bladder Cancers

229: Association of Renal Cell Carcinoma with Breast Prostate and Bladder Cancers

A case report of polysplenia with renal cell carcinoma

Polysplenia is a well-known condition in which there is malposition and malformations of the abdominal and chest organs. We present a case of renal cell carcinoma in a 68-year-old patient with polysplenia syndrome, found incidentally when he was investigated for abdominal pain. This is the third case reported with this association of renal cell carcinoma and polysplenia.

Renal Cell Carcinoma and Vasculitis: Report of Two Cases

A 63-year-old caucasian male with systemic leukocytoclastic vasculitis involving the skin, lungs, and gastrointestinal tract was found to have a renal cell carcinoma at autopsy. A 77-year-old-woman with a history of hypertension was felt to have temporal arteritis that was confirmed by biopsy. The autopsy revealed a renal cell carcinoma in association with widespread giant cell arteritis. The possible association of renal cell carcinoma with vasculitis and an assessment of the possible clinical usefulness are presented and cases of vasculitis with renal neoplasms are briefly reviewed.

Von Hippel-Lindau disease simulating polycystic kidney disease

Polycystic kidney disease and the renal manifestations of von Hippel-Lindau disease have much in common. Making the distinction between these two diseases is important. There is a strong association of renal cell carcinoma with von Hippel-Lindau disease, whereas renal cell carcinoma is rare in polycystic kidney disease. Furthermore, the many extrarenal manifestations of von Hippel-Lindau disease are serious and can be fatal while those of polycystic kidney disease are generally benign. Early diagnosis of the lesions of von Hippel-Lindau disease could lead to effective surgical treatment and prevent death. A case of von Hippel-Lindau disease is presented which was incorrectly diagnosed as polycystic kidney disease for sixteen years. The case is instructive in that the possibility of making the correct diagnosis prior to the patient's terminal illness was only through careful assessment of the family. The case is also remarkable in that the patient suffered from progressive renal failure requiring hemodialysis, which has not been associated previously with von Hippel-Lindau disease.

Reversible Renal Hypertension Secondary to Renal Arteriovenous Fistula and Renal Cell Carcinoma

A 40-year-old woman with hypertension (179/100) and a massive renal arteriovenous fistula involving most of the right kidney is reported. A 131I hippuran renogram, split urinary function studies and renal vein renins were normal. The renal arteriovenous fistula was removed by total nephrectomy and blood pressure returned to normal. A renal cell carcinoma was found within the fistula. This case confirms the association of renal cell carcinoma with renal arteriovenous fistulas and demonstrates the potential curative effects of nephrectomy for the hypertension associated with it. The normal split function studies, renogram and renal vein renins do not support the concept of secondary hyperreninemia as a causative factor in the hypertension seen with renal arteriovenous fistulas.

Amyloidosis secondary to renal carcinoma. Clinical study of 3 cases

SummaryThree cases of renal-cell carcinoma with secondary amyloidosis are presented. A nephrotic syndrome was common to the three cases. In the first case a syndrome of malabsorption dominated the clinical picture. In the second case anemia was prominent. In the third case the nephrotic syndrome was severe; resection of the tumor did not improve the nephrotic syndrome which progressed to renal failure. The patient still survives the operation since three years.The symptomes of amyloidosis, more especially of gastro-intestinal amyloidosis are reviewed. The relationship between carcinomatosis and secondary amyloidosis are examined. The authors stress the fact that the association of renal-cell carcinoma and amyloidosis is not as rare as generally believed.