Fuhrman Nuclear Grade Research Articles

Renal cell carcinoma with vena caval involvement: a contemporary clinicopathologic analysis of 53 cases

A clinicopathologic analysis of patients with renal cell carcinoma (RCC) and vena caval involvement diagnosed at our institution was performed. Multiple clinicopathologic parameters were examined. Fifty-three cases were identified. Mean patient age was 62 years (range, 40-82 years). The cohort comprised 36 of 53 (68%) men and 17 of 53 (32%) women. Mean primary tumor size was 10.4 cm (range, 3.1-21.0 cm). The breakdown of tumor stage was as follows: 37 of 53 (70%) were pT3b, 14 of 53 (26%) were pT3c, and 2 of 53 (4%) were pT4. Most of the tumors were clear cell RCC (45/53, 84.6%), although other variants were also represented. All cases were Fuhrman nuclear grade 3 (34/53, 64%) or 4 (19/53, 36%). Tumor necrosis was present in 41 of 53 (77%) cases. At the time of the initial tumor resection, 11 of 53 (21%) cases were staged pM1. Of the 42 patients staged as pMX at the time of primary tumor resection, 12 of 42 (29%) later developed metastasis, most commonly to the lungs. Of all 53 cases with these very advanced tumors, only 6 of 53 (11.3%) had positive surgical margins: 4 of 53 (7.5%) had positive vascular resection margins, and 2 of 53 (3.8%) had focally positive perinephric fat margins. The mean 5-year survival in our cohort was 50%. Our findings suggest that a select group of patients with RCC with vena caval involvement may benefit from radical nephrectomy, although some tumors may have positive vascular and/or nonvascular surgical resection margins even in the best surgical hands. Multi-institutional studies are needed to further characterize these advanced tumors from the molecular standpoint.

Correlation of diffusion tensor imaging parameters and histopathology in the evaluation of renal clear cell carcinoma

Objective To investigate the correlation between the diffusion tensor imaging (DTI) parameters and histopathology in renal clear cell carcinoma patients. Methods Thirty renal clear cell carcinoma patients with lesions more than 1 cm in diameter were retrospectively analyzed.All patients had DTI and apparent diffusion coefficient (ADC),eigenvector 1(E1),fractional anisotropy(FA) value in normal kidney and lesion were measured respectively.The lesions were analyzed according to the Fuhrman nuclear grade for pathological findings.They were divided into two groups, namely high (Ⅲ–Ⅳ)and low (Ⅰ–Ⅱ) grade groups. In addition, the cell density,micro-vessel density (MVD) of turmor were also measured.The differences between two groups in cell density,micro-vessel density were analyzed by independent samples t test, the difference among normal kidney,high and low grade groups of clear cell renal cell carcinoma were compared using ANOVA.The correlationsamong ADC,E1,FA value and cell density, micro-vessel density were analyzed using Pearson analysis. Results Fifteen cases of renal clear cell carcinoma were of low grade (level Ⅰ,8 cases, level Ⅱ,7 cases), 15 cases were of high grade (level Ⅲ,9 cases, level Ⅳ,6 cases). The cell density of low and high grade tumors were (51.73±6.73)%, and (64.87±9.08)% respectively, the microvessel density were (49.33±7.76)/HP, and (61.27±8.45)/HP respectively. There were significant differences found(t= -4.50, -4.03, P<0.05). The ADC of normal renal tissues and low, high grade renal clear cell carcinoma were (2.08±0.10) ×10-3, (1.24±0.19) × 10-3, (1.08±0.19) × 10-3 mm2/s respectively, the E1 value were (2.19±0.15)×10-3, (1.44±0.16)×10-3,(1.21±0.21)×10-3mm2/s,respectively, and the FA were 0.32±0.05, 0.29±0.08, 0.22±0.06, respectively. There were significant differences in ADC,E1,FA values (F=148.347,127.366, 11.511,P<0.05). Cell density was negatively correlated to ADC,E1, FA values (r= -0.796, -0.865, -0.730; P<0.05). The correlation between ADC,E1, FA values and MVD were negatively correlated(r= -0.739, -0.826, -0.761;P<0.05). Conclusion DTI parameters are correlated with pathological classification of renal clear cell carcinoma. Key words: Renal neoplasms; Magnetic resonance imging; Pathology

Differential Expression of PD-L1 between Primary and Metastatic Sites in Clear-Cell Renal Cell Carcinoma.

PD-L1 expression in primary clear-cell renal cell carcinoma (ccRCC) increases the likelihood of response to anti-PD-1 inhibition, but fails to identify all responders. We hypothesized that PD-L1 levels assessed in randomly selected areas of the primary tumors may not accurately reflect expression levels in metastatic lesions, which are the target of systemic therapy. Therefore, we compared PD-L1 expression in a series of primary ccRCC and their metastases. Tissue blocks from 53 primary ccRCCs and 76 corresponding metastases were retrieved. Areas with predominant and highest nuclear grade were selected. Slides were immunostained with a validated anti-PD-L1 antibody (405.9A11). Membranous expression in tumor cells was quantified using H-score. Expression in tumor-infiltrating mononuclear cells (TIMC) was quantified using a combined score. Discordant tumor cell PD-L1 staining between primary tumors and metastases was observed in 11 of 53 cases (20.8%). Overall, tumor cell PD-L1 levels were not different in primary tumors and metastases (P = 0.51). Tumor cell PD-L1 positivity was associated with higher T stage (P = 0.03) and higher Fuhrman nuclear grade (P < 0.01). Within individual lesions, PD-L1 positivity was heterogeneous and almost exclusively detected in high nuclear grade areas (P < 0.001). No difference was found in PD-L1 levels in TIMCs between primary tumors and metastases (P = 0.82). The heterogeneity of PD-L1 expression in ccRCC suggests that its assessment as a predictive biomarker for PD-1 blockade may require analysis of metastatic lesions. Notably, because PD-L1 expression was mostly detected in high nuclear grade areas, to avoid false-negative results, these areas should be specifically selected for assessment.

Body mass index and comorbidity are associated with postoperative renal function after nephrectomy.

ABSTRACTPurpose:To explore the association of body mass index (BMI) and comorbidity with renal function after nephrectomy.Materials and Methods:We retrospectively analyzed 263 patients submitted to partial or radical nephrectomy from 2000-2013. Variables assessed included BMI, Charlson Comorbidity Index (CCI), race, tobacco use, tumor histology, surgical approach, Fuhrman nuclear grade, and tumor (T) classification. Glomerular filtration rate (GFR) was estimated using the Cockroft-Gault equation, adjusted for gender. Logistic regression was performed and included all interaction terms.Results:Median follow-up was 19.6 months (IQR 5.2, 53.7). Median preoperative GFR was 86.2mL/min/1.73m2 and median postoperative GFR was 68.4mL/min/1.73m2. BMI (OR 1.07, 95%CI 1.02-1.11), CCI (OR 1.19, 95%CI 1.04-1.37), and radical nephrectomy (OR 3.09, 95%CI 1.51-6.33) were significantly associated with a decline in renal function of ≥25%.Conclusion:BMI and CCI are associated with postoperative decline in renal function after nephrectomy. Additionally, radical nephrectomy is significantly associated with decreasing renal function compared to partial nephrectomy. These findings highlight the importance of assessing patient comorbidity in the decision making process for patients presenting with a renal mass.

High expression of APRIL correlates with poor prognosis in clear cell renal cell carcinoma

IntroductionThe members of the Tumor Necrosis Factor Superfamily (TNFSF), including A PRoliferation Inducing Ligand (APRIL), have been studied in RCC and other tumors. In this study, we investigated the expression of APRIL in resected clear cell renal cell carcinoma (CCRCC) samples by immunohistochemistry (IHC) and analyzed its association with the clinicopathologic characteristics and prognosis of the patients. MethodsWe examined 206 CCRCC samples from patients who underwent radical or partial nephrectomy at Seoul National University Hospital between 1999 and 2002. Tissue microarray (TMA) blocks were made, and immunohistochemical staining for APRIL expression was performed. ResultsWe classified the IHC results as high expression or low expression. Of the 206 cases, 89 cases (43.2%) were classified as showing high expression, and 117 cases (56.8%) showed low expression. The high expression of APRIL was significantly correlated with higher Fuhrman nuclear grade and higher pathologic stage (p=0.000 and 0.004), and we observed that the high expression of APRIL was significantly correlated with the overall survival of the patients (p=0.045) and cancer-specific survival (p=0.020), but was not correlated with disease-free survival (p=0.106). In multivariate analysis adjusted for Fuhrman nuclear grade and pathologic stage, the high expression of APRIL was not an independent prognostic factor for CCRCC, as determined by overall survival (p=0.830) and cancer-specific survival (p=0.792). ConclusionsWe found that the high expression of APRIL in CCRCCs was correlated with high Fuhrman nuclear grade, high pathologic stage, and poor overall and cancer-specific survival of the patients. However, it did not correlate with disease-free survival and was not an independent prognostic factor.

Experience in nephron-sparing surgery in patients with small renal tumours

Abstract Background Nephron-sparing surgery is currently the treatment of choice for surgical removal of solid renal tumours smaller than 7 cm, in the case of a solitary kidney, bilateral renal tumours or the presence of chronic renal failure. Material and methods An observational, descriptive, retrospective and cross-sectional study was conducted. The variables evaluated were: age at diagnosis, gender, intraoperative blood loss, operative time, preoperative tumour size, hospital stay, pathology report, pTNM classification, Fuhrman nuclear grade, pre- and post-operative creatinine, monitoring for cancer. All were analysed using SPSS v 22. Results The study included 28 patients, 14 male and 14 women, with a mean age 52.3 years. The approach was lumbotomy in all patients. The mean hospital stay was 4.1 days. Mean perioperative bleeding loss was 380.3 ml. The mean preoperative creatinine was 0.96 mg/dl, with a post-operative mean of 1.12 mg/dl. Histopathology reported, 23 clear cell tumours, 2 angiomyolipomas, 2 oncocytomas, and 1 haemorrhagic cyst. Tumour staging was performed on 14 patients, with 13 patients T1bN0M0, and 1 patient T2aN0M0. In clear cell tumours, Fuhrman nuclear grade 2 was present in 16 patients and 7 patients were Fuhrman grade 3. Conclusion Nephron sparing surgery is the choice procedure of choice in patients with small renal tumours, with good functional results without significant alteration in renal function. Outcome is optimal, with a low incidence of complications.

Clear Cell-Papillary Renal Cell Carcinoma of the Kidney Not Associated With End-stage Renal Disease

Clear cell-papillary renal cell carcinoma (CC-Pap RCC) is a recently described renal tumor initially reported in the setting of end-stage renal disease (ESRD). It has unique morphologic and immunohistochemical features that differentiate it from the more common clear cell RCC and papillary RCC. Recently, these tumors have also been described in a sporadic setting. We studied 64 cases of CC-Pap RCC not associated with ESRD (57 CC-Pap RCCs and 7 cases with features of renal angiomyoadenomatous tumors [RAT] including 5 initially diagnosed as such). The morphologic features of all cases and the immunohistochemical profile of 59 cases were studied along with the clinical and molecular features of 30 and 12 cases, respectively. All the tumors were well circumscribed with a mean tumor size of 2.6 cm and showed a wide array of architectural patterns, usually mixed, including tubular (77%), papillary (62%), tubulocystic (52%), and compact nested (21%). Seventy-three percent of the cases showed areas in which the tumor nuclei had a distinct orientation away from the basement membrane. Ninety-two percent of the cases had a low Fuhrman nuclear grade (nuclear grade 2%-86%, and nuclear grade 1%-6%); however, 8% cases showed foci of Fuhrman nuclear grade 3. In 4 cases, epithelial tumor comprised <5% of the tumor; >95% of the tumor was cystic or hyalinized. The stroma varied from being minimal to occasionally prominent myxoid to hyalinized and rarely with organized amianthoid fibers or well-defined smooth muscle bundles. Pathologic stage was reliably assigned in 60 cases, of which 93.3% (56 cases) were pT1, 3.3% (2 cases) were pT2, and 3.3% (2 cases) were pT3a with extension into the perinephric fat. One case had coagulative necrosis; sarcomatoid change and vascular invasion was not identified. The tumors showed a fairly typical immunoprofile characterized by positivity for CK7 (100%), HMCK (96%), CAIX (94%), and vimentin (100%) with negativity for AMACR, RCC, and TFE3; CD10 was positive in 24%. None of the cases tested showed recurrent chromosomal imbalances by virtual karyotyping, fluorescence in situ hybridization, or 3p loss of heterozygosity analysis. VHL gene mutations were, however, noted in 3 cases (2 in exon 1 and 1 in exon 3). Clinical follow-up information was available in 47% of the patients, with a mean and median follow-up of 47 and 37 months, respectively (range, 18 to 108 mo). One case occurred in the setting of VHL syndrome and multiple benign cysts. None of the cases showed local recurrence, metastasis, or death due to disease. Morphology, immunophenotype, and molecular studies did not vary between typical cases, those with prominent smooth muscle (so-called RAT), and historically published data on cases occurring in ESRD. Our analysis confirms that CC-Pap RCC is a unique subtype of adult renal epithelial neoplasia in which tumors are frequently small, are of low nuclear grade and pathologic stage, and have extremely favorable short to intermediate range prognosis. Tumors occurring sporadically, with prominent smooth muscle stroma (so-called RAT), and occurring in ESRD are in the spectrum of the same category of tumors.

Experiencia en cirugía preservadora de nefronas en pacientes con tumores renales pequeños

BackgroundNephron -sparing surgery is currently the treatment of choice for surgical removal of solid renal tumours smaller than 7 cm, in the case of a solitary kidney, bilateral renal tumours or the presence of chronic renal failure. Material and methodsAn observational, descriptive, retrospective and cross-sectional study was conducted. The variables evaluated were: age at diagnosis, gender, intraoperative blood loss, operative time, preoperative tumour size, hospital stay, pathology report, pTNM classification, Fuhrman nuclear grade, pre- and post-operative creatinine, monitoring for cancer. All were analysed using SPSS v 22. ResultsThe study included 28 patients, 14 male and 14 women, with a mean age 52.3 years. The approach was lumbotomy in all patients. The mean hospital stay was 4.1 days. Mean perioperative bleeding loss was 380.3 ml. The mean preoperative creatinine was 0.96 mg/dl, with a post-operative mean of 1.12 mg/dl. Histopathology reported, 23 clear cell tumours, 2 angiomyolipomas, 2 oncocytomas, and 1 haemorrhagic cyst. Tumour staging was performed on 14 patients, with 13 patients T1bN0M0, and 1 patient T2aN0M0. In clear cell tumours, Fuhrman nuclear grade 2 was present in 16 patients and 7 patients were Fuhrman grade 3. ConclusionNephron sparing surgery is the choice procedure of choice in patients with small renal tumours, with good functional results without significant alteration in renal function. Outcome is optimal, with a low incidence of complications.

Relationship of pathologic factors to efficacy of sorafenib treatment in patients with metastatic clear cell renal cell carcinoma.

To evaluate the predictive value of growth patterns in patients undergoing sorafenib treatment for metastatic clear cell renal cell carcinomas (CCRCCs). Forty-eight patients were analyzed, each of whom underwent nephrectomy and received sorafenib treatment for metastatic CCRCC. Progression-free survival (PFS) was predicted using pathologic parameters, including pathologic stage, Fuhrman nuclear grade (FNG), the presence of a sarcomatoid component, lymphovascular invasion, tumor necrosis, and growth pattern. Three (6%) patients showed partial response, 20 (42%) patients showed stable disease, and 25 (52%) patients showed progressive disease. Univariate analyses demonstrated that FNG, the presence of a sarcomatoid component, tumor necrosis, and growth pattern were significantly associated with PFS. In the multivariate analysis, growth pattern was the only parameter that was significantly and independently predictive of PFS. As a novel histologic prognostic parameter, growth pattern may be useful for predicting response to sorafenib treatment.

A comparison of radiologic tumor volume and pathologic tumor volume in renal cell carcinoma (RCC).

ObjectiveTo investigate the difference between preoperative radiologic tumor volume (RTV) and postoperative pathologic tumor volume (PTV) in patients who received nephrectomy for renal cell carcinoma (RCC).Materials and MethodsWe reviewed 482 patients who underwent preoperative computed tomography (CT) within 4 weeks before radical or partial nephrectomy for renal cell carcinoma. RTV measured by a three dimensional rendering program was compared with PTV (π/6ⅹheightⅹlengthⅹwidth) measured in surgical specimen according to pathologic tumor size and histologic subtype. Correlation of the inter-quartile range (IQR) of the RTV and Fuhrman nuclear grade was also investigated.ResultsThere was a significant positive linear correlation between RTV and PTV (p<0.001, r = 0.911), and the mean RTV and mean PTV were not significantly different (79.0 vs 76.9cm3, p = 0.393). For pathologic tumor size (PTS) <4cm, the mean RTV was larger than the mean PTV (10.9 vs 7.1cm3, p<0.001). For a PTS of 4-7cm, the mean RTV was larger than the mean PTV (56.0 vs 44.7cm3, p<0.001). However, for a PTS ≥7cm, there was no statistical difference between RTV and PTV (p>0.05). Among patients with clear cell RCC, the mean RTV was significantly larger than the mean PTV (p = 0.042), not for non-clear cell group (p = 0.055). As the quartile of the RTV increased, the Fuhrman grade also increased (p<0.001).ConclusionsRTV was correlated with PTV and pathologic grade. RTV was larger than the PTV for a tumor size 7 cm or less or in clear cell RCC. RTV may be useful to measure tumor burden preoperatively.

Endoscopic Ultrasonography-Guided Fine Needle Aspiration of Kidney Masses

Scan the quick response (QR) code to the left with your mobile device to watch this article's video abstract and others. Don't have a QR code reader? Get one by searching 'QR Scanner' in your mobile device's app store. clinical management strategy is based on imaging features. A solid, contrast-enhancing renal mass seen on CT or MRI is considered malignant until proven otherwise, and operative resection is undertaken in appropriate candi- dates. A histologic diagnosis remains necessary in selected patients, such as those with radiographically indetermi- nate lesions, in those considering partial nephrectomy, and to confirm malignancy in patients unfi tf or surgery. Tissue diagnosis is critical to discern appropriate treat- ment in this subgroup. Renal biopsies are usually per- formed percutaneously under transabdominal ultrasound (US) or CT guidance. Percutaneous fine needle aspiration (FNA) can discriminate benign from malignant neoplasms in 91% of cases with histologic classification of tumor type possible in 87% of tumors. 2 Nondiagnostic/inade- quate specimens are largely owing to sampling error and occur in about 30% of cases. Data from case reports and series suggest endoscopic ultrasound (EUS)-guided FNA may provide an additional diagnostic technique for tissue acquisition of renal mass lesions.

Evaluation of major histocompatibility complex class I expression in clear cell renal cell carcinoma as a prognostic tool.

469 Background: After nephrectomy for clear cell renal cell carcinoma (ccRCC) approximately one-third of patients develop metastases. Yet, with currently used prognostic tools such as the TNM staging and the Fuhrman nuclear grade (FNG) system, it is difficult to accurately assess prognosis for each patient. Here, we evaluated Major Histocompatibility Complex Class I (MHCI) expression as a potential prognostic immune marker in ccRCC. Methods: Fifty-five post-nephrectomy patients that presented with localized ccRCC were included. All patients had four or more years of follow up. MHCI was stained in the tumor sections via immunohistochemistry. Then, via an automated image analysis algorithm MHCI expression was quantitated with the Positivity score, the ratio of positively stained pixels over the total number of pixels. Results: Mean MHCI positivity score of the cohort was 0.75 (SE= ±0.20). At the end of the follow-up period, the patients who were alive had higher MHCI expression (0.80 positivity score; SE ±0.14) than those who died of disease (0.62 positivity score; SE= ±0.16; t test, p&lt;0.0001). MHCI positivity scores above the mean were associated with increased cancer specific survival (Mantel-Cox, p=0.0021). MHCI expression was higher among patients with no recurrence (0.80; SE= ±0.16) compared to those that recurred during the study period (0.70; SE= ±0.22; t test, p=0.017); and time-to-recurrence was longer in patients with above mean MHCI positivity scores (Mantel-Cox, p=0.017). Patients who were alive with recurrence had increased MHCI expression (0.81; SE= ±0.10) compared to those who succumbed to disease recurrence (0.62; SE= ±0.25; t-test, p=0.0009). No correlation was detected between FNG and tumor expression of MHCI (ANOVA, p=0.655, F=0.423) or between stage at presentation and MHCI tumor expression (ANOVA, p=0.734, F=0.311). Conclusions: With an automated high-throughput image analysis, this cohort shows that increased MHCI expression in ccRCC is associated with improved prognosis after curative nephrectomy.

P8.02 - Overexpression of PD-1 and PD-L1 in renal cell carcinoma is associated with poor prognosis in metastatic patients treated with sunitinib

Anti vascular growth epithelial factor (VEGF) therapies are currently used in first line of metastatic clear cell renal cell carcinoma (ccRCC), but some patients are inherently resistant to these treatments. Immunotherapy based on disruption of immune checkpoints, such as Programmed Death 1 (PD-1) and Programmed Death Ligand 1 (PD-L1), has been showed promising results. PD-1 and PD-L1 are mainly expressed by T-Cells and tumor cells respectively. Interaction between PD-1 and PD-L1 down-regulates antitumor activity and could be involved in resistance to anti-VEGF therapies. This study assessed PD-1 and PD-L1 expressions in primary ccRCC of metastatic patients with sunitinib first-line treatment and its correlation with clinical outcomes. Formalin-fixed paraffin samples were obtained from primary ccRCC before any systemic treatment. Prognostic pathological criteria and clinical data were collected with a median follow up of 27 months after introduction of sunitinib. PD-1 and PD-L1 expressions were evaluated by immunohistochemistry on the most inflammatory and the highest Fuhrman nuclear grade areas respectively, considering tumor heterogeneity. Kaplan Meier survival curves were compared by log rank test. PD-1 and PD-L1 were considered overexpressed when at least a moderate to marked density of positive immune cells and at least 30% of tumor cells were positive with moderate to strong membranous staining intensity, respectively. Overexpression of both PD-1 and PD-L1 was observed in a subgroup of 17/47 primary ccRCC (36%). Patients in this subgroup compared to others had a worse progression free survival (p = 0.001) with medians of 9 months and 14 months respectively. Even if statistical significance was not reached, there was also a trend toward a worse median overall survival (18 months versus 32). This is the first study to assess the PD-1 and PD-L1 expressions in primary ccRCC of metastatic patients with sunitinib first-line treatment. The subgroup with both PD-1 and PD-L1 overexpression should be individualized as having a peculiar immune phenotype. These patients experienced poor prognosis when treated by sunitinib and may be good candidates from anti-PD-1 or anti-PD-L1 immunotherapies.

Evaluation of oxidative stress status and antioxidant capacity in patients with renal cell carcinoma

IntroductionWe evaluated and compared the serum oxidative stress and antioxidant enzymes in patients with renal cell carcinoma (RCC) and the control group.Material and methodsThe prospective study consisted of 97 patients with RCC (Group 1) and 80 age and sex matched healthy volunteers (Group 2). Group 1 and 2 were compared concerning serum mean total oxidant status (TOS), total antioxidant capacity (TAC), paraoxonase-1 (PON-1), arylesterase, total thiol, catalase (CAT), myeloperoxidase (MPO) and ceruloplasmin.ResultsPatients’ mean age was 58.5 ±12.3 and 56.9 ±15.8 years, respectively, in Group 1 and 2. No statistically significant differences were detected between the groups in terms of oxidative stress parameters and antioxidant capacity measured in the serum of patients including, TOS, TAC, PON1, arylesterase, total thiol, CAT, MPO, and ceruloplasmin levels (p >0.05 for all parameters). The PON-1 value was significantly higher in patients with pT1 stage than pT3 stage (p = 0.007). The arylesterase value was significantly higher in patients with Fuhrman's nuclear grade 3 than grade 2 (p = 0.035). There was no correlation between these parameters level and Fuhrman's nuclear grade, stage, or histopathological tumor type.ConclusionsOur results demonstrated that evaluation of these parameters in the serum of patients with localized RCC may not be used as a marker to discriminate between patients with RCC and healthy people.

Multilocular cystic renal cell carcinoma: A rare case report

Multilocular cystic renal cell carcinoma (MCRCC) is an uncommon low grade RCC with unique morphologic features. MCRCC also known as multilocular clear cell RCC is a rare cystic tumor of the kidney with an excellent outcome. MCRCC has been recognized as a separate subtype of RCC in the 2004 World Health Organization (WHO) classification of adult renal tumors. MCRCC is diagnosed on the basis of strict histological criteria according to 2004 WHO classification. It is usually included in the group of tumors of undetermined malignant potential with low nuclear grade. We present a case of MCRCC in a 43-year-old female patient who presented with pain in left lumbar region and hematuria. Left-sided radical nephrectomy was performed, and on histopathologic examination it was diagnosed as MCRCC with Fuhrman nuclear grade 1. Immunohistochemistry with epithelial membrane antigen and vimentin confirmed the diagnosis.

Transglutaminase 2 expression and its prognostic significance in clear cell renal cell carcinoma.

Background:A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2) in tumorigenesis or progression of renal cell carcinoma (RCC). The aim of this study was to examine TG2 expression and its clinicopathologic significance in a large number of human clear cell RCCs (CCRCCs).Methods:We analyzed 638 CCRCC patients who underwent partial or radical nephrectomy between 1995 and 2005. The expression of TG2 was determined by immunohistochemistry and categorized into four groups, according to staining intensity: negative (0), mild (1+), moderate (2+), and strong (3+).Results:TG2 staining intensity was negative in 8.5% of CCRCC (n=54), 1+ in 32.6% (n=208), 2+ in 50.5% (n=322), and 3+ in 8.5% (n=54). Strong TG2 expression was correlated with high Fuhrman nuclear grade (p=.011), high T category (p=.049), metastasis (p=.043) and male sex (p<.001) but not with N category.The survival analysis showed a significant association between strong TG2 expression and worse overall and cancer-specific survival (p=.027 and p=.010, respectively). On multivariate analysis, strong TG2 expression was a marginally significant prognostic indicator for Fuhrman nuclear grade and TNM staging (p=.054).Conclusions:Our study is the first to demonstrate the clinicopathologic significance of TG2 expression in a large number of human CCRCC samples. Strong TG2 expression was associated with high nuclear grade and poor prognosis.

Visceral obesity is associated with better recurrence-free survival after curative surgery for Japanese patients with localized clear cell renal cell carcinoma.

To investigate the prognostic significance of visceral obesity to predict recurrence after curative surgery for Japanese patients with localized renal cell carcinoma. The data of 285 patients who underwent curative surgery for localized renal cell carcinoma were retrospectively reviewed. Median follow-up was 36.7 months. The association between visceral obesity and recurrence-free survival rate was evaluated using the Kaplan-Meier method and Cox regression models. Visceral fat area at the level of the umbilicus measured using pre-operative computed tomography was used as an index of visceral obesity. Twenty-nine patients (10.2%) experienced recurrence. Five-year recurrence-free survival rates were 91.3% in high visceral fat area group (≥ 120 cm(2)) and 76.9% in low visceral fat area group (<120 cm(2)) (P = 0.037); however, visceral fat area was not an independent predictor of recurrence-free survival in multivariate analysis. In the patients with clear cell renal cell carcinoma, 28 patients (11.6%) experienced recurrence. Five-year recurrence-free survival rates were 88.7% in high visceral fat area group and 71.0% in low visceral fat area group (P = 0.043), and visceral fat area was an independent predictor of recurrence-free survival (hazard ratio: 1.974, P = 0.042) as well as C-reactive protein, Fuhrman nuclear grade, tumor size and microvascular invasion. In patients with organ confined clear cell renal cell carcinoma in particular, visceral fat area was also a useful and independent predictor of recurrence-free survival (hazard ratio: 2.807, P = 0.038). Body mass index was not useful in either cohort. High visceral fat area was a positive predictive biomarker for better recurrence-free survival after curative surgeries for localized clear cell renal cell carcinomas; however, body mass index was not a predictor.

Metachronous adrenal metastasis from operated contralateral renal cell carcinoma with adrenalectomy and iatrogenic Addison's disease.

Metachronous adrenal metastasis from contralateral renal cell carcinoma (RCC) surgery is an extremely rare condition. Iatrogenic Addison's disease occurring after metastasectomy (adrenalectomy) is an even rarer clinical entity. We present a case of a 68-year-old male with hematuria and left flank pain 9 years prior. The patient underwent left transperitoneal radical nephrectomy involving the ipsilateral adrenal glands due to a centrally-located, 75-mm in diameter solid mass lesion in the upper pole of the left kidney. The tumour lesion was confined within the renal capsule, and the histo-pathological examination revealed a Fuhrman nuclear grade II clear cell carcinoma. The patient underwent transperitoneal right adrenalectomy. The histopathological examination revealed metastasis of clear cell carcinoma. The patient was diagnosed with iatrogenic Addison's disease based on the measurement of serum cortisol levels and the adrenocorticotropic hormone (ACTH) stimulation test, after which glucocorticoid and mineralocorticoid replacement was initiated. The patient did not have local recurrence or new metastasis in the first year of the follow-up. The decision to perform ipsilateral adrenalectomy during radical nephrectomy constitutes a challenge, and the operating surgeon must consider all these rare factors.

What next? Choosing second-line therapy in progressive renal cell carcinoma

A 71-year-old woman presented with back pain and was incidentally found to have a left upper pole renal mass. She underwent left open partial nephrectomy; the pathology results revealed a 2.2-cm clear-cell renal cell carcinoma (RCC) with negative margins and a Fuhrman nuclear grade of 2.

Tumor VEGF expression correlates with tumor stage and identifies prognostically different groups in patients with clear cell renal cell carcinoma

ObjectivesVascular endothelial growth factor (VEGF) is a potent inducer of tumor angiogenesis and represents the key element in the pathogenesis of clear cell renal cell carcinoma (ccRCC). The aim of this study was to investigate the use of tumor VEGF expression as a parameter to identify tumor stage and prognostically different patient groups. Methods and materialsWe retrospectively collected clinical data of 137 patients treated with partial or radical nephrectomy at our institutions for organ-confined, locally advanced, and metastatic ccRCCs between 1984 and 2013. Tumor cell VEGF immunohistochemical expression was compared with pathological and clinical features including age, sex, tumor stage, and Fuhrman grade. Comparison of VEGF expression levels between tumor stages was performed via Kruskal-Wallis nonparametric test. Survival analysis was conducted via Kaplan-Meier product-limit method, and Mantel-Haenszel log-rank test was employed to compare survival among groups. ResultsMedian age at diagnosis was 61 years (range: 33–85y). Tumor stage was pT1N0M0 in 67 patients (49%), pT2N0M0 in 5 (4%), and pT3N0M0 in 25 (18%), while 40 patients (29%) had metastatic tumors at diagnosis. Fuhrman nuclear grade was G1 in 22 patients (16%), G2 in 60 (44%), G3 in 33 (24%), G4 in 13 patients (9%), and unknown in 9 patients. Tumor VEGF was differentially expressed among different stages (P<0.001) and in low (G1–2) and high (G3–4) Fuhrman grade tumors (P<0.001). No significant differences were found when stratifying by sex (P = 0.06) or age (P = 0.29). Median overall survival (OS) from partial or radical nephrectomy was 161 months (range: 1–366). We observed a significantly longer OS in patients with low (<25%) vs. high (>25%) VEGF expression levels (median OS 206 vs. 65mo, P<0.001). ConclusionsOur data show that tumor cell VEGF expression is significantly associated with tumor stage and Fuhrman grade and is able to predict patient outcome, suggesting a potential use of this parameter in identifying prognostically different patients with ccRCC.