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Aims: First described in 2014, renal cell carcinoma (RCC) with TFEB amplification (6p21) is a rare molecular subgroup whose diagnosis is challenging. The prognosis and therapeutic implications remain unclear., Methods: We report here the clinical, histological, immunohistochemical, and genetic features of nine novel cases. The pathological and immunohistochemical features were centrally reviewed by expert uropathologists. Fluorescence in situ hybridisation (FISH) confirmed the diagnosis and comparative genomic hybridisation (CGH) was performed to determine quantitative genomic alterations. We also performed an exhaustive review of the literature and compiled our data., Results: TFEB-amplified RCC were locally advanced, with initial lymph node involvement in one case and liver metastasis in another case. They were high-grade eosinophilic tumours with papillary/pseudopapillary architecture, frequent positivity for melanocytic markers, and frequent PDL1 expression. FISH demonstrated high-level TFEB amplification in six cases. One case showed concomitant TFEB translocation. CGH analysis identified complex alterations with frequent losses of 1p, 2q, 3p, 6p, and frequent 6p and 8q gains. VEGFA coamplification was identified in all cases with a lower level than TFEB. The prognosis was poor, with five patients having lymph node or distant metastases., Conclusion: TFEB-amplified RCC is a rare molecular subgroup with variable morphology whose diagnosis is confirmed by FISH analysis. The complex alterations identified by CGH are consistent with an aggressive clinical behaviour. The coamplification of VEGFA and the expression of PDL1 could suggest a potential benefit from antiangiogenics and targeted immunotherapy in combination for these aggressive tumours., (© 2022 John Wiley & Sons Ltd.)

Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19-80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDH mutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age., (© 2021. Crown.)

Background: Data evaluating the impact of positive vascular margins (PVMs) following surgical resection of non-metastatic renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus are lacking., Objective: To analyze the oncological impact of positive vascular margins following surgical resection of RCC with IVC tumor thrombus., Methods: Patients who underwent radical nephrectomy with the removal of IVC tumour thrombus for RCC between 2000 and 2019 were included. PVMs were identified from pathology reports defined as microscopically identified tumour present in the IVC wall at the site of resection or in case of thrombus was not completely removed. To achieve balance in baseline characteristics between patients with PVMs versus negative vascular margins, we used inverse probability of treatment weighting (IPTW) based on the propensity score. Local recurrence, distant metastasis and overall mortality were evaluated between groups using Cox proportional hazards regression models., Results: 209 patients were analyzed. Among them, 49 (23%) patients with PVMs were identified. Median follow-up was 55 months. After adjustment, excellent balance was achieved for most propensity score variables. In IPTW analysis, PVMs was associated with a higher risk of local recurrence (HR = 3.66; p < 0.001) without any impact on systemic recurrence (HR = 1.15; p = 0.47) or overall mortality (HR = 1.23; p = 0.48). Limitations include the sample size and unmeasured confounding., Conclusion: Our results suggest that a PVMs in patients with RCC after nephrectomy with thrombectomy is associated with a higher risk of local recurrence, however, it did not appear to influence the risk of distant metastasis or death., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Wilms' tumor (WT) is the most common renal malignancy in children. Its clinical and radiologic presentation may mimic other pediatric renal diseases, including pyonephrosis or renal abscess. The authors report a case of a 3-year-old girl presenting with pyelonephritis and right renal mass suggestive of a renal abscess, not responding to antibiotics. Further investigations were conducted, including a percutaneous renal needle core biopsy. A stage I fully necrotic WT was finally diagnosed. This amazing case of a fully necrotic WT at diagnosis demonstrates the importance of anatomopathologic analyses in pediatric renal masses, even when the infection is suspected., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To further characterise biphasic squamoid renal cell carcinoma (RCC), a recently proposed variant of papillary RCC., Methods and Results: We identified 28 tumours from multiple institutions. They typically showed two cell populations-larger cells with eosinophilic cytoplasm and higher-grade nuclei, surrounded by smaller, amphophilic cells with scanty cytoplasm. The dual morphology was variable (median 72.5% of tumour, range 5-100%); emperipolesis was found in all cases. The male/female ratio was 2:1, and the median age was 55 years (range 39-86 years). The median tumour size was 20 mm (range 9-65 mm). Pathological stage pT1a was found in 21 cases, pT1b in three, and pT3a and pT3b in one each (two not available). Multifocality was found in 32%: multifocal biphasic RCC in one case, biphasic + papillary RCC in two cases, biphasic + clear cell RCC in three cases, biphasic + low-grade urothelial carcinoma of the renal pelvis in one case, and biphasic + Birt-Hogg-Dubé syndrome in one case. Positive immunostains included: PAX8, cytokeratin (CK) 7, α-methylacyl-CoA racemase, epithelial membrane antigen, and vimentin. Cyclin D1 was expressed only in the larger cells. The Ki67 index was higher in the larger cells (median 5% versus ≤1%). Negative stains included: carbonic anhydrase 9, CD117, GATA-3, WT1, CK5/6, and CK20; CD10 and 34βE12 were variably expressed. Gains of chromosomes 7 and 17 were found in two evaluated cases. Follow-up was available for 23 patients (median 24 months, range 1-244 months): 19 were alive without disease, one was alive with recurrence, and one had died of disease (two had died of other causes)., Conclusions: Biphasic papillary RCC is a rare variant of papillary RCC, and is often multifocal., (© 2017 John Wiley & Sons Ltd.)

Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) has been recently described as a unique and indolent renal neoplasm, found in female patients with and without tuberous sclerosis complex. Although ESC RCC has a distinct morphology and frequent CK20 reactivity, its molecular karyotype has been previously studied only in few cases. We identified 19 ESC RCC from multiple institutions; all patients were female individuals without clinical features of tuberous sclerosis complex. Molecular karyotyping was performed in 13 cases (12 with informative result). The median age was 55 years (range: 32 to 79 y). The tumors were yellow-gray with a median size of 31 mm (range: 12 to 135 mm) and showed solid and cystic gross appearance. All tumors demonstrated typical microscopic features with solid areas admixed with variably sized macrocysts and microcysts. The cells showed eosinophilic cytoplasm with granular cytoplasmic stippling and round-to-oval nuclei. CK20 was positive in 14/19 (74%) cases. Stage pT1 was found in 17/19 (89%) patients (pT1a in 12, pT1b in 5); 1 patient each had pT2a and pT3a. A total of 15/16 patients with available follow-up were alive and without evidence of disease progression, after 1 to 169 months (median: 44 mo; mean: 49.6 mo); 3 died of other causes. The most common copy number gains were 16p13.3-16q23.1 (33% to 67%), 7p21.2-7q36.2 (42% to 50%), 13q14.2 (33%), and 19p12 (33%). The most common copy number losses included Xp11.21 (42%) and 22q11.23 (33%). Loss of heterozygosity was most frequently found at 16p11.2-11.1 (75%), Xq11.1-13.1 (75%), Xq13.1-21.1 (33%), 11p11.2-11.11 (33%), 9q21.1-22.2 (33%), and 9q33.1 (33%). ESC RCC demonstrates common molecular karyotype alterations, which further support its distinct nature.

Aims: Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney tumour characterized by translocations involving the transcription factor TFE3 or TFEB. tRCC was introduced into the World Health Organization classification in 2004, but much is still unknown about the natural history, clinicopathological features and outcomes of the disease. The aim of this study was to describe the landscape of fusion transcript in a large single-institution series of fluorescence in-situ hybridization (FISH)-confirmed tRCCs and then to compare it to morphological and clinical data., Methods and Results: Paired-end RNA sequencing was performed within a prospective database of the Department of Pathology, Centre Hospitalier Régional Universitaire (Lille, France). The diagnosis of tRCC was confirmed by FISH. Among a total of 1130 identified renal cell carcinomas, 21 cases (1.9%) showed rearrangement of the TFE3 (n = 20) or (TFEB) (n = 1) gene. Median patient age was 31 years (range = 15-47), and the female-to-male ratio was 6:1. Five different TFE3 fusion transcripts were identified; the most frequent TFE3 partners were PRCC (n = 4) and SFPQ (n = 4). The other partners involved were ASPCR1 (n = 1) and MED15 (n = 1) genes as well as a novel TFE3 partner, GRIPAP1., Conclusions: We identified a new fusion partner, GRIPAP1. The prognostic role of transcript type could not be determined because our number of cases was too small. Four patients (19%) died of the disease, all of which presented with a lymph node involvement at diagnosis. We confirm that tRCC can be an aggressive tumour, especially those of advanced clinical stage., (© 2017 John Wiley & Sons Ltd.)

The authors report the case of a 7-month-old girl with unilateral Wilms tumor with dilated cardiomyopathy, leading to cardiac failure and requiring intensive care. After chemotherapy and tumor removal, cardiac function has improved. This is a rare report on the association between nephroblastoma and dilated cardiomyopathy without hypertension.

We report an exceptional case of renal cell carcinoma (RCC) associated with ALK translocation in an adult. The tumor was located in the left kidney and measured 4cm. The tumor was composed of sheets of large eosinophilic cells with frequently intracytoplasmic vacuoles. The nuclei were large with a nucleolar grade 3. At immunohistochemistry, tumor cells were diffusely positive for PAX8 and vimentin and focally stained with CK7. ALK immunostaining was diffuse and fluorescent in situ hybridization showed a rearrangement of ALK in numerous tumor cells. To date, less than 17 cases of RCCs with ALK rearrangements are reported in children and adults. The prognosis remains uncertain but ALK rearrangement may be of potential value for target therapy with crizotinib., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Collecting duct carcinoma (CDC) is a kidney cancer subtype that is thought to arise from principal cells in distal parts of the collecting ducts. Some studies suggested an overlap of CDC with upper tract urothelial carcinoma (UTUC), making the pathological diagnosis challenging. Herein, we performed for the first time transcriptome sequencing of CDC and compared them to UTUC and renal cell carcinoma subtypes. We discovered that CDC displays a unique transcriptomic signature among kidney cancer subtypes, with a putative cell of origin in the distal convoluted tubules. Hierarchical unsupervised clustering reveals that the CDC signature is closer to that of other RCC subtypes than to UTUC, which is similar to that of bladder carcinoma. CDC is characterized by a metabolic shift, with impairment of oxidoreductase activity, pyruvate metabolism and the tricarboxlyic acid cycle, as well as an immunogenic response consistent with increased tumor infiltrating lymphocytes, particularly within metastatic cases. In addition, pathways differentially altered between CDC and UTUC point to a basal-like phenotype of CDC in contrast to the luminal-like signature of UTUC. We conclude that CDC harbors a pathognomonic transcriptomic signature characterized by immunogenic and a metabolic aberrations, indicating that targeting these processes might provide therapeutic options for patients.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with characteristic tumors involving multiple organ systems. Whereas renal angiomyolipoma (AML) is common in TSC, renal cell carcinoma (RCC) is rarely reported. Fifty-seven RCCs from 13 female and 5 male TSC patients were reviewed. Age at surgery ranged from 7 to 65 years (mean: 42 y). Nine patients (50%) had multiple synchronous and/or metachronous RCCs (range of 2 to 20 RCCs) and 5 had bilateral RCCs (28%). Seventeen patients (94%) had histologically confirmed concurrent renal AMLs, including 15 with multiple AMLs (88%) and 9 (50%) with AMLs with epithelial cysts. None of the 15 patients with available clinical follow-up information had evidence of distant metastatic disease from 6 to 198 months after their initial surgery (mean: 52 mo). The 57 RCCs exhibited 3 major distinct morphologies: (1) 17 RCCs (30%) had features similar to tumors previously described as "renal angiomyoadenomatous tumor" or "RCC with smooth muscle stroma"; (2) 34 RCCs (59%) showed features similar to chromophobe RCC; and (3) 6 RCCs (11%) showed a granular eosinophilic-macrocystic morphology. Distinct histologic changes were also commonly present in the background kidney parenchyma and included cysts or renal tubules lined by epithelial cells with prominent eosinophilic cytoplasm, nucleomegaly, and nucleoli. Immunohistochemically, all RCCs tested showed strong nuclear reactivity for PAX8 and HMB45 negativity. Compared with sporadic RCCs, TSC-associated RCCs have unique clinicopathologic features including female predominance, younger age at diagnosis, multiplicity, association with AMLs, 3 recurring histologic patterns, and an indolent clinical course. Awareness of the morphologic and clinicopathologic spectrum of RCC in this setting will allow surgical pathologists to better recognize clinically unsuspected TSC patients.

We reported a rare case of cutaneous metastases of renal cell carcinoma (RCC) with an Xp11.2 translocation in a 15-year-old female. Clinicians should be aware of the possibility of this uncommon site of metastasis, which can indicate multivisceral dissemination of the disease. We discuss the feasibility and opportunity of treating such a patient with multiple line of tyrosine kinase inhibitor (TKI) targeting vascular endothelial and platelet-derived growth factor receptors., (© 2014 Wiley Periodicals, Inc.)

Some renal epithelial neoplasms, such as renal angiomyoadenomatous tumor, clear cell papillary renal cell carcinoma and renal cell carcinoma with smooth muscle stroma, contain a variably prominent smooth muscle stromal component. Whether or not this leiomyomatous stroma is part of the neoplastic proliferation has not been firmly established. We studied the clonality status of 14 renal cell carcinomas with a prominent smooth muscle stromal component (four renal angiomyoadenomatous tumors/clear cell papillary carcinomas, five clear cell carcinomas, two papillary carcinomas, and three renal cell carcinomas with smooth muscle rich stroma) using the human androgen receptor assay (HUMARA). We found the leiomyomatous stromal component in all analyzable (8/14) cases to be polyclonal and therefore reactive rather than neoplastic. Based on morphological observations, we propose that the non-neoplastic leiomyomatous stromal component is likely derived from smooth muscle cells of large caliber veins located at the peripheral capsular region or within the collagenous septae of the tumors.

Aims: Several entities have been individualized recently within the family of renal neoplasms with papillary features. Clear cell papillary renal cell carcinoma (CCPRCC) was first described in patients with end-stage renal disease, but is also observed in patients with normal renal function. The objective of this study was to document the clinicopathological and immunohistochemical characteristics of CCPRCC, with a special emphasis on cyclin D1 expression., Methods and Results: The patients were 25 men and 17 women, mean age 60.7 years. Seventeen patients had a chronic renal disease. All tumours were stage pT1, with a mean diameter of 2 cm. Six tumours were multifocal. Tumours cells were mainly cuboidal, with clear cytoplasm and low-grade nuclei apically aligned. In all cases, Fuhrman nuclear grade was one or two. No necrosis or vascular invasion was seen. During follow-up (10-72 months), no metastasis or death related to the disease was observed. Immunohistochemistry showed strong and diffuse cytokeratin 7 immunoreactivity in all cases, but no labelling for AMACR or TFE3. There was diffuse nuclear cyclin D1 immunoreactivity in 83% of cases., Conclusion: CCPRCC is now a well-characterized entity. This tumour is an indolent and very low-grade neoplasm. Here we report the first study, to our knowledge, demonstrating the overexpression of cyclin D1 immunostaining by this tumour., (© 2013 John Wiley & Sons Ltd.)

MUC1 is overexpressed in human carcinomas. The transcription factor SNAIL can activate epithelial-mesenchymal transition (EMT) in cancer cells. In this study, in renal carcinoma, we demonstrate that (i) MUC1 and SNAIL were overexpressed in human sarcomatoid carcinomas, (ii) SNAIL increased indirectly MUC1 expression, (iii) MUC1 overexpression induced EMT, (iv) MUC1 C-terminal domain (MUC1-C) and β-catenin increased SNAIL transcriptional activity by interaction with its promoter and (v) blocking MUC1-C nuclear localization decreased Wnt/β-catenin signaling pathway activation and SNAIL expression. Altogether, our findings demonstrate that MUC1 is an actor in EMT and appears as a new therapeutic target., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

MUC1 is a membrane-anchored mucin and its cytoplasmic tail (CT) can interact with many signaling pathways and act as a co-transcription factor to activate genes involved in tumor progression and metastasis. MUC1 is overexpressed in renal cell carcinoma with correlation to prognosis and has been implicated in the hypoxic pathway, the main renal carcinogenetic pathway. In this context, we assessed the effects of MUC1 overexpression on renal cancer cells properties. Using shRNA strategy and/or different MUC1 constructs, we found that MUC1-extracellular domain and MUC1-CT are involved in increase of migration, cell viability, resistance to anoikis and in decrease of cell aggregation in cancer cells. Invasiveness depends only on MUC1-CT. Then, by using siRNA strategy and/or pharmacological inhibitors or peptides, we showed that sheddases ADAM10, ADAM17 and gamma-secretase are necessary for MUC1 C-terminal subunit (MUC1-C) nuclear location and in increase of invasion property. Finally, MUC1 overexpression increases ADAM10/17 protein expression suggesting a positive regulatory loop. In conclusion, we report that MUC1 acts in renal cancer progression and MUC1-C nuclear localization drives invasiveness of cancer cells through a sheddase/gamma secretase dependent pathway. MUC1 appears as a therapeutic target by blocking MUC1 cleavage or nuclear translocation by using pharmacological approach and peptide strategies.

The medical treatment of renal-cell carcinoma, and of its most frequent histologic subtype, the clear cell renal-cell carcinoma, has been changed by the emergence of targeted therapies. The development of these drugs has been made possible by more precise knowledge of molecular mechanisms involved in the carcinogenesis of these tumors. Three molecular pathways may be involved in clear cell renal-cell carcinoma: VHL/HIF/VEGF, PI3K/AKT/mTOR and MAPKinases pathways. These antiangiogenic therapies are approved for the treatment of advanced and metastatic clear cell renal-cell carcinoma. In metastatic disease, pathologists have significant and different implications: 1) in tumor biopsy, only the diagnosis of clear cell renal-cell carcinoma implies the prescription of antiangiogenic drugs, and 2) after targeted therapies, pathologists must evaluate the therapeutic effects on tumor. Consensus on macroscopic and histologic reports are needed by pathologists., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

A case of primary adenocarcinoma of the renal pelvis occurring in a 57-year-old woman who had no previous history is reported. The lesions were thought to be a renal destruction by pyelolithiasis upon symptomatology and imaging study data. A nephrectomy was thus performed. Macroscopic examination revealed voluminous and exophytic lesions surrounding lithiasis. Diagnosis of intestinal-type adenocarcinoma of the renal pelvis was established on histological examination. No evidence of other tumor localization was revealed by complete exploration. Primary adenocarcinoma of renal pelvis is a rare and often mucinous intestinal-type tumour. Chronic inflammation and renal lithiasis seem to be associated with this tumour. Few cases are reported and prognosis is doubtful. The main differential diagnosis to eliminate is secondary lesions to the kidney of adenocarcinoma from another origin. A careful pathological examination in case of pyelonephritic kidney is necessary to look for an associated tumour., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Aims: In kidney cancer, new anti-angiogenic therapies have emerged requiring parameters of effectiveness. The aim was to analyse the expression of endocan or endothelial cell-specific molecule-1, which is a proteoglycan up-regulated in presence of pro-angiogenic factors., Method and Results: We investigated 44 renal clear cell carcinomas (RCC) and 25 papillary carcinomas (PC). Circulating endocan was detected by enzyme-linked immunosorbent assays (ELISA) in 14 patients with RCC, in eight with PC and in 15 healthy volunteers. Endocan was detected by immunohistochemistry in endothelial cells in almost all the cases of RCC without immunoreactivity in tumour cells. In PC, only 5/25 tumours exhibited weak immunoreactivity. Reverse transcriptase-polymerase chain reaction study confirmed that endocan levels were strongly increased in RCC. Endocan was also detected by ELISA at levels from 3- to 10-fold higher in the sera of patients with RCC. In vitro, addition of sunitinib prevented the release of endocan in human umbilical vascular endothelial cells when induced by vascular endothelial growth factor., Conclusions: Our results showed that endocan is overexpressed in patients with RCC. Endocan could therefore appear as a marker of interest in the follow-up and may be a potential parameter to monitor the tumour response to anti-angiogenic therapeutics.

The hypoxia inducible factor (HIF) signaling pathway is known as the main renal carcinogenetic pathway. MUC1, an O-glycoprotein membrane-bound mucin, is overexpressed in clear renal cell carcinomas (cRCC) with correlation to two major prognostic factors: tumor-node-metastasis stage and nuclear Fürhman grade. We questioned whether there is a direct link between the HIF pathway and MUC1 overexpression in renal tumors. Interestingly, we observed concomitant increase of HIF-1alpha and MUC1 in metastatic cRCC group versus nonmetastatic cRCC group. Using different renal cell models and small interfering RNA assays targeting either HIF-1alpha or YC-1, a HIF-1 pharmacologic inhibitor, we showed induction of MUC1 expression under hypoxia by a HIF-dependent mechanism. Chromatin immunoprecipitation assay showed a direct binding of HIF-1alpha at the MUC1 promoter. In addition, combined site-directed mutagenesis and gel shift assay allowed the identification of two functional putative hypoxia responsive elements at -1488/-1485 and at -1510/-1507 in the promoter. Using a rat kidney model of ischemia/reperfusion, we confirmed in vivo that clamping renal pedicle for 1 hour followed by 2 hours of reperfusion induced increased MUC1 expression. Furthermore, MUC1 knockdown induced significant reduction of invasive and migration properties of renal cancer cells under hypoxia. Altogether, these results show that MUC1 is directly regulated by HIF-1alpha and affects the invasive and migration properties of renal cancer cells. Thus, MUC1 could serve as a potential therapeutic target in cRCC.

Purpose: We determined whether renal vein ostium wall invasion could be predicted by renal vein and inferior vena cava diameter on imaging. We also determined whether it is a prognostic factor for recurrence and survival after radical nephrectomy and thrombus ablation for renal cell carcinoma with an inferior vena cava tumor thrombus., Materials and Methods: From January 2000 to January 2006 nephrectomy for renal cell carcinoma was performed in 446 patients, of whom 32 (7.2%) underwent inferior vena cava thrombus extraction with complete resection of the renal vein ostium. When necessary, inferior vena cava partial and circumferential ablation was done in 5 and 8 patients, respectively, as well as replacement for thrombus adhesions. The largest coronal or axial diameter of the renal vein ostium and inferior vena cava anteroposterior diameter were measured on preoperative magnetic resonance imaging. Renal vein ostium wall invasion was assessed in all patients and determined microscopically by tumor cell infiltration into the intima. ROC curves were used to assess the value of these measurements for diagnosing patients with renal vein ostium invasion with 90% sensitivity. The risk of recurrence and survival was analyzed., Results: Renal vein ostium wall invasion was present in 13 of 32 patients (40.6%). It significantly correlated with mean +/- SD inferior vena cava anteroposterior diameter (27.8 +/- 10.2 vs 17.3 +/- 6.8 mm, p = 0.01) and with the largest mean renal vein ostium diameter (22.3 +/- 7.9 vs 12.6 +/- 6.9 mm, p = 0.01). The upper level of the inferior vena cava thrombus correlated with renal vein ostium invasion (p = 0.002). The inferior vena cava anteroposterior diameter or renal vein ostium diameter cutoff value to predict wall invasion with 90% sensitivity was 18 and 14 mm, respectively. The AUC was 0.78 for inferior vena cava diameter and 0.86 for renal vein ostium diameter. No inferior vena cava recurrence was observed. Renal vein ostium wall invasion was associated with a higher risk of recurrence and decreased specific survival (p = 0.01 and 0.03, respectively). The association of ostium renal vein wall invasion with death from renal cell carcinoma was seen on multivariate analysis after adjusting for tumor size, TNM stage and thrombus level (RR 5.9, 95% CI 1.45-30.8, p = 0.01)., Conclusions: Preoperative imaging measurements of renal vein and inferior vena cava diameter can accurately predict renal vein ostium wall invasion. Renal vein ostium wall invasion is an independent prognostic marker that is associated with a higher risk of recurrence and decreased specific survival.

Invasive urothelial carcinoma may present with many deceptive morphologic variants. We report the clinicopathologic and immunohistochemical features of 5 cases of the so-called lipid-cell variant of urothelial carcinoma. The tumors occurred in 4 men and 1 women aged from 56 to 80 years. Four cases were developed in the bladder and 1 case in the renal pelvis. All cases were revealed by a macroscopic hematuria. The tumors were composed of sheets and nests of large epithelial cells with an abundant clear multivacuolated cytoplasm mimicking lipoblasts. Nuclei were irregular, hyperchromatic, eccentric, and frequently indented by cytoplasmic vacuoles. Mucin stains (PAS, Alcian Blue) were negative. Tumor cells were strongly stained with cytokeratin 7, cytokeratin 20, and EMA but were negative with S-100 protein. In all cases, a usual high-grade urothelial carcinoma component was admixed with lipoid tumor cells. Two tumors infiltrated the bladder muscle, 2 cases invaded the bladder submucosa, and 1 case invaded the renal parenchyma. In the follow-up, despite appropriate surgical treatment, 4 patients died of the disease and 1 patient is alive without recurrence. Because of its rarity and the tumor cells' appearance, the lipoid-cell variant may be misdiagnosed and must be distinguished from liposarcoma or signet-ring cell carcinoma. In the present series, the lipoid-cell variant of urothelial carcinoma was associated with an aggressive behavior and a poor prognosis.

Context: Adult renal cell carcinoma (RCC) with rhabdoid features is a recently recognized morphologic variant of kidney carcinoma. To date, only very few studies have been published on this subject and p53 was not previously studied., Objective: To evaluate clinical attributes, morphology, and immunohistochemistry in RCC with rhabdoid component., Design: Reviewing a consecutive series of 310 RCCs, we identified 14 cases of RCC with rhabdoid features. All cases were reviewed and subjected to detailed clinical and pathologic studies with immunohistochemical evaluation of p53., Results: All tumors were clear RCCs with rhabdoid component representing from 5% to 50% of the tumor volume. Rhabdoid cells were large with a central eosinophilic intracytoplasmic inclusion and an eccentric atypical nucleus. Tumor necrosis was common (13/14) and sometimes extensive. Nine of 14 tumors were staged pT3, 4 of 14 were pT2, and only 1 tumor was pT1. On immunohistochemistry, rhabdoid cells were positive for vimentin (14/ 14), epithelial membrane antigen (11/14), and cytokeratin (9/14). Desmin and smooth muscle actin were always negative. p53 was positive in 10 of 14 tumors in the rhabdoid areas (5%-50% of tumor cells stained) but only in 5 of 14 cases in usual clear renal cell areas. In the follow-up, 10 of 14 patients developed metastases and 6 of 14 died of the disease. The median of survival was 8 months., Conclusions: We showed that RCC with rhabdoid features is a very aggressive neoplasm with a poor prognosis. We observed an overexpression of p53 in the rhabdoid component that may be implicated in the tumor dedifferentiation.

Objective: To evaluate endoluminal occlusion of the inferior vena cava (IVC) during surgical treatment of renal cell carcinoma (RCC) with either retrohepatic (level II) or suprahepatic (level III) caval tumour thrombus., Patients and Methods: From January 2000 to February 2005, 31 patients with renal vein/IVC involvement (T3b/c) of 278 who had a radical nephrectomy, were selected for review. Of these 31, 13 consecutive patients with RCC presenting a thrombus level II or III were prospectively treated with endoluminal occlusion of the free IVC cranial to the thrombus, to avoid dissection of the suprahepatic IVC or the subdiaphragmatic IVC. The occlusion balloon was positioned using transoesophageal echocardiography (TEE) control through a cavotomy at the ostium of the renal vein. Thrombectomy and radical nephrectomy were then performed. The operative duration, peri-operative bleeding, and complications during and after surgery were assessed. Overall patient survival time, disease-free survival and development of metastasis were calculated., Results: Caval thrombectomy was successful in all patients. The IVC needed to be replaced with an expanded polytetrafluoroethylene graft in three patients and a patch closure after lateral cavectomy was used in four. There was no case of air embolism. One case of asymptomatic tumour migration was detected during the procedure by TEE. The mean (sd) and median (range) operative duration was 170 (29) and 170 (120-210) min, and the mean number of units of packed red cells transfused during hospitalization was 5 (5) and 3 (0-16). There was no peri-operative mortality. The complications were one splenectomy and one early thrombosis of the IVC. The mean (range) follow-up was 22.1 (2-50) months. Distant metastases occurred in seven patients; there was no local or IVC tumour recurrence. Four patients died from metastatic progression and six are alive with no progression., Conclusion: Endoluminal occlusion of the IVC with TEE monitoring for level II and III thrombus avoided a suprahepatic or subdiaphragmatic approach to the IVC. This technique caused no major complications and was very reliable, due to TEE monitoring. Segmental resection and reconstruction of the IVC could also be used for adherent thrombi.

Purposes: We correlated clinicopathological and imaging features of multilocular cystic renal cell carcinoma (MCRCC) to propose preoperative criteria for therapeutic modalities., Materials and Methods: A total of 24 RCCs with a chiefly cystic component were identified from 1993 to 2002. In each case histological slides and available imaging studies were retrieved. Two tumor groups were defined, namely MCRCC and clear RCC with cystic change (CRCC) by intrinsic growth or necrotic degeneration. Radiological correlation using computerized tomography and magnetic resonance imaging was performed considering criteria such as an expansile nodule, cyst wall thickness and septa., Results: On imaging MCRCC presented as a multilocular cystic mass lacking an expansile nodule, and with regular thin cyst wall and septa. On pathological study MCRCC presented as complex, multilocular cystic carcinoma with septa covered by low nuclear grade clear renal tumor cells without a grossly expansile nodule. They were staged pT1 with a free clinical course. In contrast, CRCC was identified on imaging with an expansile nodule (5 mm or greater), thick, irregular cyst wall and septa. On pathological study CRCC was characterized by a grossly expansile nodule in the septa and/or cyst wall. Nuclear grade and TNM stage were higher in CRCC., Conclusions: Preoperative recognition of MCRCC is possible using strict computerized tomography and/or magnetic resonance imaging criteria. The current study confirms the low malignant potential of MCRCC. Nephron sparing surgery should be proposed when MCRCC is suspected.

The purpose of this study was to evaluate strategies used for surgical management of renal cell carcinoma with a tumoral thrombus extension in the inferior vena cava (IVC). From January 2000 to December 2001, urological and vascular surgeons jointly undertook surgical treatment on 10 patients with renal cell carcinoma and tumor thrombus in the IVC. There were five women and five men, with a mean age of 60.2 years. The limit of thrombus extension, classified according to the Neves and Zincke system, was level I (renal) in one patient, level II (infrahepatic) in one, level III (retrohepatic) in three, and level IV (atrial) in five. Exposure was achieved by chevron bilateral subcostal laparotomy associated with sternotomy in three patients, bilateral subcostal laparotomy in six, and median sternolaparotomy in one. Radical nephrectomy associated with caval thrombectomy was performed in all patients. Cardiopulmonary bypass was used in four of the five level IV patients. The fifth patient was contraindicated for cardiopulmonary bypass. Transesophageal echography (TEE)-guided endoluminal occlusion of the unobstructed infradiaphragmatic IVC was performed in patients with level III thrombus. Clamping of the IVC was performed in patients with levels I and II thrombus. All procedures were assisted by continuous TEE surveillance. No intraoperative gas or tumor emboli were detected by TEE. The mean number of red blood cell units transfused during the course of hospitalization was 9.7 (range 2-22, median 9). One patient died of multiple organ failure on the day 28 after the procedure. The mean duration of hospitalization was 16 days. The mean duration of follow-up was 9.7 months. During follow-up, two of the remaining nine patients died due to tumor recurrence. Tumor recurrence was also detected in one of the seven surviving patients. Surgery for renal cell carcinoma with tumor thrombus in the IVC must be carried out in a specialized facility with the assistance of TEE surveillance and, in some cases, cardiopulmonary bypass. Operative treatment improves the prognosis of renal cell carcinoma with tumor thrombus in the IVC. In patients with level III thrombus, TEE-guided endoluminal occlusion of the unobstructed infradiaphragmatic IVC simplifies surgical management by obviating the need for exposure of the retrohepatic and supradiaphragmatic IVC.

Primary neuroectodermal tumours (PNET) are very aggressive malignant tumours, rapidly progressing to metastasis and death. They rarely involve the kidney, as only 23 cases have been described in the literature. Renal tumours, regardless of their histology, spread to the inferior vena cava (IVC) in 4% to 10% of cases. Invasion of the inferior vena cava wall by tumour thrombus is rare and, when it occurs, is often limited to the ostium of the renal vein. The authors report a case of primary neuroectodermal tumour of the kidney with thrombus in the inferior vena cava ascending to the right atrium (level IV), invading the wall of the IVC and associated with a non-infiltrating papillary urothelial tumour of the ureter. They describe the surgical management of this tumour and present a review of the literature.

Objectives: To investigate, by real-time quantitative reverse transcriptase-polymerase chain reaction, the expression of MUC3 and vascular endothelial growth factor (VEGF) to correlate them with histologic parameters and with prognosis. Human mucins are large O-glycoproteins expressed in epithelial tissues. Deregulation of mucin genes has been demonstrated in several epithelial neoplasms. In the kidney, MUC3 is expressed in normal convoluted tubules and in renal clear cell carcinoma., Methods: Twenty-six renal clear cell carcinoma specimens were studied. For all tumors, samples of normal and tumor kidney were frozen. After RNA extraction, using ultracentrifugation through a cesium chloride cushion, VEGF and MUC3 mRNA were analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction. The pathologic parameters included Fuhrman nuclear grade and TNM stage. All follow-up data were available., Results: The median level of MUC3 and VEGF expression was greater in tumor areas compared with normal areas (P < 0.002 and P < 0.001, respectively). The MUC3 tumor/normal tissue expression ratio was greater in nuclear grade 3 tumor than in low grades (grade 1-2; P < 0.005). No statistically significant relationship was found with the prognosis for MUC3 and VEGF in our study., Conclusions: The results of this study demonstrate that MUC3 and VEGF are overexpressed in renal clear cell carcinoma, and the MUC3 expression ratio is greater in nuclear grade 3 than in grades 1 and 2 (low grades) tumor. These findings suggest the implication of MUC3 in renal carcinogenesis.

Objective: To evaluate the risk of local recurrence and metastatic spread of renal cancer treated by conservative surgery with a minimum follow-up of 5 years., Material and Methods: All patients operated for renal cancer by conservative surgery in our department between November 1989 and March 1997 were included in this retrospective study and were submitted to annual follow-up. These patients presented conventional indications (solitary T1N0M0 tumours < 4 cm) or indications of necessity (all stages)., Results: The minimum follow-up was 5 years (range: 63-143 months; median: 90 months). This series comprised 30 partial nephrectomies, 15 performed for solitary T1N0M0 tumours < 4 cm, and conservative surgery was performed by necessity in 15 patients (10 patients with T1N0M0 tumours, 5 patients with T2 or M+ tumours). All tumours less than 4 cm on imaging were less than 4 cm on the operative specimen. In stage T1N0M0 tumours, the prediction of pathological stage by preoperative imaging was accurate in 24 out of 25 cases, with 24 pT1N0M0 and 1 pT3aN0M0 on final histology. The resection margins were negative in 29 out of 30 patients. One patients with a stage T2N0M+ tumour (7.5 cm in diameter) had a positive resection margin. Two out of 30 patients developed impaired renal function after surgery to a solitary kidney. Renal function at 3 months remained identical to preoperative renal function in all other patients. For 24 patients with pT1N0M0 tumours < 4 cm, the specific recurrence-free survival was 100% (median follow-up: 90 months; range: 63 to 143 months). Among the 6 patients with T2 or M+ tumours, 5 patients (84%) died from metastatic disease at 18, 22, 24, 28 and 54 months, while 1 patient (16%) was still alive without recurrence at 119 months., Conclusion: The indication for conservative surgery for T1N0M0 renal tumours < 4 cm is a validated treatment option for unifocal renal cancer. This series confirms the data reported in the literature with a minimum follow-up of 5 years. Stage pT3a tumours on postoperative diagnosis have a high risk of recurrence and metastatic spread, which may constitute an indication for secondary radical nephrectomy. Annual surveillance by imaging is essential.

Papillary renal cell carcinoma is now a well-established entity with distinct histological and cytogenetic features. A subdivision has been proposed in correlation with prognosis. Type 1 is the most frequent subtype and appears to have a better prognosis than Type 2. The subdivision is based on microscopic criteria. To investigate these 2 types of papillary renal cell carcinoma, we have compared the clinical features, ancillary factors (TNM stage, Fuhrman grade), survival and MUC1 expression in 25 Type 1 and 12 Type 2 papillary renal cell carcinomas. Type 2 tumors were significantly associated with a higher Fuhrman grade (Grade III frequent; P <.001). Type 2 tumors were also associated with a poorer prognosis than Type 1 (P <.005). Fuhrman grade was significantly associated with prognosis (P <.005). The type and the prognosis were not correlated with the TNM stage. We have shown a differential expression of MUC1 between Type 1 and Type 2 with a polarized expression in Type 1 and a rare expression in Type 2. In conclusion we confirm that the morphologic sub-typing and Fuhrman grade are valuable factors of outcome of papillary renal cell carcinomas and that MUC1 immunostaining is useful in differentiating Type 1 and Type 2 tumors.

We studied, by immunohistochemical analysis, the expression of MUC1 and epithelial membrane antigen in 44 stage pT1 renal cell carcinomas (RCCs). Six patients had a metastatic evolution. The percentage of stained cells was determined for each tumor. All tumors and normal adjacent renal parenchyma were stained. In normal kidney, distal convoluted tubules and collecting ducts stained strongly with an apical distribution. In tumors, there was a significant statistical correlation of the MUC1 expression level with the nuclear grade and with tumor progression. High-grade tumors had more stained cells than did low-grade tumors. Metastatic tumors also were more stained than nonmetastatic lesions. By using the Kaplan-Meier method and the log-rank test, we observed that patients with fewer than 10% of stained cells had no metastatic evolution. In contrast, patients with 70% or more stained cells had significantly lower metastasis-free survival rates. We conclude that MUC1 is expressed in RCC and is associated with tumor progression in pT1 RCC.