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We prospectively evaluated the performance of combined shear wave elastography (SWE) and conventional ultrasound (US) for the characterization of 89 testicular focal masses. Testes were evaluated with B-mode, color Doppler and SWE measurements, locating a region of interest on the normal and pathologic parenchyma. Thirty-seven malignant tumors (MTs), 12 burned out tumors (BOTs), 28 Leydig cell tumors (LCTs), 2 dermoid cysts and other benign lesions were included. MTs + BOTs exhibited more microliths and macrocalcifications compared with benign lesions (p < 10 -4 ). LCTs manifested mostly a dominant peripheral vascularization pattern compared with other lesions. MTs + BOTs were stiffer compared with benign lesions (p < 2 × 10 -4 ) but with a moderate area under the receiver operating characteristic curve (AUROC) of 80%. By focusing on LCTs versus MTs + BOTs, diagnostic performance led to an AUROC of 89% for the best stiffness parameter. For combined conventional US and SWE, the diagnostic performance to differentiate all benign lesions versus MTs + BOTs and LCTs versus MTs + BOTs increased to AUROCs of 93% and 98%, respectively., (Copyright © 2018 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau ( VHL ) gene. Since this discovery, additional VHL mutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. VHL is a major tumor suppressor gene, mutations in which were first described in patients presenting with VHL disease, which is characterized by the development of highly vascularized tumors. Here, we identify a new VHL cryptic exon (termed E1') deep in intron 1 that is naturally expressed in many tissues. More importantly, we identify mutations in E1' in 7 families with erythrocytosis (1 homozygous case and 6 compound-heterozygous cases with a mutation in E1' in addition to a mutation in VHL coding sequences) and in 1 large family with typical VHL disease but without any alteration in the other VHL exons. In this study, we show that the mutations induced a dysregulation of VHL splicing with excessive retention of E1' and were associated with a downregulation of VHL protein expression. In addition, we demonstrate a pathogenic role for synonymous mutations in VHL exon 2 that altered splicing through E2-skipping in 5 families with erythrocytosis or VHL disease. In all the studied cases, the mutations differentially affected splicing, correlating with phenotype severity. This study demonstrates that cryptic exon retention and exon skipping are new VHL alterations and reveals a novel complex splicing regulation of the VHL gene. These findings open new avenues for diagnosis and research regarding the VHL-related hypoxia-signaling pathway., (© 2018 by The American Society of Hematology.)

Hereditary leiomyomatosis and renal cell carcinoma syndrome is characterized by an increased risk of agressive renal cell carcinoma, often of type 2 papillary histology, and is caused by FH germline mutations. A prominent eosinophilic macronucleolus with a perinucleolar clear halo is distinctive of hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma according to the 2012 ISUP and 2016 WHO kidney tumor classification. From an immunohistochemistry perspective, tumors are often FH-negative and S-(2-succino)-cysteine (2SC) positive. We performed a pathology review of 24 renal tumors in 23 FH mutation carriers, and compared them to 12 type 2 papillary renal cell carcinomas from FH wild-type patients. Prominent eosinophilic nucleoli with perinucleolar halos were present in almost all FH-deficient renal cell carcinomas (23/24). Unexpectedly, they were also present in 58% of type 2 papillary renal cell carcinomas from wild-type patients. Renal cell carcinoma in mutation carriers displayed a complex architecture with multiple patterns, typically papillary, tubulopapillary, and tubulocystic, but also sarcomatoid and rhabdoid. Such pattern diversity was not seen in non-carriers. FH/2SC immunohistochemistry was informative as all hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas were either FH- or 2SC+. For FH and 2SC immunohistochemistries taken separately, sensitivity of negative anti-FH immunohistochemistry was 87.5% and specificity was 100%. For positive anti-2SC immunohistochemistry, sensitivity, and specificity were 91.7% and 91.7%, respectively. All FH wild-type renal cell carcinoma were FH-positive, and all but one were 2SC-negative. In conclusion, multiplicity of architectural patterns, rhabdoid/sarcomatoid components and combined FH/2SC staining, but not prominent eosinophilic nucleoli with perinucleolar halos, differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma from type 2 papillary renal cell carcinoma with efficient FH gene. Our findings are crucial in identifying who should be referred to Cancer Genetics clinics for genetic counseling and testing.

Our aim in the study described here was to prospectively establish the feasibility of using and reproducibility of testicular shear-wave elastography in the assessment of testicular stiffness in 62 normal patients and 539 infertile men with obstructive azoospermia (OA), non-Klinefelter syndrome non-obstructive azoospermia (non-KS NOA), Klinefelter syndrome NOA (KS NOA), oligoasthenoteratozoospermia (OAT) or a left varicocele. The feasibility rate was 96.9%, with an intra-class correlation coefficient of 0.85 (95% confidence interval: 0.83-0.88). Median stiffness (interquartile range) values were 2.4 kPa (2.0, 2.9), 2.1 kPa (1.8, 2.5), 2.4 kPa (2.0, 2.7), 2.0 kPa (1.7, 2.4), 2.6 kPa (2, 3.2) and 2.2 kPa (1.8, 2.6) for men with a normal testis (n = 108), OAT (n = 689), OA (n = 119), non-KS NOA (n = 183), KS NOA (n = 70) and varicocele (n = 132), respectively. Testicular shear wave elastography is a feasible and reproducible technique. A significant positive association was found between stiffness and testis volume (p = 0.001). Testicular stiffness was higher in OA than in non-KS NOA populations (p = 1.e-10) and in KS NOA than in NOA populations (p = 2.0e-8), but the substantial number of overlapping values limited the clinical impact., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective.: Renal involvement is a rare event during primary SS (pSS). We aimed to describe the clinico-biological and histopathological characteristics of pSS-related nephropathy and its response to treatment., Methods.: We conducted a French nationwide, retrospective, multicentre study including pSS patients fulfilling American-European Consensus Group criteria or enlarged American-European Consensus Group criteria, and with biopsy-proven renal involvement., Results.: A total of 95 patients were included (median age 49 years). An estimated glomerular filtration rate (eGFR) of <60 ml/min was found in 82/95 patients (86.3%). Renal biopsy demonstrated tubulointerstitial nephritis (TIN) in 93 patients (97.9%), and frequent (75%) plasma cell infiltrates. Glomerular lesions were found in 22 patients (23.2%), mainly related to cryoglobulin. The presence of anti-SSA (76.8%) and anti-SSB (53.8%) antibodies was particularly frequent among patients with TIN and was associated with a worse renal prognosis. Eighty-one patients (85.3%) were treated, with CSs in 80 (98.8%) and immunosuppressive agents (mostly rituximab) in 21 cases (25.9%). Despite marked interstitial fibrosis at initial biopsy, kidney function improved significantly during the 12-month period following diagnosis (final eGFR 49.9 vs 39.8 ml/min/1.73 m 2 at baseline, P < 0.001). No proven benefit of immunosuppressive agents over steroid therapy alone was found in this study., Conclusion.: Renal involvement of pSS is mostly due to TIN with marked T, B and especially plasma cell infiltration. Renal dysfunction is usually isolated but can be severe. Use of CSs can improve the eGFR, but further studies are needed to define the best therapeutic strategy in this disease., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Purpose: To evaluate qualitative, semi-quantitative, and quantitative parameters obtained by dynamic contrast-enhanced (DCE)-MRI for the characterization of histologically proven, non-palpable, incidentally found intratesticular tumors., Materials and Methods: From 2006 to 2014, we included men with non-palpable, incidentally found testicular tumors on ultrasound, normal tumoral marker levels,referred for surgery. DCE-MRI data were analyzed retrospectively and independently by two radiologists blinded to the histological diagnosis. The visual enhancement patterns, time-signal intensity curves, shape of the curves (type 0-3), maximal relative enhancement (Peak), initial enhancement slope (IS), time to peak (TTP), as well as transfer constants Ktrans and Kep were compared between the tumors. The interobserver correlation was evaluated. Receiver Operating Characteristic (ROC) curves and areas under the curve (AUC) were extracted., Results: Thirty-one patients (mean age of 37.3 years) were included. Tumor mean size was 1.2±0.77 cm (min=0.3cm, max=2.8cm). Regarding the histology results, three groups were defined: Twelve stromal "benign tumors" (BT) exhibited more type 2 and type 3 curves than 12 "malignant tumors" (MT) and 7 "burned-out tumors" (BOT) (p<0.0001). BT had a higher peak (96 vs. 54 and 17%), shorter TTP (215 vs. 412 and 692 sec), higher IS (73 vs. 12 and 2 arbitrary units), higher Ktrans (255 vs. 88 and 14min -1 *1000) and higher Kep (554 vs. 159 and 48min -1 *1000) than MT and BOT, respectively (p<0.0001, p=0.0003, p<0.0001, p<0.0001 and p<0.0001, respectively). The agreement coefficient values and the AUC extracted after gathering MT with BOT varied from 0.83 to 0.96 and from 0.868 to 0.978, respectively., Conclusion: DCE-MRI may assist in differentiating between benign intratesticular stromal tumors,malignant and burned-out tumors., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The behaviour of clear cell renal cell carcinoma (CCRCC) is highly unpredictable. Despite adequate initial surgery, 20 to 30 % of patients will develop local recurrence or metastasis during follow-up. Usual clinical and pathology parameters tend to classify most patients in an intermediate prognosis group, and molecular markers to determine prognosis more accurately are needed. A key feature of CCRCC is its abundant vascularization. Factors that upregulate angiogenesis, such as hypoxia and the presence of immune cells including macrophages, also modulate tumour proliferation and metastasis. We studied angiogenesis, as defined by nestin-positive capillaries, and tumour infiltration by macrophages especially in the good prognosis pT1 subgroup of CCRCC. We assessed whether these parameters are associated with metastatic extension and survival in CCRCC. The expression of HIF1α, CAIX, nestin, CD68 and CD163 was assessed by immunohistochemistry on a tissue microarray (TMA) containing tissue samples from 257 consecutive patients with sporadic CCRCC. Factors associated with progression-free (PFS) and overall survival (OS) were analysed. The presence of nestin-positive tumour vessels was independently associated with shorter PFS in the whole cohort and in the pT1 subgroup. The presence of tumour-infiltrating macrophages was independently associated with shorter OS in the whole cohort and in the pT1 subgroup. The presence of nestin-positive endothelial cells is associated with early relapse, especially in the pT1 subgroup and may help to select patients for antiangiogenic treatment. The presence of tumour-infiltrating M2-type macrophages is a strong predictor of short survival and may be used to adapt treatment strategy.

Objective: To compare the testicular Color Doppler ultrasound (US), hormone levels, and histological results from 67 infertile men with Klinefelter syndrome (KS), vs. 66 non-KS non-obstructive azoospermic men., Methods: Scrotal US images were collected from 67 infertile KS and 66 non-obstructive, non-KS azoospermic men. The testis volume, echotexture, vascularity, and microliths were evaluated and graded. We defined the following echo pattern alteration groups: normal, striated, coarse, and measurable nodules. The vascularization was classified as low, normal, moderate, or strong. Testosterone, follicle-stimulating hormone, luteinizing hormone, and inhibin B levels were determined. Large testicular nodules were removed. A testicular biopsy and sperm extraction was performed in 18 of the KS, and all of the 66 non-KS men., Results: The mean testis volume was low in the KS, compared to the non-KS patients: i.e., 2 vs. 8 mL (P < 0.0001). The distributions in the echotexture groups differed markedly, with coarse or nodular patterns in the KS men, and normal/striated patterns in the control patients (P < 0.0001). The vascularization and microlithiasis grades were higher in the KS patients than the control men (P < 0.0001 and P < 0.001, respectively). All of the nodules removed from the KS patients were benign Leydig cell tumors, and all of the biopsies showed marked Leydig cell hyperplasia, with spermatogenesis in only two patients. The non-KS biopsies were predominantly Sertoli cell-only syndrome., Conclusions: Small testes, with a coarse or nodular echotexture, hypervascularization, and microlithiasis are associated with KS. The KS nodules were benign Leydig cell tumors/hyperplasias.

As rapidly developing patient-derived xenografts (PDX) could represent potential sources of cancer stem cells (CSC), we selected and characterized non-cultured PDX cell suspensions from four different renal carcinomas (RCC). Only the cell suspensions from the serial xenografts (PDX-1 and PDX-2) of an undifferentiated RCC (RCC-41) adapted to the selective CSC medium. The cell suspension derived from the original tumor specimen (RCC-41-P-0) did not adapt to the selective medium and strongly expressed CSC-like markers (CD133 and CD105) together with the non-CSC tumor marker E-cadherin. In comparison, PDX-1 and PDX-2 cells exhibited evolution in their phenotype since PDX-1 cells were CD133high/CD105-/Ecadlow and PDX-2 cells were CD133low/CD105-/Ecad-. Both PDX subsets expressed additional stem cell markers (CD146/CD29/OCT4/NANOG/Nestin) but still contained non-CSC tumor cells. Therefore, using different cell sorting strategies, we characterized 3 different putative CSC subsets (RCC-41-PDX-1/CD132+, RCC-41-PDX-2/CD133-/EpCAMlow and RCC-41-PDX-2/CD133+/EpCAMbright). In addition, transcriptomic analysis showed that RCC-41-PDX-2/CD133- over-expressed the pluripotency gene ERBB4, while RCC-41-PDX-2/CD133+ over-expressed several tumor suppressor genes. These three CSC subsets displayed ALDH activity, formed serial spheroids and developed serial tumors in SCID mice, although RCC-41-PDX-1/CD132+ and RCC-41-PDX-2/CD133+ displayed less efficiently the above CSC properties. RCC-41-PDX-1/CD132+ tumors showed vessels of human origin with CSC displaying peri-vascular distribution. By contrast, RCC-41-PDX-2 originated tumors exhibiting only vessels of mouse origin without CSC peri-vascular distribution.Altogether, our results indicate that PDX murine microenvironment promotes a continuous redesign of CSC phenotype, unmasking CSC subsets potentially present in a single RCC or generating ex novo different CSC-like subsets.

Background: Many cases of familial renal cell carcinoma (RCC) remain unexplained by mutations in the known predisposing genes or shared environmental factors. There are therefore additional, still unidentified genes involved in familial RCC. PBRM1 is a tumour suppressor gene and somatic mutations are found in 30-45% of sporadic clear cell (cc) RCC., Methods: We selected 35 unrelated patients with unexplained personal history of ccRCC and at least one affected first-degree relative, and sequenced the PBRM1 gene., Results: A germline frameshift mutation (c.3998&#95;4005del [p.Asp1333Glyfs]) was found in one patient. The patient's mother, his sister and one niece also had ccRCC. The mutation co-segregated with the disease as the three affected relatives were carriers, while an unaffected sister was not, according with autosomal-dominant transmission. Somatic studies supported these findings, as we observed both loss of heterozygosity for the mutation and loss of protein expression in renal tumours., Conclusions: We show for the first time that an inherited mutation in PBRM1 predisposes to RCC. International studies are necessary to estimate the contribution of PBRM1 to RCC susceptibility, estimate penetrance and then integrate the gene into routine clinical practice., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: To assess the postsurgical survival of patients with urothelial carcinoma of the bladder with pT0 tumor at pathologic examination of cystectomy specimens., Methods: A multi-institutional, retrospective database was analyzed with data from 4758 radical cystectomy (RC) patients who underwent RC without neoadjuvant chemotherapy and who were diagnosed with pT0 on the basis of the pathologic specimen. Survival curves were estimated. A multivariate Cox model was used to evaluate the association between prognosis factors and disease recurrence or survival., Results: Overall, 258 patients (5.4%) were included in the study. The median age was 64 years. At last resection, 171 tumors were invasive (at least pT2), and 87 were not. Median follow-up was 51 months. At multivariate analysis, initial location of the tumor and absence of lymphadenectomy were associated with tumor recurrence (P = 0.03 and P = 0.005, respectively) and specific mortality (P = 0.005 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of this situation. Cancer-specific and recurrence-free survival rates were 89 and 85%, respectively, at 5 years and 82 and 80%, respectively, at 10 years., Conclusions: Despite acceptable oncological outcomes, patients with a pT0 tumor at the time of RC are still at risk of recurrence and progression and should not be considered to be entirely cured. In this population, stringent follow-up according to current recommendations should be effective.

Introduction: The major cause of non-ischemic high-flow priapism is post-traumatic vascular injury leading to an arterio-lacunar fistula. However, rare causes such as tumors may induce priapism. This is the first report of a malignant glomus tumor localized in the corpora cavernosa., Aim: The aim of this case is to emphasize the importance of the initial management of priapism and to suggest new tracks on the tests to be performed when the usual exams are not sufficient., Method: We report the case of a hypervascular penile tumor responsible for high-flow priapism as the first clinical symptom of a metastatic glomus tumor. The persistent penile tumescence was initially considered to be a stuttering priapism and treated using an oral α-adrenergic as no provoking event nor fistula was found. After a 2-week reluctance, a penile magnetic resonance imaging (MRI) was performed., Results: The MRI showed a hypervascular lesion at the proximal part of the right corpora. The lesion was considered as a fistula, and a selective embolization was performed. Two weeks after embolization, the patient came back to the emergency room because of syncopes and dyspnea. Examination by cardiac ultrasound and chest computed tomography revealed the presence of cardiac, pulmonary, and subcutaneous malignant glomus tumors (glomangiosarcoma). Patient received three lines of chemotherapy, and the penile tumor was surgically removed because of persistent erectile dysfunction and perineal pain., Conclusion: This case supports the use of corporal body blood gas analysis in difficult cases to discriminate high- and low-flow priapism and penile MRI when clinical history, physical examination, and aspiration are not contributory., (© 2009 International Society for Sexual Medicine.)

A case of bladder toxoplasmosis in a 57-year-old male Caucasian patient was diagnosed with difficulty due to misleading clinical presentation. The patient presented with pollakiuria and urination burning. Imagery showed pseudotumoral thickening of the vesicle wall. Previously unknown status of HIV infection was found positive through the diagnosis of bladder toxoplasmosis. The patient died rapidly from neurological complications. This is the second published case in which bladder toxoplasmosis reveals an HIV infection., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Aims: This study aimed to determine the influence of gene candidates on mycophenolic acid (MPA) response during the first year of renal transplantation., Materials & Methods: A total of 218 renal transplant recipients who received MPA from the first day of transplantation at a fixed dose of 2 g/day were genotyped for ABCB1, ABCC2, UGT2B7, UGT1A9, SLCO1B1, SLCO1B3 and IMPDH1 polymorphisms. Clinical end points were MPA-related adverse drug reactions (ADRs) and acute rejection episodes during the first year post-transplantation., Results: After correction for multiple statistical testing, SLCO1B1 (encoding the hepatic uptake transporter OATP1B1) was the only gene associated with MPA-related ADRs, showing a 75% risk reduction in favor of a protective effect of the SLCO1B1*5 allele (p = 0.002). In vitro experiments showed that MPA metabolites MPA-phenyl-glucuronide and MPA-acyl-glucuronide are substrates of OATP1B1. Their transport was decreased in the presence of the variant transporter (OATP1B1*5)., Conclusion: These results suggest for the first time that carriers of the SLCO1B1*5 allele seem to be protected from MPA-related ADRs.

Aims: Recent studies have highlighted the presence of microchimerism in various solid allografts. The biological significance of these chimeric cells is controversial. They may be beneficial, leading to better tolerance of grafts or participating in tissue repair or, in contrast, deleterious if involved in chronic lesions. The aim was to assess the frequency and cellular nature of microchimerism in female renal grafts of male recipients by combined fluorescence in situ hybridization (FISH) for Y chromosome and immunohistochemistry and to investigate associations between intragraft microchimerism and histological lesions or allograft outcome., Methods and Results: We screened 33 renal biopsy specimens, including 11 with acute T-cell-mediated rejection and nine with transplant glomerulopathy, from 22 male recipients transplanted with female kidneys by FISH and immunohistochemistry with antibodies against smooth muscle actin (mesangial cells), CD31 (endothelial cells), KL1 (epithelial cells), CD45 (leucocyte common antigen) and glomerular epithelial protein 1 (podocytes). Tubular microchimerism was detected in 71% of the patients with a mean percentage of chimeric epithelial cells of 1.4%. Glomerular microchimerism involving podocytes, mesangial and endothelial cells was present with a mean number of chimeric cells per glomerular section of, respectively, 0.6, 2.66 and 3.53. There was an association between endothelial microchimerism and a previous episode of acute T-cell-mediated rejection., Conclusions: In conclusion, microchimerism in renal grafts occurs frequently, but at a low level and affects tubular cells and all glomerular cell compartments in human renal allografts.

Objectives: To study the prevalence and the characteristics of renal cell carcinoma (RCC) in patients with autosomal dominant polycystic kidney disease (ADPKD) in our series., Methods: We reviewed retrospectively all the nephrectomies performed in our department between 1982 and 2003 in patients with ADPKD and chronic renal failure., Results: Seventy-nine patients (42 males and 37 females) with ADPKD and chronic renal failure underwent 89 nephrectomies; in 10 of 79, both kidneys were removed but not simultaneously. Mean age was 50.4 years (range, 32-69 years). Of 79 patients, 50 had end-stage renal disease (ESRD) and were on hemodialysis or had received a transplant for >1 year. On histologic examination, 11 of 89 kidneys were diagnosed with carcinomas. There was 1 patient with bilateral tumor (tubulopapillary Ca) and 3 kidneys (27.3%) with multifocal tumors. Regarding the histologic type, there were 7 of 12 (58.3%) clear cell carcinomas and the remaining 5 (41.7%) were tubulopapillary carcinomas., Conclusions: The prevalence of RCC was higher in patients with ADPKD and ESRD, with >1 year on dialysis or renal transplantation undergoing nephrectomy according the protocol. It would be 2 to 3 times more frequent than RCC in patients with ESRD alone. The clinician should maintain a high alert of suspicion for RCC in such patients.

Purpose: Renal injury caused by ischemia-reperfusion (IR) can lead to acute renal failure or delayed graft function. Renal ischemia-reperfusion (RIR) induces inflammatory disorders via activation of arachidonic acid metabolism into prostaglandin E(2) (PGE(2)). Two inducible enzymes, COX-2 and microsomal prostaglandin E synthase (mPGES), regulate PGE(2) production. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme activated during cellular stress. Overexpression of HO-1 is beneficial in transplantation models including antigen-independent IR injury, acute and chronic allograft rejection., Materials and Methods: We investigated the effect of HO-1 induction on the COX pathway, antioxidant enzyme activities, malondialdehyde (MDA) levels, and apoptosis in rat kidneys subjected to 45 min ischemia and 1 h or 24 h reperfusion. Rats were injected intraperitoneally with either: 50 mg/kg hemin (HO-1 inducer groups: H1, H2); 50 micromol/kg ZnPP (HO-1 inhibitor groups: Hz1, Hz2); or 0.9% saline (control groups: r1, r2). Sham animals (Sh) did not undergo RIR., Results: Serum creatinine increased significantly after RIR (r vs Sh; p <0.05). Hemin treatment induced a significant decrease in serum creatinine after RIR (H vs r; p <0.05) whereas ZnPP treatment significantly increased serum creatinine levels (Sh vs Hz; p <0.05). Hemin reduced the severity of acute tubular necrosis and significantly reduced COX-2 and mPGES expression (p <0.05). Hemin did not alter depleted antioxidant enzyme activity but did decrease levels of MDA (p <0.05). Hemin also reduced caspase-3 expression., Conclusions: HO-1 decreased the degree and severity of tubular damage after IR, probably by attenuating the cytotoxic effects of inflammatory infiltrates and apoptosis.

We report clinicopathologic features of a large series of renal translocation carcinomas from a multicentric study. Diagnosis was performed by cytogenetic examination of fresh material and/or by immunochemistry with antibodies directed against the C-terminal part of transcription factor E3 (TFE3) and native transcription factor EB (TFEB) proteins. Clinical data, follow-up, and histologic features were assessed. Antibodies against CK7, CD10, vimentin, epithelial membrane antigen, AE1-AE3, E-cadherin, alpha-methylacyl-coenzyme A racemase, melan A, and HMB45 were tested on tissue microarrays. Whole-genome microarray expression profiling was performed on 4 tumors. Twenty-nine cases were diagnosed as TFE3 and 2 as TFEB renal translocation carcinomas, including 13 males and 18 females, mean age 24.6 years. Two patients had a previous history of chemotherapy and 1 had a history of renal failure. Mean size of the tumor was 6.9 cm. Thirteen cases were > or = pT3 stage. Twelve cases were N+ or M+. Mean follow-up was 29.5 months. Three patients presented metastases and 5 have died. Mixed papillary and nested patterns with clear and/or eosinophilic cells represented the most consistent histologic appearance, with common foci of calcifications regardless of the type of translocation. Using a 30 mn incubation at room temperature, TFE3 immunostainings were positive in only 82% of our TFE3 translocation carcinomas. Both TFE3 and TFEB renal translocation carcinomas expressed CD10 and alpha-methylacyl-coenzyme A racemase in all cases. An expression of E-cadherin was observed in two-third of cases. Cytokeratins were expressed in less than one-third of cases. Melanocytic markers were expressed at least weakly in all cases except two. Unsupervised clustering on the basis of the gene expression profiling indicated a distinct subgroup of tumors. TRIM 63 glutathione S-transferase A1 and alanyl aminopeptidase are the main differentially expressed genes for this group of tumors. Our results suggest that these differentially expressed genes may serve as novel diagnostic or prognostic markers.

Phyllodes tumours of the prostate are very rare tumours, as less than 40 cases have been reported in the literature. The authors report the case of a 28-year-old man managed for a phyllodes tumour of the prostate diagnosed in a context of haemospermia. The diagnosis was established by ultrasound, CT MRI and prostatic biopsies. Radical prostatectomy was performed after multidisciplinary discussion. Thirty six months after the operation, the patient was in complete remission, with spontaneous erections and had fathered a child conceived by medically assisted procreation. The authors stress the importance of nerve-sparing radical surgery and early sexual rehabilitation.

Objectives: Urothelial carcinoma is a frequent and aggressive cancer. To gain better insight into the early molecular mechanisms of bladder carcinogenesis, this study analyzed the expression levels of four selected genes (uroplakin II, TATA-BOX-binding protein (TBP/RNA) control gene (NM&#95;00394), and the two main isoforms TATp63 and deltaNp63 of p63)., Methods: We used real-time quantitative reverse transcriptase-polymerase chain reaction in dissected tissues from normal bladder, noninvasive cancer, and muscle-invasive bladder carcinoma (n = 49). The gene expression levels were compared at different stages of bladder cancer. To confirm the results on protein levels, we used immunohistochemistry on tissue microarrays of the same samples., Results: The expression of the p63 gene studied was significantly deregulated, with decreasing levels in early cancer versus normal tissue. Immunohistochemistry, performed on the same samples, using p63 antibody, confirmed the results of reverse transcriptase-polymerase chain reaction., Conclusions: The results of this study highlight that among the genes strongly deregulated in urothelial carcinoma, p63 is already abnormally expressed in the early stages.

Objectives: To evaluate the risks of local recurrence and repeat surgery after nephron-sparing surgery (NSS) in von Hippel-Lindau (VHL) disease to propose a therapeutic strategy to patients., Methods: A total of 21 patients with VHL disease and renal tumors were followed up from February 1987 to August 2005. Surgical resection of all tumors was chosen when the largest tumor exceeded a diameter of 30 mm., Results: Of the 21 patients, 18 underwent surgery at a mean age of 38.5 years (range 24 to 69). The median follow-up of the series was 100 months. Of the 17 patients treated by NSS, 8 developed a recurrence. The mean time to local recurrence was 53 +/- 38.8 months (range 10 to 115), and the recurrence tumors grew at a stable mean rate of 0.34 +/- 0.32 cm/yr (range 0.1 to 1.08). Repeat NSS was performed on the same kidney in 2 cases and eight recurrences were kept under surveillance. The disease-specific survival rate was 93.8% at 10 years. The local recurrence rate was 45.6% at 5 years and 83.7% at 10 years. The overall repeat surgery rate was 23.1% at 5 years and 63.4% at 10 years. No metastasis or chronic renal insufficiency was observed in patients undergoing NSS only., Conclusions: Five years after NSS, the risk of developing new tumors in the same kidney and the overall risk of repeat surgery was about 50% and 25%, respectively. However, the strategy of elective NSS and close surveillance preserved renal function without increasing the risk of metastasis.

The two major genes responsible for autosomal dominant polycystic kidney disease and complex tuberous sclerosis are located on chromosome 16 at position 16p13.3, separated by only a few nucleotides. A simultaneous loss of both genes has been termed "the TSC2/PKD1 contiguous gene syndrome". It has been described essentially in young children. We report 2 new cases in French adults, in whom the diagnosis has been made fortuitously on the macroscopic and microscopic examination of the nephrectomy specimen. This diagnosis should be considered for the association of a polycystic kidney disease and numerous angiomyolipomas. It is necessary to set up a specific follow-up of both diseases.

Ureteroduodenal fistulas are rare. The authors present a review of this disease in the light of a clinical case and emphasize the role of conservative management.

Mucinous tubular and spindle cell carcinomas are low-grade renal epithelial neoplasms, which were first recognized as a specific entity in the World Health Organization 2004 classification. Forty-five documented cases have been reported. We present 15 additional cases that were incidentally discovered in ten women and five men, with a mean age of 53 years. The tumor is characteristically made up of large eosinophilic regular spindle cells separated by a myxoid stroma with intercellular alcian-blue-positive clear droplets. In peripheral areas, elongated tubules and papillae covered by cubic cells are found. Until this entity had been defined, pathologists used to classify these tumors as variants of solid papillary carcinomas with compressed and elongated papillae, metanephric adenomas, and sarcomatoid carcinomas. In the literature, cytogenetic data indicate various chromosomal losses and gains, but no loss of 3p or trisomy 7 and/or trisomy 17. In two cases, we demonstrate chromosomal loss involving chromosomes 1, 4, 6, 11, 8, 13, 14, 15, 18, and 22. In our 15 cases, immunohistochemistry favored a distal tubule origin (EMA(+), AE1/AE3(+), CK7(+), CK19(+), E-cadherin(+), AMACR(+), and CD10(-)). Prognosis was favorable in our cases, while in the literature, two metastatic cases were reported. Further investigations are required to determine the frequency and true prognosis of these tumors, which are easily identifiable morphologically.

Since 1998 new entities have surfaced in renal tumor classification and have been included in the WHO 2004 classification. In this article, we will discuss the following entities: multilocular clear cell renal carcinoma, Xp11 translocation carcinoma, low grade mucinous tubular carcinoma, epithelioid angiomyolipoma, benign mixed epithelial and stromal tumor. We will investigate new concepts of hybrid oncocytoma and chromophobe renal cell carcinoma and the syndrome of Birt-Hogg-Dube which is associated to kidney tumors. At least, we will touch on new elements in the Bellini carcinoma definition.

Angiomyofibroblastoma of the scrotum is a rare and benign tumour which affect old patient. It's treatment is surgical. A case of angiomyofibroblastoma of the scrotum is reported in a 34 years old man. The literature is reviewed with special reference to the ethiopathogenesis, clinical features and treatment of this tumour entity.

Objective: The purpose of our study was to determine the MRI features of atypical focal nodular hyperplasia of the liver and to compare them to pathology findings., Materials and Methods: We retrospectively reviewed MRI and pathology findings in 27 focal nodular hyperplasia lesions with atypical MRI features. Six criteria for typical focal nodular hyperplasia were required: iso- or hypointensity on T1-weighted sequences and iso- or slight hyperintensity on T2-weighted sequences; homogeneous signal intensity; central hyperintense area on T2-weighted sequences; marked lesion contrast enhancement; accumulation of gadolinium chelates within the central area on delayed contrast-enhanced T1-weighted sequences; and absence of capsule., Results: The most common atypical radiology features included absence of, or an atypical, stellate area; heterogeneity on both T1- and T2-weighted images; and high-intensity signal on T1-weighted sequences. MRI-pathology correlation showed that T1 hyperintensity with no other atypical MRI feature (n = 3) could be explained by steatosis, sinusoidal dilatation, or hemorrhage. In addition, in two patients with lesions smaller than 3 cm in diameter, the only atypical MRI feature was absence of a stellate area., Conclusion: These findings suggest a lesion that is hyperintense on T1-weighted sequences or that lacks a stellate area but is smaller than 3 cm in diameter can be diagnosed as focal nodular hyperplasia provided all other MRI criteria for this diagnosis are present. In such cases, close monitoring on MRI without invasive diagnostic procedures may be warranted. However, in large lesions (> 3 cm) without a stellate area and in lesions with heterogeneity, histopathology examination is mandatory to rule out other diagnoses.

The mutator phenotype caused by defects in the mismatch repair system is observed in a subset of solid neoplasms characterized by widespread microsatellite instability-high (MSI-H). It is known to be very rare in non-Hodgkin lymphomas (NHL), whereas mutator NHL is the most frequent tumor subtype in mismatch repair-deficient mice. By screening a series of 603 human NHL with specific markers of the mutator phenotype, we found here 12 MSI-H cases (12/603, 2%). Of interest, we demonstrated that this phenotype was specifically associated with immunodeficiency-related lymphomas (ID-RL), because it was observed in both posttransplant lymphoproliferative disorders (9/111, 8.1%) and HIV infection-related lymphomas (3/128, 2.3%) but not in a large series of NHL arising in the general population (0/364) (P < 0.0001). The MSI pathway is known to lead to the production of hundreds of abnormal protein neoantigens that are generated in MSI-H neoplasms by frameshift mutations of a number of genes containing coding microsatellite sequences. As expected, MSI-H ID-RL were found to harbor such genetic alterations in 12 target genes with a putative role in lymphomagenesis. The observation that the MSI-H phenotype was restricted to HIV infection-related lymphomas and posttransplant lymphoproliferative disorders suggests the existence of the highly immunogenic mutator pathway as a novel oncogenic process in lymphomagenesis whose role is favored when host immunosurveillance is reduced. Because MSI-H-positive cases were found to be either Epstein-Barr virus-positive or -negative, the mutator pathway should act synergistically or not with this other oncogenic factor, playing an important role in ID-RL.

Descriptive statistics in the field of medicine are usually based on univariate analysis. However, a multivariate descriptive analysis can often be usefull to jointly describe all variables considered for study. This multivariate description is difficult to perform and visualize for more than three variables at a time. Multiple correspondence analysis (MCA) provides a means of performing multivariate description of categorical data. The method consists in projecting the data of an n-dimensional space which is constituted by the variables under study onto a succession of two-dimensional planes. The relationships between variables can then be deduced from the relative positions of the modalities of the variables on the planes. At the same time, numerical indices are used in parallel to specify and validate the observed relationships. The use of MCA is illustrated with a prospective series of renal carcinomas for which different histological characteristics are given. The main applications of MCA are detailed with comments on practical implementation.

The authors report the case of a 57-year-old woman operated in 1992 for meningeal haemangiopericytoma. Nine years later, this patient was operated for a liver tumour and then a renal tumour, which were both diagnosed as haemangiopericytoma and therefore corresponded to metastases of the primary tumour. The presence of a renal tumour in a patient previously operated for meningeal haemangiopericytoma should raise the suspicion of renal metastasis. Localized metastases can be treated by surgical resection. The possibility of late recurrence justifies annual thoraco-abdominal CT scan and bone scan for more than ten years.