Energy source comparison in en-bloc resection of bladder tumors: subanalysis of a single-center prospective randomized study.

PURPOSE: Different energy sources are employed to perform en-bloc transurethral resection of bladder tumor (ERBT). No study compared different energy sources in ERBT. The aim is to compare the different ERBT sources in terms of pathological, surgical and postoperative outcomes. METHODS: This is a sub-analysis of a prospective randomized trial enrolling patients submitted to ERBT vs conventional TURBT from 03/2018 to 06/2021 (NCT04712201). 180 patients enrolled in ERBT group were randomized 1:1:1 to receive monopolar (m-ERBT), bipolar (b-ERBT) or thulium laser (l-ERBT). Endpoints were the comparison between energies in term of pathological analysis, intra, and post-operative outcomes. RESULTS: 49 (35%) m-ERBT, 45 (32.1%) b-ERBT, and 46 (32.9%) l-ERBT were included in final analysis. The rate of detrusor muscle (DM) presence was comparable between the energies used (p = 0.796) or the location of the lesion (p = 0.662). Five (10.2%), 10 (22.2%) and 0 cases of obturator nerve reflex (ONR) were recorded in m-ERBT, b-ERBT and I-ERBT groups, respectively (p = 0.001). Conversion to conventional TURBT was higher for lesions located in the anterior wall/dome/neck (p < 0.001), irrespective from the energy used. The presence of artifact in the pathological specimen was higher for lesions at the posterior wall (p = 0.03) and trigone (p = 0.03). CONCLUSIONS: In our study, no difference in staging feasibility among energies was found. Laser energy might be beneficial in lateral wall lesions to avoid ONR. Since there is an increased risk of ERBT conversion to conventional TURBT for lesions of the anterior wall, electrocautery might be preferred over laser to avoid waste of material.

The DEpth of Endoscopic Perforation scale to assess intraoperative perforations during transurethral resection of bladder tumor: subgroup analysis of a randomized controlled trial.

PURPOSE: Bladder perforation (BP) is the most important intraoperative adverse event of transurethral resection of bladder tumor (TURBT). It is frequently underreported despite its impact on the postoperative course. There is no standardized classification of BP. The study aims to develop a classification of the depth of endoscopic bladder perforation during TURBT. METHODS: This is a sub-analysis of a prospective randomized trial enrolling 248 patients submitted to en-bloc vs conventional TURBT from 03/2018 to 06/2021. The DEpth of Endoscopic Perforation (DEEP) scale is as follows: "0" visible muscular layer with no perivesical fat; "1" visible muscle fibers with spotted perivesical fat; "2" exposition of perivesical fat; "3" intraperitoneal perforation. Logistic and linear regression models were used to investigate predictors of high-grade perforations (DEEP 2-3) and to assess whether the DEEP scale independently predicted patients' postoperative outcomes. RESULTS: A total of 146/248 (58.9%), 56/248 (22.6%), 41/248 (16.5%), 5/248 (2.0%) patients presented DEEP grade 0, 1, 2, and 3, respectively. Female gender [B coeff. 0.255 (95% CI 0.001-0.513); p = 0.05], tumor location [B coeff. 0.188 (0.026-0.339); p = 0.015], and obturator-nerve reflex [B coeff. 0.503 (0.148-0.857); p = 0.006] were independent predictors of DEEP. The scale predicted independently major complications [Odd Ratio (OR) 2.221 (1.098-4.495); p = 0.026], no post-operative chemotherapy intravesical instillation [OR 9.387 (2.434-36.200); p = 0.001], longer irrigation time [B coeff. 0.299 (0.166-0.441); p < 0.001] and hospital stay [B coeff. 0.315 (0.111-0.519); p = 0.003]. CONCLUSION: The DEEP scale provides a visual tool for grading bladder perforation during TURBT, which can help physicians standardize complication reporting and plan postoperative management accordingly.

The importance of second-look ureteroscopy implementation in the conservative management of upper tract urothelial carcinoma.

PURPOSE: The purpose of the study was to evaluate the effect of second-look ureteroscopy (SU) in the endoscopic operative work-up of patients with upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Patients with UTUC who underwent SU between 2016 and 2021 were included. Cancer detection rate (CDR) at SU was defined as endoscopic visualization of tumor. The effect of SU on recurrence-free survival (RFS), radical nephroureterectomy-free survival (RNU-FS), bladder cancer-free survival (BC-FS), and cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. Multivariate logistic regression analysis (MLR) assessed predictors of negative SU. Finally, we evaluated the effect of SU timing on oncological outcomes, classifying SUs as "early" (≤ 8 weeks) and "late" (> 8 weeks). RESULTS: Overall, 85 patients underwent SU. The CDR at SU was 44.7%. After a median follow-up was 35 (IQR: 15-56) months, patients with positive SU had a higher rate of UTUC recurrence (47.4% vs 19.1%, p = 0.01) and were more frequently radically treated (34.2% vs 8.5%, p = 0.007). Patients with high-grade disease (hazard ratio [HR]: 3.14, 95% CI 1.18-8.31; p = 0.02) had a higher risk of UTUC recurrence, while high-grade tumor (HR: 3.87, 95%CI 1.08-13.77; p = 0.04) and positive SU (HR: 4.56, 95%CI 1.05-22.81; p = 0.04) were both predictors of RNU. Low-grade tumors [odds ratio (OR): 5.26, 95%CI 1.81-17.07, p = 0.003] and tumor dimension < 20 mm (OR: 5.69, 95%CI 1.48-28.31, p = 0.01) were predictors of negative SU. Finally, no significant difference emerged regarding UTUC recurrence, RNU, BC-FS, and CSM between early vs. late SUs (all p > 0.05). CONCLUSIONS: SU may help in identifying patients with UTUC experiencing an early recurrence after conservative treatment. Patients with low-grade and small tumors are those in which SU could be safely postponed after 8 weeks.

Initial experience of robot-assisted partial nephrectomy with Hugo™ RAS system: implications for surgical setting.

PURPOSE: Hugo™ RAS system is one of the most promising new robotic platforms introduced in the field of urology. To date, no data have been provided on robot-assisted partial nephrectomy (RAPN) performed with Hugo™ RAS system. The aim of the study is to describe the setting and report the performance of the first series of RAPN performed with Hugo™ RAS system. METHODS: Ten consecutive patients who underwent RAPN at our Institution between February and December 2022 were prospectively enrolled. All RAPN were performed transperitoneally with a modular four-arm configuration. The main outcome was to describe the operative room setting, trocar placement and the performance of this novel robotic platform. Pre, intra and post-operative, variables were recorded. A descriptive analysis was performed. RESULTS: Seven patients underwent RAPN for right-side and three for left-side masses. Median tumor size and PADUA score were 3 (2.2-3.7) cm and 9 (8-9), respectively. Median docking and console time were 9.5 (9-14) and 138 (124-162) minutes, respectively. Median warm ischemia time was 13 (10-14) minutes, and one case was performed clamp-less. Median estimated blood loss was 90 (75-100) mL. One major complication (Clavien-Dindo 3a) occurred. No case of positive surgical margin was recorded. CONCLUSION: This is the first series to prove the feasibility of Hugo™ RAS system in the setting of RAPN. These preliminary results may help new adopters of this surgical platform to identify critical steps of robotic surgery with this platform and explore solutions before in-vivo surgery.

Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: a study of 62 new tumors in 59 patients.

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.

DNA Methylation Urine Biomarkers Test in the Diagnosis of Upper Tract Urothelial Carcinoma: Results from a Single-Center Prospective Clinical Trial.

PURPOSE: The correct risk categorization and staging of upper tract urothelial cancer (UTUC) is key for disease management. Computerized tomography urography and urinary cytology have limited accuracy for risk stratification of UTUC. Ureteroscopy may increase the risk of bladder cancer recurrence. Recently, Bladder EpiCheckTM (EpiCheck) showed a high accuracy in the detection of bladder cancer. The aim of the study is to investigate the diagnostic accuracy of EpiCheck in the clinical management of UTUC and to compare it with urinary cytology. MATERIALS AND METHODS: In this single-arm, blinded, prospective, single-center study (February 2019-December 2020), all patients who were candidates for ureteroscopy for suspicion of UTUC were included. Bladder and upper urinary tract (UUT) samples were collected before ureteroscopy to test for cytology and Epicheck. EpiCheck accuracy was calculated in bladder and UUT samples and compared to cytology. RESULTS: EpiCheck resulted diagnostic in 83/86 (97%) and 73/75 (97%) of UUT and bladder samples. Histology was positive in 47/83 (57%) and 42/73 (58%) cases, respectively. In UUT samples, EpiCheck yielded a sensitivity/specificity/ negative predictive value (NPV)/positive predictive value of 83%/79%/77%/84% vs 59%/88%/61%/87% of cytology. The sensitivity/NPV for high-grade tumors was 96%/97% for EpiCheck vs 71%/86% for cytology. EpiCheck indicated ureteroscopy in 45/80 (56%) patients, missing 17%/4% of all/high-grade UTUC with 9% of unnecessary ureteroscopy. In bladder samples, the sensitivity/NPV for high-grade tumors was 71%/88% for EpiCheck and 59%/87% for cytology. CONCLUSIONS: Epicheck may be an important tool to decrease the number of unnecessary ureteroscopy. The clinical implementation of EpiCheck in UTUC warrants further investigation in multicentric prospective randomized trials.

Contemporary outcomes of bladder carcinoma in situ treated with an adequate bacille Calmette-Guérin immunotherapy.

OBJECTIVE: To assess whether bacillus Calmette-Guérin (BCG) responsiveness after initiation of an adequate BCG treatment (at least five of six instillations of induction and at least two of three instillations of maintenance) impacts oncological outcomes in patients with carcinoma in situ (CIS) of the bladder treated with BCG immunotherapy. PATIENTS AND METHODS: Data were available for 193 patients with bladder CIS with or without associated cTa/cT1 disease who received an adequate BCG treatment between 2008 and 2015. Bladder biopsies were taken at 6 months and patients were then stratified as either BCG responsive (negative biopsies) or BCG unresponsive (positive biopsies). Inverse probability weighting (IPW)-adjusted Kaplan-Meier and IPW-adjusted Cox regression were performed to compare progression-free survival (PFS), radical cystectomy-free survival (RCFS), overall survival OS, and cancer-specific survival (CSS) in the two groups. RESULTS AND LIMITATIONS: Comparing the BCG-responsive and BCG-unresponsive groups, IPW-adjusted Kaplan-Meier analysis revealed, respectively, a median (interquartile range) of PFS of 9 (5-15) vs 48.5 (28-77) months (P = 0.001), a RCFS of 11 (9-15) vs 49 (24-76) months (P < 0.001), and a CSS of 25 (13-60) vs 109 (78-307) months (P = 0.004). On IPW-adjusted Cox regression analysis, BCG-unresponsive patients had a worse PFS (hazard ratio [HR] 3.40, 95% confidence interval [CI] 1.59-7.27), RCFS (HR 3.52, 95% CI 1.77-7), and CSS (HR 4.42, 95% CI 1.95-10.01). We found no significant differences for OS. CONCLUSION: Using an IPW method we found that lack of response after initiation of an adequate BCG treatment has prognostic implications beyond identification of complete response in patients with CIS. BCG-unresponsive patients, satisfying the novel definition of BCG unresponsive, showed a poor PFS, RCFS, and CSS. In this setting, the patients should be counselled regarding RC as a first option or enrolled in a clinical trial if they refuse RC or are unfit for surgery.

Genetic dissection of spermatogenic arrest through exome analysis: clinical implications for the management of azoospermic men.

PURPOSE: Azoospermia affects 1% of men and it can be the consequence of spermatogenic maturation arrest (MA). Although the etiology of MA is likely to be of genetic origin, only 13 genes have been reported as recurrent potential causes of MA. METHODS: Exome sequencing in 147 selected MA patients (discovery cohort and two validation cohorts). RESULTS: We found strong evidence for five novel genes likely responsible for MA (ADAD2, TERB1, SHOC1, MSH4, and RAD21L1), for which mouse knockout (KO) models are concordant with the human phenotype. Four of them were validated in the two independent MA cohorts. In addition, nine patients carried pathogenic variants in seven previously reported genes-TEX14, DMRT1, TEX11, SYCE1, MEIOB, MEI1, and STAG3-allowing to upgrade the clinical significance of these genes for diagnostic purposes. Our meiotic studies provide novel insight into the functional consequences of the variants, supporting their pathogenic role. CONCLUSION: Our findings contribute substantially to the development of a pre-testicular sperm extraction (TESE) prognostic gene panel. If properly validated, the genetic diagnosis of complete MA prior to surgical interventions is clinically relevant. Wider implications include the understanding of potential genetic links between nonobstructive azoospermia (NOA) and cancer predisposition, and between NOA and premature ovarian failure.

SIU-ICUD on bladder cancer: pathology.

Many changes have been made during these last years and concepts for understanding bladder cancer have evolved. We make an update with the latest findings of the WHO (World Health Organistaion) 2016, ICCR (International Collaboration on Cancer Reporting) and other official organisms and try to show the latest developments. In this document we provide new consensus guidelines and insights. We kept this document short and concise providing consensus guidelines to clinicians for the best patient care, it should be easy to understand for a non pathologists. We focussed on several burning issues, such as the anatomical and histological understanding of the bladder wall, the prognostic significance of grading and the most challenging problems in staging, we underline our needs from the clinicians such as clinical information, we further discuss the histological subtypes of bladder cancer, which is an extremely important issue in the light of molecular classifications and give prognostic insights. Furthermore, we discuss the ICCR worldwide consensus reporting, urinary cytology with the Paris system and several issues such as frozen section specimen.

Biallelic TSC2 Mutations in a Patient With Chromophobe Renal Cell Carcinoma Showing Extraordinary Response to Temsirolimus.

mTOR inhibitors are used to treat renal cell carcinoma (RCC). Treatment response is variable and appears to correlate with genetic alterations that activate mTOR signaling. Recently, everolimus was suggested to be more effective than sunitinib in chromophobe RCC (chRCC), a tumor with frequent mTOR pathway defects. This report presents the genomic and functional characterization of a metastatic chRCC that showed complete response at metastatic sites and 80% reduction in primary tumor size upon temsirolimus treatment. After surgery, the patient remained disease-free for 8 years after temsirolimus therapy. Whole-exome sequencing (WES) revealed 2 somatic variants in TSC2, a critical negative regulator of mTOR: a splicing defect (c.5069-1G>C) and a novel missense variant [c.3200_3201delinsAA; p.(V1067E)]. In vitro functional assessment demonstrated that the V1067E substitution disrupted TSC2 function. Immunohistochemistry in the tumor tissues revealed increased phosphorylated S6 ribosomal protein, indicating mTOR pathway activation. In conclusion, WES revealed TSC2 inactivation as the likely mechanism for this extraordinary response to temsirolimus. These findings support high efficacy of mTOR inhibitors in a subset of patients with chRCC and propose sequencing of mTOR pathway genes to help guide therapy.

The World Health Organization 2016 classification of testicular germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel.

Since the last World Health Organization (WHO) classification scheme for tumours of the urinary tract and male genital organs, there have been a number of advances in the understanding, classification, immunohistochemistry and genetics of testicular germ cell tumours. The updated 2016 draft classification was discussed at an International Society of Urological Pathology Consultation on Testicular and Penile Cancer. This review addresses the main updates to germ cell tumour classification. Major changes include a pathogenetically derived classification using germ cell neoplasia in situ (GCNIS) as a new name for the precursor lesion, and the distinction of prepubertal tumours (non-GCNIS-derived) from postpubertal-type tumours (GCNIS-derived), acknowledging the existence of rare benign prepubertal-type teratomas in the postpubertal testis. Spermatocytic tumour is adopted as a replacement for spermatocytic seminoma, to avoid potential confusion with the unrelated usual seminoma. The spectrum of trophoblastic tumours arising in the setting of testicular germ cell tumour continues to expand, to include epithelioid and placental site trophoblastic tumours analogous to those of the gynaecological tract. Currently, reporting of anaplasia (seminoma or spermatocytic tumour) or immaturity (teratoma) is not required, as these do not have demonstrable prognostic importance. In contrast, overgrowth of a teratomatous component (somatic-type malignancy) and sarcomatous change in spermatocytic tumour indicate more aggressive behaviour, and should be reported.

Gleason grade 4 prostate adenocarcinoma patterns: an interobserver agreement study among genitourinary pathologists.

AIMS: To assess the interobserver reproducibility of individual Gleason grade 4 growth patterns. METHODS AND RESULTS: Twenty-three genitourinary pathologists participated in the evaluation of 60 selected high-magnification photographs. The selection included 10 cases of Gleason grade 3, 40 of Gleason grade 4 (10 per growth pattern), and 10 of Gleason grade 5. Participants were asked to select a single predominant Gleason grade per case (3, 4, or 5), and to indicate the predominant Gleason grade 4 growth pattern, if present. 'Consensus' was defined as at least 80% agreement, and 'favoured' as 60-80% agreement. Consensus on Gleason grading was reached in 47 of 60 (78%) cases, 35 of which were assigned to grade 4. In the 13 non-consensus cases, ill-formed (6/13, 46%) and fused (7/13, 54%) patterns were involved in the disagreement. Among the 20 cases where at least one pathologist assigned the ill-formed growth pattern, none (0%, 0/20) reached consensus. Consensus for fused, cribriform and glomeruloid glands was reached in 2%, 23% and 38% of cases, respectively. In nine of 35 (26%) consensus Gleason grade 4 cases, participants disagreed on the growth pattern. Six of these were characterized by large epithelial proliferations with delicate intervening fibrovascular cores, which were alternatively given the designation fused or cribriform growth pattern ('complex fused'). CONCLUSIONS: Consensus on Gleason grade 4 growth pattern was predominantly reached on cribriform and glomeruloid patterns, but rarely on ill-formed and fused glands. The complex fused glands seem to constitute a borderline pattern of unknown prognostic significance on which a consensus could not be reached.

Update for the practicing pathologist: The International Consultation On Urologic Disease-European association of urology consultation on bladder cancer.

The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting.

ΔNp63 expression is a protective factor of progression in clinical high grade T1 bladder cancer.

PURPOSE: Several risk factors have been claimed to predict the progression of clinically high grade T1 bladder tumors. However, these factors are not specific enough to define which patients should be treated immediately with radical cystectomy. Therefore, it is critical to identify molecular markers that can help provide individualized, risk stratified decision making. Our main goal was to evaluate the role of total p63, p53 and ΔNp63 expression in cases of clinically high grade T1 bladder cancer progression. MATERIALS AND METHODS: Total p63, p53 and ΔNp63 expression was analyzed by immunohistochemistry in 134 clinically high grade T1 tumors. We assessed clinical progression to muscle invasive disease or radical cystectomy as a patient outcome end point. Survival analysis was done for recurrence-free, progression-free, disease specific and overall survival. RESULTS: A total of 132 patients (98.5%) underwent repeat transurethral resection. Cases of early progression (less than 3 months) were excluded from study to avoid under staging. Of the tumors 90 (67.2%) showed ΔNp63 expression loss. During a median followup of 62.1 months 19 patients (14.2%) progressed to muscle invasive disease. The progression rate was 21.1% in patients with tumors characterized by ΔNp63 loss but no progression was observed in those with tumors with ΔNp63 expression (p <0.001). There was no difference in the number of patients who underwent repeat transurethral resection, had associated carcinoma in situ, showed lymphovascular invasion or received followup intravesical bacillus Calmette-Guérin courses. CONCLUSIONS: ΔNp63 expression is a favorable prognostic factor in clinically high grade T1 bladder cancer. This marker identifies patients at low risk for progression who could benefit from conservative therapy with transurethral bladder tumor resection and bacillus Calmette-Guérin, avoiding over treatment with immediate radical cystectomy.

Handling and reporting of orchidectomy specimens with testicular cancer: areas of consensus and variation among 25 experts and 225 European pathologists.

AIMS: The handling and reporting of testicular tumours is difficult due to their rarity. METHODS AND RESULTS: A survey developed by the European Network of Uro-Pathology (ENUP) and sent to its members and experts to assess the evaluation of testicular germ cell tumours. Twenty-five experts and 225 ENUP members replied. Areas of disagreement included immaturity in teratomas, reported by 32% of experts but 68% of ENUP. Although the presence of rete testis invasion was reported widely, the distinction between pagetoid and stromal invasion was made by 96% of experts but only 63% of ENUP. Immunohistochemistry was used in more than 50% of cases by 68% of ENUP and 12% of experts. Staging revealed the greatest areas of disagreement. Invasion of the tunica vaginalis without vascular invasion was interpreted as T1 by 52% of experts and 67% of ENUP, but T2 by the remainder. Tumour invading the hilar adipose tissue adjacent to the epididymis without vascular invasion was interpreted as T1: 40% of experts, 43% of ENUP; T2: 36% of experts, 30% of ENUP; and T3: 24% of experts, 27% of ENUP. CONCLUSIONS: There is remarkable consensus in many areas of testicular pathology. Significant areas of disagreement included staging and reporting of histological types, both of which have the potential to impact on therapy.

The reasons behind variation in Gleason grading of prostatic biopsies: areas of agreement and misconception among 266 European pathologists.

AIMS: The Gleason scoring system underwent revision at the International Society of Urological Pathology (ISUP) conference in 2005. It is not known how uropathologists have interpreted its recommendations. METHOD AND RESULTS: A web-based survey to European Network of Uropathology members received replies from 266 pathologists in 22 countries. Eighty-nine per cent claimed to follow ISUP recommendations. Key areas of disagreement included the following. Smoothly rounded cribriform glands were assigned Gleason pattern (GP) 3 by 51% and GP 4 by 49%. Necrosis was diagnosed as GP 5 by 62%. Any amount of secondary pattern of higher grade in needle biopsies was included in the Gleason score by 58%. Tertiary GP of higher grade on needle biopsies was included in the Gleason score by only 58%. If biopsy cores were embedded separately, only 56% would give a Gleason score for each core/slide examined; 68% would give a concluding Gleason score and the most common method was a global Gleason score (77%). Among those who blocked multiple biopsy cores together, 46% would only give an overall Gleason score for the case. CONCLUSION: Misinterpretation of ISUP 2005 is widespread, and may explain the variation in Gleason scoring seen. Clarity and uniformity in teaching ISUP 2005 recommendations is necessary.

Intraductal carcinoma of the prostate: interobserver reproducibility survey of 39 urologic pathologists.

The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, χ(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions.

[Pathological consideration of indolent and clinically non-significant prostate cancer definition]. / Consideraciones anatomopatológicas a la definición de cáncer de próstata indolente y clínicamente insignificante.

INTRODUCTION: Serum PSA determination has provoked a great increase of prostatic biopsies and detection of neoplasias that passed inadvertent in the past. When these neoplasias are excised a non-negligible number of them have low biologic aggressiveness and may be considered as indolent or clinically non-significant, so that the possibility of conservative attitude is taken into consideration. OBJECTIVE: How to recognize clinically non-significant carcinomas is one of the main challenges and is based on clinical criteria, but mainly pathological. The objective of this review is to analyze the state of this issue. METHODS: We selected those articles reviewing the topic in a general view over the last ten years. RESULTS/CONCLUSIONS: Trying to be as specific as possible search criteria have been refined to Gleason grade with an increase of Gleason 4 patterns (all cribiform patterns). In cases with two separated foci of carcinoma in the same biopsy core, it has been proposed to include as neoplasia the non-tumoral tissue between them. Obviously, with this there is lower sensitivity and it entails that there is no unanimous agreement (or consensus) about how to establish the criteria of clinically non-significant carcinoma. Therefore, once again, it is completely mandatory that urologists and pathologists work together, and while no consensus is reached both must know perfectly the guidelines of the center they work in.

The Role of 99mTc-Sestamibi Single-photon Emission Computed Tomography/Computed Tomography in the Diagnostic Pathway for Renal Masses: A Systematic Review and Meta-analysis.

CONTEXT: The diagnostic accuracy of current imaging techniques in differentiating benign from malignant neoplasms in the case of indeterminate renal masses is still suboptimal. OBJECTIVE: To evaluate the diagnostic accuracy of 99mTc-sestamibi (SestaMIBI) single-photon emission tomography computed tomography (SPECT)/CT in characterizing indeterminate renal masses by differentiating renal oncocytoma and hybrid oncocytic/chromophobe tumor (HOCT) from (1) all other renal lesions and (2) all malignant renal lesions. Secondary outcomes were: (1) benign versus malignant; (2) renal oncocytoma and HOCT versus clear cell (ccRCC) and papillary (pRCC) renal cell carcinoma; and (3) renal oncocytoma and HOCT versus chromophobe renal cell carcinoma (chRCC). EVIDENCE ACQUISITION: A literature search was conducted up to November 2022 using the PubMed/MEDLINE, Embase, and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to identify eligible studies. Studies included were prospective and retrospective cross-sectional studies in which SestaMIBI SPECT/CT findings were compared to histology after renal mass biopsy or surgery. EVIDENCE SYNTHESIS: Overall, eight studies involving 489 patients with 501 renal masses met our inclusion criteria. The sensitivity and specificity of SestaMIBI SPECT/CT for renal oncocytoma and HOCT versus all other renal lesions were 89% (95% confidence interval [CI] 70-97%) and 89% (95% CI 86-92%), respectively. Notably, for renal oncocytoma and HOCT versus ccRCC and pRCC, SestaMIBI SPECT/CT showed specificity of 98% (95% CI 91-100%) and similar sensitivity. Owing to the relatively high risk of bias and the presence of heterogeneity among the studies included, the level of evidence is still low. CONCLUSIONS: SestaMIBI SPECT/CT has good sensitivity and specificity in differentiating renal oncocytoma and HOCT from all other renal lesions, and in particular from those with more aggressive oncological behavior. Although these results are promising, further studies are needed to support the use of SestaMIBI SPECT/CT outside research trials. PATIENT SUMMARY: A scan method called SestaMIBI SPECT/CT has promise for diagnosing whether kidney tumors are malignant or not. However, it should still be limited to research trials because the level of evidence from our review is low.