Natural history of histologically benign PIRADS 4-5 lesions in multiparametric MRI: Real-life experience in an academic center.

INTRODUCTION: The follow-up findings of patients who underwent prostate biopsy for prostate image reporting and data system (PIRADS) 4 or 5 multiparametric magnetic resonance imaging (mpMRI) findings and had benign histology were retrospectively reviewed. METHODS: There were 190 biopsy-naive patients. Patients with at least 12 months of follow-up between 2012 and 2023 were evaluated. All MRIs were interpreted by two very experienced uroradiologists. Of the patients, 125 had either cognitive or software fusion MR-targeted biopsies with 4 + 8/10 cores. The remaining 65 patients had in-bore biopsies with 4-5 cores. Prostate-specific antigen (PSA) levels below 4 ng/mL were defined as PSA regression following biopsy. PIRADS 1-3 lesions on new MRI images were classified as MRI regression. RESULTS: Median patient age and PSA were 62 (39-82) years and six (0.4-33) ng/mL, respectively, at the initial work-up. During a median follow-up period of 44 months, 37 (19.4%) patients were lost to follow-up. Of the remaining 153 patients, 82 (53.6%) had persistently high PSA. Among them, 72 (87.8%) had repeat mpMRI within 6-24 months which showed regressive findings (PIRADS 1-3) in 53 patients (73.6%) and PIRADS 4-5 index lesion persistence in 19 cases (26.4%). The latter group was recommended to have rebiopsy. Of these 19 patients, 16 underwent MRI-targeted rebiopsy. Prostate cancer was diagnosed in six (37.5%) patients and of these four (25%) were clinically significant (>Grade Group 1). Totally, clinically significant prostate cancer was detected in 4/153 (2.6%) patients followed up. CONCLUSION: Patients should be warned against the relative relaxing effect of a negative biopsy after identification of PIRADS 4-5 index lesion. While PSA decrease was observed in many patients during follow-up, persistent MRI findings were present in nearly a quarter of patients with persistently high PSA. A rebiopsy is warranted in these patients, with significant prostate cancer diagnosed in a quarter of patients with rebiopsy.

The role of PSMA PET/CT in predicting downgrading in patients with Gleason score 4+4 prostate cancer in prostate biopsy.

BACKGROUND: To investigate the predictable parameters associated with downgrading in patients with a Gleason score (GS) 8 (4+4) in prostate biopsy after radical prostatectomy. METHODS: We retrospectively analyzed 62 patients with a GS of 4+4 on prostate biopsy who underwent robotic radical prostatectomy between 2017 and 2022. RESULTS: 38 of 62 (61.2%) were downgraded. In multivariable logistic regression model, Ga-68 prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) SUV max was independent predictor of downgrading (OR 0.904; p = 0.011) and a Logistic Regression model was constructed using the following formula: Y = 1.465-0.95 (PSMA PET/CT SUV max). The model using this variable correctly predicted the downgrading in 72.6% of patients. The AUC for PSMA PET/CT SUV max was 0.709 the cut off being 8.8. A subgroup analysis was performed in 37 patients who had no other European Association of Urology (EAU) high risk features. 25 out of 37 (67.5%) were downgraded, and 21 of these 25 had organ confined disease. Low PSMA SUV max (<8.1) and percentage of GS 4+4 biopsy cores to cancer bearing cores (45.0%) were independently associated with downgrading to GS 7. CONCLUSION: PSMA PET/CT can be used to predict downgrading in patients with GS 4+4 PCa. Patients with GS 4+4 disease, but no other EAU high risk features, low percentage of GS 4+4 biopsy cores to cancer bearing cores, and a low PSMA PET/CT SUV max are associated with a high likelihood of the cancer reclassification to intermediate risk group.

Molecular Characterization of Juxtaglomerular Cell Tumors: Evidence of Alterations in MAPK-RAS Pathway.

Juxtaglomerular cell tumor (JGCT) is a rare neoplasm, part of the family of mesenchymal tumors of the kidney. Although the pathophysiological and clinical correlates of JGCT are well known, as these tumors are an important cause of early-onset arterial hypertension refractory to medical treatment, their molecular background is unknown, with only few small studies investigating their karyotype. Herein we describe a multi-institutional cohort of JGCTs diagnosed by experienced genitourinary pathologists, evaluating clinical presentation and outcome, morphologic diversity, and, importantly, the molecular features. Ten JGCTs were collected from 9 institutions, studied by immunohistochemistry, and submitted to whole exome sequencing. Our findings highlight the morphologic heterogeneity of JGCT, which can mimic several kidney tumor entities. Three cases showed concerning histologic features, but the patient course was unremarkable, which suggests that morphologic evaluation alone cannot reliably predict the clinical behavior. Gain-of-function variants in RAS GTPases were detected in JGCTs, with no evidence of additional recurrent genomic alterations. In conclusion, we present the largest series of JGCT characterized by whole exome sequencing, highlighting the putative role of the MAPK-RAS pathway.

Delphi: A Democratic and Cost-Effective Method of Consensus Generation in Transplantation.

The Thrombotic Microangiopathy Banff Working Group (TMA-BWG) was formed in 2015 to survey current practices and develop minimum diagnostic criteria (MDC) for renal transplant TMA (Tx-TMA). To generate consensus among pathologists and nephrologists, the TMA BWG designed a 3-Phase study. Phase I of the study is presented here. Using the Delphi methodology, 23 panelists with >3 years of diagnostic experience with Tx-TMA pathology listed their MDC suggesting light, immunofluorescence, and electron microscopy lesions, clinical and laboratory information, and differential diagnoses. Nine rounds (R) of consensus resulted in MDC validated during two Rs using online evaluation of whole slide digital images of 37 biopsies (28 TMA, 9 non-TMA). Starting with 338 criteria the process resulted in 24 criteria and 8 differential diagnoses including 18 pathologic, 2 clinical, and 4 laboratory criteria. Results show that 3/4 of the panelists agreed on the diagnosis of 3/4 of cases. The process also allowed definition refinement for 4 light and 4 electron microscopy lesions. For the first time in Banff classification, the Delphi methodology was used to generate consensus. The study shows that Delphi is a democratic and cost-effective method allowing rapid consensus generation among numerous physicians dealing with large number of criteria in transplantation.

Intraoperative Frozen Section via Neurosafe During Robotic Radical Prostatectomy in the Era of Preoperative Risk Stratifications and Primary Staging With mpMRI and PSMA-PET CT: Is There a Perfect Candidate?

BACKGROUND: We aimed to analyze the effect of preoperative risk assessment including Ga-68 PSMA PET and multiparametric magnetic resonance imaging (mpMRI) on nerve sparing practices, positive surgical margin (PSM) rates and oncological outcomes based on a comparison between patients underwent RARP with and without Neurosafe (NS). METHODS: Patients underwent RARP with NS (RARP-NS) or without (RARP-only) NS retrospectively evaluated. Suspicion for extracapsular extension on mpMRI and/or Ga-68 PSMA PET was recorded as i(imaging)T3. NS was performed according to the Martini-Klinik technique. PSM at preserved bundle side were called PSM at region of interest (ROI) while the others were elsewhere. RESULTS: A total of 208 patients (90 in RARP-NS, 118 in RARP-only groups) were included. Preoperatively the RARP-only group showed significantly higher mean PSA (p = .01) and PIRADS 5 (p = .002) findings and had more D'Amico high risk (DAHR) patients (p = .08). The overall PSM rates for pT2 versus pT3 disease were 7.5% versus 21.6 and 15.6% versus 55% in RARP-NS and RARP-only groups, respectively. NS resulted in more bilaterally preserved bundles (81.1% vs. 66.3%) and less PSM at the ROI (3.3% vs. 23.4%) than RARP-only group. NS outperformed RARP-only in all clinical settings had its highest differential benefit in more bilateral nerve sparing and less PSM at ROI in patients with both DAHR and iT3 disease. BCR rates were 2.2% and 2.5% for RARP-NS and RARP only groups, respectively (p = .4). One patient in RARP-NS and 9 in RARP-only groups had PSA persistence (p = .02). CONCLUSION: RARP-NS led to more preserved bundles with less PSM. It was especially useful in DAHR patients with preoperative extracapsular extension suspicion in imaging simultaneously.

Non-choriocarcinomatous trophoblastic tumors of testis in postchemotherapy retroperitoneal lymph node dissections.

Non-choriocarcinomatous trophoblastic tumors (NCTTs) are seldomly diagnosed in male genital tract. As they have been recently described among the testicular germ cell tumor (TGCT) variants, pathologists' familiarity with their morphology is limited. We searched our electronic hospital records covering the years 2000-2017 for post-chemotherapy retroperitoneal TGCT metastectomies. Slides of all cases with viable tumor were retrieved from the archives and reviewed. Cases suspected of N-CTT morphologies were subjected to immunohistochemistry. Twelve NCTTs were identified, 9 of which were unseen or misdiagnosed by the original pathologists: Cystic trophoblastic tumor (CTT) (n = 5), placental site trophoblastic tumor (n = 2), epithelioid trophoblastic tumor (ETT) (n = 4), and coinciding PSTT + ETT (n = 1). Eight of these were associated with mature teratoma components, and one case (ETT) contained embryonal carcinoma and yolk sac tumor in addition to teratoma. Ten patients were clinically N1 at the time of primary tumor detection and orchiectomy. One patient had burned-out primary testicular tumor. Six patients were clinical M1a at presentation, while one male was cM1b. Six patients had mildly elevated ß-HCG (≤ 410 mIU/ml) just prior to retroperitoneal lymph node dissections (RPLND), while the others had normal ß-HCG levels. All patients had follow-ups ranging from 8 to 118 months (mean 42.3 months). Three patients died of disease-related and two of unrelated causes. In conclusion, because NCTTs are rare and newly described tumor types, their diagnosis is difficult and most of them are missed in post-chemotherapy RPLNDs. The majority of patients exhibit normal or slightly elevated ß-HCG levels. N-CTTs are usually accompanied by other components of TGCT, the most common being teratoma. Despite the high survival rate of the patients, our study points to the unpredictable evolution of NCTT cases, which may concur with a high-stage or progressive disease.

Cytoplasmic WT1 in IgA nephropathy, an indicator of poor prognosis associated with mesangial/peri-mesangial C4d.

BACKGROUND: We aimed to investigate the immuno-histochemical expression of C4d, ADAM10 and WT1 in kidney biopsies of immunoglobulin A nephropathy (IgAN) patients and correlate the findings with clinical, laboratory and histopathologic features in the hope of defining new parameters to better understand the pathogenesis of the disease, and predict prognosis. MATERIALS AND METHODS: Paraffin-embedded kidney biopsy samples of 128 IgAN patients were immuno-histochemically treated with C4d and ADAM10/WT1 dual stain. Results were evaluated according to Oxford classification parameters, epidemiologic features, laboratory findings at presentation and clinical follow-up. RESULTS: We observed C4d positivity in 40.6% of our patients, 25% of which was mesangial/peri-mesangial (m/pm) staining. Only m/pmC4d positivity statistically correlated with progression to end-stage renal disease (ESRD). M/pmC4d positive patients had statistically significantly higher baseline proteinuria levels, presence of crescents and > 25% segmental sclerosis of glomeruli. There was cytoplasmic staining of WT1 in 11.2% of cases. Presence of cWT1 correlated with m/pmC4d positivity and progression to ESRD. There was no glomerular ADAM10 detected and tubular expression of this protein did not relate to amount of tubular damage or other parameters. CONCLUSION: This study is the first to show that cWT1is involved in IgAN and appears as an independent variable for worse prognosis.

Fluorescence-guided extended pelvic lymphadenectomy during robotic radical prostatectomy.

We evaluated and described the impact of prostatic indocyanine green (ICG) injection on extended pelvic lymph node (LN) dissection (ePLND) in robotic-assisted radical prostatectomy (RARP). Between January 2019 and December 2021, we included consecutive 50 PCa patients who underwent ePLND during RARP with (n = 25) or without (n = 25) prostatic ICG injection. ICG injection was performed during abdominal port placement and robot docking. Pelvic LNs reflecting green color were initially excised and then the template was completed. The outcomes of two groups were compared. Overall, nine (36%) and five (20%) of the patients had metastatic LN involvement in the ICG and non-ICG groups, respectively. Of the 509 dissected LNs in the ICG group, 122 (23.9%) were fluorescence active. 20 LNs (3.9%) were metastatic in this group, 9 (45%) of which were ICG+. 408 LNs were resected on the non-ICG group with 8(1.9%) being metastatic. Eight (88.9%) of nine pN+ patients were florescent positive in the ICG group. Out of six patients with pN+ disease, Ga68 PSMA-PET/CT detected positive LNs preoperatively. In addition to preoperative Ga68 PSMA-PET/CT investigation, ICG-guided ePLND might increase identification and removal of metastatic LNs duirng RARP. Improvements in staging and oncologic outcomes may also be seen in intermediate- and high-risk patients.

Pathological Accuracy in Prostate Cancer: Single-Center Outcomes of 3 Different Magnetic Resonance Imaging-Targeted Biopsy Techniques and Random Systematic Biopsy.

OBJECTIVE: The aim of this study is to compare systematic, cognitive fusion, in-bore, and software fusion prostate biopsies regarding rates of and risk factors for pathological upgrading. MATERIAL AND METHODS: Charts of 291 patients with systematic biopsy (n = 105), magnetic resonance imaging- targeted cognitive fusion (n = 58), in-bore (n = 68), and software fusion biopsy (n = 60), and who subsequently underwent radical prostatectomy were retrospectively evaluated. The degree of similarity between the grade groups reported in the biopsy and radical prostatectomy pathology results was recorded. Analyses of the associated factors for concordance and discordance were performed with univariate and multivariate methods. RESULTS: The concordance rates were as follows: systematic biopsy = 42.8%, cognitive fusion-targeted biopsy = 50%, in-bore fusion-targeted biopsy = 61.8, and software fusion biopsy = 58.4%. The upgrade rate of systematic biopsy (46.6%) was higher than cognitive fusion-targeted biopsy (27.6%), in-bore fusiontargeted biopsy (26.4%), and software fusion-targeted biopsy (18.3%). The number of positive cores was significantly associated with grade group concordance for the systematic biopsy group (P = .040). Within the cognitive fusion-targeted biopsy cohort, number of positive cores was the only parameter that exhibited a significant association with grade group concordance in multivariate analysis (P = .044). Considering the in-bore fusion-targeted biopsy group, maximum tumor length was statistically significant (P = .021). In the software fusion-targeted biopsy group, low prostate volume was found to be the only significant predictor for grade group accordance (P = .021). CONCLUSION: Magnetic resonance imaging-targeted biopsy techniques showed higher concordance and lower upgrade rates compared to systematic biopsy. For systematic biopsy and cognitive fusion-targeted biopsy, the number of positive cores was associated with grade group concordance, while maximum tumor length in in-bore fusion-targeted biopsy and low prostate volume for in-bore fusion-targeted biopsy were associated with grade group concordance. Among the MRI-targeted biopsy methods, in-bore fusion-targeted biopsy and software fusion-targeted biopsy were more accurate than cognitive fusion-targeted biopsy in terms of grade group.

Relationships of autonomic dysfunction with disease severity and neuropathic pain features in fibromyalgia: is it really a sympathetically maintained neuropathic pain?

Background: The pathophysiology of fibromyalgia (FM) involves many mechanisms including central nervous system sensitization theory, autonomic nervous system (ANS) dysfunction, and recently small fiber neuropathy. While the small fiber neuropathy itself can cause ANS dysfunction and neuropathic pain (NP), it is still unknown whether ANS problems have an association with severity of disease and NP in patients with FM. The aim of this study was to evaluate ANS dysfunction in FM patients and to explore possible associations of ANS dysfunction with disease severity and NP. Methods: Twenty-nine FM patients and 20 healthy controls were included in this cross-sectional study. Participants were tested using sympathetic skin responses (SSR) and R-R interval variation analyses for sympathetic and parasympathetic ANS dysfunction, respectively. Disease severity and somatic symptoms of patients with FM were evaluated using the ACR-2010 scales and Fibromyalgia Impact Questionnaire, and NP symptoms were evaluated using the Pain Detect Questionnaire and Douleur Neuropathique questionnaire. Results: FM patients were found to have ANS dysfunction characterized by increased sympathetic response and decreased parasympathetic response. SSR amplitudes were found to be correlated with a more severe disease. Although non-significant, NP severity tended to be associated with a decrease in sympathetic and parasympathetic activities. Conclusions: ANS dysfunction may play a role in the pathophysiology of FM. The trend of decreased ANS functions in FM patients exhibiting NP contradicts the notion that FM is a sympathetically maintained NP and may be explained with small fiber involvement.

The Impact of Visible Tumor (PI-RADS ≥ 3) on Upgrading and Adverse Pathology at Radical Prostatectomy in Low Risk Prostate Cancer Patients: A Biopsy Core Based Analysis.

BACKGROUND: The objective of this study was to investigate the impact of the characteristics of a single visible tumor (Prostate Imaging-Reporting and Data System [PI-RADS]≥3) on upgrading and adverse pathology at radical prostatectomy (RP) in biopsy naïve low risk prostate cancer (PCa) patients. MATERIALS AND METHODS: We retrospectively reviewed 64 biopsy naïve patients from 3 different referral centers between 2018 and 2020 with a PSA<10, cT1c disease, a single PI-RADS≥ 3 index lesion in multiparametric-MRI (mp-MRI), all bearing a GG 1 tumor sampled software fusion biopsy, who underwent RP. Preoperative clinical variables including the localization, number and tumor burden of positive cores for each PI-RADS category were related to upgrading and adverse pathology (GG>2 and/or pT3 and/or lymph node positive disease) at RP. RESULTS: Overall 37 patients (57.8%) were upgraded with a significant difference of upgrading in PI-RADS3 (30.0%) versus PI-RADS 4 (67.6%) (P = .007) and PI-RADS 4-5 (70.5%) lesions (P = .002). Thirty-three of 37 GG1 tumors were upgraded to GG2, while 6 of these 33 (18.2%) had adverse pathology as well. Overall 9 patients (14.1%) had adverse pathology at RP all harboring PI-RADS4-5 lesions. The number of positive cores differed significantly between the upgraded and nonupgraded patients. Adverse pathology group had significantly higher tumor volume at RP. CONCLUSION: PI-RADS4-5 lesions are the independent predictors of upgrading and adverse pathology in low risk PCa with visible tumors. Upgrading and adverse pathology were closely related to the number of positive combined cores reflecting the role of tumor volume. This should be kept in mind in shared decision making of an individual patient with low risk disease and a visible tumor.

Testicular Germ-Cell Tumors with Spermatic Cord Involvement: A Retrospective International Multi-Institutional Experience.

The 8th Edition of the American Joint Committee on Cancer (AJCC) Staging Manual designates discontinuous involvement of spermatic cord soft tissue by testicular germ cell tumors as a metastatic deposit. We conducted a retrospective international multi-institutional study to validate the current recommendations. Thirty-three (72%) nonseminomatous and 13 (28%) seminomatous testicular germ cell tumors were collected from 15 institutions in America, Europe, and Asia. Testicular tumor size ranged from 1.3 to 18.0 cm (mean: 6.1). Cases were classified as discontinuous involvement of spermatic cord soft tissue (n = 26), continuous cord involvement (n = 17), or cord lymphovascular invasion (n = 3). The mean follow-up was 39 months. Clinical stage for discontinuous involvement of spermatic cord soft-tissue patients was I (local disease) in 2/24 (8%), II (regional disease) in 6/24 (25%), and III (distant disease) in 16/24 (67%) cases; 16 (67%) patients presented with distant metastasis. Clinical stage for continuous cord involvement patients was I in 9/17 (53%), II in 4/17 (23%), and III in 4/17 (23%); 4 (23%) patients presented with distant metastasis. Disease progression was seen in 4 patients with discontinuous involvement of spermatic cord soft tissue and 5 with continuous cord-involvement (p = 0.699). When comparing discontinuous and continuous cord involvement, a significant difference was found in cord margin status (p = 0.044), spermatic cord tumor size (p = 0.016), lymph-node involvement (p = 0.037), distant metastasis (p = 0.010), individual clinical stage (p = 0.003), and nonadvanced vs. advanced disease (p = 0.003) at presentation. In multivariate analysis, after adjusting for age, histology, testicular tumor size, percent of embryonal carcinoma, lymphovascular invasion, and cord margin status, discontinuous involvement of spermatic cord soft tissue was significantly associated (p = 0.011) with advanced clinical stage at presentation. Our findings support the designation of metastatic disease for discontinuous involvement of spermatic cord soft tissue, as introduced by the 8th edition of the AJCC staging.

Can remote ischemic preconditioning counteract the renal functional deterioration attributable to partial nephrectomy under warm ischemia? Results of an animal study.

BACKGROUND: To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function. METHODS: Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning. RESULTS: IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05). CONCLUSION: RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels.

The Genitourinary Pathology Society Update on Classification and Grading of Flat and Papillary Urothelial Neoplasia With New Reporting Recommendations and Approach to Lesions With Mixed and Early Patterns of Neoplasia.

The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in bladder neoplasia with a focus on issues relevant to the practicing surgical pathologist for the understanding and effective reporting of bladder cancer, emphasizing particularly on the newly accumulated evidence post-2016 World Health Organization (WHO) classification. The work is presented in 2 manuscripts. Here, in the first, we revisit the nomenclature and classification system used for grading flat and papillary urothelial lesions centering on clinical relevance, and on dilemmas related to application in routine reporting. As patients of noninvasive bladder cancer frequently undergo cystoscopy and biopsy in their typically prolonged clinical course and for surveillance of disease, we discuss morphologies presented in these scenarios which may not have readily applicable diagnostic terms in the WHO classification. The topic of inverted patterns in urothelial neoplasia, particularly when prominent or exclusive, and beyond inverted papilloma has not been addressed formally in the WHO classification. Herein we provide a through review and suggest guidelines for when and how to report such lesions. In promulgating these GUPS recommendations, we aim to provide clarity on the clinical application of these not so uncommon diagnostically challenging situations encountered in routine practice, while also importantly advocating consistent terminology which would inform future work.

Pathology associated with adherent perirenal fat and its clinical effect.

INTRODUCTION: The dissection of perirenal fat is of critical importance to kidney surgery and ease of dissection is more important when using minimally invasive approaches. This study aimed to determine the clinical, radiological, and pathological significance of adherent perirenal fat (APF). MATERIALS AND METHODS: This prospective study included 22 patients scheduled for partial nephrectomy and 40 patients for donor nephrectomy. Intraoperative fat dissection time was recorded, and the complexity of perirenal fat dissection was surgeon-classified as easy, moderate, and difficult. Perirenal fat and subcutaneous fat thickness were measured. Measurement of perirenal fat depth and the Hounsfield unit (HU) for both perirenal and subcutaneous fields were performed using computed tomography (CT) images. All specimens were submitted for histopatological analysis. Researchers in each arm were blinded to other researchers' data. RESULTS: Mean age of the patients was 51.3 ± 12.7 years. Mean perirenal fat dissection time was 15.0 ± 13.5 minutes. Patient demographics, BMI, nor occupational status differed between the 3 complexity of perirenal fat dissection groups. Radiological findings showed that there was a significant correlation between perirenal fat depth and complexity of perirenal fat dissection (P < .05), but not with HU measurements or subcutaneous fat thickness. Surgeon classification of the complexity of perirenal fat dissection was in accordance with the duration of dissection (P < .05). Perinephric fat contained more fibrous tissue in the patients with histologically proven APF than in those without (P < .05). CONCLUSIONS: APF is a challenge during kidney surgery. Difficult dissection prolongs the duration of perirenal fat dissection and surgery. Perirenal fat thickness measured via preoperative CT might be used to predict APF.

Significance of caveolin-1 immunohistochemical staining differences in biopsy samples from kidney recipients with BK virus viremia.

BK virus infections which usually remains asymptomatic in healthy adults may have different clinical manifestations in immunocompromised patient population. BK virus reactivation can cause BK virus nephropathy in 8% of kidney transplant patients and graft loss may be seen if not treated. Clathrin or Caveolar system is known to be required for the transport of many viruses from Polyomaviruses family including BK viruses. In this study, kidney transplant patients with BK virus viremia were divided into two groups according to the BK virus nephropathy found in kidney biopsy (Group I: Viremia+, Nephropathy+ / Group II: Viremia+, Nephropathy-). Kidney biopsies were examined with immunohistochemical staining to determine the distribution and density of the Caveolin-1 and Clathrin molecules. Immunohistochemical staining of the 31 pathologic specimens with anti-caveolin-1 immunoglobulin revealed statistically significant difference between group-I and group-II. The number of the specimens stained with anti-caveolin-1 was less in group I. On the other hand, we did not find any difference between the groups regarding the anti-clathrin immunochemical analysis. According to these findings, caveolin-1 expression differences in kidney transplant patients may be important in disease progression.

68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography for Primary Lymph Node Staging Before Radical Prostatectomy: Central Review of Imaging and Comparison with Histopathology of Extended Lymphadenectomy.

BACKGROUND: Results from prospective trials have shown higher accuracy of prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) in detection of lymph node metastasis (LNM) compared to conventional imaging. OBJECTIVE: To evaluate the accuracy of 68Ga-PSMA-11 PET/CT for LNM detection in patients undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (PLND). DESIGN, SETTING, AND PARTICIPANTS: Between June 2014 and November 2020, 96 patients with 68Ga-PSMA PET/CT for primary staging underwent RP and extended PLND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The results from 68Ga-PSMA PET/CT were compared with histologic data from primary PLND in 96 patients. All 68Ga-PSMA PET/CT scans were centrally reviewed. RESULTS AND LIMITATIONS: Of 96 patients, 15.6% (n = 15) harbored LNMs. The median prostate-specific antigen at 68Ga-PSMA PET/CT was 8.0 ng/ml (interquartile range 5.5-11.7). The majority of patients had intermediate- (52.1%) or high-risk disease (41.7%). Biopsy grade group 4 and 5 was present in 22.9% and 15.6%, respectively. The 68Ga-PSMA PET/CT scans identified eight of 15 patients (53.3%) as LN-positive (true positive). The calculated per-patient sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 68Ga-PSMA PET/CT in the detection of LNM were 53.3%, 98.8%, 88.9%, 92.0%, and 91.7%, respectively. The per-patient sensitivity and specificity in the detection of LNMs larger than 2 mm were 61.5% and 98.8%, respectively. The main limitation is the retrospective design of the study. CONCLUSIONS: 68Ga-PSMA PET/CT is accurate in lymph node staging and the results support its use for primary staging of prostate cancer. PATIENT SUMMARY: We compared prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) findings with histopathology results after extended lymph node dissection and showed that it is accurate in detecting lymph node metastases. Our results support the use of PSMA PET/CT for primary staging of prostate cancer.

Practice patterns related to prostate cancer grading: results of a 2019 Genitourinary Pathology Society clinician survey.

PURPOSE: To survey urologic clinicians regarding interpretation of and practice patterns in relation to emerging aspects of prostate cancer grading, including quantification of high-grade disease, cribriform/intraductal carcinoma, and impact of magnetic resonance imaging-targeted needle biopsy. MATERIALS AND METHODS: The Genitourinary Pathology Society distributed a survey to urology and urologic oncology-focused societies and hospital departments. Eight hundred and thirty four responses were collected and analyzed using descriptive statistics. RESULTS: Eighty percent of survey participants use quantity of Gleason pattern 4 on needle biopsy for clinical decisions, less frequently with higher Grade Groups. Fifty percent interpret "tertiary" grade as a minor/<5% component. Seventy percent of respondents would prefer per core grading as well as a global/overall score per set of biopsies, but 70% would consider highest Gleason score in any single core as the grade for management. Seventy five percent utilize Grade Group terminology in patient discussions. For 45%, cribriform pattern would affect management, while for 70% the presence of intraductal carcinoma would preclude active surveillance. CONCLUSION: This survey of practice patterns in relationship to prostate cancer grading highlights similarities and differences between contemporary pathology reporting and its clinical application. As utilization of Gleason pattern 4 quantification, minor tertiary pattern, cribriform/intraductal carcinoma, and the incorporation of magnetic resonance imaging-based strategies evolve, these findings may serve as a basis for more nuanced communication and guide research efforts involving pathologists and clinicians.

Diagnostic ability of Ga-68 PSMA PET to detect dominant and non-dominant tumors, upgrading and adverse pathology in patients with PIRADS 4-5 index lesions undergoing radical prostatectomy.

BACKGROUND: To evaluate the additive role of Ga-68 PSMA PET as a primary staging tool in patients bearing prostate cancer in single PIRADS 4 or 5 index lesions. METHODS: Eighty-one biopsy-naive patients with preoperative mpMRI and Ga-68 PSMA PET who underwent radical prostatectomy (RP) were evaluated retrospectively. Forty-nine patients had PIRADS 4 and 32 had PIRADS 5 index lesions. The localization, grade, and volumetric properties of dominant (DT) and non-dominant tumors (NDT) in RP were compared to the index lesions of mpMRI and Ga-68 PSMA PET. RESULTS: The median age and PSA level were 62 (IQR; 59-69) years and 7 (IQR; 2-8) ng/ml, respectively. Ga-68 PSMA PET detected DTs in 100% of the patients including 13 patients in whom mpMR failed. In 45 patients an NDT was reported in RP. Ga-68 PSMA PET accurately detected NDT in 24 of 45 (53.3%) patients. Six patients (12.2%) in PIRADS 4 and 8 (25%) in PIRADS 5 group showed upgrading. In PIRADS 4, Ga-68 PSMA PET localized DT in all patients with upgraded tumors whereas mpMRI missed exact location in 2 of 6 (33.3%). In PIRADS 5 both mpMRI and Ga-68 PSMA PET accurately located all DTs. Overall detection rates of extracapsular extension (ECE) and seminal vesicle invasion (SVI) by mpMRI were 51.1% and 53.8%, respectively. Ga-68 PSMA PET detected ECE and SVI in 27.9% and 30.7%, respectively. When mpMRI and Ga-68 PSMA PET were used in combination detection rates of ECE and SVI increased to 65.1 and 61.5%. Ga-68 PSMA PET-detected six of ten patients with positive lymph nodes whereas mpMRI could not identify any. CONCLUSIONS: Ga-68 PSMA PET has a better diagnostic accuracy in detecting DT, NDT, upgrading, adverse pathology in patients with PIRADS 4 index lesions. However, mpMRI better predicted ECE and SVI than Ga-68 PSMA PET.

The 2019 Genitourinary Pathology Society (GUPS) White Paper on Contemporary Grading of Prostate Cancer.

CONTEXT.­: Controversies and uncertainty persist in prostate cancer grading. OBJECTIVE.­: To update grading recommendations. DATA SOURCES.­: Critical review of the literature along with pathology and clinician surveys. CONCLUSIONS.­: Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace "tertiary grade pattern" in radical prostatectomy (RP) with "minor tertiary pattern 5 (TP5)," and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) "atypical intraductal proliferation (AIP)" is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.