World Health Organization/International Society Of Urological Pathology Research Articles

CT-based radiomics model using stability selection for predicting the WHO/ISUP grade of clear cell renal cell carcinoma.

This study aimed to develop a model to predict World Health Organization/International Society of Urological Pathology (WHO/ISUP) low-grade or high-grade clear cell renal cell carcinoma (ccRCC) using 3D multi-phase enhanced computed tomography (CT) radiomics features (RFs). CT data of 138 low-grade and 60 high-grade ccRCC cases were included. RFs were extracted from four CT phases: non-contrast phase (NCP), cortico-medullary phase (CMP), nephrographic phase (NP), and excretory phase (EP). Models were developed using various combinations of RFs and subjected to cross-validation. There were 107 RFs extracted from each phase of the CT images. The NCP-EP model had the best overall predictive value (AUC = 0.78), but did not significantly differ from that of the NCP model (AUC = 0.76). By considering the predictive ability of the model, the level of radiation exposure, and model simplicity, the overall best model was the Conventional image and clinical features (CICFs)-NCP model (AUC = 0.77; sensitivity 0.75, specificity 0.69, positive predictive value 0.85, negative predictive value 0.54, accuracy 0.73). The second-best model was the NCP model (AUC = 0.76). Combining clinical features with unenhanced CT images of the kidneys seems to be optimal for prediction of WHO/ISUP grade of ccRCC. This noninvasive method may assist in guiding more accurate treatment decisions for ccRCC. This study innovatively employed stability selection for RFs, enhancing model reliability. The CICFs-NCP model's simplicity and efficacy mark a significant advancement, offering a practical tool for clinical decision-making in ccRCC management.

Renal Cell Carcinoma With Tumor Thrombus: A Case Series in Puerto Rico.

Renal cell carcinoma (RCC) is one of the most common types of kidney cancer. While RCC tends to present as a localized tumor, a notable proportion may present with distant metastasis. In some instances, RCC may also present with intravascular tumor extension, often called tumor thrombus (TT). Its presence confers a worse prognosis and has important implications for the tumor's staging and treatment. Despite extensive documentation of RCC TT in the US, limited data exists regarding its presentation, management, and outcomes in Puerto Rico(PR). This study aims to broaden the available information on RCC TT, emphasizing surgical management and outcomes. We also provide descriptive data on patient demographics and clinical presentation to improve decision-making among clinicians caring for Puerto Rican men and women. In this single-center, retrospective study, we evaluated patients who underwent partial or total nephrectomy at Saint Luke's Episcopal Medical Center between 2018 and 2022. Data was abstracted from electronic health records (EHR). Patients without documented evidence of TT during the peri-operative period were excluded from the study. A total of 220 patient records were evaluated, of which 12met the inclusion criteria for the study. Caseswere categorized using the latestRCCTT guidelines. Central tendency measurements were used to describe the sample distribution. The mean was considered to make assumptions regarding the prevalent observations, and the median was considered to rule out possible outliers.Categorical data were evaluated using proportion analyses, including TT extension level and BMI variables. Fisher's exact test evaluated the association between the World Health Organization/International Society of Urological Pathology(WHO/ISUP) grade and TT extension level. Most patients lacked TT-related symptoms. Themost severe presenting symptom was a pulmonary embolism (8.3%). Hypertension (83.3%), BMIgreater than 25 at the time of diagnosis (75%), and type 2 diabetes mellitus (66.7%) were the most common comorbid conditions within our cohort. Nearly 75% ofpatients underwent laparoscopic radical nephrectomy with TT resection. One left-sided level III case was managed by laparoscopic-assisted open radical nephrectomy with a right subcostal incision. There were zero intraoperative complications and two postoperative complications. The histopathological reports of all cases were consistent with clear cell carcinoma, and half of the cases (n=6) were WHO/ISUP G4. All patients are alive and free of disease. RCCis a common renal neoplasm in PRthatcanpresent withintravascular tumor extension.Our findings do not establish a definitive association between BMI, tumor size, WHO/ISUP grading, and TT extension level. Our study shows that laparoscopic removal of RCC TT is a safe and effective approach. However, the generalizability of our findings is limited by the study's design and sample size. Future research should focus on identifying predictive markers, establishing effective screening protocols, and determining if our hybrid approach has comparable outcomes to the standard open approach.

Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1–4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1–2) or a high-grade group (WHO/ISUP grade 3–4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5–18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6–17.4) in the high-grade group and 28.0 months (21.1–34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0–10.0) for the high-grade group and 10.0 months (6.8–13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135–2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.

Collateral vessels on preoperative enhanced computed tomography for predicting pathological grade of clear cell renal cell carcinoma: A retrospective study

ObjectivesTo retrospectively evaluate the association between the presence of collateral vessels and grade of clear cell renal cell carcinoma (ccRCC) and whether the presence of collateral vessels could serve as a predictor to differentiate high- and low-grade ccRCC. Materials and MethodsFrom May 2018 to September 2022, a total of 160 ccRCC patients with pathological diagnosis were enrolled in this study. Patients were divided into a high-grade group and a low-grade group according to World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading system. The significant variables were extracted based on the univariate analyses using Student t test, Mann-Whitney U test, Chi-square test or Fisher’s exact test. Multivariate logistic regression analyses were performed to determine independent factors among extracted variables. We calculated the sensitivity, specificity and their 95% confidence intervals (CI) of collateral vessels for predicting high WHO/ISUP grade to quantify its predictive performance. Furthermore, to investigate the additional predictive contribution of collateral vessels, a primary model and a control model were constructed to predict WHO/ISUP grade. The primary model included all extracted significant variables and the control model included significant variables except collateral vessels. ResultsThe proportion of ccRCC patients with collateral vessels was significantly larger in high-grade ccRCC than those in low-grade ccRCC (87.5 % vs. 26.8 %, P < 0.001). Multivariate logistic regression analyses showed that the presence of collateral vessels was an independent predictor for high WHO/ISUP grade (P < 0.001). The sensitivity and specificity of the presence of collateral vessels for differentiating high- and low-grade ccRCC were 87.5 % (95 % CI 0.753–0.941) and 73.2 % (95 % CI 0.643–0.806) respectively. Including collateral vessels in predictive model improves predictive performance for WHO/ISUP grade, increasing the area under the curve (AUC) value from 0.889 to 0.914. ConclusionThe presence of collateral vessels has high sensitivity and specificity for differentiating high- and low-grade ccRCC and can improve the predictive performance for high WHO/ISUP grade.

Analysis of the relationship between PI-RADS scores and the pathological results of targeted biopsy based on MRI

Objective: To analyze the relationship between Prostate Imaging Reporting and Data System (PI-RADS) scores and the pathological results of transperineal magnetic resonance-ultrasound fusion guided biopsy. Methods: The clinical data, magnetic resonance imaging (MRI) results and prostate puncture biopsies of 517 patients who were assigned to PI-RADS score of 4 or 5 and underwent transperineal magnetic resonance-ultrasound fusion guided biopsy at The First Affiliated Hospital of Nanjing Medical University from June 2019 to March 2022 were retrospectively analyzed. Patients were divided into the PI-RADS 4 and PI-RADS 5 groups according to their PI-RADS scores and were stratified by their prostate specific antigen (PSA) values (PSA<10 ng/ml vs. PSA 10-20 ng/ml). The pathological negative rates from the biopsy, the distribution of the grade groups according to the grading system by World Health Organization/International Society of Urological Pathology (WHO/ISUP), the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CsPCa)between the groups were compared. Results: 369 patients with a PI-RADS score of 4 and 148 patients with a PI-RADS score of 5 were included in our research. The overall detection rates of PCa and CsPCa were 77.8% (402/517) and 66.7% (345/517), respectively. In the PI-RADS 4 group, patients with prostate negative biopsies or in WHO/ISUP 1, 2, 3, 4, or 5 grade groups accounted for 28.2%, 12.7%, 20.1%, 17.1%, 18.4% and 3.5%, respectively, whereas in the PI-RADS 5 group the rates were 7.4%, 6.8%, 22.3%, 22.3%, 26.4%, and 14.9%, respectively. The difference was statistically significant (P<0.001). The detection rates of PCa and CsPCa in the PI-RADS 4 group [71.8% (265/369) vs. 59.1% (218/369), P<0.001] were lower than those of the PI-RADS 5 group [92.6% (137/148) vs. 85.8% (127/148), P<0.001]. In the PI-RADS 4 group, the proportion of patients classified into WHO/ISUP 4-5 grade groups was lower than that of patients in the PI-RADS 5 group [22.0% (81/369) vs 41.2% (61/148) (P<0.001)]. The detection rates of PCa and CsPCa in the PSA<10 ng/ml stratification were less than that in the PSA 10-20 ng/ml stratification[74.1% (281/379) vs. 87.7% (121/138), P=0.001], and [60.9% (231/379) vs. 82.6% (114/138), P<0.001]. For patients with PSA<10 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS5 group [70.9% (217/306) vs. 87.7% (64/73), P=0.003], and [56.2% (172/306) vs. 80.8% (59/73), P<0.001]. For those with a PSA value of 10-20 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group [76.2% (48/63) vs. 97.3% (73/75), P<0.001], and [73.0% (46/63) vs. 90.7% (68/75), P=0.006]. There were statistically significant differences in the proportions of patients with prostate negative biopsy and those falling into WHO/ISUP grade groups 1, 2, 3, 4, or 5 (P<0.001) between the PI-RADS 4 group and the PI-RADS 5 group in both stratifications. Conclusions: In this study, the detection rates of CsPCa and PCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group. With the increase of PI-RADS scores, the detection rate of high-grade PCa increased. The same results held for patients with PSA<10 ng/ml or with PSA 10-20 ng/ml.

68Ga]Ga‑LNC1007 PET/CT in the evaluation of renal cell carcinoma: comparison with 2-[18F]FDG/[68Ga]Ga-PSMA PET/CT.

To compare the potential efficiency of [68Ga]Ga-LNC1007 with 2-[18F]FDG/[68Ga]Ga-PSMA PET/CT for detecting renal cell carcinoma (RCC) and to explore parameters derived from [68Ga]Ga-LNC1007 PET/CT for discriminating pathological characteristics in RCC. Twenty-five RCC patients confirmed by pathology were enrolled in this prospective study. The maximum standardized uptake value (SUVmax), mean SUV (SUVmean), gross tumor volume (GTV) and total lesion-tracer (TL-tracer) of lesions were calculated from the corresponding PET/CT images. Pathological characteristics included World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and adverse pathological features (tumor necrosis or sarcomatoid or rhabdoid feature). [68Ga]Ga-LNC1007 PET/CT showed a higher detection rate for primary lesions than 2-[18F]FDG and [68Ga]Ga-PSMA (LNC1007 vs. FDG: 13/17 vs. 4/17, P = 0.005; LNC1007 vs. PSMA: 9/11 vs. 6/11, P = 0.361). [68Ga]Ga-LNC1007 PET/CT showed higher SUVmax (6.6 vs. 3.7, P = 0.005), SUVmean (4.1 vs. 2.3, P = 0.001) and TBR (2.6 vs. 1.7, P = 0.011) compared with 2-[18F]FDG PET/CT, and it also showed higher TBR (2.9 vs. 0.5, P = 0.003), TBR-delay (2.8 vs. 0.3, P = 0.003), GTV (84.1 vs. 42.9, P = 0.003) and TL-tracer (442.7 vs. 235.8, P = 0.008) compared with [68Ga]Ga-PSMA PET/CT. SUVmax and TBR derived from [68Ga]Ga-LNC1007 PET/CT could effectively differentiate WHO/ISUP grade (3-4 vs. 1-2) and adverse pathological features (positive vs. negative) (SUVmax: AUC 0.81, P = 0.04; AUC 0.80, P = 0.033; TBR: AUC 0.84, P = 0.026; AUC 0.85, P = 0.014). The SUVmax was positively correlated with the FAP expression, integrin αvβ3 expression and the total expression of FAP and integrin αvβ3 (r = 0.577, P = 0.006, r = 0.701, P < 0.001, and r = 0.702, P < 0.001, respectively). [68Ga]Ga-LNC1007 is a promising tracer for RCC imaging and can effectively identify aggressive pathological characteristics of RCC.

The application of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy with a new robotic system KangDuo Surgical Robot-01: Initial experience

ObjectiveTo assess the feasibility of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy (rRAPN) with a new robotic platform called KangDuo Surgical Robot-01 (KD-SR-01) system (Suzhou KangDuo Robot Co., Ltd., Suzhou, China) and discuss its surgical technique. MethodsA 44-year-old male patient was admitted with a 2.5 cm tumor on dorsolateral upper pole of the left kidney. The R.E.N.A.L. nephrometry score of this patient was 4x. This patient underwent rRAPN with KD-SR-01. The perinephric fat between the tumor and Gerota's fascia was preserved, which was used for internal suspension traction during tumor resection. Postoperative follow-up data were collected. ResultsThe surgery was successfully carried out with a duration of 127 min, in which the docking time was 6 min 25 s and console time was 60 min. The warm ischemia time was 19 min 53 s, and the estimated blood loss was 0 mL. The pathological histology showed a pathological tumor stage 1a clear cell renal cell carcinoma, with a negative surgical margin. The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade of this patient was Grade 2. No recurrence was observed during the 6-month follow-up. ConclusionInternal suspension in rRAPN is feasible and effective with use of the new robotic system KD-SR-01.

Renal Neoplasia Occurring in Patients With PTEN Hamartoma Tumor Syndrome : Clinicopathologic Study of 12 Renal Cell Carcinomas From 9 Patients and Association With Intrarenal "Lipomas".

The aim of this study was to assess the histopathologic spectrum of renal tumors in patients with PTEN hamartoma tumor syndrome (PHTS), with a specific focus on potential features predictive of the underlying syndrome. A multi-institutional study was conducted to obtain clinical and pathologic data on renal tumors arising in patients with PHTS, either diagnosed by germline mutational analysis or clinical criteria for Cowden syndrome. Histologic sections of the renal tumors were re-reviewed for classification. Twelve renal epithelial tumors from 9 patients were identified (4 males and 5 females, with a mean age of 41.8y), 7 of whom carried germline PTEN mutations. All 12 renal epithelial tumors were renal cell carcinomas (RCCs): 5 were chromophobe RCCs, 4 papillary RCCs, and 3 RCC not otherwise specified. Pathologic stage distribution was: 7 (59%) pT1a, 2 (17%) pT1b, 1 (8%) pT2a, 1 (8%) pT2b, and 1 (8%) pT3a. World Health Organization/International Society of Urological Pathology (WHO/ISUP) histologic grade was applicable in 7 (54%) nonchromophobe tumors: 4 (57%) G2, 2 (29%) G3, and 1 (14%) G4. An unexpected histologic finding was the presence of 2 patients with incidental microscopic collections of intrarenal adipocytes that had no features of angiomyolipoma (and were negative with 2 sensitive PEComa markers: cathepsin-K and GPNMB); both were classified as lipoma/"lipomatous hamartomas." The average follow-up interval was 67.8 months (13 to 172mo): 5 patients had no evidence of disease, 2 were lost to follow-up, 1 died of other (non-PHTS) causes (ie, prostate cancer), and 1 was alive with metastatic RCC to the lung (RCC not otherwise specified with rhabdoid differentiation). All tumors showed loss of nuclear PTEN staining by immunohistochemistry. Fumarate hydratase was retained and 2SC was negative in all papillary RCCs. CK7 was moderate-strong/diffuse positive in 4 of 5 chromophobe RCCs and in 3 of 4 papillary RCCs. Renal epithelial tumors associated with PHTS represent a heterogeneous group of RCCs, but classic chromophobe and papillary RCC are most common. The majority have a favorable clinical behavior as would be predicted by subtype. In contrast to other hereditary renal neoplasia syndromes, morphologic features of the RCCs do not allow identification of PHTS-associated neoplasia with any degree of specificity in the absence of clinical setting and/or prior history, but the presence of microscopic "lipomas" within the kidney may provide a clue in rare cases. Therefore, clinical suspicion and genetic counseling with germline testing remain necessary for identifying PHTS-associated RCC.

Hypoxia inducible factors and hypoxia associated factor expression profiles and prognostic significance in renal cell carcinomas

Hypoxia Inducible Factor-1 alpha and Hypoxia Inducible Factor-2 alpha (HIF-1α and HIF-2α) are crucial in Renal Cell Carcinoma (RCC) formation. Hypoxia Associated Factor (HAF) prompts HIF-1α degradation regardless of oxygen levels, but no such link exists for HIF-2α. This study encompassed 239 cases, where tissue microarray (TMA) sections were exposed to HIF-1α, HIF-2α, and HAF antibodies. Staining intensity and tumor cell percentage determined scores for HIF-1α, HIF-2α, and HAF, with median histoscore establishing "high" or "low" cutoffs. Among the cases, 64.9% (155 cases) were negative for HIF-1α, 17.6% (42 cases) displayed low, and another 17.6% (42 cases) showed strong HIF-1α expression. HIF-1α expression correlated significantly with histological type and World Health Organization/International Society of Urological Pathology (WHO/ISUP) nuclear grade. Regarding HIF-2α, 15.5% (37 cases) were negative, 23.4% (56 cases) exhibited low, and 61.1% (146 cases) displayed high expression, with larger tumor size in the high HIF-2α group. Among 239 cases, 41.4% (99 cases) were negative for HAF, 36.8% (88 cases) showed low, and 21.8% (52 cases) displayed high HAF scores. HAF expression correlated with WHO/ISUP nuclear grade and metastasis presence. Notably, HIF-2α staining intensity directly correlated with increased HAF intensity (rho=0.146; p=0.024), while HIF-1α intensity decrease corresponded with heightened HAF intensity, showing a statistically significant negative correlation (rho=-0.180; p=0.005). In this rare examination of tumor tissue, a reverse connection between HIF-1α and HAF expression was uncovered, while a linear link emerged between HIF-2α and HAF expression. Overall, this study established that HIF-1α, HIF-2α, and HAF expression are associated with an unfavorable prognosis.

Prognostic value of tumour contour irregularity on surgical strategies for T1bN0M0 renal cell carcinoma: A multi-institutional study

PurposeTo determine the prognostic value of tumour contour irregularity degree (CID) in surgical strategy options for T1bN0M0 renal cell carcinoma (RCC). Materials and methodsWe performed a retrospective multi-institutional review of 489 patients with T1bN0M0 RCC treated between January 2009 and June 2019. Cox regression and Kaplan-Meier analyses were performed to analyse the impact of CID on disease-free survival (DFS). ResultsThe median follow-up time was 55 months (interquartile range, 40–81 months) for 55 (11.2 %) patients with metastasis or recurrence. Logistic analysis indicated that CID was associated with World Health Organization/International Society of Urological Pathology (WHO/ISUP) grades III–IV (odds ratio, 1.015; 95 % confidence interval [CI], 1.008–1.023; p < 0.001). After being classified into high CID (≥50 %) and low CID (<50 %) groups, those with a high CID showed a significantly higher ratio of WHO/IUSP grades III–IV (74/277 [26.7 %] vs 25/212 [11.8 %]) and shorter DFS than the low CID group (p < 0.001). Multivariable Cox regression showed that partial nephrectomy (PN; hazard ratio [HR], 1.889; 95 % CI, 1.020–3.499; p = 0.043), high CID (HR, 6.685; 95 % CI, 2.776–16.100; p < 0.001), and WHO/ISUP grade III–IV (HR, 1.950; 95 % CI, 1.100–3.458; p = 0.022) were independent prognostic factors for DFS. The Kaplan-Meier plot showed that PN had a DFS rate comparable to that of radical nephrectomy (RN; p = 0.994). In the low CID group, patients who underwent PN showed comparable DFS to those who underwent RN (p = 0.903). Furthermore, patients with a high CID tended to have worse DFS in the PN versus RN group (p = 0.044). Multivariable Cox regression showed that PN (HR, 2.049; 95 % CI, 1.065–3.942; p = 0.032) and WHO/ISUP grade III–IV (HR, 2.148; 95 % CI, 1.189–3.881; p = 0.011) were independent prognostic factors of DFS in the high CID group. ConclusionsCID is a reliable preoperative parameter which is positively correlated with WHO/ISUP grade and can help with surgical decision-making in patients with T1bN0M0 RCC.

Prediction of World Health Organization /International Society of Urological Pathology (WHO/ISUP) Pathological Grading of Clear Cell Renal Cell Carcinoma by Dual-Layer Spectral CT

To evaluate whether the dual-layer spectral computed tomography urography (DL-CTU) images could predict WHO/ISUP pathological grading of clear cell renal cell carcinoma (ccRCC). We retrospectively included patients (n=50) with pathologically confirmed ccRCC who underwent preoperative DL-CTU (from October 2017 to February 2021). They were divided into low-grade (WHO/ISUP 1/2, n=30) and high-grade groups (WHO/ISUP 3/4, n=20). The lesion size, attenuation (HU), iodine concentration (IC), normalized IC(NIC), and other quantitative characteristics were compared between the two groups. HU, IC, and NIC were obtained by plotting ROI with two different methods (circular ROI in the solid component or irregular ROI along the tumor edge containing tumor necrotic components). Receiver operating characteristic curves and multivariable model were used to evaluate the ability of parameters to predict WHO/ISUP grade. Transverse diameter (TD) of low-grade tumors was smaller, and HU in the non-contrast phase of the second method (HU-U-2) was lower than that of high-grade tumors (34.21±15.14 mm vs. 46.50 ± 20.68 mm, 27.33 ± 6.65 HU vs. 31.36 ± 6.09 HU, p< 0.05). The NIC in the nephrographic phase by the two methods (NIC-N-1 and NIC-N-2) of low-grade was higher than that of the high-grade group (0.78± 0.19 vs.0.58 ± 0.22, 0.73 ± 0.42 vs. 0.46 ± 0.22, p< 0.05). The final multivariable model composed of TD, HU-U-2, and NIC-N-1 could predict ccRCC grade with the area under the curve, sensitivity, specificity, and accuracy of 0.852, 70%, 90%, and 82%. Quantitative indicators in DL-CTU images could help predict the WHO/ISUP grade of ccRCC.

An exploratory study of CT radiomics using differential network feature selection for WHO/ISUP grading and progression-free survival prediction of clear cell renal cell carcinoma.

To explore the feasibility of predicting the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and progression-free survival (PFS) of clear cell renal cell cancer (ccRCC) using the radiomics features (RFs) based on the differential network feature selection (FS) method using the maximum-entropy probability model (MEPM). 175 ccRCC patients were divided into a training set (125) and a test set (50). The non-contrast phase (NCP), cortico-medullary phase, nephrographic phase, excretory phase phases, and all-phase WHO/ISUP grade prediction models were constructed based on a new differential network FS method using the MEPM. The diagnostic performance of the best phase model was compared with the other state-of-the-art machine learning models and the clinical models. The RFs of the best phase model were used for survival analysis and visualized using risk scores and nomograms. The performance of the above models was tested in both cross-validated and independent validation and checked by the Hosmer-Lemeshow test. The NCP RFs model was the best phase model, with an AUC of 0.89 in the test set, and performed superior to other machine learning models and the clinical models (all p <0.05). Kaplan-Meier survival analysis, univariate and multivariate cox regression results, and risk score analyses showed the NCP RFs could predict PFS well (almost all p < 0.05). The nomogram model incorporated the best two RFs and showed good discrimination, a C-index of 0.71 and 0.69 in the training and test set, and good calibration. The NCP CT-based RFs selected by differential network FS could predict the WHO/ISUP grade and PFS of RCC.

Associations between tumor grade, contrast-enhanced ultrasound features, and microvascular density in patients with clear cell renal cell carcinoma: a retrospective study.

Clear cell renal cell carcinoma (ccRCC) comprises 70% of all renal cell carcinomas (RCCs). Currently, the most important prognostic factor for this type of carcinoma is the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade. However, nonsurgical methods are rarely used to determine a tumor's WHO/ISUP grade, thus limiting the development of nonsurgical therapies. Due to variations in microvascular density (MVD) at different stages of tumor growth, contrast-enhanced ultrasound (CEUS) features may provide a noninvasive method for evaluating the WHO/ISUP grade of ccRCC. In this study, we analyzed confirmed cases of ccRCC using CEUS features. We also used CD34 and CD31 antibodies to determine MVD. The heterogeneity of CD34 and CD31 expressions were used to determine different degrees of angiogenesis. When compared to WHO/ISUP grade I/II (G1/G2) tumors, grade III/IV (G3/G4) tumors had reduced peak intensity (PI) (P=0.006), time to peak (TTP) (P<0.001), and relative enhancement percentage index (∆PI%) (P<0.001). However, the frequency of incomplete pseudocapsule (P=0.049) and slow wash-in (P=0.001) was significantly higher in G3/G4 tumors. A cut-off value of ∆PI% <33.15% (P<0.001) allowed identification of G3/G4 tumors with an area under the curve (AUC) of 0.80 [95% confidence interval (CI): 0.70 to 0.91) and a sensitivity of 80%. The mean CD34+ MVD (P<0.001) and CD31+ MVD (P<0.001) were significantly lower in G3/G4 tumors. A positive correlation was revealed between ∆PI% and MVD. There was a statistically significant difference in the density of undifferentiated vessels between the slow wash-in and fast wash-in cases (P<0.001). The features of CEUS are effective for differentiating G3/G4 tumors from G1/G2. There was a positive correlation detected between ∆PI% and MVD, and the density of undifferentiated vessels showed a significant difference between slow wash-in and fast wash-in cases. These findings indicate that CEUS can enable the sonographic visualization of tumor angiogenesis and thus be considered an acceptable method for the nonsurgical assessment of tumor microvascular distribution and grade.

Predicting the WHO/ISUP Grade of Clear Cell Renal Cell Carcinoma Through CT-Based Tumoral and Peritumoral Radiomics.

ObjectivesThis study aims to establish predictive logistic models for the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grades of clear cell renal cell carcinoma (ccRCC) based on tumoral and peritumoral radiomics.MethodsA cohort of 370 patients with pathologically confirmed ccRCCs were included in this retrospective study between January 2014 and December 2020 according to the WHO/ISUP grading system. The volume of interests of triphasic computed tomography images were depicted manually using the “itk-SNAP” software, and the radiomics features were calculated. The cohort was segmented into the training cohort and validation cohort with a random proportion of 7:3. After extraction of radiomics features by analysis of variance (ANOVA) or Mann-Whitney U test, correlation analysis, and the least absolute shrinkage and selection operator (LASSO) method, the logistic models of tumoral radiomics (LR-tumor) and peritumoral radiomics (LR-peritumor) were developed. The LR-peritumor was subdivided into LR-peritumor-2mm, LR-peritumor-5mm, and LR-peritumor-10mm, and the LR-peritumor-2mm was subdivided into LR-peritumor-kid and LR-peritumor-fat based on the neighboring tissues of ccRCCs. Finally, an integrative model of tumoral and peritumoral radiomics (LR-tumor/peritumor) was built. The value of areas under the receiver operator characteristics curve (AUCs) was calculated to assess the efficacy of the models.ResultsThere were 209 low-grade and 161 high-grade ccRCCs enrolled. The AUCs of LR-tumor in CT images of venous phase were 0.802 in the training cohort and 0.796 in the validation cohort. The AUCs were higher in the LR-peritumor-2mm than those in LR-peritumor-5mm and LR-peritumor-10mm (training cohort: 0.788 vs. 0.788 and 0.759; validation cohort: 0.787 vs. 0.785 and 0.758). Moreover, the AUCs of LR-peritumor-fat were higher compared with those of LR-peritumor-kid. The LR-tumor/peritumor displayed the highest AUCs of 0.812 in the training cohort and 0.804 in the validation cohort.ConclusionsThe tumoral and peritumoral radiomics helped to predict the WHO/ISUP grades of ccRCCs. On the diagnostic performance of peritumoral radiomics, better results were seen for the LR-peritumor-2mm and LR-peritumor-fat.

Predictive Factors Affecting Metastasis of Small Renal Mass and Its Prognostic Analysis

Background:The incidence of small renal mass (SRM) increases, and the prognosis of SRM is poor once metastasized. Therefore, we conducted this study to assess the clinical and pathological characteristics of SRM to determine the risk factors that influence the metastasis and prognosis of SRM.Methods:A small renal mass is defined as a solid tumor mass with the largest diameter of 4 cm or less on the pathological diagnosis. The metastasis is confirmed by imaging or pathological examination. We retrospectively included 40 patients with metastatic SRM (mSRM) treated in the department of urology of Peking University Third Hospital from October 2002 to October 2020. Meanwhile, 358 patients with nonmetastatic SRM treated in our hospital from January 2015 to December 2017 were selected as controls. Clinicopathologic features were compiled.Results:Multivariate logistic regression analysis showed that age (P = .027, odds ratio [OR] = 1.037, 95% confidence interval [CI] 1.004-1.070), clinical symptoms (P < .001, OR = 4.311, 95% CI 1.922-9.672), World Health Organization/International Society of Urological Pathology (WHO/ISUP) nuclear grade 3/4 (P = .004, OR = 7.637, 95% CI 1.943-30.012; P = .004, OR = 20.523, 95% CI 2.628-160.287), and lymphatic invasion (P = .030, OR = 15.844, 95% CI 1.314-191.033) were risk factors for distant metastasis of SRM. Once metastasis occurs, the prognosis of SRM is poor. Multivariate Cox regression analysis of the prognosis of mSRM showed that age (P = .016, hazard ratio [HR] = 1.125, 95% CI 1.022-1.239), preoperative serum creatinine (P = .041, HR = 1.003, 95% CI 1.000-1.005), vascular invasion (P = .041, HR = 1.003, 95% CI 1.000-1.005), and metastasis (P < .001, HR = 24.069, 95% CI 4.549-127.356) were risk factors for overall survival (OS), and only metastasis (P < .001, HR = 9.52, 95% CI 5.43-16.7) was a risk factor for progression-free survival (PFS) of SRM.Conclusions:SRM with advanced age, clinical symptoms, high pathological nuclear grade, and lymphatic invasion are more likely to have distant metastasis. And SRM with older age, poor preoperative basic renal function, pathological vascular invasion, and metastasis have worse OS.

MP38-19 THE GLEASON PROGNOSTIC PERSPECTIVE APPLIED TO THE pT1 UROTHELIAL CARCINOMA HETEROGENEITY

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I (MP38)1 Sep 2021MP38-19 THE GLEASON PROGNOSTIC PERSPECTIVE APPLIED TO THE pT1 UROTHELIAL CARCINOMA HETEROGENEITY Gustavo Mendonça, Karen Ferrari, Athanase Billis, and Leonardo Reis Gustavo MendonçaGustavo Mendonça More articles by this author , Karen FerrariKaren Ferrari More articles by this author , Athanase BillisAthanase Billis More articles by this author , and Leonardo ReisLeonardo Reis More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002053.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Current bipolar high/low grade World Health Organization/International Society of Urological Pathology (WHO/ISUP) bladder urothelial carcinoma grading relies on the highest pathologic specimen, not reflecting its inherent heterogeneity. METHODS: We studied 312 consecutive pT1 non-muscle invasive bladder carcinomas (NMIBC) submitted to transurethral resections (TURB) and adjuvant BCG until 2015 to propose and validate a prognostic clustering of a grading system that considers the primary (most common) and secondary (second most common or higher even focal) grades as 1, 2 or 3 according to the 1973 World Health Organization system. A final score was obtained which ranged from 2 (1+1) to 6 (3+3). RESULTS: Recurrence was diagnosed in 115 (36.9%), progression in 83 (26.6%) and cancer-specific death in 50 patients (16%). Mean time to recurrence, progression, and death of disease was 31.7±35.9, 44.5±47.6 and 50.4±51.2 months, respectively. Grade 3 presence (cluster 2+3, 3+2 or 3+3); independently predicted progression, p<0.001, HR 3.11, 95%CI 1.88-5.14; and grade 3 predominance (cluster 3+2 or 3+3); independently predicted death of disease, p<0.001, HR 3.39, 95%CI 1.88-5.10. CONCLUSIONS: Utilizing the established grading system WHO 1973 engenders a significantly better stratification of bladder cancer patients with clinical implication. Grade 3 presence and predominance are independent predictors of progression and death of disease, respectively. Source of Funding: none © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e702-e702 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gustavo Mendonça More articles by this author Karen Ferrari More articles by this author Athanase Billis More articles by this author Leonardo Reis More articles by this author Expand All Advertisement Loading ...

Tumour Behaviour of Low-Grade Papillary Urothelial Carcinoma: A Single-Centre Retrospective Study

Background and objectiveCarcinoma of the urinary bladder is the most common urological cancer, and it accounts for 3.9% of all cancer cases in men. Patients with the subset of noninvasive low-grade papillary urothelial carcinoma (LG-UrCa) are at higher risk for tumour recurrence. In this study, we aimed to analyse the histopathological features of LG-UrCa and to correlate those with recurrence potential as well as disease stage and grade progression.Materials and methodsWe conducted a retrospective study from January 2016 to December 2018. All cases with presenting biopsy initially reported as LG-UrCa were included in the study. All cases with initial biopsy reported as high-grade papillary urothelial carcinoma (HG-UrCa) were excluded from the study. We used the 2016 World Health Organization/International Society of Urological Pathology (WHO/ISUP) guidelines for the classification of papillary urothelial neoplasm.ResultsA total of 48 initially diagnosed cases of LG-UrCa were identified. Two out of 48 cases were reclassified as high-grade urothelial carcinoma and were excluded from the study. The mean age of patients at presentation was 56.7 years. The mean duration of follow-up was 19.8 months. The mean size of initial tumours was 3.4 cm. Tumour recurrence was encountered in 14 (30.4%) of 46 patients. Out of the four patients who had high-grade progression (8.7%), two also developed TNM stage progression. These two patients eventually underwent radical cystectomy. Patients with larger initial tumour sizes were found to have an increased tumour recurrence rate (p=0.009). Patients with multiple lesions at initial diagnosis had a significantly higher tumour recurrence rate than those with a single tumour (p=0.02). There was no significant difference with regard to intravesical Bacillus Calmette-Guérin (BCG) and tumour recurrence (p=0.065). None of the clinicopathological parameters were significantly associated with the grade and/or stage progression.ConclusionBased on our findings, patients with larger initial tumour size and tumour multiplicity at presentation had an increased tumour recurrence rate.

Noninvasive evaluation of tumor immune microenvironment in patients with clear cell renal cell carcinoma using metabolic parameter from preoperative 2-[18F]FDG PET/CT.

Nowadays, it is necessary to explore effective biomarkers associated with tumor immune microenvironment (TIME) noninvasively. Here, we investigated whether the metabolic parameter from preoperative 2-[18F]FDG PET/CT could provide information related to TIME in patients with clear cell renal cell carcinoma (ccRCC). Ninety patients with newly diagnosed ccRCC who underwent 2-[18F]FDG PET/CT prior to surgery were retrospectively reviewed. The immunological features included tumor-infiltrating lymphocytes (TILs) density, programmed death-ligand 1 (PD-L1) expression, and tumor immune microenvironment types (TIMTs). TIMTs were classified as TIMT I (positive PD-L1 and high TILs), TIMT II (negative PD-L1 and low TILs), TIMT III (positive PD-L1 and low TILs), and TIMT IV (negative PD-L1 and high TILs). The relationship between maximum standardized uptake value (SUVmax) in the primary lesion from 2-[18F]FDG PET/CT and immunological features was analyzed. Cox proportional hazards analyses were performed to identify the prognostic factors for disease-free survival (DFS) after nephrectomy. Tumors with high TILs infiltration showed remarkable correlation with elevated SUVmax and aggressive clinicopathological characteristics, such as high World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade. PD-L1 expression on tumor cells was positively associated with WHO/ISUP grade and negatively correlated with body mass index (BMI). However, no correlation was observed between SUVmax and PD-L1 expression, regardless of its spatial tissue distribution. SUVmax of TIMT I and IV was higher than that of TIMT II, but there was remarkable difference merely between TIMT II and IV. In multivariate analysis, SUVmax (P = 0.022, HR 3.120, 95% CI 1.175-8.284) and WHO/ISUP grade (P = 0.046, HR 2.613, 95% CI 1.017-6.710) were the significant prognostic factors for DFS. Six cases (16.2%) with normal SUVmax showed disease progression, while 25 cases (71.4%) with elevated SUVmax experienced disease progression. Conversely, the immunological features held no prognostic value. Our findings demonstrated that 2-[18F]FDG PET/CT could provide metabolic information of TIME for ccRCC patients and develop image-guided therapeutic strategies accordingly. Patients with elevated preoperative SUVmax should be seriously considered, and perioperative immunotherapy might be beneficial for them.

Comparing World Health Organization/International Society of Urological Pathology Grading and Fuhrman Grading with the Prognostic Value of Nuclear Area in Patients with Renal Cell Carcinoma

This study was undertaken to compare Fuhrman grading with World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading and stereologically measured nuclear area in patients with Clear Cell Renal Cell Carcinoma (ccRCC) or Papillary Renal Cell Carcinoma (PRCC) and to evaluate the independent predictive value of Fuhrman, WHO/ISUP and stereologically measured nuclear area combined with necrosis in a series of patients with ccRCC in relation to cancer-specific survival. In all, 124 cases of ccRCC and PRCC were included. All slides were blindly scored by two trained pathologists according to the Fuhrman and WHO/ISUP grading systems. Nuclear measurements were performed on digitally scanned slides in Visiopharm® and correlated to survival. Analysis of ccRCC and PRCC cases showed that application of WHO/ISUP grading resulted in a significant downgrading of cases from G2 to G1, when comparing with Fuhrman grading. Neither of these patients experienced progression. Cancer specific survival estimates in 101 ccRCC patients showed that WHO/ISUP grading was slightly superior in predicting cancer-specific survival. Novel models included WHO/ISUP grading and mean nuclear area (MNA) each of which combined with necrosis. Both demonstrated an increased ability to predict cancer-specific survival. The study demonstrates that WHO/ISUP grading provides superior prognostic information compared to Fuhrman grading and stereologically measured nuclear area. Necrosis in combination with either WHO/ISUP grading or MNA adds additional prognostic information.

Accuracy of Subclassification and Grading of Renal Tumors on Fine Needle Aspiration Cytology Alone

Background: Fine needle aspiration (FNA) of renal masses can distinguish between benign and malignant neoplasms in 73–94% of cases. Previous studies suggested the correct subclassification of renal cell carcinomas (RCCs) by cytomorphology can be achieved in up to 80% of cases. However, as RCCs become increasingly subclassified by molecular signatures, correct subclassification based on cytology alone is increasingly difficult. Design: Two FNA passes (2 stained with Diff-Quik® and 2 with the Papanicolaou method) were performed on all fresh nephrectomy specimens for a 1-year period. There were 30 cases in this study, with 29 primary renal tumors and 1 case of metastatic lung adenocarcinoma. Each case was assigned a random number and came with 2 slides (1 from each staining method). Eight cytopathologists were asked to provide a diagnosis and the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading if applicable. Fleiss’ Kappa and Cohen’s Kappa equations were used to look at inter-rater variability. Results: When compared to the surgical pathology diagnosis, the average percent correct diagnosis for all cytopathologist was 35%. Chromophobe RCCs had the best average percent accuracy at 72% followed by clearcell RCC at 48%. Average accuracy for grading RCCs was 40%. Inter-rater variability among the cytopathologists for all RCC diagnoses was fair with a Fleiss’ Kappa coefficient of 0.28. For the WHO/ISUP grade, the weighted coefficient for each pathologist ranged from 0.11 to 0.45, ranging from fair to moderate, respectively. Conclusions: Renal tumors are difficult to classify on cytopathology alone. Core needle biopsy and ancillary studies are necessary if diagnosis will change management.