Low-grade Urothelial Carcinoma Research Articles

Diagnostic value of a comprehensive, urothelial carcinoma-specific next-generation sequencing panel in urine cytology and bladder tumor specimens.

Urine cytology can reliably diagnose high-grade urothelial carcinoma (HGUC) but not low-grade urothelial carcinoma (LGUC), and a more sensitive test is needed. Previously, a pilot study highlighted the possible diagnostic utility of next-generation sequencing (NGS) in identifying both LGUC and HGUC in urine cytology specimens. Twenty-eight urine ThinPrep cytology specimens and preceding or subsequent bladder tumor biopsy/resection specimens obtained within 3 months were included in the study (LGUC, n = 15; HGUC, n = 13). A customized, bladder-specific NGS panel was performed; it covered 69 frequently mutated or altered genes in urothelial carcinoma (UC) that were reported by The Cancer Genome Atlas and the Catalogue of Somatic Mutations in Cancer. The sequencing results were compared between the urine cytology specimens and the corresponding bladder tumor biopsies/resections. TP53 was the most frequently identified mutation in HGUC cases (11 of 13 [85%]). PIK3CA and KDM6A were the most frequently identified mutations in LGUC: they occurred in 7 of 15 cases (47%) and in 6 of 15 cases (40%), respectively. Additional frequent mutations identified in the panel included ARID1A (n = 5), EP300 (n = 4), LRP1B (n = 3), ERBB2 (n = 2), STAG2 (n = 2), FGFR3 (n = 3), MLL (n = 2), MLL3 (n = 2), CREBBP1 (n = 1), RB1 (n = 1), and FAT4 (n = 1). Overall, the concordance between the cytology and surgical specimens was 75%. The sensitivity and specificity for identifying mutations in urine cytology specimens were 84% and 100%, respectively. A bladder-specific NGS panel increases the sensitivity and specificity of urine cytology's diagnostic utility in both low- and high-grade tumors and may serve as a noninvasive surveillance method in the follow-up of patients with UC harboring known mutations.

Expression of Semaphorin 3A in Malignant and Normal Bladder Tissue: Immunohistochemistry Staining and Morphometric Evaluation.

Simple SummarySemaphorin 3A (Sema3A) was shown to play a significant role in different neoplasms. In a previous study by our team, we showed that Sema3A is overexpressed in patients with urothelial carcinoma (UC). In this study, we analyzed 43 specimens from patients with the entire spectrum of UC and compared them with samples from 14 normal urothelium using immunostaining and computerized morphometry. The results showed that patients with UC had intense Sema3A staining in the apical layer of the mucosa compared to patients without UC. Moreover, patients with higher grade UC showed intense Sema3A staining across all mucosal layers.Introduction: Our previous studies showed elevated levels of Semaphorin3a (Sema3A) in the urine of patients with urothelial cancer compared to healthy patients. The aim of this study was to analyze the extent of Sema3A expression in normal and malignant urothelial tissue using immune-staining microscopic and morphometric analysis. Materials and Methods: Fifty-seven paraffin-embedded bladder samples were retrieved from our pathology archive and analyzed: 14 samples of normal urothelium, 21 samples containing low-grade urothelial carcinoma, 13 samples of patients with high-grade urothelial carcinoma, 7 samples containing muscle invasive urothelial carcinoma, and 2 samples with pure urothelial carcinoma in situ. All samples were immunostained with anti Sema3A antibodies. The area of tissue stained with Sema3A and its intensity were analyzed using computerized morphometry and compared between the samples’ groups. Results: In normal bladder tissue, very light Sema3A staining was demonstrated on the mucosal basal layer and completely disappeared on the apical layer. In low-grade tumor samples, cells in the basal layer of the mucosa were also lightly stained with Sema3A, but Seama3A expression intensified upon moving apically, reaching its highest level on apical cells exfoliating to the urine. In high grade urothelial tumors, Seama3A staining was intense in the entire thickness of the mucosa. In samples containing carcinoma in situ, staining intensity was high and homogenous in all the neoplastic cells. Conclusions: Sema3A may be serve as a potential non-invasive marker of urothelial cancer.

Is Diagnosis of Low-Grade Urothelial Carcinoma Possible in Urine Cytology?

Background:Urine cytology is a useful modality, primarily for the diagnosis and follow-up surveillance of high-grade urothelial carcinoma (HGUC). Its utility in diagnosing low-grade urothelial carcinoma (LGUC) remains controversial because of low reported sensitivity compared to cystoscopy.Aim:To study the cytomorphology of LGUC in voided urine samples and analyze its utility in diagnosis.Materials and Methods:This is a retrospective study of one year, including 48 voided urine samples in cases which were confirmed as LGUC on subsequent histology. Urine cytology smears of these cases, originally stained with Papanicolaou stain were reviewed, critically analyzed and the specific cytomorphologic and cystoscopic findings were documented.Results:On review 18 samples were re-categorized as LGUC which included 10 samples initially diagnosed as Negative for HGUC, 2 as Atypical Urothelial Cells – Not Otherwise Specified (AUC-NOS) and 6 as Suspicious for Carcinoma. In addition, another 3 samples with initial diagnosis of LGUC remained as LGUC on review. Thus, a total of 21 LGUC samples were identified after the review. 26 (54%) samples with a diagnosis of negative for HGUC remained negative even after review, as the tumor cells were not identified either due to sampling error or unrecognizable morphology. One (2%) samples of AUC-NOS remained the same on review due to very scant atypical cells. In 21 LGUC samples, cytology showed a dual population of benign differentiated urothelial cells and small urothelial cells with subtle nuclear atypia such as irregular and thickened nuclear membrane with increased nuclear cytoplasmic ratio. In 12 false negative LGUC samples, the diagnostic cells were camouflaged by their subtle nuclear atypia coupled with an overwhelming background of differentiated benign urothelial cells as both appeared almost similar in morphology. Papillary fragments were identified only in 2 samples.Conclusions:Diagnosis of LGUC on cytology is challenging and depends on the presence of diagnostic cells, pick up of diagnostic cells on screening and accurate interpretation. Special attention to papillary fragments and aforementioned nuclear atypia should be paid as tumor cells may resemble normal urothelial cells and can be easily missed.

Noninvasive papillary urothelial neoplasia (NIPUN): Renaming cancer

Papillary urothelial neoplasm of low malignant potential (PUNLMP) terminology remains controversial given its reported recurrence rate, its low interobserver diagnostic reproducibility, and its morphologic and molecular genetic overlap with low-grade noninvasive papillary urothelial carcinoma. By contrast, referring to any noninvasive tumor as a “carcinoma” is also controversial. PUNLMP and low-grade noninvasive papillary urothelial carcinomas cannot be reliably distinguished from one another even by experienced pathologists. As both tumors are treated in an identical manner and have similar rates of recurrence and progression, attempting to make this distinction is unnecessary and of little clinical value. These tumor types should therefore be combined into a single category for grading purposes. We propose that all tumors currently classified as either PUNLMP or low-grade noninvasive papillary urothelial carcinoma be termed low-grade noninvasive papillary urothelial neoplasms (NIPUN). This could improve interobserver reproducibility without sacrificing the prognostic utility of histologic grading. PUNLMP terminology should be discontinued and the term “carcinoma” should be reserved only for tumors showing histologic evidence of invasion.

Five-year Survival Rate of Bladder Cancer in Iran during 2001-2007

Background & Objective:Bladder cancer is the fourth most common cancer in men and the most common cancer in women, comprising 8% of all males and 3% of female tumors. The present study aimed to estimate the five-year survival rates of bladder cancer in Iran.Methods:Information on 3,337 registered cases of bladder cancer was obtained from the Office of National Cancer Registry in the Ministry of Health and Medical Education (MOH & ME). A telephone survey was conducted to gather additional information, such as survival status, demographic, and clinical profile. Kaplan–Meier estimates of five-year survival rates were calculated according to the age of diagnosis, gender, pathological type, and provincial pole.Results and Conclusion:Overall five-year survival rate was 77%. According to the pathologic type, five-year survival rates were 81%, 66%, 81%, 42%, 77%, and 82% in low-grade urothelial carcinoma, high-grade urothelial carcinoma, adenocarcinoma, undifferentiated carcinomas, Squamous Cell Carcinomas (SCCs), and other tumors, respectively. Additionally, those tumors were 93%, 88%, 81%, 64%, and 44% among patients whose average ages at diagnosis were < 50, 50–59, 60–59, 70–79, and > 80 years old, respectively. Our study revealed that age and histological type were the major prognostic factors for survival in patients with bladder cancer. Therefore, given the histologic features of the tumor and patients with advanced age, a continuous screening would be highly warranted.

Machine Learning Based Classification from Whole-Slide Histopathological Images Enables Reliable and Interpretable Diagnosis of Inverted Urothelial Papilloma

Inverted urothelial papilloma (IUP) is a benign neoplasm of the urinary tract that accounts for less than 1% of urothelial tumors. It is diagnostically challenging for pathologists to distinguish histological features of IUP from other subtypes of non-invasive urothelial carcinoma, such as inverted Ta urothelial carcinoma (UCInv) and low-grade Ta urothelial carcinoma (UCLG). Using a machine learning approach, we analyzed the H&E-stained whole-slide histopathological images of 64 IUP (the largest cohort to date), 69 UCInv, and 92 UCLG samples, and propose a reliable, reproducible, and interpretable machine learning pipeline to classify IUP from other non-invasive urothelial carcinomas. The results showed that our method could achieve area under the ROC of 0.913 and 0.920 for classifying IUP from UCInv and UCLG, respectively, which is superior to competing methods, including deep learning-based methods. Testing of the classification models on an external validation dataset confirmed that our model can effectively identify IUP with high accuracy. Our results suggest that the proposed machine learning pipeline can robustly and accurately capture histopathological differences between IUP and other urothelial carcinoma subtypes, which can be extended to identify other rare cancer subtypes with limited samples and has the potential to expand the clinician’s armamentarium for accurate diagnosis. Funding: This work was supported in part by Indiana Precision Health Initiative to Kun Huang and Jie Zhang. Declaration of Interest: None to declare. Ethical Approval: This research was approved by the Institutional Review Boards of participating institutions.

Metastatic Clinically-Aggressive Non-Invasive Low-Grade Urothelial Carcinoma Arising Post Autologous Transplant - Case Report and Review of the Literature

Metastatic Clinically-Aggressive Non-Invasive Low-Grade Urothelial Carcinoma Arising Post Autologous Transplant - Case Report and Review of the Literature

Isolation of low grade urinary bladder tumors carrying bad prognosis using KI-67 labeling index

Introduction: Even among low grade bladder tumors, there are some which have been found to carry bad prognosis for progression, recurrence and survival. Accurately pinpointing these cases at the time of diagnosis just with the help of routine histopathology is problematic. Ki-67 immunostaining may potentially be of help in identifying such cases, making administration of additional treatment modalities like chemotherapy and radiotherapy possible. There is scarcity of such studies in our country. The present study aims to correlate Ki-67 labeling index with the histopathological type and grade, pathological stage and mitotic index of urinary bladder tumors. Objective: Objective of the study is to consider the possibility of using Ki-67 labeling index to identify those low grade urinary bladder tumors which carry bad prognosis. Materials and Methods: All trans-uretheral resection of bladder tumor (TURBT) specimens in our institute were analyzed for their histopathological grade, pathological stage, mitotic index and Ki-67 labeling index in the period extending from from August 2015 to December 2016. The clinical data were analyzed retrospectively and statistically. SPSS Version 23 (SPSS Inc.,Chicago, IL, USA) software was utilized for all statistical analyses. Chi-square analysis was utilized for comparison of groups. Results with P Results: Ki-67 expression in Low grade urothelial carcinoma (LGUC) showed variation from 1.4% to 41%. The papillary urothelial neoplasm of low malignant potential (PUNLMP) cases showed variation from 16 -17%. And the only case of transitional cell papilloma in the study was found to have expression of 9%.Conclusion: Cases of high (more than 20%) Ki-67 MIB-1 labeling index can be segregated even from among those cases with low histopathological grade, low mitotic index and pTa histopathological stage. Such cases are candidates for multimodality treatment including radiotherapy, chemotherapy etc. Keywords: Bladder tumors,

Diagnostic value of probe-based confocal laser endomicroscopy versus conventional endoscopic biopsies of non-muscle invasive bladder tumors: a pilot study

Purpose The standard procedure for diagnostics and follow-up for non-muscle invasive bladder cancer (NMIBC) is cystoscopy in the outpatient clinic. Suspicious lesions are biopsied for histopathological assessment. This pilot study aimed to evaluate the ability of Confocal Laser Endomicroscopy (CLE) to rule out High Grade Urothelial Carcinoma (HGUC) to select patients for in-office fulguration. Materials and methods We performed a prospective non-randomized, single surgeon study. Intraoperative CLE was performed independently by the surgeon and a blinded on-site uropathologist. Following the procedure, a CLE evaluation was performed by another blinded urologist. Lesions were classified as normal/inflammatory, Low Grade Urothelial Carcinoma (LGUC) or HGUC. With the histological evaluations as the gold standard we calculated sensitivity, specificity, PPV and NPV for HGUC and the accuracy for each CLE assessor. The primary outcome was the NPV for HGUC for the surgeon. Results Twelve patients with a total of 34 lesions were included. Six lesions were flat and 28 were exophytic. On histopathology, 25 lesions were classified as normal/inflammatory or LGUC, while nine were classified as HGUC. For the surgeon, the uropathologist and the second urologist, the sensitivity was 44%, 78% and 22%, respectively. Specificities for the three observers were 84%, 68% and 96%. This corresponded to PPVs for HGUC of 50%, 47% and 67% and NPV for HGUC of 81%, 89% and 77%. Conclusions In our hands the NPV of CLE is not high enough for it to be considered an alternative to histopathological assessment of bladder lesions.

CK20 and CK5/6 Immunohistochemical Staining of Urothelial Neoplasms: A Perspective

Cytokeratins belong to the family of intermediate filaments. They are expressed in a highly specific manner in epithelial cells where they play a crucial role in the integrity and mechanical stability of the cells. Several types of cytokeratins have been described in normal as well as neoplastic urothelium. In the case of urothelial neoplasms expression of CK20 and CK5/6 has been shown in several studies to have diagnostic and prognostic implications. Thus, low-grade urothelial carcinoma manifests CK expression limited to the umbrella cells, while high-grade tumors usually have an expression in the entire thickness of the urothelium except for the basal layer. CK5/6 expression on the other hand is expressed in the basal cells in all low-grade and some high-grade urothelial carcinomas. Diffuse CK20 staining accompanied by loss of CK5/6-positive basal layer is usually associated with aggressive clinical behavior. Double staining of the slides for these cytokeratins may facilitate proper interpretation and correlation.

Usefulness of Fluorescent Urine Cytology in the Diagnosis of Urothelial Carcinoma

Five-aminolevulinic acid, an amino acid that is metabolized in the cytoplasm to become protoporphyrin IX, is used in photodynamic diagnosis in various carcinomas because it accumulates in higher concentrations in tumor tissue than in normal tissue. 5-Aminolevulinic acid-induced fluorescent urine cytology is more sensitive than conventional urine cytology only in low grade urothelial carcinoma (UC), but it showed a tendency for higher sensitivity in high grade UC. To increase the number of patients and reconsider our previous findings, we compared the sensitivity and specificity of preoperative urine cytology and fluorescent urine cytology in 343 patients diagnosed as having UCs pathologically (215 bladder cancers, 128 upper tract UCs) and 197 non-cancer patients at Osaka Rosai Hospital from March 2013 to December 2019. The sensitivities of fluorescent urine cytology and conventional urine cytology were 81.1% and 63.3% (p<0.001), respectively, and specificities were 92.9% and 93.9% (p=0.84), respectively. The sensitivity of fluorescent urine cytology was superior to that of conventional urine cytology in both low grade UC (76.8% vs 41.1%, p<0.001) and high grade UC (83.1% vs 74.0%, p=0.023).

532\xa0nm green-light laser vaporization of upper tract urothelial carcinoma

BackgroundEndoscopic management of low risk upper tract urothelial carcinoma (UTUC) may be considered in select clinical scenarios, which allows sparing the morbidity of radical nephroureterectomy while achieving acceptable oncological outcomes and preservation of kidney function. Herein, we present a case with UTUC in a solitary kidney managed with 532 nm laser vaporization through a percutaneous approach.Case presentationThe patient in this video (Additional file 1) is an 85-year-old woman who presented with a bulky tumor in the collecting system of a congenital solitary left kidney, which was a biopsy proven low grade urothelial carcinoma. Prior to the procedure, a lower pole percutaneous nephrostomy tube was successfully placed under sedation by Interventional Radiology. The procedure was done in a prone split leg position. The mass, which was predominantly localized to the renal pelvis was efficiently vaporized with the 532 nm laser in a systematic manner with continuous irrigation of normal saline through the cystoscope. The patient was discharged home on postoperative day 2 with the nephroureterostomy catheter open to drainage. This catheter was subsequently clamped and removed two weeks later without complications. Follow up uretroscopy showed excellent treatment response and the patient remains well without complications.ConclusionThis case report details the potential utility of 532 nm laser vaporization of UTUC, however, ongoing studies are required to demonstrate peri-operative safety and durable oncologic efficacy.

Cytologically targeted next-generation sequencing: a synergy for diagnosing urothelial carcinoma

Cytology and cystoscopy are used to detect urothelial carcinoma (UC), but together they still fail to detect some UC cases and are not suitable for screening asymptomatic individuals. Mutations are present in more than 98% of UC, mutations have therapeutic significance, and they can be detected by next generation sequencing (NGS) in urine samples. We review the role of NGS in UC detection. Comprehensive literature review on UC genetics, economics of NGS, and previous reports of UC detection by NGS. The raw costs of NGS have decreased to about 14,000 base pairs per penny, making it appear economically feasible to use NGS widely. Reported NGS assays fall short of predicted sensitivity. Decreased sensitivity is attributed to a low frequency of mutant alleles in many urine samples. Attempts to increase the percentage of mutant alleles, by using cell-free urinary DNA, or by using cell sorting and microfluidics, have been unsuccessful or remain unproven. However, cytologic examination can immediately enable NGS: Urine cytologies with sufficient proportions of abnormal cells could be directly triaged to NGS with high sensitivity for UC detection. For cases with a low proportion of abnormal cells, cytologically targeted microdissection of cells for NGS should maintain sensitivity and decrease sequencing costs. Cytologically targeted urothelial cells for NGS could allow a screening test for low grade UC. Cytology is immediately poised to allow NGS to improve the diagnosis of UC, allowing NGS to be an ancillary test for atypical cytologies, and potentially allowing a screening test for low-grade UC.

Urinary tract cytology: a cytologic-histopathologic correlation with The Paris System, an institutional study

Urothelial carcinoma (UC) requires lifelong monitoring, commonly through urinary cytology and cystoscopy. Urine cytology has a relatively high sensitivity for detecting high-grade urothelial carcinoma (HGUC); however, its sensitivity for low-grade urothelial neoplasm (LGUN) is significantly lower with wide interobserver variability. The Paris System (TPS) was proposed to create standardized diagnostic categories with defined cytomorphologic criteria. We attempt to evaluate diagnostic efficacy of identifying UC using TPS through cytologic-histologic correlation. A retrospective search identified 170 cases of urine cytology cases with concurrent biopsies collected during a 2-year time period at University of Rochester Medical Center. Patient age, sex, smoking history, prior malignancy diagnoses, cystoscopy findings, specimen collection method, UroVysion results, and 1-year follow-up of surgical pathology cases were included. Cytologic-histologic correlation was identified in 59% of cases, with 18% true positives and 41% true negatives. Discordant results were identified in 41% of cases; of these, 4% were false positives, 11% false negatives, 12% potential sampling bias, and 14% were low-grade urothelial carcinoma (LGUC). The analysis of this 2-year study finds a positive predictive value of urine cytology for HGUC to be 81%, a negative predictive value of 79%, a sensitivity of 61%, a specificity of 91%, and an accuracy of 79%. Our results support TPS's ability to improve the reliability and accuracy of interpretations in urine cytology for HGUC. Nevertheless, additional studies are essential to improve the diagnostic accuracy of LGUN, and urine adequacy, in order to improve patient care and early detection, while identifying potential sampling bias.

Developing a Machine Learning Algorithm for Identifying Abnormal Urothelial Cells: A Feasibility Study

Introduction: Urine cytology plays an important role in diagnosing urothelial carcinoma (UC). However, urine cytology interpretation is subjective and difficult. Morphogo (ALAB, Boston, MA, USA), equipped with automatic acquisition and scanning, optical focusing, and automatic classification with convolutional neural network has been developed for bone marrow aspirate smear analysis of hematopoietic diseases. The goal of this preliminary study was to determine the feasibility of developing a machine learning algorithm on Morphogo for identifying abnormal urothelial cells in urine cytology slides. Methods: Thirty-seven achieved abnormal urine cytology slides from cases with the diagnosis of atypical urothelial cells and above (suspicions or positive for UC) were obtained from 1 hospital. A pathologist (J.R.) reviewed the slides and manually selected and annotated representative cells to feed into Morphogo with following categories: benign (urothelial cells, squamous cells, degenerated cells, and inflammatory cells), atypical cells, and suspicious cells. Initial validation of the algorithm was performed on a subset of the original 37 cases. Urine samples from additional 12 unknown cases with various histological diagnoses (6 cases of high-grade urothelial carcinoma (HGUC), 1 case of low-grade urothelial carcinoma (LGUC), 1 case of prostate adenocarcinoma, 1 case of renal cell carcinoma, and 4 cases of non-neoplastic conditions) were collected from another hospital for initial blind testing. Results: A total of 1,910 benign and 1,978 abnormal (atypical and suspicious) cells from 37 slides were annotated for developing and training of the algorithm. This algorithm was validated on 27 slides that resulted in identification of at least 1 abnormal cell per slide, with a total of 200 abnormal cells, and an average of 7.4 cells per slide. Of the 12 unknown cases tested, the original cytology was positive for tumor cells in 2 HGUC samples. Morphogo was abnormal (atypical or suspicious) for 6 samples from patients with UC, including one with LGUC and one with prostate adenocarcinoma. Conclusion: Morphogo machine learning algorithm is capable of identifying abnormal urothelial cells. Further validation studies with a larger number of urine samples will be needed to determine if it can be used to assist the cytological diagnosis of UC.

Complications Associated With Ureteroscopic Management of Upper Tract Urothelial Carcinoma

ObjectivesTo compile and examine safety data from clinical studies of endoscopic management of patients with low-grade upper tract urothelial carcinoma (UTUC) to identify rates and factors associated with reported complications. MethodsOvid Medline and Ovid Medline Daily (with Embase as secondary search) including citations from 1946-2018 were queried using the following terms: ureteroscopy, ureter, catheter, endoscopy, complication, adverse events, morbidity, ablation, laser, upper tract urothelial carcinoma, ureteral stricture, ureteral stenosis, and ureteral injury. Abstracts were reviewed for relevance; diagnostic studies, case studies, and reviews were excluded. ResultsThirty-eight publications (7 prospective, 31 retrospective) representing >1100 patients were identified. Ureteral stricture was the most frequently reported complication (studies; rates) (26/38; 0-27%), with incidence associated with number of procedures and treatment method. Bleeding, infection, and fever were most common with adjuvant treatment (BCG or mitomycin). Serious and fatal complications were rare. ConclusionsUreteral stricture is the most frequent complication of endoscopic UTUC management but can be managed successfully in most cases. Most complications were minor. Although additional prospective studies are needed, these results support the safety of ureteroscopic management of UTUC in appropriately selected patients.

Prognostic Implications of Deep Muscle Invasion and High Grade for Bladder Urothelial Carcinoma.

IntroductionUrothelial carcinoma (UC) is the most common bladder cancer. The most censorious pathological aspect of UC is deep muscle invasion and tumor grade. In this study, we assessed the prognostic implications of tumor grade and deep muscle invasion in UC.MethodsIt was a retrospective cross-sectional study conducted at the Department of Histopathology, Liaquat National Hospital, from July to December 2019. The data were collected over five years from January 2014 till December 2018. Records from archives of the anatomic pathology were searched, clinical characteristics were recorded, and histopathological slides were reviewed. Histological parameters, including tumor grade and muscle invasion, were evaluated. Records of patient follow-up were assessed by reviewing clinical records. Recurrence of UC and overall survival was also recorded. Multivariate binary logistic regression was applied for variables that were significant on univariate logistic regression. Survival analysis was performed using the Kaplan-Meier method.ResultsThe mean age of the patients was 63.39 ± 14.1 years. More than half (53%) cases were of low-grade papillary UC. Disease recurrence was observed in 53 (39.1%) patients, whereas the mortality rate was 16.6%. In our study, 49 (32.5%) patients were found to have deep muscle invasion. By multivariate analysis, we found that the deep muscle invasion was significantly associated with male gender and grade. In addition, a significant association of high-tumor grade with survival status of the patients was noted.ConclusionsA high proportion of UC cases in our study were found to have deep muscle invasion and high-tumor grade. Moreover, a significant association of deep muscle invasion with tumor grade and an association of tumor grade with survival signify the prognostic value of these factors in UC.

Reappraisal of the papillary urothelial neoplasm of low malignant potential (PUNLMP).

Although the papillary urothelial neoplasm of low malignant potential (PUNLMP) diagnostic category was retained in the updated 2016 World Health Organisation (WHO) classification of tumours of the urinary system, there still exists a great deal of controversy regarding the biological behaviour of these tumours. We review PUNLMP tumours and histological grading with an emphasis on the histomorphological, genetic and clinical similarities between PUNLMP and low-grade non-invasive papillary urothelial carcinoma. A literature search using PubMed was performed. All relevant literature concerning PUNLMP and the grading of urothelial tumours was reviewed. PUNLMPs cannot be reliably distinguished from low-grade non-invasive papillary urothelial carcinomas based on the histomorphological criteria outlined in the WHO 2004/2016 classification system. PUNLMPs and low-grade non-invasive papillary urothelial carcinomas are not only morphologically similar, but also share similar molecular genetic alterations and a similar risk of recurrence and progression. In addition, there are no consensus recommendations for a different method of treatment and follow-up for these two tumour types. Attempting to distinguish PUNLMP from low-grade papillary urothelial carcinoma adds an unnecessary level of complexity to the grading and classification of urothelial tumours. We feel that PUNLMP terminology should be abandoned and that all such tumours should be classified as low-grade carcinomas until more objective determinants of clinical outcome can be established.

Assessing the Impact of the Absence of Detrusor Muscle in Ta Low-grade Urothelial Carcinoma of the Bladder on Recurrence-free Survival

BackgroundObtaining detrusor muscle (DM) in transurethral resection of bladder tumor (TURBt) specimen is considered a surrogate marker of resection quality. However, evidence was principally investigated in high-risk tumors. Therefore, DM sampling for low-grade (LG) urothelial carcinoma (UC) remains poorly investigated and certainly requires further investigation. ObjectiveTo assess whether the absence of DM in TURBt specimen has a negative impact on recurrence-free survival (RFS) in patients with a Ta LG UC. Design, setting, and participantsA multicenter TURBt database was queried for “LG, Ta, UC of the bladder.” All patients treated between 1996 and 2018 with tumor grade assessed according to both 1973 World Health Organization and 2004 WHO/International Society of Urological Pathology grading classifications and with a minimum follow-up of 1 yr were included. Patients with a previous history of high-grade UC, upper urinary tract UC, or bladder tumor differentiations other than UC were excluded. InterventionTURBt. Outcome measurements and statistical analysisBaseline demographic, clinical, and pathologic data were analyzed. The European Organization for Research and Treatment of Cancer (EORTC) risk group was recorded. Kaplan-Meier analysis was performed to assess the predictive role of clinical and pathologic data for RFS. Univariable and multivariable Cox regression analyses were performed to identify the predictors of recurrence. Results and limitationsOverall, 521 patients were included. At Kaplan-Meier analysis, the low-risk cohort displayed significantly higher RFS than the intermediate-risk cohort (1-yr RFS 87% vs 79%; log-rank p = 0.007). At univariable Cox regression analysis, only gender, multiple tumors, tumor diameter ≥3 cm, and EORTC risk group were significant predictors of recurrence. Absence of DM had no impact on RFS. Multivariable Cox regression analysis confirmed gender and EORTC risk group as independent predictors of recurrence. ConclusionsAbsence of DM in TURBt specimen has negligible role in RFS of patients with Ta LG tumors of the bladder. Patient summaryIn this study, we assessed the role that detrusor muscle (DM) in transurethral resection of bladder tumor specimen has in recurrence-free survival, in patients with a Ta low-grade urothelial carcinoma of the bladder. Absence of DM has no impact on tumor recurrence; therefore, it does not require additional attention.

Imaging in gynecological disease (18): clinical and ultrasound characteristics of urinary bladder malignancies.

To describe the clinical and ultrasound characteristics of urinary bladder malignancies diagnosed on transvaginal ultrasound in women presenting with suspected gynecological problems. This was a multicenter retrospective study of women with a histological diagnosis of urinary bladder malignancy that was suspected on transvaginal ultrasound examination. The cases were collected from three centers that specialize in the use of pelvic ultrasound and had been examined between January 2007 and October 2018. Clinical data were obtained from the computer databases and all tumor images were assessed by two of the authors (D.J. and J.K.) to identify characteristic sonographic patterns. We compared the characteristics of tumors between women presenting with symptoms suspicious of urinary bladder malignancy and those without such symptoms. Thirty women with a confirmed diagnosis of urinary bladder malignancy on histological examination were included. Median age at diagnosis was 70.5 (range 36-88) years. The most common presenting symptom was postmenopausal bleeding, which was recorded in 18 (60%) women. Ten (33%) women had symptoms suspicious of bladder malignancy, of whom six had unexplained visible hematuria, three had unexplained recurrent urinary tract infections and one had dysuria and microhematuria. On histological examination, 23 (77%) women were diagnosed with primary bladder malignancy whilst seven (23%) had metastases in the bladder from other primary tumors. Out of 23 primary tumors, 21 (91%) were of urothelial origin (12 low grade and nine high grade). Most low-grade urothelial carcinomas appeared on ultrasound as irregular papillary growth (11/12, 92%) and were moderately to highly vascular on color Doppler examination (8/12, 67%). The ultrasound appearances of primary non-urothelial and metastatic tumors varied, without a clear common morphological tumor pattern. The tumors found in women with symptoms suggestive of bladder malignancy did not differ unequivocally from those detected in other women in terms of size, ultrasound morphology, vascularity or histological type. Urinary bladder malignancies can be detected in patients undergoing transvaginal ultrasound examination for suspected gynecological problems. Primary urothelial cancers have a relatively uniform morphological pattern, whilst the appearances of other bladder malignancies are more variable. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.