Bladder Biopsies Research Articles

Histopathologic Patterns of Urinary Bladder Lesions and Associated Factors in Hawassa University Comprehensive Specialized Hospital, Sidama Region, Ethiopia

Background: Urinary bladder lesions, non-neoplastic and neoplastic, are collectively responsible for significant morbidity and mortality throughout the world. Bladder cancer is a prevalent disease affects a significant number of individuals each year worldwide. The most common non-neoplastic and neoplastic lesion of the urinary bladder is non-specific cystitis and urothelial carcinoma respectively. Objectives: The aim of this study is to describe histopathologic patterns of urinary bladder lesions and associated risk factors in Hawassa University Comprehensive Specialized Hospital from January 2017 to December 2023. Methods: A 7-year cross sectional study was conducted to describe histologically diagnosed bladder lesions and associated factors at Hawassa University Comprehensive Specialized Hospital from January 2017 to December 2023. Results: This study comprised a total of 182 patients who have bladder biopsies at Hawassa University Comprehensive Specialized Hospital, Pathology department from January 2017 to December 2023. Out of which 21 cases (12.1%) are non-neoplastic, while 152 cases (83%) are neoplastic. Nine cases (4.9%) have a descriptive diagnosis. With 139 (90.44%) cases, urothelial neoplasms have the highest frequency form all neoplastic lesions. Ninety-seven cases, or 69.8%, of urothelial neoplasms were invasive; of them, 78 (80.4%) were high grade cases. Low-grade noninvasive papillary carcinomas, which accounted for 24 instances. One case is a cystectomy specimen, and the remaining 181 cases are TURBT. The age range of 50-59 years was the most frequent accounting for 39 (21.4%) of all cases, with a male to female (M: F) ratio of 2.9:1. The most frequent presenting symptom in 146 (85.7%) of patients was hematuria. Conclusions: This study demonstrates that 139 (90.44%) of the neoplastic bladder lesions were bladder neoplasms of urothelial origin, 97 (69.8%) of which are invasive urothelial carcinoma with rising numbers each year and implying the burden in the region.

Understanding the long‐term impact of the COVID‐19 pandemic on non‐muscle‐invasive bladder cancer outcomes: 12‐Month follow‐up data from the international, prospective COVIDSurg Cancer study

AbstractObjectiveThe objective of this study was to report the 12‐month oncological outcomes for patients with non‐muscle‐invasive bladder cancer (NMIBC) within the prospective, international COVIDSurg Cancer study.Patients and methodsEligible patients were aged ≥18 years and scheduled for elective surgical management of NMIBC with curative intent (transurethral resection of bladder tumour [TURBT] or bladder biopsy) from 21 January to 14 April 2020. The primary outcome was disease recurrence within 12 months of previous elective TURBT/bladder biopsy. Secondary outcomes included disease progression within 12 months of previous elective TURBT/bladder biopsy, site‐declared delay to surgery from diagnosis as a consequence of COVID‐19 and deviation in standard care due to COVID‐19. Comparisons were made to cohorts from the pre‐pandemic era.ResultsBladder cancer accounted for 2.2% (n = 446) of patients in the COVIDSurg Cancer study, with data contributed by 27 centres across 12 countries internationally. Within this included cohort, 229 patients had NMIBC and 12‐month follow‐up data available. On application of National Institute for Health and Care Excellence (NICE) criteria, 47.2% were classified as having high‐risk disease. Overall disease recurrence and progression rates were 29.3% and 9.7% at 12 months, respectively. In purely high‐risk pre‐pandemic cohorts, the International Bladder Cancer Group (IBCG) estimates a recurrence rate of 25% at 12 months, and the European Association of Urology (EAU) NMIBC 2021 scoring model estimates a 12‐month progression rate of 3.5%. As a consequence of the COVID‐19 pandemic, 10.9% of patients had site‐declared delay to TURBT/bladder biopsy; 7.4% did not undergo intravesical therapy or had early discontinuation of this; 9.2% did not undergo early repeat resection for high‐risk disease; and 18.3% had a delay to cystoscopic follow‐up surveillance.ConclusionsThis prospective study indicates that there were widespread deviations in usual care for NMIBC during the pandemic and that 12‐month oncological outcomes appear to be impaired compared to published pre‐pandemic outcomes.

Modulation of the tumor microenvironment in non-muscle-invasive bladder cancer by OncoTherad® (MRB-CFI-1) nanoimmunotherapy: effects on tumor-associated macrophages, tumor-infiltrating lymphocytes, and monoamine oxidases.

Non-muscle-invasive bladder cancer (NMIBC) presents management challenges due to its high recurrence rate and a complex tumor microenvironment (TME). This study investigated the effects of OncoTherad® (MRB-CFI1) nanoimmunotherapy on the TME of BCG-unresponsive NMIBC, focusing on alterations in monoamine oxidases (MAO-A and MAO-B) and immune markers: CD163, FOXP3, CD8, and CX3CR1. A comparative analysis of immunoreactivities was made before and after OncoTherad® treatment and an immune score (IS) was established to evaluate the correlation between immunological changes and clinical outcomes. Forty bladder biopsies of twenty patients were divided into 2 groups (n = 20/group): 1 (pre-treatment biopsies); and 2 (post-treatment biopsies). Our results showed stable MAO-A levels but a significant (p < 0.05) decrease in MAO-B immunoreactivity after treatment, suggesting OncoTherad®'s efficacy in targeting the tumor-promoting and immunosuppressive functions of MAO-B. Significant (p < 0.05) reductions in CD163 and FOXP3 immunoreactivities were seen in post-treatment biopsies, indicating a decreased presence of M2 macrophages and Tregs. Corroborating with these results, we observed reductions in tumor histological grading, focality and size, factors that collectively enhanced recurrence-free survival (RFS) and pathological complete response (PCR). Moreover, elevated IFN-γ immunoreactivities in treated biopsies correlated with increased counts of CD8+ T cells and higher CX3CR1 expression, underscoring OncoTherad®'s enhancement of cytotoxic T cell functionality and overall antitumor immunity. The IS revealed improvements in immune responses post-treatment, with higher scores associated with better RFS and PCR outcomes. These findings validate OncoTherad®'s capability to modify the bladder cancer microenvironment favorably, promoting effective immune surveillance and response.

Impact of Age, Period, Cohort, Region, Race, and Health Services on Bladder Cancer Mortality in Brazil: A 23-Year Ecological Study.

Bladder cancer is one of the most economically costly types of cancer, but few studies have evaluated its mortality considering the factors that impact this outcome. This study aimed to investigate the impact of sociodemographic factors, period, cohort, and health services on bladder cancer mortality. This ecological study analyzed bladder cancer mortality data in Brazil from 2000 to 2022 and evaluated sociodemographic variables (race, region of residence), socioeconomic variables (gross domestic product per capita, Gini index of household income per capita, number of health professionals per inhabitant, expenditure on public health services, and consultations per inhabitant), and bladder cancer diagnosis and treatment procedures. These data were subjected to statistical analysis, which revealed that after the age of 50, there was a progressive increase in the risk of bladder cancer. Indigenous people had the lowest mortality rate, while white people had a significantly greater mortality rate than black and brown people. The North Region and Northeast Region presented the lowest mortality rates, whereas the South Region presented the highest mortality rates. In the South and Southeast Regions, a higher GDP was related to lower mortality. In the South, higher mortality was associated with a lower number of consultations per inhabitant per region. Fewer bladder punctures/aspirations and bladder biopsies were associated with higher mortality rates. In oncology, more procedures, such as total cystectomy, cystoenteroplasty, and total cystectomy with a single shunt, do not reduce the mortality rate. These results can serve as guidelines for adjusting public health policies.

Eosinophilic cystitis-an obscure case of obstructive uropathy in infancy.

We report on an infant with features of intermittent obstructive uropathy, acute kidney injury, hypertension and type 4 renal tubular acidosis (RTA) despite urethral catheterisation and fluid resuscitation. Radiological findings showed upper tract dilatation, likely bilateral vesicoureteric junction obstruction and bladder base thickening which was concerning for possible malignancy. Renal biopsy demonstrated eosinophilic infiltrate, suggestive of kidney involvement. Bladder biopsy was diagnostic for eosinophilic cystitis (EC) showing mature degranulating eosinophils. EC is a rare, easily treatable and important differential of bladder mass in children which may present with an atypical obstructive uropathy. This report adds to the limited literature of this condition within the paediatric population. EC should be considered early in children presenting with eosinophilia, urinary tract obstruction and kidney dysfunction, with uncertain aetiology. This case also highlights the need for detailed imaging, including visualisation of the bladder base, in cases of likely obstructive uropathy.

Mitochondrial viability in neurogenic bladder urothelium after sigmoidocolocystoplasty. Implications for persistent vesicoureteral reflux.

We investigated whether inflammatory cell infiltration (ICI), fibrosis, and mitochondrial viability of the neurogenic bladder urothelium are involved in the mechanism of persistent vesicoureteral reflux (VUR) after sigmoidocolocystoplasty (SCP). Bladder biopsies obtained 1994-2023 from 62 neurogenic bladder patients were examined by hematoxylin and eosin for ICI, Masson's trichrome for fibrosis, and immunofluorescence for urothelial growth differentiation factor 15 (GDF15; a mitochondrial stress-responsive cytokine) (positive/negative) and heat shock protein 60 (HSP60; a mitochondrial matrix marker) (strong ≥ 50%/weak≤ 50%) expression. GDF15 + /weak HSP60 indicated compromised mitochondrial viability. Cystometry measured neobladder compliance/capacity. Mean ages (years) at SCP and bladder biopsies were 9.4 ± 4.6 and 14.2 ± 7.1, respectively. VUR was present in 38/62 patients (51 ureters) at SCP and resolved with SCP alone in 4/38 patients, with SCP and ureteroneocystostomy in 17/38, and persisted in 17/38. Fibrosis was significantly denser in GDF15 + (n = 24)/weak HSP60 (n = 31) compared with GDF15- (n = 38)/strong HSP60 (n = 31) (p < 0.001 and p < 0.01, respectively). Differences in ICI were significant for GDF15 + vs. GDF15- (p < 0.05) but not for HSP60. Patients with VUR after SCP had higher incidence of GDF15 + /weak HSP60 compared with cases without VUR (p < 0.05 and p < 0.001, respectively). Viability of mitochondria appears to be compromised with possible etiologic implications for VUR persisting after SCP.

Retrospective review of bladder biopsy instead of skin biopsy provided clue for the diagnosis of neuronal intranuclear inclusion disease.

The purpose of this study is to present a case of a patient with a negative skin biopsy who was diagnosed with neuronal intranuclear inclusion disease (NIID) through a retrospective review of a bladder biopsy specimen obtained 10 years ago. The patient initially presented with encephalitis-like symptoms, including fever, headache, and abnormal mental behavior. However, the DWI hyperintensity in the corticomedullary junction indicated the possibility of NIID. Due to the negative results of the skin biopsy, we initially refrained from hastily diagnosing the patient with NIID. However, 6 months later, the patient was readmitted to the hospital due to similar symptoms, and a follow-up MRI showed significant enlargement of the lesions at the corticomedullary junction. This time we identified intranuclear inclusions in her tissue specimens from bladder surgery. Subsequently, genetic testing was performed, leading to the diagnosis of NIID in the patient. Our case report indicates that detecting intranuclear inclusions from previous surgical specimens, rather than relying solely on skin biopsy, could significantly enhance diagnostic methods for NIID.

Comparison of Interobserver Variability Between Two Grading Systems Used for Urothelial Carcinoma

Background: Inter-observer variability among pathologists' reports has been a significant challenge in the diagnosis of diseases, especially cancers. Designing a grading system with minimal inter-observer variability can help achieve more accurate diagnoses. Objectives: We aimed to determine whether the grading system proposed by Cheng and colleagues (Cheng’s grading system) can improve inter-observer variability among pathologists in grading urothelial cancer, compared with the World Health Organization (WHO) grading system (2004/2016). Methods: Four pathologists examined all slides of bladder biopsy samples diagnosed as urothelial carcinoma, available in the archives of Imam Reza Hospital, Mashhad, Iran, from 2019 to 2022. Each pathologist reported the tumor grade based on both grading systems, independently of previous answers or the reports of their colleagues. Results: Of 132 samples, the majority were from men (84.1%); the mean age of patients was 66.56±11.31 years. For low and high grades of the WHO system and grade II in Cheng’s grading system, κ = 0.602; agreement was lower for grade III (κ = 0.439) and higher for grade IV (κ = 0.690) compared with the WHO grading system. There was significant agreement among the pathologists in all tumor characteristics, with excellent agreement for stromal invasion (κ = 0.790) and muscular invasion (κ = 0.884), fair to good agreement for WHO 2004/2016 grading (κ = 0.602) and Cheng’s grading (κ = 0.574) overall, and poor agreement for tumor heterogeneity (κ = 0.360). Conclusions: Both grading systems demonstrated favorable agreement among pathologists, without significant differences between the two systems. These results confirm the appropriateness of both grading systems.

Histological Spectrum of Urinary Bladder Biopsies with Special Emphasis on Unusual Non-urothelial Tumours

Histological Spectrum of Urinary Bladder Biopsies with Special Emphasis on Unusual Non-urothelial Tumours

Urachal Carcinoma: Insights From a National Database

IntroductionUrachal carcinoma (UrC) is a rare, nonurothelial malignancy, comprising less than 1% of all bladder cancers. It usually affects males in their fifth to sixth decade and is often diagnosed at an advanced stage with metastasis. This study examines UrC population characteristics and management. MethodsWe identified UrC patients from bladder biopsies or TURB in the PearlDiver Mariner database (2010-2022). Descriptive statistics detailed patient characteristics. Student's T-Tests compared ages for partial vs. radical cystectomy, and Fisher's exact test compared SDOH presence. Significance was set at P < .05. Analyses used R version 3.6.0 within PearlDiver's software. ResultsAmong 2475 UrC patients (mean age 69.2 ± 9.2 years, 73.1% men), most were in the south (36.5%), outpatient settings (84.5%), and privately insured (65.3%). A total of 418 (16.2%) had at least 1 SDOH. Imaging before diagnosis was used in 65.74% of patients, primarily ultrasound. Smoking was present in 54.5%, diabetes in 42.9%, and obesity in 25.2%. After diagnosis, 1246 (50.34%) had localized disease; 407 underwent radical cystectomy and 330 partial cystectomy. Patients undergoing radical cystectomy were older (66.74 ± 8.13 years) compared to those undergoing partial cystectomy (60.55 ± 12.92 years) (P < .001), with SDOH factors more prevalent in the partial cystectomy group (P = .03). ConclusionUrC is a rare, often advanced-stage cancer predominantly affecting older men. Our study shows a trend towards partial cystectomy for localized UrC. Further research is needed to personalize surgery and integrate multidisciplinary approaches for better outcomes.

Exploring the Histopathological Landscape of Urinary Bladder Diseases: A Tertiary Care Center Study.

Introduction Urinary bladder lesions encompass a wide spectrum, from benign inflammatory conditions to malignant neoplasms, presenting diagnostic and therapeutic challenges. Urothelial carcinoma predominates among bladder malignancies, exhibiting diverse clinical presentations and prognoses. Objective This study aimed to delineate the histopathological spectrum of urinary bladder lesions and correlate demographic profiles, clinical features, and cystoscopic findings with various bladder lesions. Methods This prospective descriptive observational study spanned 24 months at a tertiary care center, involving 65 cases of urinary bladder biopsies, including transurethral resection of bladder tumors, cystoscopic biopsies, and cystectomy specimens. The histopathological examination followed the WHO 2022 classification of urinary bladder tumors and the American Joint Committee on Cancer eighth edition staging. Clinical data, including age, gender, cystoscopic findings, and presenting symptoms, were correlated with histopathological diagnoses to explore the spectrum of bladder lesions. Results Neoplastic lesions predominated, constituting 92.3% of cases, with urothelial carcinoma comprising 83.33% of these cases. Among neoplastic lesions, invasive high-grade urothelial carcinoma (36.7%) and non-invasive low-grade papillary urothelial neoplasm (20.0%) were the most frequently observed subtypes. Non-neoplastic lesions accounted for 7.7%, including various forms of cystitis. Hematuria was the predominant presenting symptom (81.5%), while cystoscopic examinations revealed that most lesions were situated in the lateral bladder wall. High-grade urothelial carcinomas were mostly associated with muscularis propria invasion. Conclusion This study underscores the critical role of histopathological examination in diagnosing and managing urinary bladder diseases and distinguishing between non-neoplastic and neoplastic lesions. Urothelial carcinoma, prevalent among older age groups, often demonstrated muscle invasion indicative of high-grade tumors. Including the muscle layer in cystoscopic biopsies is crucial for an accurate diagnosis. Conversely, though less common, non-neoplastic conditions encompass various forms of cystitis. These findings highlight the importance of precise diagnostic tools such as cystoscopy and histopathological examination for the early detection and management of bladder neoplasms. Histopathological assessment offers essential prognostic guidance, aids in precise staging and grading, and directs tailored treatment strategies.

Bladder-resident bacteria associated with increased risk of recurrence after electrofulguration in women with antibiotic-recalcitrant urinary tract infection.

Antibiotic-recalcitrant recurrent urinary tract infection (rUTI) is has become increasingly observed in postmenopausal women. Therefore, when standard antibiotic therapies have failed, some elect electrofulguration (EF) of areas of chronic cystitis when detected on office cystoscopy. EF is thought to remove tissue-resident bacteria that have been previously detected in the bladder walls of postmenopausal women with rUTI. We hypothesized that increased bladder bacterial burden may be associated with incomplete rUTI resolution following EF. Following IRB approval, bladder biopsies were obtained from 34 consenting menopausal women electing EF for the advanced management of rUTI. 16S rRNA FISH was performed using both universal and Escherichia probes and tissue-resident bacterial load was quantified. Time to UTI relapse after EF was recorded during a six-month follow-up period and the association of bladder bacterial burden and clinical covariates with UTI relapse was assessed. We observed bladder-resident Escherichia in 52% of all participants and in 92% of participants with recent E. coli UTI. Time-to-relapse analysis revealed that women with high bladder bacterial burden as detected by the universal probe had a significantly ( p =0.035) higher risk of UTI within six months of EF (HR=3.15, 95% CI: 1.09-9.11). Interestingly, bladder-resident Escherichia was not significantly associated ( p =0.26) with a higher risk of UTI relapse (HR= 2.14, 95% CI: 0.58-7.90). We observed that total bladder bacterial burden was associated with a 3.1x increased risk of rUTI relapse within six months. Continued analysis of the relationship between bladder bacterial burden and rUTI outcomes may provide insight into the management of these challenging patients.

Rare exonic CELSR3 variants identified in Bladder Exstrophy Epispadias Complex.

Bladder exstrophy epispadias complex (BEEC) is a rare congenital anomaly of unknown etiology, although, genetic and environmental factors have been associated with its development. Variants in several genes expressed in the urogenital pathway have been reported as causative for bladder exstrophy in human and murine models. The expansion of next-generation sequencing and molecular genomics has improved our ability to identify the underlying genetic causes of similarly complex diseases and could thus assist with the investigation of the molecular basis of BEEC. The objective was to identify the presence of rare heterozygous variants in genes previously implicated in bladder exstrophy and correlate them with the presence or absence of bladder regeneration in our study population. We present a case series of 12 patients with BEEC who had bladder biopsies performed by pediatric urology during bladder neck reconstruction or bladder augmentation. Cases were classified as "sufficient" or "insufficient" (n = 5 and 7, respectively) based on a bladder volume of greater than or less than 40% of expected bladder size. Control bladder tissue specimens were obtained from patients (n = 6) undergoing biopsies for conditions other than bladder exstrophy. Whole exome sequencing was performed on DNA isolated from the bladder specimens. Based on the hypothesis of de novo mutations, as well as the potential implications of autosomal dominant conditions with incomplete penetrance, each case was evaluated for autosomal dominant variants in a set of genes previously implicated in BEEC. Our review of the literature identified 44 genes that have been implicated in human models of bladder exstrophy. Our whole exome sequencing data analysis identified rare variants in two of these genes among the cases classified as sufficient, and seven variants in five of these genes among the cases classified as insufficient. We identified rare variants in seven previously implicated genes in our BEEC specimens. Additional research is needed to further understand the cellular signaling underlying this potentially genetically heterogeneous embryological condition.

Chronic schistosomiasis infection and obstetric fistula repair outcomes in Lubango, Angola: A retrospective chart review

AbstractObjectiveTo assess the association between chronic schistosomiasis infection, determined by bladder biopsies, and vesicovaginal (VVF) repair outcomes at an urban hospital in Angola. Other objectives were to quantify the prevalence of chronic schistosomiasis among patients with VVF and to assess agreement between pelvic X‐rays and bladder biopsies for chronic schistosomiasis diagnosis.MethodsIn this retrospective chart review, data were collected on patients who underwent VVF repair between 1 June 2022 and 30 November 2022 including: age, number of previous fistula repairs, Goh classification of fistula, X‐ray and biopsy results, fistula repair outcome, perioperative complications and postoperative incontinence. Age and number of previous repairs were described using means with standard deviations. Goh classification, X‐ray and biopsy results, fistula repair outcome, perioperative complications, and postoperative incontinence were described using frequencies. Parametric and nonparametric tests and Cohen's κ were calculated using R software and Excel.ResultsOf the 76 charts retrieved, 60 met inclusion criteria. The overall fistula repair failure rate was 26.7% (n = 16). There was no difference in the fistula repair failure rate between those with (26.9%) and without (26.5%) evidence of chronic schistosomiasis infection (χ2 = 2.33 e‐31, 95% confidence interval [CI]: −0.30, 0.28). The prevalence of chronic schistosomiasis was 43.3%. There was no agreement between X‐ray and biopsy in diagnosing chronic schistosomiasis infection (Cohen's κ = 0.23, 95% CI: −0.001, 0.47).ConclusionThere was no difference in the chance of fistula repair failure between those with evidence of chronic schistosomiasis infection and those without.

Antitumor mechanisms of OncoTherad (MRB-CFI-1) nanoimmunotherapy involving monoamine oxidases: Clinical implications in BCG-unresponsive non-muscle invasive bladder cancer.

e14597 Background: Bacillus Calmette-Guérin (BCG) immunotherapy has been the gold standard treatment for non-muscle invasive bladder cancer (NMIBC) for nearly half a century. However, many high-risk patients experience recurrence, including those who progress and eventually become unresponsive to BCG. The emergence of new immunotherapeutic agents has revolutionized the treatment of various tumor types, including urothelial carcinoma. In this context, our research group has developed OncoTherad (MRB-CFI-1) immunotherapy, which has shown promising results in cancer treatment, particularly in NMIBC. Given the inherent complexity of the immune response, patient selection and the development of biomarkers to guide the identification of individuals who will derive the greatest benefit from a specific immunotherapy remain crucial. Over the past years, several studies have demonstrated the upregulation of monoamine oxidases (MAOs) in tumor progression and metastasis. Therefore, the objectives of this present study were to characterize the effects of OncoTherad (MRB-CFI-1) on the modulation of MAOs (MAO-A and MAO-B) in the bladder of patients with BCG-unresponsive NMIBC. Methods: A total of 40 bladder biopsies from patients with BCG-unresponsive NMIBC treated with OncoTherad (MRB-CFI-1) were collected and analyzed from Paulínia Municipal Hospital (HMP). These samples were then divided into two groups (n=20 per group): Group 1 (biopsy before OncoTherad treatment) and Group 2 (biopsy after OncoTherad treatment). Subsequently, the samples underwent immunohistochemical analyses for MAO-A and MAO-B. The retrospective anonymous study was approved by the local ethics committee (Clinical Trial: RBR-6swqd2). Results: Our results demonstrated high immunoreactivities for both MAO-A and MAO-B in the bladder tumor microenvironment prior to OncoTherad (MRB-CFI-1) treatment, confirming that the pattern reported in literature studies can also be observed in NMIBC. Total immunoreactivities for MAO-A did not differ statistically between bladder biopsies of Groups 1 and 2, indicating that this treatment does not interfere with the action of MAO-A in bladder tissue. In contrast, immunoreactivities for MAO-B were significantly lower (p&lt;0.05) in the Group 2 when compared to Group 1 suggesting that this immunotherapy reversed the immunosuppressive state and tumor progression induced by MAO-B. Conclusions: Taken together, our results support the use of MAO-B as a biomarker for clinical response to OncoTherad (MRB-CFI-1) immunotherapy.

A case report of urogenital schistosomiasis

Schistosomiasis, a parasitic disease widespread in tropical regions, is primarily caused by Schistosoma haematobium. Although rare in Western countries like France, it remains a major public health issue. Diagnosis relies on detecting the parasite's eggs in urine and bladder biopsies. Prevention involves awareness campaigns, annual treatment with praziquantel in high-prevalence areas, and treatment of infested waters. The case of a 17-year-old Senegalese girl presenting with lower urinary tract symptoms (LUTS) was reported. Analyses revealed the presence of schistosomiasis eggs in her urine. After treatment with praziquantel and corticosteroids, she developed acute urinary retention requiring catheterization. Further examinations confirmed urogenital schistosomiasis, necessitating surgical intervention.

Abstract IA007: Tumor HLA-E expression and cytomegalovirus infection modulate NK cell activity in human bladder cancer

Abstract The intersection of viral infections and cancer therapy presents a complex landscape for immunotherapy strategies, particularly in solid tumors, where treatments such as systemic chemotherapy and targeted radiation are standard. Largely unexplored in solid tumors are the effects of human herpes virus-5 (HHV-5) also known as HCMV that imprints both lifelong effects on natural killer (NK) cells as well progressive effects on T cells with aging. HCMV is an extremely successful virus as it rarely kills the host outside of settings of compromised immunity, e.g. transplantation and advanced HIV-1 infection. HCMV is not considered a comorbidity in patients with solid tumors. Our group has identified reactivated cytomegalovirus (HCMV), found in bladder tissues post treatment, including infection of monocytes, fibroblasts, and even tumor cells, suggesting a viral influence that extends beyond traditional perspectives on cancer treatment resistance and response. We have observed spread of infection in both settings of BCG-treated non-muscle-invasive bladder cancer (NMIBC) as well as MIBC treated with gemcitabine and cisplatin chemotherapy. HCMV infection leads to the development of “adaptive” NK cells that express the activating isoform of NKG2A: NKG2C, which are likely expanded in response to HCMV reactivation and have established functions for controlling virus reactivation. Our central hypothesis is that certain treatments may reactivate HCMV, potentially greatly altering the biology within the tumor microenvironment (TME) and providing a framework to exploit NK cells for immunotherapy strategies. In a cohort of NMIBC patients (N=90) receiving BCG therapy at Mount Sinai, we profiled patients’ serum for HCMV-IgG (N=47 HCMV seropositive; N=43 HCMV seronegative) and observed a significantly improved recurrence-free survival in HCMV seropositive patients (HR=0.58, p=0.03). Further, HCMV-seropositive patients with circulating NKG2C+ adaptive NK cells experienced a near perfect response to BCG therapy (p=0.0002). Strikingly, in situ imaging and RNAscope analyses of patient tumors before and after BCG therapy revealed strong presence of active viremia in tumors. Further, analysis of on-treatment bladder biopsies after tumor resection demonstrated the presence of adaptive NK cells in HCMV+ bladder tissues, but only after exposure to BCG therapy and tissue-derived adaptive NK cells expressed high levels of chemokine receptors, CXCR3 and CXCR4 as well as tissue-residency markers, suggesting a mechanisms for trafficking to the bladder and taking up residence for subsequent antitumor control against recurrence. Impact and Translation: Our findings suggest that adaptive NK cells mediate response to immunotherapies for solid tumors as well as provide preclinical models for adoptive transfer therapies targeting NK cells. Additionally, if HCMV reactivation is widespread across solid tissues in response to systemic therapies, it may prove a critical comorbidity to consider in design of treatment strategies and in clinical trials. Citation Format: Amir Horowitz. Tumor HLA-E expression and cytomegalovirus infection modulate NK cell activity in human bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr IA007.

Localized Urinary Bladder Amyloidosis as Urothelial Cancer Mimicker.

Localized amyloidosis of the bladder is rare and often mimics bladder malignancy. It is typically associated with the extracellular deposition of monoclonal light chains, either κ or λ. The cause is unknown, but it is thought to be due to chronic inflammation/cystitis. To highlight the importance of localized urinary bladder amyloidosis as a rare mimicker of urothelial malignancy and elucidate its clinical, histopathologic, and cytopathologic manifestations. Cases of urinary bladder amyloidosis diagnosed during 2000-2023 were retrieved retrospectively from pathology archives. Electronic medical records, including cystoscopy findings and pathology slides including Congo red stain, were reviewed. Here we present 6 patients with localized urinary bladder amyloidosis. Four of the 6 patients were women, with ages ranging from 46 to 69 years, and a mean age of 58 years. Five of 6 patients presented with hematuria, while in 1 patient, bladder amyloidosis was discovered incidentally. Cystoscopy findings invariably were concerning for malignancy, with raised erythema in 5 patients and fungating mass protruding into the bladder lumen in 1 patient. Bladder biopsies and urine cytology were negative for malignancy in all cases. Congo red-positive amyloid deposits involved lamina propria with sparing of the detrusor muscle. In 5 cases, the deposits were typed as derived from the λ light chain, whereas no information was available for 1 patient. Subsequent clinical workup ruled out systemic amyloidosis. These cases of urinary bladder amyloidosis highlight the importance of considering rare amyloidosis in the differential diagnosis of hematuria and cystoscopy with a lesion mimicking malignancy.

Practical application of the Paris system for reporting urinary cytology

Objective: To validate the diagnostic performance of the Paris system for reporting urinary cytology (TPS). Methods: A total of 7 046 urine cytology samples from 3 402 patients collected in the Department of Pathology, Beijing Hospital, China from January 2020 to January 2022 were analyzed. 488 patients had a biopsy or resection specimen during the follow-up period of 6 months. The sensitivity, specificity, risk of malignancy (ROM) and risk of high-grade malignancy (ROHM) of the TPS were evaluated using histological diagnosis as the golden standard. Results: Among the 7 046 samples, high-grade urothelial carcinoma (HGUC) accounted for 5.7% (399/7 046), suspicious for high-grade urothelial carcinoma (SHGUC) for 3.2% (227/7 046), atypical urothelial cells (AUC) for 8.4% (593/7 046), and negative for high-grade urothelial carcinoma (NHGUC) for 72.9% (5 139/7 046) including low-grade urothelial neoplasm (LGUN) for 0.8% (59/7 046) and insufficient samples for 9.8% (688/7 046). 488 patients had a bladder biopsy or resection in the follow-up of six months, including 314 males and 174 females, aged 27 to 92 years (average, 66 years). The ROHM of TPS was 94.7% in HGUC, 83.3% in SHGUC, 41.3% in AUC and 18.8% in NHGUC. The sensitivity and specificity of urine cytology were 70.1% (169/241) and 97.0% (162/167), respectively. The negative predictive value of NHGUC was 69.2% (162/234). Conclusions: The study has shown that TPS classification has high sensitivity and specificity, high ROHM for HGUC and SHGUC, and high negative predictive value for NHGUC. The application of TPS reporting system can better interpret the clinical significance of cytology samples, improve the accuracy of urine cytopathology and ensure continuous diagnostic consistency.

Innervation pattern of the unclosed detrusor muscle in classic bladder exstrophy: a study of patients with urothelial overexpression of nerve growth factor

PurposeAn overexpression of nerve growth factor (NGF) in the urothelium is discussed to lead to neuronal hyperinnervation of the bladder detrusor. The aim was to assess the sensory and sympathetic innervation of the detrusor in unclosed exstrophic bladders patients with known overexpression of NGF in the urothelium.MethodsFull-thickness bladder biopsies were prospectively obtained from 34 infants at delayed primary bladder closure between 01/2015 and 04/2020. The bladder biopsies were immunohistochemically stained with antibodies against S100, calcitonin gene-related peptide (anti-CGRP), Neurofilament 200 (anti-NF200), and tyrosine-hydroxylase (anti-TH). Specimens from 6 children with congenital vesicoureterorenal reflux (VUR) served as controls.ResultsThere was no statistically significant difference in nerve fiber density in any of the immunohistochemical assessments (anti-S100 [p = 0.210], anti-CGRP [p = 0.897], anti-NF200 [p = 0.897]), and anti-TH [p = 0.956]) between patients with BE and patients with VUR. However, we observed a trend toward lower nerve fiber densities in exstrophic detrusor.ConclusionOverall our results showed an unharmed innervation pattern in this cohort but a lower density of nerve fibers in the detrusor compared to controls. Further studies in patients after successful primary closure are needed to clarify the potential impact of the urothelial overexpression of NGF modulating the innervation pattern in exstrophic bladders.