Papillary Urothelial Neoplasm Of Low Malignant Potential Research Articles

Benign urinary bladder masses: rare entities

BackgroundThis study aimed to present the characteristics and outcomes of benign urinary bladder masses, as well as the characteristics of the patients diagnosed with such lesions.MethodsA single-center, cross-sectional, retrospective study was conducted. The study involved patients who underwent transurethral resection of the primary bladder tumor over a four-year period (May 2017–2021) and were subsequently diagnosed with a benign bladder lesion.ResultsOut of 478 patients who underwent transurethral resection of the primary bladder tumor, 26 (5.4%) were diagnosed with a benign bladder lesion. The most common benign bladder lesion was urothelial papilloma (50%, 13 patients). The majority of patients with urothelial papilloma were men (76.9%) and had a history of smoking (61.5%). The mean age was 62 years. Most were diagnosed accidentally (69.2%), while others presented with hematuria (23.1%) or dysuria (7.7%). Most urothelial papillomas had a macroscopic polypoid appearance (61.5%), and most of them were solitary (84.6%), with a mean size amounting to 1 cm. Only one patient experienced a recurrence and developed papillary urothelial neoplasm of low malignant potential (PUNLMP). Cystitis cystica/glandularis and polypoid cystitis were the second most commonly diagnosed benign bladder lesion, each identified in 3 patients. Singular cases of leiomyoma, inflammatory myofibroblastic tumor, chondroma, paraganglioma, villous adenoma, eosinophilic cystitis (pseudotumor), and ectopic prostatic tissue are described.ConclusionBenign bladder lesions constitute a group of various rare entities that can clinically and radiologically mimic urothelial carcinoma, but mostly show a good prognosis and a low incidence of recurrence.

Bladder Neoplasia in Pediatric Patients-A Single-Center Experience Including a Case Series.

Objective: Bladder lesions like urothelial carcinoma are rare in the first two decades of life. A biopsy of the bladder or urinary cytological examination is seldom required. Gross painless hematuria is the most relevant clinical syndrome. Methods: A retrospective analysis of surgical pathology records collected between 1984 and 2014 at our institution was performed in a search for cases of urothelial neoplasms originating within the urinary bladder in pediatric patients. Diagnoses were confirmed based on pathologic examination using the 2004 World Health Organization (WHO) classification system. We selected keywords such as bladder neoplasia, bladder lesion, urothelial neoplasia, rhabdomyosarcoma, and children. In addition, we describe clinical presentation and diagnostic procedures as well as treatment and follow-up of two patients. A review of the literature was performed to analyze recommendations concerning diagnostic staging, treatment, and follow-up examinations as well as surveillance of urothelial tumors in the pediatric population. Results: Screening the pathology database of the Institute of Medical Genetics and Pathology of the University Hospital Basel between 1988 and 2014 yielded 287 samples involving the urinary bladder, 110 autopsies, 135 biopsies, and 42 cytology specimens. Of these, most samples originated from malformations and inflammation. Only five were tumors: two were urothelial tumors and three were rhabdomyosarcomas. The majority of specimens comprised resections of the diverticula or distal ureter. Our case reports include two patients with a urothelial tumor. Among the urothelial tumors, one was a papillary urothelial neoplasm of low malignant potential (PUNLMP). Painless hematuria was the directing clinical symptom. The tumor was investigated by FISH, and a 9p21 deletion was found. The second tumor-like lesion was a fibroepithelial polyp arising from the bladder neck. Conclusions: Bladder tumors in children are rare and mostly consist of urothelial and mesenchymal neoplasms. Rhabdomyosarcoma is the most common malignant bladder tumor in childhood. Similar to adult urothelial neoplasms, the loss of 9p21 is also implicated in urothelial neoplasms in childhood. Despite an increasing number of case reports and small series published within the last 2 decades, general treatment protocols including recommendations for staging, tumor markers, and follow-up examinations are still not yet available for this tumor entity in the pediatric population.

A retrospective study on expression and clinical significance of PHH3, Ki67 and P53 in bladder exophytic papillary urothelial neoplasms.

Exophytic papillary urothelial neoplasms (EPUN) are difficult to diagnose pathologically and are well-known for their heterogeneous prognoses. Thus, searching for an objective and accurate diagnostic marker is of great clinical value in improving the outcomes of EPUN patients. PHH3 was reported to be expressed explicitly in the mitotic phase of the cell cycle, and recent studies have shown that PHH3 expression was associated with the differential diagnosis and prognosis of many tumors. However, its significance in EPUN remains unclear. This study aimed to determine the expression of PHH3 in different EPUN, compare its expression with cell-cycle related proteins Ki67 and P53, and analyze its significance in the differential diagnosis and prognostic value for high-grade papillary urothelial carcinoma (HGPUC), low-grade papillary urothelial carcinoma (LGPUC), papillary urothelial neoplasm of low malignant potential (PUNLMP) and urothelial papilloma (UP). We retrospectively analyzed the pathological diagnosis and clinical features of 26 HGPUC cases, 43 LGPUC cases, 21 PUNLMP cases and 11 UP cases. PHH3, Ki67 and P53 were detected by immunohistochemistry in 101 EPUN cases samples. The cut-off values of PHH3 mitosis count (PHMC), HE mitosis count (HEMC), Ki67 and P53 in the different EPUN were determined using the ROC curve. The distribution of counts in each group and its relationship with clinical parameters and prognosis of EPUN patients were also analyzed. The determination coefficient (R2=0.9980) of PHMC were more potent than those of HEMC (R2=0.9734) in the EPUN mitotic counts microscopically by both pathologists. Of the 101 EPUN cases investigated, significant positive linear correlations were found between PHMC and HEMC, PHMC and Ki67, and HEMC and Ki67 (P<0.0001). In HGPUC, LGPUC, PUNLMP and UP, a decreasing trend was observed in the median and range of PHMC/10HPFs, HEMC/10HPFs, Ki67 (%) and P53 (%). PHMC, HEMC, Ki67 and P53 were associated with different clinical parameters of EPUN. PHMC, HEMC, Ki67 and P53 were found to exhibit substantial diagnostic values among different EPUN and tumor recurrence. Based on the ROC curve, when PHMC was >48.5/10HPFs, a diagnosis of HGPUC was more likely, and when PHMC was >13.5/10HPFs, LGPUC was more likely. In addition, when PHMC was >5.5/10HPFs, the possibility of non-infiltrating LGPUC was greater. Kaplan-Meier survival curve analysis showed that the median recurrence-free survival (RFS) for cases with PHMC > 13.5/10HPFs and HEMC > 14.5/10HPFs were 52.5 and 48 months, respectively, and their respective hazard ratio was significantly higher (Log-rank P<0.05). PHH3 exhibited high specificity and sensitivity in diagnosing EPUN. Combined with HEMC, Ki67 and P53, it can assist in the differential diagnosis of EPUN and estimate its clinical progression with high predictive value to a certain extent.

Survival and Analysis of Prognostic Factors for Bladder Malignancies in Children and Adolescents: A Population-based Study

To explore the clinicopathological features and prognosis of pediatric patients with malignant bladder tumors in a population-based cohort. The database Surveillance, Epidemiology, and End Results (SEER) was used to evaluate all pediatric patients diagnosed with malignant bladder tumors between 1975 and 2018. The log-rank test was used to compare survival curves. Kaplan-Meier estimations were used to create survival curves based on various parameters. The Cox proportional hazards model was utilized to determine the factors that were independently related to mortality. A total of 263 children and adolescents with bladder malignancies were assessed. Papillary urothelial neoplasms of low malignant potential (PUNLMP) were the most frequent histologic subtype (35.1%), while embryonal rhabdomyosarcoma was more common during the first decade of life. Survival rates varied significantly by age at diagnosis, with older patients showing better outcomes. When compared to other subtypes, PUNLMP had the highest overall survival rates (3- and 5-year were 99.2% and 98.3%, respectively). Multivariate analysis of the entire cohort showed that SEER stage and surgery were significant independent predictors of progression to disease-specific death in this model. Bladder malignancies are rare in children and adolescents. The prognosis for them varies. Localized stage was independently associated with superior survival and surgery could extend survival time.

PREVALANCE OF UROTHELIAL CARCINOMA, ITS HISTOLOGICAL GRADE AND TYPE IN URINARY BLADDER OVER A PERIOD OF 2 YEARS: A STUDY IN A TERTIARY HOSPITAL IN CENTRAL INDIA

BACKGROUND:-Urinary bladder carcinoma is well known to show many histological divergent differentiation. The histological variants have important diagnostic, prognostic and therapeutic implications. The aim of the study was to find the prevalence of urothelial carcinoma in a tertiary care centre and to find the proportion of different histological grades and types of urothelial carcinoma. MATERIAL AND METHODS:- A retrospective monocentric study was done between April 2020 and April 2022 which includes 37 bladder biopsies which were received in the histopathology section of the Department of Pathology, Gajra raja medical college. Patients who refuse to give consent and those having cystitis were excluded from the study. RESULTS AND OBSERVATIONS :- Out of total 37 cases which were reviewed, the mean age was 62 years, with a male predominance (M:F ratio-3.16). Out of 37 cases, there were 8 cases each of highgrade urothelial carcinoma(21.6 %), high grade urothelial carcinoma with invasion ( 21.6 %) and high grade papillary urothelial carcinoma with invasion ( 21.6 %). There were 4 cases of high grade urothelial carcinoma with invasion with squamous differentiation ( 10.8 %), one case each of recurrent high grade urothelial carcinoma with invasion ( 2.7 %), well differentiated invasive glandular adenocarcinoma NOS (2.7%) and invasive micropapillary urothelial carcinoma with squamous differentiation ( 2.7 % ), two cases each of low grade urothelial carcinoma - 2 cases ( 5.4 %), low grade papillary urothelial carcinoma ( 5.4%) and papillary urothelial neoplasm of low malignant potential ( PUNLMP) ( 5.4 %). CONCLUSION Urinary bladder carcinoma is more common in male than females. Average age of presentation is 62 years in present study. High grade urothelial carcinoma ( 83.8 %) is more common compared to low grade ( 10.8% ). H&amp;E staining with ancillary techniques like immunohistochemistry or molecular it can be very effective in to analyse histological variants to better understand this invasive disease hence aiding in further management of patients.

Relationship between Metabolic Syndrome on Grade and Stage of Urothelial Carcinoma of Bladder

Introduction: Bladder cancer is the ninth most common cancer in the world, with 430,000 new cases diagnosed in 2012. Carcinoma bladder occurs with an overall incidence of 2.25% (10,000 annually), 3.67% among males and 0.83% for females. Metabolic syndrome (MS) is characterized by overweight, hypertension, elevated blood glucose, and dyslipidaemia. Cigarette smoking and occupational exposure are the main risk factors for upper tract urothelial carcinoma and urinary bladder cancer. Objective: To elucidate the relationship between metabolic syndrome on grade and stage of urothelial carcinoma of bladder. Methods: We retrospectively analyzed study was carried out at Dept. of Urology, Sir Salimullah Medical College Hospital, Dhaka, Bangladesh from January to December 2021. One hundred (100) patients who were first time detected cases of carcinoma bladder and were operated. Consent was required for surgical procedure as mandatory for the procedure. Patient related factors (Age, height and weight), histopathological analysis (stage and grade,) and comorbid conditions (the presence of hypertension, diabetes mellitus, and triglyceride level and body mass index) were evaluated. Non-invasive papillary urothelial neoplasms of low malignant potential (PUNLMP), Ta and T1 tumors were classified as lower stage and T2, T3, and T4 tumors as higher stage bladder cancers. Stasticial Analyses was done using chi-square tests and logistic regression analysis. Results: Total 100 patients 82 (82%) were males and 18(18%) were females with mean age of 65.5±4.8 years. MS was found in 32 (32%) patients. Hypertriglyceridemia, Hypertension, Diabetes mellitus (DM) and BMI ≥25 kg/m2 were present in 25%, 32%, 25%, and 40% of patients respectively. The pathological characteristic between patients with or without MS is demonstrated. Metabolic syndrome was significantly associated with histologic grade (p&lt;0.05) and stage (p=0.04) of bladder cancer. Components such as diabetes (p=0.005, OR=1.92) and ....

Pediatric urothelial bladder neoplasm

Urothelial bladder neoplasm (UBN) is an uncommon lesion in children and adolescents, without established follow-up protocol defined for this patient group. To report our experience and long-term follow-up data on pediatric patients with urothelial carcinoma of the urinary bladder. In this retrospective two center study, we analyzed the perioperative and long-term follow-up data of nine pediatric patients, who presented with neoplasms of urothelial origin within the urinary bladder between 2000 and 2021. Nine patients were identified with a mean age of 11.9 years (range 4-19 years) and median follow up of 48 months (range 12-160 month). 7 were male. Gross hematuria was the most common presenting symptom, occurring in 6 patients, followed by accidental finding on US, performed for other reasons. Cystoscopy was performed under general anesthesia, and transurethral resection of the bladder tumors was carried out in the same session. All patients had a solitary tumor with a mean size of 11mm (range 6-15mm). Pathology revealed 3 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP), 5 cases of low grade (LG) noninvasive urothelial carcinoma (UC) and one case of high-grade (HG) UC invading lamina propria (pT1). All 8 patients with low grade tumor underwent follow up according to adult follow-up protocols without tumor recurrences to date. The single patient with HG pT1 UC, a 14-year-old female after renal transplantation, who was not eligible for intravesical bacillus Calmette-Guerin (BCG) installations due to immunosuppression, underwent 6 sessions of Radiofrequency-induced Thermo-chemotherapy with mitomycin, without complications. She had no recurrence to date, during a 4-year post treatment follow up. Pediatric non muscle invasive bladder cancer (NMIBC), seems to have a good prognosis with infrequent recurrences, which might be in favor of a more spacious follow up plan with less invasive diagnostic modalities as opposed to adult NMIBC population. To the best of our knowledge this is the single description of Heated Intravesical Chemotherapy efficacy for HG UC in the pediatric population.

Bladder cancer recurrence in papillary urothelial neoplasm of low malignant potential (PUNLMP) compared to G1 WHO 1999: a population-based study

Objective Papillary urothelial neoplasm of low malignant potential (PUNLMP) and stage TaG1 non-muscle invasive bladder cancer (NMIBC) represent separate categories in current WHO 1999 grade definitions. Similarly, PUNLMP and Ta low-grade are separate entities in the WHO 2004/2016 grading system. However, this classification is currently questioned by reports showing a similar risk of recurrence and progression for both categories. Patients and methods In this population-based study, risk estimates were evaluated in patients diagnosed with PUNLMP (n = 135) or stage TaG1 (n = 2176) NMIBC 2004–2008 with 5-year follow-up registration in the nation-wide Bladder Cancer Data Base Sweden (BladderBaSe). The risk of recurrence was assessed using multivariable Cox regression with adjustment for multiple confounders (age, gender, marital status, comorbidity, educational level, and health care region). Results At five years, 28/135 (21%) patients with PUNLMP and 922/2176 (42%) with TaG1 had local recurrence. The corresponding progression rates were 0.7% (1/135) and 4.0% (86/2176), respectively. A higher relative risk of recurrence was detected in patients with TaG1 tumours compared to PUNLMP (Hazard Ratio 1.6, 95% CI 1.2–2.0) at 5-year follow-up, while progression events were too few to compare. Conclusions The difference in risk of recurrence between primary stage TaG1 and PUNLMP stands in contrast to the recently adapted notion that treatment and follow-up strategies can be merged into one low-risk group of NMIBC.

Inverted papilloma, a Crying wolf of the urinary bladder

Inverted papilloma is a benign, non-invasive and innoxious bladder tumour rarely seen. These tumours are associated with chronic urinary tract infection, bladder neck obstruction, and they appear similar to other bladder tumours. Inverted papilloma is diagnosed on histopathological examination. We report a case of inverted papilloma who presented and appeared as bladder tumour but on subsequent pathological examination diagnosed as inverted papilloma. Keywords: Inverted papilloma; Benign; TCC (Transitional cell carcinoma); PUNLMP (Papillary urothelial neoplasm of low malignant Potential)

Clinicopathological study of urothelial neoplasms in urinary bladder with special reference to expression of Her2/neu and Ki-67 in malignant lesions

Urothelial carcinomas are the fourth most common tumors worldwide. Studies have shown that Her2/neu is associated with increased tumour grade and Ki‐67 is related to tumour recurrence and stage progression. As no such study has been undertaken is this region, the present study was aimed to establish Her2/neu and Ki-67 as novel prognostic markers of urothelial neoplasms.: To evaluate the clinical profile of urothelial neoplasms and correlate the expression of Her2/neu and Ki-67 in urothelial carcinomas.Observational and cross-sectional study (January 2018-May 2019) in a tertiary care hospital in Eastern India.: 40 specimens of urothelial neoplasms were studied. Clinical history of patients was collected. Microscopic examination was done to assess tumour stage and histological grade. Immunohistochemistry with Her2/neu and Ki-67 was performed.: Statistical Package for the Social Sciences SPSS (version 20.0, IBM, Chicago, IL, USA) for windows software.: 8 cases were diagnosed as low grade non-invasive urothelial carcinoma, 31 cases as infiltrating urothelial carcinoma and 1 case as papillary urothelial neoplasm of low malignant potential (PUNLMP). 96.8% of infiltrating carcinomas and 87.5% of low grade non-invasive carcinomas showed Ki-67 positivity. Moderate-to-strong Her2/neu overexpression (2+ or 3+) was observed in only 21% of the cases.: The expression of Ki-67 increased with increase in the grade of the tumour which was suggestive of the prognostic importance of Ki-67. Her2/neu positivity was seen in infiltrating cases. No significant association between the tumor grade and Her2/neu expression, indicated the need for further studies with a larger population group.

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.

Histopathological Spectrum of Neoplastic and Non Neoplastic Lesions of Urinary Bladder- A Retrospective Study

Introduction: Urinary bladder encompasses a wide variety of lesions, both neoplastic and non neoplastic responsible for significant morbidity and mortality throughout the world. All bladder lesions require biopsy because of their lack of distinctive features. Urinary bladder cancer is the 9th most common cancer worldwide accounting for 6% and 2% of the cancer incidence in men and women, respectively. Aim: To analyse the histopathological spectrum of bladder specimens with neoplastic and non neoplastic lesions, and categorising them according to recent 2016 World Health Organisation (WHO) classification. Materials and Methods: The present study was conducted from January to June 2020 at Subharti Medical College, Meerut, Uttar Pradesh, India. Retrospective data was retrieved from a period of 10 years from January 2010-December 2019. Histopathological analysis of all the urinary bladder biopsies and radical cystectomy/cystoprostectomy specimens received during this period was done on basis of light microscopic examination of Haematoxylin and Eosin (H&amp;E) stained slides. Lesions were categorised into non neoplastic and neoplastic. The neoplastic lesions were classified based on WHO classification 2016 and staging as per 8th edition of American Joint Committee on Cancer (AJCC). Descriptive data analysis was done. Results: Total 252 cases were evaluated. A total of 200 (79%) cases were neoplastic and 52 (21%) cases were diagnosed as non neoplastic with majority of cases being cystitis. Male to female ratio was 7:1. The most common age group was 4th to 7th decade. In neoplastic category, urothelial tumours constituted 194 (97%) cases with Infiltrating Urothelial Carcinoma (IUC) being 118 (60.8%) cases. In non invasive lesions majority 27 (35.6%) cases were Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP) followed by urothelial carcinoma in situ and papillary urothelial neoplasm of low grade. Entities other than urothelial tumours encountered in the present study were primary adenocarcinoma, small cell carcinoma, melanosis and metastasis from prostate. TNM staging showed lamina propria invasion (pT1) in 59 (37%) cases, followed by pT2 tumours invading muscle in 56 (35%) cases. Conclusion: Proper knowledge of histologic characteristics of various bladder lesions is of utmost importance as few benign conditions mimic neoplastic and few serve as preneoplastic conditions, misdiagnosis may cause further any unnecessary treatment procedure. With a multidisciplinary approach, early diagnosis and immediate intervention can have a better survival and provide a more comfortable life to the patient.

Importance of cytokeratin-20 expression in papillary urothelial neoplasia

Purpose: The aim of this study is to determine the role of Cytokeratin 20 (CK20) expression in the diagnosis of papillary urothelial neoplasms of the bladder, and its relationship with histological grade, recurrence and other prognostic factors.&#x0D; Materials and Methods: Patients diagnosed with papillary urothelial neoplasm of bladder transurethral resection (TUR) specimens between January 2011 and December 2016 were retrospectively analyzed. Of the 136 selected patients, 32 (24%) were diagnosed with urothelial papilloma, 8 (6%) with papillary urothelial neoplasm of low malignant potential (PUNLMP), 36 (26%) with low grade non-invasive papillary urothelial carcinoma (LGNIPUC), 12 (9%) with high grade non-invasive papillary urothelial carcinoma (HGNIPUC) and 48 (35%) were diagnosed with high grade invasive papillary urothelial carcinoma (HGIPUC). There was no patient diagnosed with LGIPUC. The correlation between CK20 expression and histological grade, tumor recurrence, presence of progression and presence/absence of invasion was investigated.&#x0D; Results: There was a significant difference between PUNLMP and LGNIPUK in terms of CK20 expression in favor of LGNIPUK. Also there was a significant correlation between histological grade, presence of invasion, recurrence, progression and CK20 expression in patients diagnosed with Papillary Urothelial Neoplasm. &#x0D; Conclusion: This study supports that CK20 is an important marker in the differentiation between PUNLMP and LGNIPUC, as well as in the determination of histological grade in urothelial carcinomas.

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,

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.

Combined lectin- and immuno-histochemistry (CLIH) for applications in cell biology and cancer diagnosis: Analysis of human urothelial carcinomas.

Lectin histochemistry (LHC) and immunohistochemistry (IHC), which demonstrate the composition and localisation of sugar residues and proteins in cell membranes, respectively, are generally used separately. Using these two methods, we previously demonstrated that malignant transformation of urothelial cells results in the alterations of protein glycosylation and reduced expression of urothelium-specific integral membrane proteins uroplakins (UPs). However, the correlation between these changes was not studied yet. To evaluate this correlation, we developed innovative method, which we named Combined Lectin- and Immuno-Histochemistry (CLIH). We used human biopsies of 6 normal urothelia and 9 papillary urothelial carcinomas, i.e. 3 papillary urothelial neoplasms of low malignant potential (PUNLMP), 3 non-invasive papillary urothelial carcinomas of low grade (pTa, l.g.), and 3 invasive papillary urothelial carcinomas of high grade (pT1, h.g.). We tested five different protocols (numbered 1-5) of CLIH on paraffin and cryosemithin sections and compared them with LHC and IHC performed separately. Additionally, we carried out western and lectin blotting with antibodies against UPs and lectins Amaranthus caudatus agglutinin (ACA), Datura stramonium agglutinin (DSA), and jacalin, respectively. We showed that incubation with primary antibodies first, followed by the mixture of secondary antibodies and lectins is the most efficient CLIH method (protocol number 5). Additionally, 300 nm thick cryo-semithin sections enabled better resolution of co-localisation between sugar residues and proteins than 5 mm thick paraffin sections. In the normal urothelium, CLIH showed co-localisation of lectins ACA and jacalin with UPs in the apical plasma membrane (PM) of superficial umbrella cells. In papillary urothelial carcinomas, all three lectins (ACA, DSA and jacalin) labelled regions of apical PM, where they occasionally co-localised with UPs. Western and lectin blotting confirmed the differences between normal urothelium and papillary urothelial carcinomas. Our results show that CLIH, when used with various sets of lectins and antigens, is a useful, quick, and reliable method that could be applied for basic cell biology research as well as detailed subtyping of human urothelial carcinomas.

Recent advances in pediatric bladder malignancies.

Urothelial pediatric neoplasms are relatively rare. Papillary urothelial neoplasms of low malignant potential (PUNLMPs) and rhabdomyosarcoma (RMS) are the most common bladder malignancies in the pediatric population. Clinical presentation encompasses macroscopic hematuria or lower urinary tract symptoms (or both) or is detected incidentally at imaging. Tumors arising from the bladder can originate from any of its four histological layers (urothelium, lamina propria, detrusor, and adventitia) and are divided into tumors that have an epithelial origin (arising from the urothelium) and those that have a non-epithelial origin (mesenchymal neoplasms). RMS is the most common malignant tumor of the urinary bladder in children younger than 10 years. Deriving from the embryonic mesenchymal cell, the histopathologic subtypes of RMS are embryonal RMS (>90%) and alveolar histology (<10%). Pre-treatment imaging should be carried out by computed tomography (CT) or at present is more likely with magnetic resonance imaging of the pelvis. Chest CT and bone scintigraphy are used to screen for metastases. In selected cases, a positron emission tomography scan may be recommended to evaluate suspicious lesions. The current prognostic classification considers age, histologic subtype, tumor site, size, and extent (nodal or distant metastases). Staging is based on pre-operative findings, group is based on intra-operative findings and pathology, and risk stratification is derived from both stage and group data. Pre-operative chemotherapy is the most common first-line intervention for bladder/prostate RMS, before surgery or radiation therapy. Collaborative groups such as the Soft Tissue Sarcoma Committee of the Children’s Oncology Group and the European Pediatric Soft Tissue Sarcoma Study Group endorse this therapy. PUNLMPs are generally solitary, small (1–2 cm), non-invasive lesions that do not metastasize. Therapy is usually limited to a transurethral resection of the bladder tumor. About 35% are recurrent and around 10% of them increase in size if they are not treated.

The Association of A Number of Predictive Factors for The Recurrence of Papillary Urothelial Neoplasm of Low Malignant Potential: Prognostic Analysis From Multiple Academic Centers.

To identify clinically useful predictors for the recurrence of papillary urothelial neoplasm of low malignant potential (PUNLMP), we reviewed the clinical information of patients who were diagnosed and treated in multiple tertiary-care academic facilities. Between February 2007 and April 2015, 95 patients diagnosed with PUNLMP after transurethral resection of bladder (TURB) were included in this study. Age, gender, body mass index, smoking history, the presence or absence of previous history of urothelial neoplasm, the presence or absence of gross hematuria, cytological results at the time of diagnosis, tumor diameter, and multiplicity of tumor were estimated as variablesfor analysis. Cox regression tests were used for identifying predictive factors for recurrence of PUNLMP. Sixty-nine cases of PUNLMP were de novo primary bladder PUNLMPs without known urothelial lesions in the urinary tract, and 26 PUNLMPs were identified on surveillance biopsies of patients with a previous history of urothelial neoplasm. During the follow-up period, recurrences developed in 13 patients (13.7%). Recurrence rates were 4.2% and 9.5% at 12 and 24 months, respectively. On univariate and multivariate Cox regression analyses, previous history of urothelial neoplasm [95% confidence interval (CI): 0.057-0.604, hazard ratio (HR) = 0.185, P = .005] and multiplicity of tumors [95% CI = 0.064-0.584, HR = 0.193, P = .004] were identified as independent predictors for recurrence-free survival of patients with PUNLMP. Tumor multiplicity and previous history of urothelial neoplasm are independent prognostic factors forprediction of recurrence of PUNLMP. More careful and closer follow-up should be recommended for PULNMPpatients with tumor multiplicity or a previous history of urothelial neoplasm.

Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, noninvasive bladder tumors in 2019?

BackgroundPapillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors. ObjectivesTo analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points. Materials and methodsIndividual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018. ResultsPUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990–2000) to 3.2% (2000–2010) and to 1.1% (2010–2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP. ConclusionsThe proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas.

P119 - Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, non-invasive bladder tumors in 2019?

P119 - Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, non-invasive bladder tumors in 2019?