Urothelial Neoplasia Research Articles

Applicability of the Paris System for veterans: high rates of undiagnosed low-grade urothelial neoplasia

The Paris System for Reporting Urinary Cytology (TPS) is a recently developed standardized terminology system. It is well-established that urine cytology has low sensitivity for detecting low-grade urothelial neoplasia (LGUN). Though the majority of tumors are low-grade, surveillance of these lesions is important to monitor for possible progression. Herein, we compared TPS to our veteran integrated system network (VISN) to assess its applicability. We also introduced semi-quantitative scoring to further evaluate cytomorphologic features of high-grade urothelial carcinoma (HGUC). Voided and instrumented urine cytology specimens and concurrent biopsies were reviewed from Sept 2018 - Jan 2020. Cytologic diagnoses reported using the VISN institutional system were reevaluated by staff cytopathologists and categorized according to TPS. A semi-quantitative scoring system to evaluate cytomorphologic features was devised. Cytology and surgical specimens from 105 patients were reviewed. The VISN and TPS reporting systems were compared and showed similar sensitivities and specificities for the detection of HGUC. Rates of biopsy-proven LGUN were high for the negative for high-grade urothelial carcinoma category (NHGUC; 27/53, 50.9%) and atypical urothelial cells (AUC; 14/30; 46.7%) compared to suspicious/positive (0/22, 0%) categories. Major and minor criteria as outlined in TPS were evaluated semi-quantitatively. Urine cytology has limited sensitivity for LGUN regardless of the cytologic reporting system used. There was a high rate of LGUN following NHGUC/AUC diagnoses in the Veteran population. Coarse chromatin was determined to be the least sensitive criterion for the detection of high-grade lesions and irregular chromatin rim was most specific.

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.

Etiological study of urinary bladder carcinoma in patients presenting to tertiary care centre

Background: Urothelial carcinoma is the most common invasive cancer of the urinary tract. Lately, there has been an increased incidence of urothelial neoplasia due to exposure to a wide range of potentially carcinogenic substances. Studies of involved factors led to the concept of existence of a so-called malignization terrain, which claims that individual genetic predisposition and chronic exposure to carcinogens act synergistically leading to the appearance of urothelial carcinomas of the bladder. Aim of the research was to find out the common etiological factors of bladder cancer in this part of India.Methods: The study included 100 patients of bladder carcinoma reporting to Sri Guru Ram Das Hospital, Amritsar from March 2018 to December 2019. A detailed history was taken to have the insight of various etiological factors of the disease. The data was entered in Microsoft excel spreadsheet and analysis was done using statistical package for social sciences (SPSS) version 21.0.Results: The most common blood group associated with CA UB was A +ve (39%) followed by B +ve (29%). 89% of the cases of CA UB were non-smokers predominantly attributed to type of patients coming to our tertiary care institute which are from a rural background (73%) and are mostly Sikhs (80%) and Sikhs are traditionally non-smokers. 80% were farmers by occupation who have exposure to pesticides, insecticides, weedicides and herbicides routinely.Conclusion: In our study majority of the patients turned out to be non-smokers and A +ve blood group in contrast to the strong predilection of smoking and bladder cancer.

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.
 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.
 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. 
 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.

Applicability of the Paris System for Veterans: High Rates of Low-grade Urothelial Neoplasia in Negative and Atypical Urines and its Impact on Cytologic Reporting

Applicability of the Paris System for Veterans: High Rates of Low-grade Urothelial Neoplasia in Negative and Atypical Urines and its Impact on Cytologic Reporting

Cell blocks in urine cytopathology: do they add value to the diagnosis? A pilot study

The utility of cell block (CB) preparation is well established in cytopathology. Despite 23.3% of College of American Pathologists-accredited laboratories using CB with liquid-based preparations on urine cytology (UC) cases, there are very few studies on their performance. To determine their usefulness, we conducted a retrospective review of UC cases that received CB. We identified 27 UC cases with ThinPrep (TP) and CB preparation between 2016 and 2020 at our institution. Clinical history and follow-up data were compiled. A blinded review of TP alone, and TP together with CB, was performed by 2 pathologists and 2 cytotechnologists. Diagnoses were rendered in accordance with The Paris System for Reporting Urine Cytology. Blood and acute inflammation were common background elements in cases that received CB preparation. In total, CB upgraded the diagnosis in 7 of 27 cases (26%). The maximum utility of CB preparation was seen in indeterminate cases where 60% (6 of 10) were upgraded, including 71% (5 of 7) of atypical urothelial cells (AUC) and 30% (1 of 3) of suspicious for high-grade urothelial carcinoma (HGUC). One case (1 of 12, 8%) diagnosed as negative for HGUC on TP was diagnosed as low-grade urothelial neoplasia on CB. Our results demonstrate that adjunct use of CB preparation aids in a definitive diagnosis on AUC category and may be helpful in cases with cell clusters or tissue fragments, or cases suspicious for HGUC. Further correlation studies are warranted in this area to expand our knowledge about the utility of CBs in urine cytology.

The Paris system of Reporting Urinary Cytology: Strengths and opportunities.

The Paris system for reporting urinary cytopathology (TPS) was created to address inherent weaknesses inherent in the practice of urinary cytopathology. While urothelial cytology has always performed well at finding high grade, genetically unstable urothelial carcinoma, it performs poorly when it comes to detecting low-grade urothelial neoplasia. TPS intends to improve the utility of urothelial cytology by focusing on what is important, high-grade urothelial carcinoma. This article is a snapshot of the current state of TPS as it heads into its second edition. Successes are described and further developments are considered.

Abstract B01: Validation of a novel cytologic biomarker for urothelial carcinoma

Abstract Introduction: Cytology and cystoscopy have limited sensitivity and specificity for the diagnosis of urothelial carcinoma (UC), due to inflammatory atypia, sampling errors, and other clinicopathologic factors that may obscure test results. Therefore, there remains a clinical need to identify biomarkers to improve the diagnostic accuracy to detect UC. Keratin 17 (K17) is an embryologic cytokeratin that functions as an oncoprotein to promote the degradation of tumor suppressors that drive tumorigenesis. Published work from our group established that K17 is highly expressed in UC and confirmed specificity for UC by immunohistochemical localization of K17 in tissue biopsies of both low-grade and high-grade UCs (Babu et al., Mod Pathol, 2018). Objective: The objective of the current study was to develop an immunocytochemical (ICC) assay to determine K17 is a sensitive and specific biomarker to enhance diagnostic accuracy for UC in urine cytology. Methods: 80 ThinPrep CytoLyt-fixed urine specimens, collected at Stony Brook Medicine in 2018, including 39 with a clinicopathologic diagnosis of UC based on current cytologic diagnosis, and/or a history of biopsy confirmed UC within one year (+/-) of urine cytology specimen collection. K17 ICC was performed by indirect immunoperoxidase methods and K17 test results were scored based on the detection of immunoreactive urothelial cells and not on an assessment of cytologic atypia. The sensitivity and specificity of urine K17 ICC for detection of urothelial neoplasia was calculated by comparison of ICC test results with the cytologic diagnosis and/or the histologic diagnosis of positive cystoscopic biopsy specimens (papillary urothelial neoplasm of low malignant potential [PUNLMP, n=1] or greater). Samples that had no history of abnormal urine cytologic or biopsy diagnosis were categorized as negative for urothelial neoplasia. Results: Relative to the final clinicopathologic diagnosis of UC (n=38) or PUNLMP (n=1), K17 ICC had a sensitivity of 100% (95% CI: 91-100%) and specificity of 90% (95% CI: 77-96%). The positive predictive value was 90% (95% Cl: 78-96%) and the negative predictive value was 100% (95% Cl: 90-100%). Comparing ICC test results to cytologic and biopsy diagnoses, K17 ICC was positive in 9/23 (39%) cases with negative urine cytology. Of these 9 cases, 4 cases had biopsy confirmed UC. K17 ICC was positive in 4/11 (36%) of cases with inflammatory/reactive changes. Of these 4 cases, 3 had biopsy-confirmed UC. K17 ICC was positive in 14/30 (46%) of cases with mild atypia. Of these 14 cases, 12 had biopsy-confirmed UC and 1 had PUNLMP. K17 ICC was positive in 16/16 (100%) of cases with moderate atypia (n=8), severe atypia (n=3), or UC (n=5), all with biopsy-confirmed UC. Conclusions: K17 ICC is a novel and highly sensitive and specific diagnostic test for underlying biopsy-confirmed UC among samples with inflammatory/reactive changes, cytologic atypia, or positive urine cytology. Thus, the K17 test could serve as an adjunct to guide the clinical management of UC cases. Citation Format: Sruthi Babu, Lucia Roa-Peña, Ina Chan, Nam W. Kim, Sholeh Jahanfard, Luisa F. Escobar-Hoyos, Kenneth R. Shroyer. Validation of a novel cytologic biomarker for urothelial carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B01.

Do repeated transurethral procedures under general anesthesia influence mortality in patients with non-invasive urothelial bladder cancer? A Danish national cohort study

Purpose: To investigate the effect of repeated transurethral procedures under general anesthesia on overall mortality in patients with non-invasive bladder cancer.Materials and methods: All Danish residents with non-invasive papillary urothelial carcinoma or primary urothelial carcinoma in situ diagnosed between 1 January 2000 and 1 January 2011 were included and followed until death or 31 March 2017. All transurethral procedures under general anesthesia, intravesical instillation therapy, recurrences and progression to invasive disease or cystectomy were recorded during follow-up. Associations between treatments and overall mortality were evaluated using multivariable regression analysis adjusted for age, gender, comorbidities and socioeconomic status. The effect of disease progression on mortality was removed by censoring patients at the time of progression or cystectomy.Results: Risk of death increased with the number of transurethral procedures under general anesthesia for Ta low- and high-grade tumors compared to patients who had only one procedure; after eight or more procedures the risk of death increased by 28% and 83%, respectively. There was no similar relationship for carcinomas in situ. In total, 36–52% of procedures under general anesthesia did not identify urothelial neoplasia.Conclusions: Repeated transurethral procedures under general anesthesia appear to be associated with increased risk of death in patients with primary non-invasive papillary urothelial carcinoma. Furthermore, a substantial number of procedures were without findings of neoplasia, indicating that too many patients are admitted for transurethral procedures under GA. Attempts should be taken to reduce unnecessary transurethral procedures under GA, e.g. by improved outpatient diagnosis of urothelial neoplasia.

Comparison of urine cytology diagnostic reports before and after the implementation of the Paris System classification system in China.

In 2013, The Paris System for Reporting Urinary Cytology (TPS) was developed as a uniform practical urine cytology system that could be applied worldwide. Here, we investigated the effectiveness of TPS diagnostic approach compared with that of the traditional urine cytological diagnosis method used in China. Based on the diagnostic criteria of TPS, 412 urine samples from 143 patients with histological follow-up data were retrospectively analysed, and the diagnoses were compared with the original cytological diagnoses. In total, 110 patients were histologically diagnosed with high-grade urothelial carcinoma (HGUC), and 33 patients were diagnosed with low-grade urothelial neoplasia. Based on the traditional urine cytological analysis method, 50 patients (34.9%) were diagnosed as negative, 48 patients (33.6%) were diagnosed as having atypical urothelial cells, and 45 patients (31.5%) were diagnosed as positive. After reclassification using TPS, urine samples from 11 cases (7.7%) were categorised as unsatisfactory, 34 cases (23.8%) were negative, 21 cases (14.7%) were categorised as having atypical urothelial cells, 12 cases (8.4%) were diagnosed as suspicious for HGUC, 59 cases (41.2%) were diagnosed with HGUC, and six cases (4.2%) were reclassified as having low-grade urothelial neoplasia. Thus, after implementing TPS criteria, the sensitivity for positive malignancy diagnoses (HGUC alone) increased from 38.2% to 50.9%, while the specificity of the diagnosis was barely changed. The Paris System for Reporting Urinary Cytology greatly contributes to the standardisation of urine cytology reports and significantly improves the diagnostic sensitivity for HGUC.

Oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in Denmark

Objective: To report the oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in a large study sample.Materials and methods: This was a nationwide multicenter registry-based cohort study of all patients with upper urinary tract urothelial neoplasia in Denmark found to be eligible for nephroureterectomy between April 2004 and April 2017 (N = 1384). Primary endpoints were intravesical recurrence-free survival and overall survival. Survival probabilities were estimated with Kaplan–Meier and the log-rank test to compare survival curves. Association with clinical outcomes was studied using univariate and multivariate Cox proportional hazards.Results: Intravesical recurrence-free survival was 72% [95% confidence interval (CI) 69–75%] at 5 years and 70% (95% CI 67–73%) at 10 years. Patients with muscle-invasive disease had a significantly lower rate of intravesical recurrence [hazard ratio (HR) = 0.46, p < 0.0001] and patients with high-grade tumors had a significantly higher rate of incident intravesical recurrence compared to low-grade tumors (HR = 1.65, p = 0.001). The overall survival was 76% (95% CI 74–79%) at 5 years and 64% (95% CI 60–70%) at 10 years. Patients with higher age (p = 0.008) and muscle-invasive disease (p < 0.0001) had worse overall survival. When comparing surgical approaches, laparoscopic nephroureterectomy versus open nephroureterectomy did not differ in intravesical recurrence-free survival but was associated with shorter postoperative hospital stay (p < 0.0001) and better overall survival (p = 0.02).Conclusions: We report the oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in a large sample and give insights into predictive factors with significant impact.

TERT Promoter Mutation is a Diagnostic and Differential Diagnostic Marker for Tumors with Urothelial Origin

Telomerase reverse transcriptase (TERT) promoter mutations have been found in approximately 60–80% of bladder urothelial cancers and its variants of all grades anywhere in the urinary tract. The TERT promoter mutations occur early in urothelial neoplasia and are biomarkers for neoplasm development, recurrence, diagnosis, differential diagnosis, and potentially a therapeutic target. This review highlighted the role of TERT promoter mutations in urothelial tumorigenesis, and the potential clinical implications.

The Paris System for reporting urinary cytology in daily practice with emphasis on ancillary testing by multiprobe FISH

AimsThe Paris System (TPS) was introduced in the diagnostic routine with the goal to simplify and standardise diagnostic reporting of urinary cytology. The diagnostic categories of TPS are based on...

Urinary bladder leiomyosarcoma with osteoclast-like multinucleated giant cells: a case report

BackgroundBladder leiomyosarcoma is the most frequent mesenchymal neoplasm of the bladder. However, the rarity of the disease and some morphological aspects could give serious problems to differential diagnosis.Case presentationA 86-year-old male patient was referred to our institution to undergo endoscopic low-urinary-tract re-evaluation 2 months after the detection of a “low-grade urothelial neoplasia” in urinary cytology. A TURBT (transurethral resection of bladder tumor) was performed and revealed a tumor extending for 3.5 cm with thin stalk peduncle on the left lateral wall of the bladder, cephalad and lateral to the left ureteral orifice. The exophytic part of the tumor was resected with the underlying bladder wall. Histologically, the tumor showed a quite complex pattern, composed of spindle cells, with often invasion to the surrounding bladder muscular wall, and the presence of numerous multinucleated, osteoclast-like giant cells, scattered throughout the neoplasia.ConclusionsHere we report a unique case of urinary bladder leiomyosarcoma with osteoclast-like multinucleated giant cells (OGCs). These cells, confounding the morphological aspect, indeed showed an immunohistochemical phenotype of non-neoplastic origin (most likely a histiocyte/macrophage differentiation). We feel that the presence of the OGCs within this tumor is reactive. Nevertheless, more research is necessary to understand the role of OGCs in urinary bladder tumors and leiomyosarcoma, in paticular.

Carcinoma In Situ With Plasmacytoid Features: A Clinicopathologic Study of 23 Cases.

Although there are 5 well-described morphologic patterns of (nonglandular) urothelial carcinoma in situ (CIS), we have encountered a novel pattern of flat urothelial carcinoma with plasmacytoid features characterized by a triad of morphologic findings including abnormal architecture with cellular rounding, enlarged nuclei with eccentric nuclear localization, and dense globular eosinophilic cytoplasm. A total of 23 cases of plasmacytoid CIS (mean age: 74.1 y, range: 58 to 91 y) were collected and reviewed. We excluded cases in which the diagnostic biopsy had any of the following findings admixed in the same tissue biopsy sample as the plasmacytoid CIS: traditional patterns of CIS, noninvasive glandular CIS, papillary urothelial carcinoma, or invasive carcinoma. Immunostains for CK20, CD44, p53, and e-cadherin were performed on available blocks. History of prior urothelial neoplasia, prior treatment, and clinical follow-up were obtained from medical records and pathology re-review. Immunohistochemical analysis of plasmacytoid CIS showed diffuse/strong CK20 reactivity in 96% of cases (23/24), an abnormal p53 reactivity pattern (either overexpression or "null phenotype") in 37% of cases (7/19), absence of CD44 reactivity in the neoplastic cells in 63% of cases (15/24), and retained membranous e-cadherin expression in 100% of cases (18/18). Clinical follow-up (average follow-up time: 37.7 mo, range: 7 to 115 mo) showed recurrence/new occurrence in 52% of cases (12/23), including all 4 of the 23 patients who initially presented with de novo plasmacytoid CIS (ie, no prior or concomitant urothelial neoplasia). The histologic features, the immunophenotype, the association with other forms of urothelial neoplasia, and the risk of recurrence and progression in de novo lesions support that plasmacytoid CIS represents a novel pattern of flat urothelial carcinoma. These histologic features may be more subtle than in other more typical patterns of CIS and should be carefully distinguished from therapy-related/reactive changes.

SAT-336 Non-Neoplastic Renal Diseases Are Common and Underdiagnosed in Nephroureterectomy Specimens

The relationship between chronic kidney disease and renal malignancies is increasingly being recognized. Non-neoplastic kidney diseases can be diagnosed in up to 15% of tumor nephrectomy specimens from kidney cancer patients. We conducted this study to evaluate the non-neoplastic renal parenchyma of nephroureterectomy specimens of urothelial neoplasia of the renal pelvis.

Keratin 17 is a sensitive and specific biomarker of urothelial neoplasia

There is a clinical need to identify novel biomarkers to improve diagnostic accuracy for the detection of urothelial tumors. The current study aimed to evaluate keratin 17 (K17), an oncoprotein that drives cell cycle progression in cancers of multiple anatomic sites, as a diagnostic biomarker of urothelial neoplasia in bladder biopsies and in urine cytology specimens. We evaluated K17 expression by immunohistochemistry in formalin-fixed, paraffin embedded tissue specimens of non-papillary invasive urothelial carcinoma (UC) (classical histological cases), high grade papillary UC (PUC-LG), low grade papillary UC (PUC-HG), papillary urothelial neoplasia of low malignant potential (PUNLMP), and normal bladder mucosa. A threshold was established to dichotomize K17 status in tissue specimens as positive vs. negative, based on the proportion of cells that showed strong staining. In addition, K17 immunocytochemistry was performed on urine cytology slides, scoring positive test results based on the detection of K17 in any urothelial cells. Mann–Whitney and receiver operating characteristic analyses were used to compare K17 expression between histologic diagnostic categories. The median proportion of K17 positive tumor cells was 70% (range 20–90%) in PUNLMP, 30% (range 5–100%) in PUC-LG, 20% (range 1–100%), in PUC-HG, 35% (range 5–100%) in UC but staining was rarely detected (range 0–10%) in normal urothelial mucosa. Defining cases in which K17 was detected in ≥10% of cells were considered positive, the sensitivity of K17 in biopsies was 89% (95% CI: 80–96%) and the specificity was 88% (95% CI: 70–95%) to distinguish malignant lesions (PUC-LG, PUC-HG, and UC) from normal urothelial mucosa. Furthermore, K17 immunocytochemistry had a sensitivity of 100% and a specificity of 96% for urothelial carcinoma in 112 selected urine specimens. Thus, K17 is a sensitive and specific biomarker of urothelial neoplasia in tissue specimens and should be further explored as a novel biomarker for the cytologic diagnosis of urine specimens.

Detection of pagetoid urothelial intraepithelial neoplasia extending to the vagina by cervical screening cytology: a case report with renewed immunochemical summary

BackgroundPagetoid spread of urothelial carcinoma (UC) to the lower genital tract is quite a rare and diagnostically challenging condition. Pagetoid urothelial intraepithelial neoplasia extending to the vagina is difficult to diagnose, especially in remote recurrences without symptomatic or macroscopic lesions typical to Paget disease. However, its identification by cervical screening cytology is important because UC is often characterized by a long history of relapse.Case presentationA 68-year-old Japanese postmenopausal woman developed brown vaginal discharge after radical cystectomy for bladder cancer (high-grade UC, pT2a pN0 cM0 [Union for International Cancer Control, 8th edition]) concomitant with focal in-situ UC in the urethra. She had a history of left renal pelvis UC, which was surgically removed 9 months before the radical cystectomy. Gynecologic examination of the lower genital tract was unremarkable although cervical screening cytology demonstrated severely atypical cells with pleomorphism repeatedly. Cervical colposcopy and diagnostic conization revealed no cervical neoplasm. In retrospect, immunocytochemical p16/Ki-67 dual staining for the previous cervical screening was negative for p16 labeling, and the neoplastic cells were positive for cytokeratins 7 and 20, p63, and GATA binding protein 3. No high-risk human papillomavirus genotype was identified by an automated DNA chip system using liquid-based cytology samples. Eleven months post-cystectomy, punch biopsy of the vulva and vagina confirmed intraepithelial UC in the juxtaposed squamous epithelium with pagetoid spread demonstrating positivity for specific urothelial markers: uroplakins II and III and thrombomodulin. Concurrent invasive malignancy was ruled out, and CO2 laser vaporization of the vulvar and vaginal lesion was performed. The patient remained alive without evidence of invasive malignancy for 14 months after the radical cystectomy for bladder cancer.ConclusionsTo detect recurrent pagetoid urothelial intraepithelial neoplasia with pagetoid spread in the lower genital tract, pathologists should recognize the history of prior UC with special attention to absence of p16 labeling in cervical cytology as a pointer to the diagnosis of urothelial cancer. Using further biopsy and immunohistochemical confirmation of UC relapse, investigation to rule out invasive malignancies and careful follow-up throughout the patient’s lifetime is recommended.

Histomorphological spectrum of urothelial tumors according to WHO/ISUP consensus classification (2016): Tertiary care center study

Background: Neoplastic urinary bladder lesions are responsible for significant morbidity and mortality throughout the world. The WHO/ISUP consensus classification (2016) for Urothelial tumors reflects an improved understanding and knowledge of the morphological types. The new diagnostic categories will increase the diagnostic reproducibility, clinicopathological correlation and prognostication. The most important criterion for optimal cancer treatment is a correct classification of the tumor. Aim & Objectives: The aim is to study Histomorphological spectrum of urothelial tumors according to World Health Organization / International Society of Urological Pathology consensus classification (2016) and to determine age and sex distribution of urothelial tumors. Material & Method: Study included 300 urothelial tumor specimens, conducted over a period 15 months, extending from March 2016 to May 2017. H & E stained sections were examined for morphologic diagnosis of urothelial neoplasm. An attempt was made to classify urothelial neoplasm according to WHO/ISUP consensus classification (2016) by two senior consultants of the department. Results: Among 300 cases, 14.33% cases were diagnosed as Infiltrating urothelial carcinoma, 85.66% cases were of Non-invasive urothelial neoplasia. Amongst which Non-invasive papillary urothelial carcinoma, low grade were most common that is 55.33% cases. Maximum no. of cases was diagnosed (33%) in 61-70 years of age group and male Female ratio being 3:1.Conclusion: This study documents a high frequency of non-invasive than infiltrating type of urothelial neoplasm. Non-invasive papillary urothelial carcinoma, low grade constitutes the commonest of urothelial tumors. Urothelial tumors are seen commonly in seventh decade with overall a male predominance.

Diagnostic utility of CK20, p53 and KI67 to differentiate between Papillomas/Non-Invasive papillary urothelial Neoplasm of low malignant potential/non-invasive papillary urothelial carcinoma, low grade

Background: Urinary Bladder cancer is the 7th most common cancer worldwide, with an estimated 260,000 new cases occurring each year in men and 76,000 in women. It is estimated that approximately 70-80% of patients with newly diagnosed bladder cancer present with non-invasive or early invasive. The problem arise mostly in distinguishing urothelial papilloma from non-invasive PUNLMP & papillary carcinoma especially low grade noninvasive ones. It is very important to distinguish these entities to design the therapeutic and monitoring strategies for these patients and it is difficult on the basis of histological features alone. Aim & Objectives: To study histomorphological spectrum of urothelial tumors according to WHO/ISUP consensus (2004) and to study pattern of expression of CK20, p53 LI & Ki67 LI to differentiate between Papillomas/PUNLMP/PUCLG.Material & Method: In this study 300 consecutive cases were taken from March 2016 to May 2017. Cases were histomorphologically classified according to WHO/ISUP (2004) classification & investigated the role of IHC panel of CK20, p53 & Ki67 to evaluate their utility for the diagnosis & to differentiate between Papilloma/PUNLMP/PUCLG. Results: Out of 300 cases, 48 cases were required IHC (CK20, p53, Ki67) for final diagnosis. Out of 48 cases, 16 were diagnosed as PUCLG, 10 were diagnosed as PUNLMP. Urothelial papilloma and Inverted urothelial papilloma were diagnosed in 13 and 9 cases respectively.Conclusion: The WHO/ISUP (2004) classification for bladder tumor enables to diagnose urothelial tumors into clinically and prognostically relevant entities. IHC panel of CK20, p53 & Ki67 may be a useful diagnostic marker in Papillary urothelial neoplasms, especially Non-invasive urothelial neoplasias at the lower end of the spectrum & help to differentiate papilloma/PUNLMP/PUCLG with borderline histological features.