Urothelial Papilloma Research Articles

Holmium: yttrium-aluminum-garnet (Ho:YAG) laser for resection of bladder tumor in a pediatric patient

Bladder tumours are rare in children, with only 0.4% of cases occurring in the first 2 decades of life. Herein, a pediatric patient who underwent TUR-B with a holmium: yttrium-aluminum-garnet ( Ho:YAG) laser is presented. Its histopathology was reported as urothelial papilloma.

MRI Findings of Inverted Urothelial Papilloma of the Bladder.

The objective of this study was to characterize MRI findings of inverted urothelial papilloma of the bladder. Data pertaining to 16 patients with 18 pathologically proven inverted urothelial papillomas of the bladder who had undergone MRI were retrospectively collected from seven institutions. The shape and surface characteristics of the tumors were evaluated using T2-weighted MR images. In addition, the signal intensity of inverted urothelial papillomas was visually assessed on T1-weighted, T2-weighted, and DW images and on early and delayed phase contrast-enhanced images. The shape of the 18 inverted urothelial papillomas of the bladder was classified as polypoid with a stalk for 16 tumors (89%) and polypoid without a stalk for two tumors (11%). All stalks were surrounded by urine in the bladder. A total of 15 of the tumor surfaces (83%) were nonpapillary and three (17%) were papillary. All 12 of the inverted urothelial papillomas for which evaluable T1-weighted images were available were isointense with the bladder wall. The lesions had a slightly higher signal intensity than the bladder wall in 15 of the patients (83%) and showed isointensity with the bladder wall in three patients (17%). A total of three patients (17%) had tiny hyperintense foci noted on T2-weighted images. All 16 of the inverted urothelial papillomas examined by DWI had very high signal intensity. All 13 of the lesions for which early phase images were obtained using dynamic contrast-enhanced MRI showed strong enhancement. When compared with early phase images, delayed phase images of the same 13 lesions showed that enhancement was stronger in two lesions (15%), similar in six lesions (46%), and weaker in five lesions (38%). On MRI, the typical appearance of inverted urothelial papillomas of the bladder is a polypoid shape with a nonpapillary surface and a thin short stalk surrounded by urine. Cystic foci are also occasionally seen within the tumor.

Immunohistochemistry and Fluorescence In Situ Hybridization Can Inform the Differential Diagnosis of Low-Grade Noninvasive Urothelial Carcinoma with an Inverted Growth Pattern and Inverted Urothelial Papilloma.

Urothelial carcinoma (UC) comprises a heterogeneous group of epithelial neoplasms with diverse biological behaviors and variable clinical outcomes. Distinguishing UC histological subtypes has become increasingly important because prognoses and therapy can dramatically differ among subtypes. In clinical work, overlapping morphological findings between low-grade noninvasive UC (LGNUC), which exhibits an inverted growth pattern, and inverted urothelial papilloma (IUP) can make subclassification difficult. We propose a combination of immunohistochemistry (IHC) and molecular cytogenetics for subtyping these clinical entities. In our study, tissue microarray immunohistochemical profiles of Ki-67, p53, cytokeratin 20 (CK20) and cyclinD1 were assessed. Molecular genetic alterations such as the gain of chromosomes 3, 7 or 17 or the homozygous loss of 9p21 were also assessed for their usefulness in differentiating these conditions. Based on our analysis, Ki-67 and CK20 may be useful for the differential diagnosis of these two tumor types. Fluorescence in situ hybridization (FISH) can also provide important data in cases in which the malignant nature of an inverted urothelial neoplasm is unclear. LGNUC with an inverted growth pattern that is negative for both Ki-67 and CK20 can be positively detected using FISH.

Transurethral Resection of the Bladder Tumour as a Treatment Method in Children with Transitional Cell Carcinoma of the Bladder--Analysis of Our Material and Literature Review.

Bladder cancer occurs mainly in adults. In children, younger than 10 years in particular, it is very rare. The aim of the study is to retrospectively evaluate the efficacy of transurethral resection of the bladder tumour (TUR-BT) of transitional cell carcinoma (TCC) of the bladder in children. Transurethral resection of the bladder tumour was performed in 7boys aged 4to 17 years (median 12.1years). In all cases laboratory tests, ultrasound, and cystoscopic tumour biopsy were carried out prior to the resection. Doxorubicin was additionally instilled intravesically as one dose in two patients. The Foley catheter was left in the bladder for 1to 4days (median 1.85 days). The follow-up period ranged from 10 months to 10 years (median 4years). Papillary urothelial neoplasm of low malignant potential (PUNLMP) was diagnosed in 5patients and urothelial papilloma in 2. Local recurrence was observed in one case two years after the resection. In all other cases complete remission was achieved. Transitional cell carcinoma of the bladder in children is usually benign and endoscopic treatment (TUR-BT) seems to be the treatment of choice. To determine afollow-up schedule amore substantial group of children with bladder cancer should be analysed.

Molecular characteristics of urothelial neoplasms in children and young adults: a subset of tumors from young patients harbors chromosomal abnormalities but not FGFR3 or TP53 gene mutations

Urothelial neoplasms in children and young adult patients are rare and hypothesized to have a lower rate of recurrence and progression than those of older adults. Because of their rarity, data regarding molecular abnormalities in these tumors are limited. We studied molecular characteristics of urothelial neoplasms from patients under age 30 years using UroVysion fluorescence in situ hybridization (chromosomes 3, 7, 17, and 9p21) and DNA mutational analysis for the FGFR3 and TP53 genes. Seventeen tumors were identified in patients 6–26 years of age, including low-grade papillary urothelial carcinoma (n=10), high-grade papillary urothelial carcinoma (n=5), urothelial papilloma (n=1), and papillary urothelial neoplasm of low malignant potential (n=1). No tumor demonstrated mutation of FGFR3 or TP53. Chromosomal abnormalities were detected only in patients aged ≥19 years: two low-grade urothelial carcinomas had loss of 9p21 as a sole chromosomal abnormality and three high-grade urothelial carcinomas had other or multiple chromosomal abnormalities. Under age 19 years, no tumor showed molecular abnormalities with either method (five low-grade papillary urothelial carcinomas and one each of high-grade papillary urothelial carcinoma, papillary urothelial neoplasm of low malignant potential, and urothelial papilloma). Our results support the idea that mutations of the FGFR3 and TP53 genes are rare or absent in urothelial neoplasms of young patients. In contrast, chromosomal abnormalities detected by UroVysion fluorescence in situ hybridization are sometimes present in patients above 19–20 years of age. This finding supports the recently proposed hypothesis that an age of 19–20 years separates distinct molecular pathways of urothelial carcinogenesis.

Metastatic renal cell carcinoma to the urinary bladder: a report of 11 cases.

Metastatic renal cell carcinoma (RCC) to the urinary bladder is rarely seen. Herein, we report the histologic subtypes, immunohistochemical characteristics, and prognosis of 11 patients with metastatic RCC to the urinary bladder. The mean age at the time of diagnosis of metastatic RCC to the bladder was 66 years (range, 58 to 79 y). There were 9 male and 2 female patients. Four patients presented with hematuria, 2 with urinary retention/obstruction, and 1 with bladder calculi. Four patients were asymptomatic and presented for surveillance cystoscopy, wherein they were found to have bladder masses. Nine patients had prior histories of RCC. The remaining 2 patients presented with metastatic clear cell RCC to the bladder and were subsequently found to have renal masses. The average time between nephrectomy and metastasis to the bladder was 20.7 months (range, 0 to 87 mo). Of the 10 patients with radical/partial nephrectomy, 7 cases were clear cell (2 with sarcomatoid features), 2 papillary, and 1 chromophobe with histologic fidelity between the primary and metastasis. Of cases with available data, the primaries' ISUP nucleolar grades were 2 (n=2), 3 (n=4), and 4 for the 2 cases with sarcomatoid features. In 8 cases, the bladder RCC undermined overlying urothelium with extensive urothelial denudation, and in 3 cases the RCC was free floating without attachment to the urothelium. The 1 chromophobe RCC metastasized with pagetoid spread to a preexisting urothelial papilloma. PAX8 immunohistochemistry was used to confirm the diagnosis in 2 cases. Three patients have no evidence of disease (7, 9, and 13 mo). Two are alive with disease after chemotherapy (30, 37 mo). Six patients are dead of disease with multiorgan metastases; 4 are dead after therapy (5, 8, 25, 28 mo), and two died without radiation or chemotherapy at 10 and 71 months. Metastatic RCC to the urinary bladder is uncommon, with most cases clear cell RCC. In some cases, evidence supports "drop metastases" as the mechanism of spread and patients have relatively long survival. However, in other cases spread to the bladder is in the setting of metastases to other sites, and these patients tended to die relatively shortly after their bladder metastases.

Bladder urothelial neoplasms in pediatric age: Experience at three tertiary centers

Urothelial bladder neoplasms (UBN) typically occur in patients in their sixth or seventh decade of life while they are infrequent in children and young adults. They occur in 0.1-0.4% of the population in the first two decades of life. Their management is controversial and paediatric guidelines are currently unavailable. To further expound the available data on the outcome of patients younger than 18 year old diagnosed with UBN. We retrospectively reviewed the files of all the consecutive paediatric patients with UBN treated in three tertiary paediatric urology units from January 1999 to July 2013. Lesions were classified according to the 2004 WHO/ISUP criteria as urothelial papillomas (UP), papillary urothelial neoplasm of low malignant potential (PUNLMP), low-grade urothelial carcinoma (LGUC), and high-grade urothelial carcinoma (HGUC). The table shows the results. Management after TURB varied among centres. One centre recommended only follow-up US at increasing intervals whereas another follow-up US plus urine cytologies and endoscopies, every three months in the first year, and at increasing intervals thereafter. After a median follow-up of 5 years (range 9 months-14.5 years), none of the patients showed disease recurrence or progression. UBN is an uncommon condition in children and adolescents and, unlike in adults, its incidence, follow-up and outcome still controversial. Paediatric guidelines are currently lacking and management varies among centres. Gross painless haematuria is the most common presenting symptom. Therefore, this symptom should never be underestimated. US is generally the first investigation and additional imaging seems unnecessary. TURB often allows for complete resection. Lesions are generally solitary, non-muscle invasive, and low-grade (mainly UP and PUNLMP). Ideal follow-up protocol is the most controversial point. Reportedly, recurrence or progression during follow-up is uncommon in patients under 20 years, recurrence rate 7% and a single case of progression reported so far. Accordingly, a follow-up mainly based on serial US might be considered in this age group compared to adults where also serial endoscopies and urine cytologies are recommended. In the selection of the follow-up investigations, it should also be taken into consideration that urine cytology has a low sensibility in the detection of low-grade lesions while cystoscopy in young patients requires a general anaesthesia and hospitalization, and carries an increased risk of urethral manipulation. UBN is a rare condition in children. Ultrasound is generally accurate in order to visualize the lesion, and TURB can treat the condition. Lesions are generally low-grade and non-muscle invasive, but high-grade lesions can also be detected. In present series, after TURB, follow-up US monitoring at increasing intervals was used at all centres, follow-up cystoscopies were added in two centres, but with different schedules. Urine cytologies were considered only at one centre. After a median follow-up of 5 years (range 9 months-14.5 years), none of the patients showed recurrence or progression of the disease.

HRAS mutations are frequent in inverted urothelial neoplasms.

Inverted urothelial papilloma (IUP) is an uncommon neoplasm of the urinary bladder with distinct morphologic features. Studies regarding the role of human papillomavirus (HPV) in the etiology of IUP have provided conflicting evidence of HPV infection. In addition, little is known regarding the molecular alterations present in IUP or other urothelial neoplasms, which might demonstrate inverted growth pattern like low-grade or high-grade urothelial carcinoma (UCA). Here, we evaluated for the presence of common driving somatic mutations and HPV within a cohort of IUPs, (n = 7) noninvasive low-grade papillary UCAs with inverted growth pattern (n = 5), and noninvasive high-grade papillary UCAs with inverted growth pattern (n = 8). HPV was not detected in any case of IUP or inverted UCA by either in situ hybridization or by polymerase chain reaction. Next-generation sequencing identified recurrent mutations in HRAS (Q61R) in 3 of 5 IUPs, described for the first time in this neoplasm. Additional mutations of Ras pathway members were detected including HRAS, KRAS, and BRAF. The presence of Ras pathway member mutations at a relatively high rate suggests this pathway may contribute to pathogenesis of inverted urothelial neoplasms. In addition, we did not find any evidence supporting a role for HPV in the etiology of IUP.

Long term outcome of primary urothelial papilloma: a single institution cohort

The aim of this study was to investigate the long term outcome of primary urothelial papilloma (UP). We retrieved 41 primary UP, diagnosed between January 2000 and December 2009. Follow-up was obtained by searching pathology and clinical electronic databases. Mean patient age was 57 years (range 30-84 years), with a male-to-female ratio of 1.9:1. Mean follow-up was 81 months (range 3-127 months). In 37 (90.2%) patients, no recurrence and/or progression were documented and no subsequent higher grade neoplasms were diagnosed. Three male patients were diagnosed with UP at 1, 31, and 43 months after the initial resection; the repeat diagnosis of UP at 1 month likely represented an incomplete resection. Thus, only two of 41 patients (4.9%) had a recurrent UP. One of these patients had a subsequent papillary urothelial neoplasm of low malignant potential (PUNLMP), 17 months after the recurrent UP (48 months after the initial UP). Only one additional male had a subsequent PUNLMP, 76 months after the initial UP. Thus, only two of 41 patients (4.9%) had a subsequent PUNLMP, both presenting with haematuria. Primary UP does not progress to UC when diagnosed using strict criteria, when no previous or concurrent neoplasms are documented, and when complete initial resection is performed.

Age and Gender Relation in Ureterial Tumors Detected with Transurethral Resection

Bladder tumors are biologically and chemically hazardous tumors that still remains as high morbidity and mortality rates even though the improvements of diagnosis and treatment in clinical field. Ureteral tumors constitutes about 90% of all bladder tumors and their biological behaviour vary from benign lesions to agressive cancers. In our study 66 diagnosed bladder biopsy and transureteral resection material were analysed retrospectively through the database of pathology department of Iskenderun State Hospital between january 2011 and November 2013.When only the bladder tumor cases were examined, 26 (59.65%) male and 3 (10.35%) female patients were detected. The age average of these tumor cases was 63.86±14.84 and ages were varied from 28-84. The 29 patients of tumor cases were consisted of 1 (1.52%) carcinoma in situ, 2 methastathic cancers, 1 papilloma, 2 low malignity potential papillary neoplasia, 14 low grade papillary carcinoma and 9 high grade papillary carcinoma. We observed that urothelial papilloma and low malignant potential papillary carcinoma has low rates and the percentage of low grade papillary carcinoma has high rates according to smilar studies. Unlikely the other studies, we found that the high grade papillary ureteral carcinoma can seen in further ages than low grade papillary ureteral carcinoma.In the light of our study, we recommend to keep in mind that malignant tumors of ureterium can be seen in all age groups and gender.

Long-term Clinical Outcome of Inverted Urothelial Papilloma Including Cases With Focal Papillary Pattern: Is Continuous Surveillance Necessary?

To investigate the necessity for continuous cystoscopic surveillance of inverted papilloma (IP), including tumors exhibiting mixed morphology (IP with focal papillary architecture). We retrieved all cases of de novo ("primary") IP, diagnosed in our institution during 10 years (from January 2000 to December 2009), from the information database. Patients with a history of urothelial carcinoma or concurrent urothelial carcinoma were excluded. Surveillance was performed by routine cystoscopy, and follow-up was obtained from our institutional and regional clinical and pathology databases. We identified 35 patients with IP, including 3 with focal papillary architecture. Mean patient age was 60 years (range, 26-88) with male-to-female ratio of 1.9:1. Most common tumor location was urinary bladder (86%), followed by urethra (14%). Focal papillary architecture was identified in 3 patients (aged 51, 52, and 78 years). Mean follow-up was 66 months (median 68; range, 11-132). Only 1 male patient (age 81) had a subsequent diagnosis of IP on follow-up cystoscopy at 9 months; no recurrence or progression was documented in the other patients diagnosed with IP. The absence of progression of IP on long-term follow-up in this study strongly argues against the need of continuous surveillance for patients in whom (1) strict diagnostic criteria are followed, (2) a complete resection can be ascertained, and (3) no previous or concurrent urothelial malignancies are documented. In this study, the 3 patients with IP showing focal papillary architecture had a benign course, similar to the previously documented cases.

Epithelial Urinary Bladder Tumors From Cows With Enzootic Hematuria

Thirty-nine epithelial bladder tumor samples from 37 animals affected with bovine enzootic hematuria (BEH) were selected for immunohistochemical studies. The expression of structural proteins such as uroplakin III (UPIII) and cytokeratin 7 (CK7) and the cell cycle-related proteins cyclin D1 and p53 were evaluated in urothelial papillomas and carcinomas. Loss of UPIII and CK7 expression was seen in both high-grade and high-stage urothelial carcinomas (P < .001 and P < .02). Cyclin D1 expression showed no statistically significant association with grade or stage. In contrast, p53 immunoreactivity was positive in high-grade and high-stage carcinomas (P < .05 and P < .01), confirming its association with the highest malignant behavior of the bladder tumors in BEH.

Human Papillomavirus is Not an Etiologic Agent of Urothelial Inverted Papillomas

Inverted papilloma of the urinary bladder is rare, accounting for <1% of all bladder neoplasms. Although there is general consensus that inverted papilloma is benign in nature, little is known about its pathogenesis. Some have suggested that human papillomavirus (HPV) plays an etiologic role in the development of this neoplasm. These claims have not been adequately substantiated, and there is controversy as to the role of HPV in other urinary bladder neoplasms as well. To further investigate a possible etiologic role of HPV in urothelial neoplasia, we evaluated 27 inverted papillomas of the urinary bladder for the presence of HPV. Both immunohistochemical and in situ hybridization (ISH) studies for HPV and immunohistochemical analysis for p16, a surrogate marker for HPV infection, were used to assess HPV infection status. In the urinary bladder inverted papillomas of these 27 patients (age range, 35 to 78 y; M:F ratio, 11:1), no HPV was detected by HPV immunohistochemistry or by ISH. Immunoreactivity to p16 was detected in 11/27 (41%) of the cases. Expression of p16 is seen inconsistently within these neoplasms and does not correlate with the presence of HPV antigens or genes by immunohistochemistry or ISH, respectively. Therefore, p16 is not a reliable surrogate marker for HPV infection in urothelial inverted papilloma. Our findings indicate the absence of HPV in urothelial inverted papillomas. HPV testing should not be used as a diagnostic adjunct for inverted papilloma cases.

Abstract 4071: Angiogenin enhances proliferation, progression and angiogenesis in human bladder cancer.

Abstract Introduction: Angiogenin (ANG) is a member of RNase A family and regulates synthesis of various proteins. ANG is reported to act on both vascular endothelial cells and cancer cells. Although it has been demonstrated that upregulated ANG plays important roles on cellular proliferation, migration and angiogenesis in several malignancies, there are very few reports addressing the relationship between ANG expression and bladder cancer. The aim of this study is to investigate the biological function of ANG in bladder cancer. Methods: UROtsa (benign urothelial cell line), RT4 (urothelial papilloma cell line), KU7 (non-invasive bladder cancer) and T24 (invasive bladder cancer) were used in this study. ANG-overexpressing stable clones in UROtsa were created using plasmid DNA transfection and ANG down-regulation in KU7 and T24 were created using siRNA transfection or short-hairpin RNA (shRNA) transfection. Proliferation assay, migration/invasion assay, anchorage-independent colony formation assay in soft agar and in-vitro Matrigel tube formation assay using HUVEC were carried out with conditioned media. ANG overexpression clone (UROtsa) and ANG shRNA expressing clones (KU7 and T24) were subcutaneously injected into nude mice to investigate whether ANG expression increase tumorigenicity and tumor growth in vivo. Results: Higher level of ANG was expressed in cancer cell lines, KU7 and T24, compared to non-cancer cell lines, UROtsa and RT4. Proliferation assay and soft agar assay revealed that ANG expression was associated with cell growth and anchorage independent growth in the mediation of dephophorylation of ERK1/2 and JNK/SAPK. Migration was inhibited significantly by knocking down ANG in KU7 (non-invasive cancer), while invasion was inhibited in T24 (invasive cancer). An in vitro Matrigel angiogenesis assay demonstrated that conditioned media collected from ANG overexpressing stable clones resulted in increased tube formation as compared to the control clone in UROtsa, while the tube formation ability was decreased by knocking down ANG in cancer cells. In tumorigenicity testing in nude mice, tumor growth was correlated with higher expression of ANG. Four weeks after inoculation of cells in nude mice, there was a significant difference in tumor size in all the cell lines (UROtsa control vs ANG overexpression, KU7 control shRNA vs ANG shRNA, T24 control shRNA vs ANG shRNA), suggesting that ANG expression supported tumorigenicity and tumor growth. Conclusions: These results suggest that ANG overexpression enhances tumor growth and progression. ANG secreted from cancer cells promotes angiogenesis in bladder cancer. Therefore, ANG may be a potential therapeutic target in bladder cancer. Citation Format: Makito Miyake, Steve Goodison, Evan Gomes Giacosia, Jeongsoon Kim, Shanti Ross, Ge Zhang, Charles J. Rosser. Angiogenin enhances proliferation, progression and angiogenesis in human bladder cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4071. doi:10.1158/1538-7445.AM2013-4071

Premalignant lesions of the urinary bladder

Although most carcinomas of the bladder occur de novo, some vesical lesions progress to malignancy over time. These lesions appear morphologically benign, but often harbour genetic changes that signify their malignant potential. Despite their benign appearance, accurate identification is important given that these patients will require close follow-up. In addition to this some lesions may mimic carcinoma, and as a consequence, misdiagnosis could result in serious over-treatment. In this review, we discuss the clinical and histological features as well as the differential diagnosis of lesions of the bladder that have the potential to progress to cancer. Specifically, we present the features of flat, papillary and atypical urothelial hyperplasia, urothelial papilloma, urothelial dysplasia, intestinal metaplasia, keratinising squamous metaplasia, verrucous squamous hyperplasia and condyloma acuminatum and examine the molecular and clinical evidence relating to their malignant potential.

Coincidence of HPV11-Positive Urethral Condyloma Acuminatum and HPV-Negative Multiple Bladder Papillomas in a Female

Human papillomaviruses (HPVs) are associated with proliferative lesions in a variety of human epithelial types. A 38-year-old female presented with a diagnosis of urethral condyloma acuminatum. She underwent transurethral resection of the urethral condyloma. At that time, multiple (five) bladder tumors were simultaneously found and also removed by transurethral resection. Four of the bladder tumors were diagnosed as squamous papilloma, and the other was urothelial inverted papilloma. Postoperative course was uneventful. Genomic DNA was extracted from 10 μm thick sections of each bladder tumor as well as urethral condyloma. Then, 16 types of HPV DNA sequences were assessed with the PapiPlex method using genomic DNA samples extracted from each bladder tumor as well as urethral condyloma. HPV-11 was detected in DNA extracted from the urethral condyloma, while no HPV DNA sequences were positive in any of the genomic DNA samples extracted from the bladder tumors.

A Case Report of an Inverted Papilloma of the Prostatic Urethra and a Synchronous Low-Grade Papillary Carcinoma of the Bladder

Inverted urothelial papilloma is a rare benign tumour and represents one of the urothelial lesions with inverted morphology. Accurate diagnosis and differentiation from other inverted lesions is important because its proper clinical management and expected clinical outcomes are distinctly different. Here we describe a case of a large inverted urothelial papilloma of the prostatic urethra and a synchronous non-invasive low-grade papillary urothelial carcinoma of the bladder in a 60-year-old man. We focus on the differential diagnosis of inverted urothelial papilloma.

Expression of Claudins and Their Prognostic Significance in Noninvasive Urothelial Neoplasms of the Human Urinary Bladder

The members of the claudin family are major integral transmembrane protein constituents of tight junctions. Normal and neoplastic tissues can be characterized by unique qualitative and quantitative distribution of claudin subtypes, which may be related to clinicopathological features. Differential diagnosis and prognosis of nonmuscle invasive tumor entities of urinary bladder epithelium are often challenging. The aim was to investigate the expression profile of claudins in inverted urothelial papillomas (IUPs), urothelial papillomas (UPs), papillary urothelial neoplasms of low malignant potential (PUNLMPs), and intraepithelial (Ta), low-grade urothelial cell carcinomas (LG-UCCs) in order to reveal potential prognostic and differential diagnostic values of certain claudins. Claudin-1, -2, -4, and -7 protein expressions detected by immunohistochemistry and clinical data were analyzed in 15 IUPs, 20 UPs, 20 PUNLMPs, and 20 LG-UCCs. UPs, PUNLMPs, and LG-UCCs showed significantly decreased claudin-1 expression in comparison to IUPs. LG-UCCs expressing claudin-4 over the median were associated with significantly shorter recurrence-free survival. PUNLMPs expressing claudin-1 over the median revealed significantly longer recurrence-free survival. High claudin-1 protein expression might help to differentiate IUP from UPs, PUNLMPs, and LG-UCCs. High claudin-4 expression may determine an unfavorable clinical course of LG-UCCs, while high claudin-1 expression in PUNLMP was associated with markedly better clinical outcome.

1753 RECURRENCE AND PROGRESSION RATES OF UROTHELIAL PAPILLOMAS OF THE URINARY BLADDER

You have accessJournal of UrologyBladder Cancer: Superficial1 Apr 20111753 RECURRENCE AND PROGRESSION RATES OF UROTHELIAL PAPILLOMAS OF THE URINARY BLADDER Ali Amin, Sheila Faraj, Alcides Chaux, Turki Al-hussain, Roni Cox, Michael Nagar, and George J. Netto Ali AminAli Amin Baltimore, MD More articles by this author , Sheila FarajSheila Faraj Baltimore, MD More articles by this author , Alcides ChauxAlcides Chaux Baltimore, MD More articles by this author , Turki Al-hussainTurki Al-hussain Baltimore, MD More articles by this author , Roni CoxRoni Cox Baltimore, MD More articles by this author , Michael NagarMichael Nagar Baltimore, MD More articles by this author , and George J. NettoGeorge J. Netto Baltimore, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2080AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urothelial papilloma (UP) is a rare tumor of the genitourinary tract, usually seen in younger patients as an isolated, small papillary lesion. A recurrence rate of 0–31% and a lower than 10% risk of progression have been previously reported in UP. The aim of this study is to evaluate the clinical outcome of patients with UP diagnosed in one institution. This is, to the best of our knowledge, the largest series on the long term follow up of urothelial papilloma. METHODS Fifty-three cases diagnosed between 1998 and 2009 as primary UP (without previous history of a higher grade lesion) were retrieved from the archives of our department. Medical records were reviewed and the primary care physician was contacted for follow-up information. Recurrence was defined as the subsequent development of any type of neoplastic urothelial lesion while progression was defined as the development of subsequent lesion of higher histological grade (urothelial dysplasia, papillary urothelial neoplasm of low malignant potential [PUNLMP], low or high-grade papillary urothelial carcinoma). Follow-up ranged from 1–60 months (mean 16.6, median 12 months). RESULTS The mean of age for the patients was 67.4 y (range 24–90 years). Overall recurrence was identified in 19 cases (35%); recurrence without progression was observed in 2 cases (3.7%) after a mean duration of 22.0 months (range 5–39 months), and recurrence with progression in 17 cases (32%) after a mean duration of 11.6 months (range 1–34 months) from initial UP diagnosis. The difference between the mean intervals of recurrence with and without progression was not statistically significant. None of the patients developed invasive urothelial carcinoma. Most frequent progression was to low-grade urothelial carcinoma in 7 cases (13%) followed by high-grade urothelial carcinoma (4 cases, 7%), urothelial dysplasia and PUNLMP (3 cases each, 5%). None of the 53 patients died of urothelial carcinoma; however seven patients died from unrelated causes. CONCLUSIONS Although none of our patients developed invasive urothelial carcinoma or died of urothelial carcinoma, we found a relatively high rate of recurrence and progression in our UP cohort compared to previous series. Additional studies are still needed to evaluate the current risk of recurrence and progression in urothelial papillomas. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e703 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ali Amin Baltimore, MD More articles by this author Sheila Faraj Baltimore, MD More articles by this author Alcides Chaux Baltimore, MD More articles by this author Turki Al-hussain Baltimore, MD More articles by this author Roni Cox Baltimore, MD More articles by this author Michael Nagar Baltimore, MD More articles by this author George J. Netto Baltimore, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Etiological role of human papillomavirus infection for inverted papilloma of the bladder

The status of human papillomavirus (HPV) infection in urothelial inverted papilloma was examined in the present study. Formalin-fixed and paraffin-embedded tissues from eight cases of inverted papilloma of the bladder were studied. The presence of HPV-DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri-Max HPV genotyping kit. Immunohistochemical analysis for p16-INK4a, mcm7, HPV-E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as inverted papilloma with atypia, while the remaining five were typical cases. HPV-18 was detected in two cases, including one inverted papilloma with atypia, and HPV-16 was detected in four cases, including one inverted papilloma with atypia. Multiple HPV type infection was detected in one typical case and one atypical case. High-risk HPV was present in all HPV-positive cases. Cellular proteins, p16-INK4a and mcm7, which are surrogate markers for HPV-E7 expression, were detected in all HPV-positive cases, and their levels were higher in inverted papilloma with atypia than in typical cases. In contrast, HPV-E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical inverted papilloma tissue. High-risk HPV infection may be one of the causes of urothelial inverted papilloma, and inverted papilloma with atypia may have malignant potential.