Papillary urothelial neoplasm of low malignant potential of the urinary bladder: clinicopathologic and outcome analysis from a single academic center
Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231, USA.Human pathology (Impact Factor: 2.77). 07/2011; 42(11):1799-803. DOI: 10.1016/j.humpath.2011.03.006
Few long-term single-center studies have addressed the outcome of patients with papillary urothelial neoplasms of low malignant potential. Our study evaluates the behavior of these tumors occurring as primary urinary bladder lesions. For this purpose, 34 primary in-house cases diagnosed and treated between 1998 and 2008 were identified from our medical records. Upon review, 3 cases were upgraded to noninvasive low-grade urothelial carcinomas and excluded from further evaluation. During follow-up (range, 3-108 months; mean, 42 months), 13 patients developed recurrences; and 9 patients progressed to a noninvasive higher grade lesion (8 to low-grade and 1 to high-grade urothelial carcinomas). None of our patients developed stage progression (>pTa) or died of bladder cancer. Size of the primary tumor was associated with the risk of recurrence (P = .043), whereas the number of episodes of recurrence was associated with the likelihood of grade progression (P = .034). In conclusion, recurrences were observed in 42% of all our patients, with a grade progression rate of 29%. None of our patients developed invasive carcinoma or died as a consequence of their disease. Considering the low but definitive risk of recurrence and grade progression, appropriate clinical follow-up of patients with primary papillary urothelial neoplasm of low malignant potential is warranted.
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ABSTRACT: A uniform grading system for bladder cancer will allow for valid comparison of treatment results among different centers. The introduction of the World Health Organization (2004)/International Society of Urological Pathology classification is a welcome step toward standardization of treatment and follow-up regimens. The greatest source of controversy with the World Health Organization (2004)/International Society of Urological Pathology classification system centers on the diagnosis of papillary urothelial neoplasm of low malignant potential. Some feel that papillary urothelial neoplasm of low malignant potential terminology increases the complexity of histologic grading and does not accurately reflect biologic potential. Papillary urothelial neoplasm of low malignant potential is a low-grade papillary urothelial neoplasm with a substantial incidence of recurrence and progression. In the distinction of papillary urothelial neoplasm of low malignant potential from noninvasive low-grade papillary urothelial carcinoma, there is considerable interobserver variability. For these reasons, some investigators believe that papillary urothelial neoplasm of low malignant potential is, in essence, an entity that was previously designated grade 1 urothelial carcinoma in the World Health Organization 1973 grading system. In addition, treatment and follow-up regimens for patients with papillary urothelial neoplasm of low malignant potential do not typically differ from those prescribed for low-grade, noninvasive urothelial carcinoma, further minimizing the clinical need for the papillary urothelial neoplasm of low malignant potential distinction to be made. We propose abandonment of the terminology "papillary urothelial neoplasm of low malignant potential" in bladder tumor classification. Full-genome searches for prognostic and predictive molecular gene expression signatures as cancer markers have shown significant promise. Recent advances in the molecular grading of these tumors may eventually supplant traditional morphologic grading systems, allowing a more precise and objective assessment of the tumors' biologic potentials.
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ABSTRACT: The classification and grading of the noninvasive, intraepithelial neoplasms of the urothelium are based on the morphological pattern of growth, i.e., papillary and flat (and endophytic), and on their degree of architectural and cytologic abnormalities. Recent advances in the morphological, molecular and quantitative evaluation of these lesions have contributed to the refinement of the current classification and grading schemes. However, some controversies on the precise criteria and terminology, especially when the papillary lesions are concerned, are still present.
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ABSTRACT: Changes in the expression of the mismatch repair (MMR) genes hMSH2, hMLH1, hMSH6 and hPMS2 reflect dysfunction of the DNA repair system that may allow the malignant transformation of tissue cells. The aim of the present study was to address the mRNA expression profiles of the mismatch DNA repair system in cancerous and precancerous urothelium. This is the first study to quantify MMR mRNA expression by applying quantitative real-time PCR (qPCR) and translate the results to mRNA phenotypic profiles (r, reduced; R, regular or elevated) in bladder tumors [24 urothelial cell carcinomas (UCCs) and 1 papillary urothelial neoplasm of low malignant potential (PUNLMP)] paired with their adjacent normal tissues (ANTs). Genetic instability analysis was applied at polymorphic sites distal or close to the hMSH2 and hMLH1 locus. Presenting our data, reduced hMSH2, hMSH6 and hPMS2 mRNA expression profiles were observed in cancerous and precancerous urothelia. Significantly, the ANTs of UCCs revealed the highest percentages of reduced hMSH2 (r(2)), hMSH6 (r(6)) and hPMS2 (p(2)) mRNA phenotypes relative to their tumors (P<0.03). In particular, combined r(2)r(6) (P<0.02) presented a greater difference between ANTs of low-grade UCCs vs. their tumors compared with ANTs of high-grade UCCs (P= 0.000). Reduced hMLH1 (r(1)) phenotype was not expressed in precancerous or cancerous urothelia. The hMSH6 mRNA was the most changed in UCCs (47.8%), while hMSH2, hMLH1 and hPMS2 showed overexpression (47.8, 35 and 30%, respectively) that was associated with gender and histological tumor grading or staging. Genetic instability was rare in polymorphic regions distal to hMLH1. Our data reveal a previously unrecognized hMSH2 and hMSH6 mRNA combined phenotype (r(2)r(6)) correlated with a precancerous urothelium and show that hMLH1 is transcriptionally activated in precancerous or cancerous urothelium. In the present study, it is demonstrated that reduction of hMSH6 mRNA is a frequent event in bladder tumorigenesis and reflects a common mechanism of suppression with hMSH2, while alterations of hMSH2 or hMLH1 mRNA expression in UCCs does not correlate with the allelic imbalance of polymorphic regions harboring the genes.
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