The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in bladder neoplasia with a focus on issues relevant to the practicing surgical pathologist for the understanding and effective reporting of bladder cancer, emphasizing particularly on the newly accumulated evidence post-2016 World Health Organization (WHO) classification. The work is presented in 2 manuscripts. Here, in the first, we revisit the nomenclature and classification system used for grading flat and papillary urothelial lesions centering on clinical relevance, and on dilemmas related to application in routine reporting. As patients of noninvasive bladder cancer frequently undergo cystoscopy and biopsy in their typically prolonged clinical course and for surveillance of disease, we discuss morphologies presented in these scenarios which may not have readily applicable diagnostic terms in the WHO classification. The topic of inverted patterns in urothelial neoplasia, particularly when prominent or exclusive, and beyond inverted papilloma has not been addressed formally in the WHO classification. Herein we provide a through review and suggest guidelines for when and how to report such lesions. In promulgating these GUPS recommendations, we aim to provide clarity on the clinical application of these not so uncommon diagnostically challenging situations encountered in routine practice, while also importantly advocating consistent terminology which would inform future work.

Department of Histopathology and Molecular Diagnostics University Hospital Careggi Florence Italy

Department of Pathology All India Institute of Medical Sciences New Delhi Delhi India

Department of Pathology and Laboratory Medicine Cumming School of Medicine University of Calgary Calgary AB Canada

Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis IN

Department of Pathology and Laboratory Medicine University of Tennessee Health Science Memphis

Department of Pathology Charles University Prague Faculty of Medicine and University Hospital in Plzen Plzen Czech Republic

Department of Pathology Immunology and Laboratory

Department of Pathology Koc University School of Medicine Istanbul Turkey

Department of Pathology Mayo Clinic Rochester MN

Department of Pathology Michigan Medicine University of Michigan Ann Arbor MI

Department of Pathology Microbiology and Immunology Vanderbilt University Medical Center Nashville TN

Department of Pathology Montreal QC

Department of Pathology Oregon Health Science University OR

Department of Pathology Taipei Veterans General Hospital Taipei Taiwan

Department of Pathology The University of Alabama at Birmingham Birmingham AL

Department of Pathology The University of Texas MD Anderson Cancer Center

Department of Pathology Tufts Medical Center Boston MA

Department of Pathology University of Chicago Chicago IL

Department of Pathology University of Erlangen Nuremberg Erlangen Germany

Department of Pathology University of Washington School of Medicine Seattle WA

Department of Pathology Vienna General Hospital

Department of Urology Comprehensive Cancer Center Medical University Vienna Vienna General Hospital Vienna Austria

Department of Urology Keck School of Medicine of University of Southern California Los Angeles CA

Departments of Pathology

Departments of Pathology and Laboratory Medicine

GRC 5 Predictive ONCO URO AP HP Urology Pitie Salpetriere Hospital Sorbonne University Paris France

Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University Moscow Russia

Institute of Pathology University Medicine Essen University of Duisburg Essen Essen

Medical University Department of Pathology Hôpital Tenon Sorbonne University

Medicine

Oncology The Johns Hopkins Medical Institutions Baltimore MD

Robert J Tomsich Pathology and Laboratory Medicine Institute Cleveland Clinic Cleveland OH

Urology

Urology Emory University School of Medicine Atlanta GA

Urology Service Department of Surgery Memorial Sloan Kettering Cancer Center New York NY

Urology Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center Dallas TX

See more in PubMed

Moch H, Humphrey PA, Ulbright TM, et al. WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition. Lyon, France: International Agency for Research on Cancer; 2016.

Melicow MM. Histological study of vesical urothelium intervening between gross neoplasms in total cystectomy. J Urol. 1952;68:261–279.

Melicow MM, Hollowell JW. Intra-urothelial cancer: carcinoma in situ, Bowen’s disease of the urinary system: discussion of thirty cases. J Urol. 1952;68:763–772.

Koss LG. Bladder cancer from a perspective of 40 years. J Cell Biochem Suppl. 1992;16I:23–29.

Utz DC, Zincke H. The masquerade of bladder cancer in situ as interstitial cystitis. J Urol. 1974;111:160–161.

Melick WF, Escue HM, Naryka JJ, et al. The first reported cases of human bladder tumors due to a new carcinogen-xenylamine. J Urol. 1955;74:760–766.

Koss LG. Armed Forces Institute of Pathology. Tumors of the Urinary Bladder Vol 11, 2nd ed. Washington, DC: Armed Forces Institute of Pathology; 1975.

Nagy GK, Frable WJ, Murphy WM. Classification of premalignant urothelial abnormalities. A Delphi study of the National Bladder Cancer Collaborative Group A. Pathol Annu. 1982;17 (pt 1):219–233.

Mostofi FK, Sesterhenn IA. Pathology of epithelial tumors & carcinoma in situ of bladder. Prog Clin Biol Res. 1984;162A:55–74.

Murphy WM, Beckwith JB, Farrow GM. Tumors of the Kidney, Bladder, and Related Urinary Structures, 3rd ed. Washington, DC: Armed Forces Institute of Pathology; 1994.

Amin MB, Murphy WM, Reuter VE, et al. Rosen PP, Fechner RE. Controversies in the pathology of transitional cell carcinoma of the urinary bladder. Part I, Chapter I: reviews of patholog y, Vol. 1. Chicago: ASCP Press; 1996:1–39.

Epstein JI, Amin MB, Reuter VR, et al. The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol. 1998;22:1435–1448.

Humphrey PA, Moch H, Cubilla AL, et al. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. Eur Urol. 2016;70:106–119.

Comperat EM, Burger M, Gontero P, et al. Grading of Urothelial Carcinoma and The New “World Health Organisation Classification of Tumours of the Urinary System and Male Genital Organs 2016”. Eur Urol Focus. 2019;5:457–466.

Lopez-Beltran A, Cheng L, Andersson L, et al. Preneoplastic non-papillary lesions and conditions of the urinary bladder: an update based on the Ancona International Consultation. Virchows Arch. 2002;440:3–11.

van Oers JM, Adam C, Denzinger S, et al. Chromosome 9 deletions are more frequent than FGFR3 mutations in flat urothelial hyperplasias of the bladder. Int J Cancer. 2006;119:1212–1215.

Hartmann A, Moser K, Kriegmair M, et al. Frequent genetic alterations in simple urothelial hyperplasias of the bladder in patients with papillary urothelial carcinoma. Am J Pathol. 1999;154:721–727.

Hodges KB, Lopez-Beltran A, Davidson DD, et al. Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features. Hum Pathol. 2010;41:155–162.

Cheng L, Cheville JC, Neumann RM, et al. Natural history of urothelial dysplasia of the bladder. Am J Surg Pathol. 1999;23:443–447.

Cheng L, Cheville JC, Neumann RM, et al. Flat intraepithelial lesions of the urinary bladder. Cancer. 2000;88:625–631.

McKenney JK. Precursor lesions of the urinary bladder. Histopathology. 2019;74:68–76.

Kunju LP, Lee CT, Montie J, et al. Utility of cytokeratin 20 and Ki-67 as markers of urothelial dysplasia. Pathol Int. 2005;55:248–254.

Mallofre C, Castillo M, Morente V, et al. Immunohistochemical expression of CK20, p53, and Ki-67 as objective markers of urothelial dysplasia. Mod Pathol. 2003;16:187–191.

Murata S, Iseki M, Kinjo M, et al. Molecular and immunohistologic analyses cannot reliably solve diagnostic variation of flat intraepithelial lesions of the urinary bladder. Am J Clin Pathol. 2010;134:862–872.

Sun W, Zhang PL, Herrera GA. p53 protein and Ki-67 overexpression in urothelial dysplasia of bladder. Appl Immunohistochem Mol Morphol. 2002;10:327–331.

Lawless ME, Tretiakova MS, True LD, et al. Flat urothelial lesions with atypia: interobserver concordance and added value of immunohistochemical profiling. Appl Immunohistochem Mol Morphol. 2018;26:180–185.

Arias-Stella JA III, Shah AB, Gupta NS, et al. CK20 and p53 immunohistochemical staining patterns in urinary bladder specimens with equivocal atypia. Arch Pathol Lab Med. 2018;142:64–69.

McIntire P, Khan R, Kilic I, et al. Immunohistochemistry in the workup of bladder biopsies: Frequency, variation and utility of use at an academic center. Ann Diagn Pathol. 2019;41:124–128.

Comperat E, Jacquet SF, Varinot J, et al. Different subtypes of carcinoma in situ of the bladder do not have a different prognosis. Virchows Arch. 2013;462:343–348.

Sangoi AR, Falzarano SM, Nicolas M, et al. Carcinoma in situ with plasmacytoid features: a clinicopathologic study of 23 cases. Am J Surg Pathol. 2019;43:1638–1643.

Mai KT, Busca A, Belanger EC. Flat intraurothelial neoplasia exhibiting diffuse immunoreactivity for CD44 and cytokeratin 5 (urothelial stem cell/basal cell markers): a variant of intraurothelial neoplasia commonly associated with muscle-invasive urothelial carcinoma. Appl Immunohistochem Mol Morphol. 2017;25:505–512.

Nguyen JK, Przybycin CG, McKenney JK, et al. Immunohistochemical staining patterns of Ki-67 and p53 in florid reactive urothelial atypia and urothelial carcinoma in situ demonstrate significant overlap. Hum Pathol. 2020;98:81–88.

Neal DJ, Amin MB, Smith SC. CK20 versus AMACR and p53 immunostains in evaluation of urothelial carcinoma in situ and reactive atypia. Diagn Pathol. 2020;15:61.

Aron M, Luthringer DJ, McKenney JK, et al. Utility of a triple antibody cocktail intraurothelial neoplasm-3 (IUN-3-CK20/CD44s/p53) and alpha-methylacyl-CoA racemase (AMACR) in the distinction of urothelial carcinoma in situ (CIS) and reactive urothelial atypia. Am J Surg Pathol. 2013;37:1815–1823.

Long ED, Shepherd RT. The incidence and significance of vaginal metaplasia of the bladder trigone in adult women. Br J Urol. 1983;55:189–194.

Ahmad I, Barnetson RJ, Krishna NS. Keratinizing squamous metaplasia of the bladder: a review. Urol Int. 2008;81:247–251.

Khan MS, Thornhill JA, Gaffney E, et al. Keratinising squamous metaplasia of the bladder: natural history and rationalization of management based on review of 54 years experience. Eur Urol. 2002;42:469–474.

Guo CC, Fine SW, Epstein JI. Noninvasive squamous lesions in the urinary bladder: a clinicopathologic analysis of 29 cases. Am J Surg Pathol. 2006;30:883–891.

Warrick JI, Kaag M, Raman JD, et al. Squamous dysplasia of the urinary bladder: a consecutive cystectomy series. Int J Surg Pathol. 2016;24:306–314.

Yang Z, Epstein JI. Urothelial carcinoma in situ of the bladder with glandular differentiation: report of 92 cases. Am J Surg Pathol. 2018;42:971–976.

Gordetsky J, Epstein JI. Intestinal metaplasia of the bladder with dysplasia: a risk factor for carcinoma? Histopathology. 2015;67:325–330.

Dadhania V, Czerniak B, Guo CC. Adenocarcinoma of the urinary bladder. Am J Clin Exp Urol. 2015;3:51–63.

Xin Z, Zhao C, Huang T, et al. Intestinal metaplasia of the bladder in 89 patients: a study with emphasis on long-term outcome. BMC Urol. 2016;16:24.

Pires-Luis AS, Martinek P, Alaghehbandan R, et al. Molecular genetic features of primary nonurachal enteric-type adenocarcinoma, urachal adenocarcinoma, mucinous adenocarcinoma, and intestinal metaplasia/adenoma: review of the literature and next-generation sequencing study. Adv Anat Pathol. 2020;27:303–310.

Barrington JW, Fulford S, Griffiths D, et al. Tumors in bladder remnant after augmentation enterocystoplasty. J Urol. 1997;157:482–485; discussion 485–486.

Armah HB, Krasinskas AM, Parwani AV. Tubular adenoma with high-grade dysplasia in the ileal segment 34 years after augmentation ileocystoplasty: report of a first case. Diagn Pathol. 2007;2:29.

Lin TP, Chen M, Hsu JM, et al. Adenocarcinoma arising from tubulovillous adenoma in a native bladder following gastrocystoplasty. Pediatr Surg Int. 2014;30:123–126.

Smith AK, Hansel DE, Jones JS. Role of cystitis cystica et glandularis and intestinal metaplasia in development of bladder carcinoma. Urology. 2008;71:915–918.

Acosta AM, Sholl LM, Fanelli GN, et al. Intestinal metaplasia of the urinary tract harbors potentially oncogenic genetic variants. Mod Pathol. 2021;34:457–468.

Amin A, Murati-Amador B, Lombardo KA, et al. Analysis of intestinal metaplasia without dysplasia in the urinary bladder reveal only rare mutations associated with colorectal adenocarcinoma. Appl Immunohistochem Mol Morphol. 2020;28:786–790.

Jordan AM, Weingarten J, Murphy WM. Transitional cell neoplasms of the urinary bladder. Can biologic potential be predicted from histologic grading? Cancer. 1987;60:2766–2774.

Akgul M, MacLennan GT, Cheng L. Distinct mutational landscape of inverted urothelial papilloma. J Pathol. 2019;249:3–5.

Isharwal S, Hu W, Sarungbam J, et al. Genomic landscape of inverted urothelial papilloma and urothelial papilloma of the bladder. J Pathol. 2019;248:260–265.

Holmang S, Hedelin H, Anderstrom C, et al. Recurrence and progression in low grade papillary urothelial tumors. J Urol. 1999;162:702–707.

Holmang S, Andius P, Hedelin H, et al. Stage progression in Ta papillary urothelial tumors: relationship to grade, immunohistochemical expression of tumor markers, mitotic frequency and DNA ploidy. J Urol. 2001;165:1124–1128; discussion 1128–1130.

Pan CC, Chang YH, Chen KK, et al. Prognostic significance of the 2004 WHO/ISUP classification for prediction of recurrence, progression, and cancer-specific mortality of non-muscle-invasive urothelial tumors of the urinary bladder: a clinicopathologic study of 1515 cases. Am J Clin Pathol. 2010;133:788–795.

Maxwell JP, Wang C, Wiebe N, et al. Long-term outcome of primary papillary urothelial neoplasm of low malignant potential (PUNLMP) including PUNLMP with inverted growth. Diagn Pathol. 2015;10:3.

Bosschieter J, Hentschel A, Savci-Heijink CD, et al. Reproducibility and prognostic performance of the 1973 and 2004 World Health Organization Classifications for grade in non-muscle-invasive bladder cancer: a multicenter study in 328 bladder tumors. Clin Genitourin Cancer. 2018;16:e985–e992.

Rieken M, Shariat SF, Kluth L, et al. Comparison of the EORTC tables and the EAU categories for risk stratification of patients with nonmuscle-invasive bladder cancer. Urol Oncol. 2018;36:8.e17–8.e24.

Varma M, Delahunt B, van der Kwast T. Grading noninvasive bladder cancer: World Health Organisation 1973 or 2004 may be the wrong question. Eur Urol. 2019;76:413–415.

Comperat E, Amin M, Reuter V. Reply re: Murali Varma, Brett Delahunt, Theodorus van der Kwast. Grading noninvasive bladder cancer: World Health Organisation 1973 or 2004 May Be the Wrong Question. Eur Urol 2019;76:413-5: Two decades of World Health Organisation/International Society of Urological Pathology Bladder Cancer Grading: time to reflect on accomplishments and plan refinement in the molecular era, not regress to readoption of a 45-year-old classification. Eur Urol. 2019;76:416–417.

Soukup V, Capoun O, Cohen D, et al. Prognostic performance and reproducibility of the 1973 and 2004/2016 World Health Organization Grading Classification Systems in non-muscle-invasive bladder cancer: a European Association of Urology Non-muscle Invasive Bladder Cancer Guidelines Panel Systematic Review. Eur Urol. 2017;72:801–813.

Lokeshwar SD, Ruiz-Cordero R, Hupe MC, et al. Impact of 2004 ISUP/WHO classification on bladder cancer grading. World J Urol. 2015;33:1929–1936.

Bosschieter J, Hentschel AE, Savci-Heijink CD, et al. Objectifying grade in Ta-T1 urothelial carcinomas of the bladder using proliferative and quantitative markers: a multicentre study in 310 bladder tumors. Urol Oncol. 2019;37:530.e1–530.e8.

Zaleski M, Gogoj A, Walter V, et al. Mitotic activity in noninvasive papillary urothelial carcinoma: its value in predicting tumor recurrence and comparison with the contemporary 2-tier grading system. Hum Pathol. 2019;84:275–282.

van Rhijn BW. Combining molecular and pathologic data to prognosticate non-muscle-invasive bladder cancer. Urol Oncol. 2012;30:518–523.

Cheng L, Neumann RM, Nehra A, et al. Cancer heterogeneity and its biologic implications in the grading of urothelial carcinoma. Cancer. 2000;88:1663–1670.

Reis LO, Taheri D, Chaux A, et al. Significance of a minor high-grade component in a low-grade noninvasive papillary urothelial carcinoma of bladder. Hum Pathol. 2016;47:20–25.

Gofrit ON, Pizov G, Shapiro A, et al. Mixed high and low grade bladder tumors—are they clinically high or low grade? J Urol. 2014;191:1693–1696.

Schubert T, Danzig MR, Kotamarti S, et al. Mixed low- and high-grade non-muscle-invasive bladder cancer: a histological subtype with favorable outcome. World J Urol. 2015;33:847–852.

Babjuk M, Bohle A, Burger M, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol. 2017;71:447–461.

Brausi M, Oddens J, Sylvester R, et al. Side effects of Bacillus Calmette-Guerin (BCG) in the treatment of intermediate- and high-risk Ta, T1 papillary carcinoma of the bladder: results of the EORTC genito-urinary cancers group randomised phase 3 study comparing one-third dose with full dose and 1 year with 3 years of maintenance BCG. Eur Urol. 2014;65:69–76.

Comperat E, Varinot J, Moroch J, et al. A practical guide to bladder cancer pathology. Nat Rev Urol. 2018;15:143–154.

van Rhijn BW, Musquera M, Liu L, et al. Molecular and clinical support for a four-tiered grading system for bladder cancer based on the WHO 1973 and 2004 classifications. Mod Pathol. 2015;28:695–705.

Jansen I, Lucas M, Savci-Heijink CD, et al. Three-dimensional histopathological reconstruction of bladder tumours. Diagn Pathol. 2019;14:25.

Glaser AK, Reder NP, Chen Y, et al. Light-sheet microscopy for slide-free non-destructive pathology of large clinical specimens. Nat Biomed Eng. 2017;1:0084.

van Royen ME, Verhoef EI, Kweldam CF, et al. Three-dimensional microscopic analysis of clinical prostate specimens. Histopathology. 2016;69:985–992.

Jansen I, Lucas M, Bosschieter J, et al. Automated detection and grading of non-muscle-invasive urothelial cell carcinoma of the bladder. Am J Pathol. 2020;190:1483–1490.

Pan CC, Chang YH, Chen KK, et al. Constructing prognostic model incorporating the 2004 WHO/ISUP classification for patients with non-muscle-invasive urothelial tumours of the urinary bladder. J Clin Pathol. 2010;63:910–915.

Toll AD, Epstein JI. Invasive low-grade papillary urothelial carcinoma: a clinicopathologic analysis of 41 cases. Am J Surg Pathol. 2012;36:1081–1086.

Lawless M, Gulati R, Tretiakova M. Stalk versus base invasion in pT1 papillary cancers of the bladder: improved substaging system predicting the risk of progression. Histopathology. 2017;71:406–414.

Roupret M, Babjuk M, Burger M, et al. European Association of Urology Guidelines on upper urinary tract urothelial carcinoma: 2020 update. Eur Urol. 2021;79:62–79.

Beltran AL, Cheng L, Montironi R, et al. Clinicopathological characteristics and outcome of nested carcinoma of the urinary bladder. Virchows Arch. 2014;465:199–205.

Choi HK, Jarkrans T, Bengtsson E, et al. Image analysis based grading of bladder carcinoma. Comparison of object, texture and graph based methods and their reproducibility. Anal Cell Pathol. 1997;15:1–18.

Spyridonos P, Cavouras D, Ravazoula P, et al. Neural network-based segmentation and classification system for automated grading of histologic sections of bladder carcinoma. Anal Quant Cytol Histol. 2002;24:317–324.

Desai S, Lim SD, Jimenez RE, et al. Relationship of cytokeratin 20 and CD44 protein expression with WHO/ISUP grade in pTa and pT1 papillary urothelial neoplasia. Mod Pathol. 2000;13:1315–1323.

Comperat E, Camparo P, Haus R, et al. Aurora-A/STK-15 is a predictive factor for recurrent behaviour in non-invasive bladder carcinoma: a study of 128 cases of non-invasive neoplasms. Virchows Arch. 2007;450:419–424.

Barbisan F, Mazzucchelli R, Santinelli A, et al. Immunohistochemical evaluation of global DNA methylation and histone acetylation in papillary urothelial neoplasm of low malignant potential. Int J Immunopathol Pharmacol. 2008;21:615–623.

Choi W, Porten S, Kim S, et al. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell. 2014;25:152–165.

Rebola J, Aguiar P, Blanca A, et al. Predicting outcomes in non-muscle invasive (Ta/T1) bladder cancer: the role of molecular grade based on luminal/basal phenotype. Virchows Arch. 2019;475:445–455.

Sikic D, Keck B, Wach S, et al. Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis. PLoS One. 2017;12:e0179602.

Choi W, Ochoa A, McConkey DJ, et al. Genetic alterations in the molecular subtypes of bladder cancer: illustration in the cancer genome atlas dataset. Eur Urol. 2017;72:354–365.

Readal N, Epstein JI. Papillary urothelial hyperplasia: relationship to urothelial neoplasms. Pathology. 2010;42:360–363.

Bell AE, Abrahamson DS, McRae KN. Reading retardation:a 12-year prospective study. Implications for the pediatrician. J Pediatr. 1977;91:363–370.

Taylor DC, Bhagavan BS, Larsen MP, et al. Papillary urothelial hyperplasia. A precursor to papillary neoplasms. Am J Surg Pathol. 1996;20:1481–1488.

Lowenthal BM, Sahoo D, Amin MB, et al. Urothelial proliferation of unknown malignant potential involving the bladder: histopathologic features and risk of progression in de novo cases and cases with prior neoplasia. Arch Pathol Lab Med. 2020;144:853–862.

Chow NH, Cairns P, Eisenberger CF, et al. Papillary urothelial hyperplasia is a clonal precursor to papillary transitional cell bladder cancer. Int J Cancer. 2000;89:514–518.

Amin MB, McKenney JK. An approach to the diagnosis of flat intraepithelial lesions of the urinary bladder using the World Health Organization/International Society of Urological Pathology consensus classification system. Adv Anat Pathol. 2002;9:222–232.

Amin MB, Smith SC, Reuter VE, et al. Update for the practicing pathologist: the International Consultation on Urologic Disease-European association of urology consultation on bladder cancer. Mod Pathol. 2015;28:612–630.

Mazzucchelli R, Scarpelli M, Galosi AB, et al. Pathology of upper tract urothelial carcinoma with emphasis on staging. Int J Immunopathol Pharmacol. 2014;27:509–516.

McKenney JK, Gomez JA, Desai S, et al. Morphologic expressions of urothelial carcinoma in situ: a detailed evaluation of its histologic patterns with emphasis on carcinoma in situ with microinvasion. Am J Surg Pathol. 2001;25:356–362.

Swierczynski SL, Epstein JI. Prognostic significance of atypical papillary urothelial hyperplasia. Hum Pathol. 2002;33:512–517.

Hodges KB, Lopez-Beltran A, Maclennan GT, et al. Urothelial lesions with inverted growth patterns: histogenesis, molecular genetic findings, differential diagnosis and clinical management. BJU Int. 2011;107:532–537.

Gutierrez CM, Alemozaffar M, Osunkoya AO. Invasive high-grade urothelial carcinoma of the bladder, renal pelvis, ureter, and prostatic urethra arising in a background of urothelial carcinoma with an inverted growth pattern: a contemporary clinicopathological analysis of 91 cases. Hum Pathol. 2019;92:18–24.

Terada T. Inverted variant of urothelial carcinoma of the urinary bladder: a report of three cases and a proposal for a new clinicopathologic entity. Int J Clin Exp Pathol. 2013;6:766–770.

Amin MB, McKenney JK, Paner GP, et al. ICUD-EAU International Consultation on Bladder Cancer 2012: Pathology. Eur Urol. 2013;63:16–35.

Arslankoz S, Kulac I, Ertoy Baydar D. The influence of inverted growth pattern on recurrence for patients with non-invasive low grade papillary urothelial carcinoma of bladder. Balkan Med J. 2017;34:464–468.

Jones TD, Zhang S, Lopez-Beltran A, et al. Urothelial carcinoma with an inverted growth pattern can be distinguished from inverted papilloma by fluorescence in situ hybridization, immunohistochemistry, and morphologic analysis. Am J Surg Pathol. 2007;31:1861–1867.

Almassi N, Pietzak EJ, Sarungbam J, et al. Inverted urothelial papilloma and urothelial carcinoma with inverted growth are histologically and molecularly distinct entities. J Pathol. 2020;250:464–465.

Williamson SR, Zhang S, Lopez-Beltran A, et al. Telomere shortening distinguishes inverted urothelial neoplasms. Histopathology. 2013;62:595–601.

McDaniel AS, Zhai Y, Cho KR, et al. HRAS mutations are frequent in inverted urothelial neoplasms. Hum Pathol. 2014;45:1957–1965.

Ehsani L, Osunkoya AO. Expression of MLH1 and MSH2 in urothelial carcinoma of the renal pelvis. Tumour Biol. 2014;35:8743–8747.

Oxley JD, Cottrell AM, Adams S, et al. Ketamine cystitis as a mimic of carcinoma in situ. Histopathology. 2009;55:705–708.

Lopez-Beltran A, Montironi R, Raspollini MR, et al. Iatrogenic pathology of the urinary bladder. Semin Diagn Pathol. 2018;35:218–227.

Lopez-Beltran A, Paner GP, Montironi R, et al. Iatrogenic changes in the urinary tract. Histopathology. 2017;70:10–25.

Lopez-Beltran A, Luque RJ, Mazzucchelli R, et al. Changes produced in the urothelium by traditional and newer therapeutic procedures for bladder cancer. J Clin Pathol. 2002;55:641–647.

Amin MB, Trpkov K, Lopez-Beltran A, et al. Members of the ISUP Immunohistochemistry in Diagnostic Urologic Pathology Group. Best practices recommendations in the application of immunohistochemistry in the bladder lesions: report from the International Society of Urologic Pathology consensus conference. Am J Surg Pathol. 2014;38:e20–e34.