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Pathology of bladder neoplasms

Cristina Magi-Galluzzi, MD, PhD
Ming Zhou, MD, PhD
Section Editor
Derek Raghavan, MD, PhD, FACP, FASCO
Deputy Editor
Michael E Ross, MD


Bladder cancer is the most common malignancy involving the urinary system. Urothelial (transitional cell) carcinoma is the predominant histologic type in the United States and Europe, where it accounts for 90 percent of all bladder cancers. In other areas of the world, non-urothelial carcinomas are more frequent. Much less commonly, urothelial cancers can arise from other sites in the urinary tract, including the renal pelvis, ureter, or urethra. (See "Epidemiology and risk factors of urothelial (transitional cell) carcinoma of the bladder", section on 'Epidemiology'.)

The pathology of bladder neoplasms will be reviewed here. Clinical aspects of these different tumor types are discussed separately. (See "Clinical presentation, diagnosis, and staging of bladder cancer" and "Non-urothelial bladder cancer".)

The College of American Pathologists (CAP) bladder cancer checklists (www.cap.org) provide guidelines for diagnosis and reporting of bladder cancer in biopsy, transurethral resection, and cystectomy specimens.


Several systems have been used to grade and classify bladder neoplasms. The system proposed by the World Health Organization (WHO) in 1972 distinguished papillomas from grade I, II, and III papillary transitional cell carcinomas [1].

In 1998, WHO and the International Society of Urologic Pathologists (ISUP) published a consensus classification system for urothelial (transitional cell) neoplasms [2]. The clinical significance of this schema was validated by subsequent studies, and in 2004, it was accepted as the standard classification schema [3]. The 2016 WHO system used the same classification [4].

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Literature review current through: Nov 2017. | This topic last updated: Apr 18, 2017.
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  1. Histological typing of urinary tumors, Mostofi FK, Sobin LH, Torloni H (Eds), World Health Organization, Geneva 1973.
  2. Epstein JI, Amin MB, Reuter VR, Mostofi FK. 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.
  3. and Genetics of Tumors of the Urinary System and Male Genital Organs. In: World Health Organization Classification of Tumors, Epstein JI, Eble JN, Sesterhenn I, Sauter G (Eds), IARC Press, Lyon, France 2004. p.93.
  4. Moch H, Humphrey PA, Ulbright TM, Reuter VE. WHO Classification of Tumours of the Urinary System and Male Genital Organs, WHO Press, Geneva 2016.
  5. Reuter VE. The pathology of bladder cancer. Urology 2006; 67:11.
  6. Epstein JI, Amin MB, Reuter VE. Bladder biopsy interpretation. In: Biopsy Interpretation Series, Lippincott Williams & Wilkins, Philadelphia 2004.
  7. Murphy WM. Tumors of the Kidney, Bladder, and Related Urinary Structures, 3rd, AFIP, Washington DC 1994.
  8. Grignon DJ. Neoplasms of the Urinary Bladder. In: Urologic Surgical Pathology, Bostwich DG, Eple NJ (Eds), Mosby, St. Louis 1997.
  9. Ro JY, Ayala AG, el-Naggar A. Muscularis mucosa of urinary bladder. Importance for staging and treatment. Am J Surg Pathol 1987; 11:668.
  10. Amin MB, Murphy WM, Reuter VE. Controversies in the pathology of transitional cell carcinoma of the urinary bladder. Part II. In: Reviews of Pathology, Rosen PP, Flechner RE (Eds), ASCP Press, Chicago 1997. p.72.
  11. Jimenez RE, Keane TE, Hardy HT, Amin MB. pT1 urothelial carcinoma of the bladder: criteria for diagnosis, pitfalls, and clinical implications. Adv Anat Pathol 2000; 7:13.
  12. Larsen MP, Steinberg GD, Brendler CB, Epstein JI. Use of Ulex europaeus agglutinin I (UEAI) to distinguish vascular and "pseudovascular" invasion in transitional cell carcinoma of bladder with lamina propria invasion. Mod Pathol 1990; 3:83.
  13. Reuter VE. Lymphovascular invasion as an independent predictor of recurrence and survival in node-negative bladder cancer remains to be proven. J Clin Oncol 2005; 23:6450.
  14. Chang WC, Chang YH, Pan CC. Prognostic significance in substaging ofT1 urinary bladder urothelial carcinoma on transurethral resection. Am J Surg Pathol 2012; 36:454.
  15. Mazzucchelli R, Cheng L, Lopez-Beltran A, et al. Clinicopathological significance of lymphovascular invasion in urothelial carcinoma. Anal Quant Cytopathol Histpathol 2012; 34:173.
  16. Murphy WM, Soloway MS. Urothelial dysplasia. J Urol 1982; 127:849.
  17. 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.
  18. Cheng L, Cheville JC, Neumann RM, Bostwick DG. Natural history of urothelial dysplasia of the bladder. Am J Surg Pathol 1999; 23:443.
  19. Cheng L, Cheville JC, Neumann RM, Bostwick DG. Flat intraepithelial lesions of the urinary bladder. Cancer 2000; 88:625.
  20. Murphy WM, Busch C, Algaba F. Intraepithelial lesions of urinary bladder: morphologic considerations. Scand J Urol Nephrol Suppl 2000; :67.
  21. Elliott GB, Moloney PJ, Anderson GH. "Denuding cystitis" and in situ urothelial carcinoma. Arch Pathol 1973; 96:91.
  22. Miyamoto H, Miller JS, Fajardo DA, et al. Non-invasive papillary urothelial neoplasms: the 2004 WHO/ISUP classification system. Pathol Int 2010; 60:1.
  23. Bladder Cancer: 2nd International Consultation on Bladder Cancer, 2, M. Soloway and S. Khoury (Ed), International Consultation on Urologic Diseases, Vienna 2012.
  24. Fine SW, Humphrey PA, Dehner LP, et al. Urothelial neoplasms in patients 20 years or younger: a clinicopathological analysis using the world health organization 2004 bladder consensus classification. J Urol 2005; 174:1976.
  25. McKenney JK, Amin MB, Young RH. Urothelial (transitional cell) papilloma of the urinary bladder: a clinicopathologic study of 26 cases. Mod Pathol 2003; 16:623.
  26. Al Bashir S, Yilmaz A, Gotto G, Trpkov K. Long term outcome of primary urothelial papilloma: a single institution cohort. Pathology 2014; 46:37.
  27. Magi-Galluzzi C, Epstein JI. Urothelial papilloma of the bladder: a review of 34 de novo cases. Am J Surg Pathol 2004; 28:1615.
  28. Ho H, Chen YD, Tan PH, et al. Inverted papilloma of urinary bladder: is long-term cystoscopic surveillance needed? A single center's experience. Urology 2006; 68:333.
  29. Kunze E, Schauer A, Schmitt M. Histology and histogenesis of two different types of inverted urothelial papillomas. Cancer 1983; 51:348.
  30. Cameron KM, Lupton CH. Inverted papilloma of the lower urinary tract. Br J Urol 1976; 48:567.
  31. Summers DE, Rushin JM, Frazier HA, Cotelingam JD. Inverted papilloma of the urinary bladder with granular eosinophilic cells. An unusual neuroendocrine variant. Arch Pathol Lab Med 1991; 115:802.
  32. Broussard JN, Tan PH, Epstein JI. Atypia in inverted urothelial papillomas: pathology and prognostic significance. Hum Pathol 2004; 35:1499.
  33. Sung MT, Maclennan GT, Lopez-Beltran A, et al. Natural history of urothelial inverted papilloma. Cancer 2006; 107:2622.
  34. Brown AL, Cohen RJ. Inverted papilloma of the urinary tract. BJU Int 2011; 107 Suppl 3:24.
  35. Picozzi S, Casellato S, Bozzini G, et al. Inverted papilloma of the bladder: a review and an analysis of the recent literature of 365 patients. Urol Oncol 2013; 31:1584.
  36. Lee TK, Chaux A, Karram S, et al. Papillary urothelial neoplasm of low malignant potential of the urinary bladder: clinicopathologic and outcome analysis from a single academic center. Hum Pathol 2011; 42:1799.
  37. Pich A, Chiusa L, Formiconi A, et al. Biologic differences between noninvasive papillary urothelial neoplasms of low malignant potential and low-grade (grade 1) papillary carcinomas of the bladder. Am J Surg Pathol 2001; 25:1528.
  38. Bladder Cancer, 2, Soloway M, Khoury S (Eds), 2nd International Consultation on Bladder Cancer, Vienna 2012.
  39. Pons F, Orsola A, Morote J, Bellmunt J. Variant forms of bladder cancer: basic considerations on treatment approaches. Curr Oncol Rep 2011; 13:216.
  40. Eble JN, Young RH. Carcinoma of the urinary bladder: a review of its diverse morphology. Semin Diagn Pathol 1997; 14:98.
  41. López-Beltrán A, Martín J, García J, Toro M. Squamous and glandular differentiation in urothelial bladder carcinomas. Histopathology, histochemistry and immunohistochemical expression of carcinoembryonic antigen. Histol Histopathol 1988; 3:63.
  42. Wasco MJ, Daignault S, Zhang Y, et al. Urothelial carcinoma with divergent histologic differentiation (mixed histologic features) predicts the presence of locally advanced bladder cancer when detected at transurethral resection. Urology 2007; 70:69.
  43. Scosyrev E, Ely BW, Messing EM, et al. Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710). BJU Int 2011; 108:693.
  44. Holmäng S, Johansson SL. The nested variant of transitional cell carcinoma--a rare neoplasm with poor prognosis. Scand J Urol Nephrol 2001; 35:102.
  45. Drew PA, Furman J, Civantos F, Murphy WM. The nested variant of transitional cell carcinoma: an aggressive neoplasm with innocuous histology. Mod Pathol 1996; 9:989.
  46. Cox R, Epstein JI. Large nested variant of urothelial carcinoma: 23 cases mimicking von Brunn nests and inverted growth pattern of noninvasive papillary urothelial carcinoma. Am J Surg Pathol 2011; 35:1337.
  47. Leroy X, Leteurtre E, De La Taille A, et al. Microcystic transitional cell carcinoma: a report of 2 cases arising in the renal pelvis. Arch Pathol Lab Med 2002; 126:859.
  48. Kamat AM, Dinney CP, Gee JR, et al. Micropapillary bladder cancer: a review of the University of Texas M. D. Anderson Cancer Center experience with 100 consecutive patients. Cancer 2007; 110:62.
  49. Edgerton N, Sirintrapun SJ, Munoz M, et al. Micropapillary urothelial carcinoma of the urinary bladder: a clinicopathological analysis of 24 cases. Int J Urol 2011; 18:49.
  50. Wang J, Wang FW. The Natural History, Treatment Pattern, and Outcomes of Patients With Micropapillary Bladder Carcinoma. Am J Clin Oncol 2015; 38:472.
  51. Sangoi AR, Beck AH, Amin MB, et al. Interobserver reproducibility in the diagnosis of invasive micropapillary carcinoma of the urinary tract among urologic pathologists. Am J Surg Pathol 2010; 34:1367.
  52. Lopez-Beltran A, Cheng L. Histologic variants of urothelial carcinoma: differential diagnosis and clinical implications. Hum Pathol 2006; 37:1371.
  53. Ross JS, Wang K, Gay LM, et al. A high frequency of activating extracellular domain ERBB2 (HER2) mutation in micropapillary urothelial carcinoma. Clin Cancer Res 2014; 20:68.
  54. Tamas EF, Nielsen ME, Schoenberg MP, Epstein JI. Lymphoepithelioma-like carcinoma of the urinary tract: a clinicopathological study of 30 pure and mixed cases. Mod Pathol 2007; 20:828.
  55. Gulley ML, Amin MB, Nicholls JM, et al. Epstein-Barr virus is detected in undifferentiated nasopharyngeal carcinoma but not in lymphoepithelioma-like carcinoma of the urinary bladder. Hum Pathol 1995; 26:1207.
  56. Iezzoni JC, Gaffey MJ, Weiss LM. The role of Epstein-Barr virus in lymphoepithelioma-like carcinomas. Am J Clin Pathol 1995; 103:308.
  57. Williamson SR, Zhang S, Lopez-Beltran A, et al. Lymphoepithelioma-like carcinoma of the urinary bladder: clinicopathologic, immunohistochemical, and molecular features. Am J Surg Pathol 2011; 35:474.
  58. Amin MB, Ro JY, Lee KM, et al. Lymphoepithelioma-like carcinoma of the urinary bladder. Am J Surg Pathol 1994; 18:466.
  59. Dinney CP, Ro JY, Babaian RJ, Johnson DE. Lymphoepithelioma of the bladder: a clinicopathological study of 3 cases. J Urol 1993; 149:840.
  60. Zukerberg LR, Harris NL, Young RH. Carcinomas of the urinary bladder simulating malignant lymphoma. A report of five cases. Am J Surg Pathol 1991; 15:569.
  61. Sahin AA, Myhre M, Ro JY, et al. Plasmacytoid transitional cell carcinoma. Report of a case with initial presentation mimicking multiple myeloma. Acta Cytol 1991; 35:277.
  62. Zhang XM, Elhosseiny A, Melamed MR. Plasmacytoid urothelial carcinoma of the bladder. A case report and the first description of urinary cytology. Acta Cytol 2002; 46:412.
  63. Tamboli P, Amin MB, Mohsin SK, et al. Plasmacytoid variant of non-papillary urothelial carcinoma. Mod Pathol 2000; 13:116A.
  64. Fritsche HM, Burger M, Denzinger S, et al. Plasmacytoid urothelial carcinoma of the bladder: histological and clinical features of 5 cases. J Urol 2008; 180:1923.
  65. Ricardo-Gonzalez RR, Nguyen M, Gokden N, et al. Plasmacytoid carcinoma of the bladder: a urothelial carcinoma variant with a predilection for intraperitoneal spread. J Urol 2012; 187:852.
  66. Lopez-Beltran A, Pacelli A, Rothenberg HJ, et al. Carcinosarcoma and sarcomatoid carcinoma of the bladder: clinicopathological study of 41 cases. J Urol 1998; 159:1497.
  67. Reuter VE. Sarcomatoid lesions of the urogenital tract. Semin Diagn Pathol 1993; 10:188.
  68. Wright JL, Black PC, Brown GA, et al. Differences in survival among patients with sarcomatoid carcinoma, carcinosarcoma and urothelial carcinoma of the bladder. J Urol 2007; 178:2302.
  69. Torenbeek R, Blomjous CE, de Bruin PC, et al. Sarcomatoid carcinoma of the urinary bladder. Clinicopathologic analysis of 18 cases with immunohistochemical and electron microscopic findings. Am J Surg Pathol 1994; 18:241.
  70. Torenbeek R, Hermsen MA, Meijer GA, et al. Analysis by comparative genomic hybridization of epithelial and spindle cell components in sarcomatoid carcinoma and carcinosarcoma: histogenetic aspects. J Pathol 1999; 189:338.
  71. Sarma KP. Squamous cell carcinoma of the bladder. Int Surg 1970; 53:313.
  72. Lagwinski N, Thomas A, Stephenson AJ, et al. Squamous cell carcinoma of the bladder: a clinicopathologic analysis of 45 cases. Am J Surg Pathol 2007; 31:1777.
  73. Grignon DJ, Ro JY, Ayala AG, et al. Primary adenocarcinoma of the urinary bladder. A clinicopathologic analysis of 72 cases. Cancer 1991; 67:2165.
  74. Gill HS, Dhillon HK, Woodhouse CR. Adenocarcinoma of the urinary bladder. Br J Urol 1989; 64:138.
  75. Johnson DE, Hodge GB, Abdul-Karim FW, Ayala AG. Urachal carcinoma. Urology 1985; 26:218.
  76. Kakizoe T, Matsumoto K, Andoh M, et al. Adenocarcinoma of urachus. Report of 7 cases and review of literature. Urology 1983; 21:360.
  77. Sheldon CA, Clayman RV, Gonzalez R, et al. Malignant urachal lesions. J Urol 1984; 131:1.
  78. Whitehead ED, Tessler AN. Carcinoma of the urachus. Br J Urol 1971; 43:468.
  79. Kumar N, Khosla D, Kumar R, et al. Urachal carcinoma: clinicopathological features, treatment and outcome. J Cancer Res Ther 2014; 10:571.
  80. Tamboli P, Mohsin SK, Hailemariam S, Amin MB. Colonic adenocarcinoma metastatic to the urinary tract versus primary tumors of the urinary tract with glandular differentiation: a report of 7 cases and investigation using a limited immunohistochemical panel. Arch Pathol Lab Med 2002; 126:1057.
  81. Torenbeek R, Lagendijk JH, Van Diest PJ, et al. Value of a panel of antibodies to identify the primary origin of adenocarcinomas presenting as bladder carcinoma. Histopathology 1998; 32:20.
  82. Wang HL, Lu DW, Yerian LM, et al. Immunohistochemical distinction between primary adenocarcinoma of the bladder and secondary colorectal adenocarcinoma. Am J Surg Pathol 2001; 25:1380.
  83. Cheng L, Jones TD, McCarthy RP, et al. Molecular genetic evidence for a common clonal origin of urinary bladder small cell carcinoma and coexisting urothelial carcinoma. Am J Pathol 2005; 166:1533.
  84. Bates AW, Baithun SI. Secondary neoplasms of the bladder are histological mimics of nontransitional cell primary tumours: clinicopathological and histological features of 282 cases. Histopathology 2000; 36:32.
  85. Silver SA, Epstein JI. Adenocarcinoma of the colon simulating primary urinary bladder neoplasia. A report of nine cases. Am J Surg Pathol 1993; 17:171.
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