Anatomy of the Urinary Bladder Revisited: Implications for Diagnosis and Staging of Bladder Cancer

  • Victor E. ReuterEmail author


The anatomy of the urinary bladder is complex. Surface urothelium may invaginate into the lamina propria and metaplastic changes in this epithelium can mimic invasive carcinoma. The lamina propria may be of variable thickness depending on the location within the bladder and it may or may not contain components of muscularis mucosae, which can be misinterpreted as muscularis propria. Since the layers of muscularis propria are usually irregular, establishing the presence of extravesical extension by tumor can be a challenge. Further complicating the issue, prior transurethral resections can induce changes in the cellular composition of the bladder wall, in essence masking normal anatomical landmarks. Since pathological stage is the most significant risk factor in predicting disease progression, understanding the microscopic anatomy of the viscus is of great importance.


Urinary bladder Anatomy Pathologic staging Lamina propria Muscularis mucosae Muscularis propria 


  1. 1.
    Reuter VE. Histology for pathologists. 2nd ed. Sternberg SS, editor. New York: Raven Press; 1998. pp. 835–47.Google Scholar
  2. 2.
    Reuter VE. The urothelial tract: renal pelvis, ureter, urinary bladder, and urethra. In: Reuter VE, editor. Sternberg’s diagnostic surgical pathology. 2. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2004. pp. 2035–81.Google Scholar
  3. 3.
    Moore K. The urinary system. In: Moore K, editor. The developing human. 3rd ed. Philadelphia: WB Saunders; 1982. pp. 267–8.Google Scholar
  4. 4.
    Moore KL. The pelvis and perineum. In: Moore KL, editor. Clinically oriented anatomy. 2nd ed. Baltimore: Williams & Wilkens; 1985. pp. 362–5.Google Scholar
  5. 5.
    Tanagho E. Campbell’s urology. In: Walsh PC RA, Stamey TA, editors. Anatomy of the lower urinary tract. 6 ed. Philadelphia: WB Saunders; 1992. pp. 49–54.Google Scholar
  6. 6.
    Mahadevia PS, Koss LG, Tar IJ. Prostatic involvement in bladder cancer. Prostate mapping in 20 cystoprostatectomy specimens. Cancer. 1986;58(9):2096–102.CrossRefPubMedGoogle Scholar
  7. 7.
    Utz DC, Farrow GM, Rife CC, Segura JW, Zincke H. Carcinoma in situ of the bladder. Cancer. 1980;45(7 Suppl):1842–8.PubMedGoogle Scholar
  8. 8.
    Ro JY, Ayala AG, el-Naggar A, Wishnow KI. Seminal vesicle involvement by in situ and invasive transitional cell carcinoma of the bladder. Am J Surg Pathol. 1987;11(12):951–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Tanagho EA, Smith DR, Meyers FH. The trigone: anatomical and physiological considerations. 2. In relation to the bladder neck. J Urol. 1968;100(5): 633–9.PubMedGoogle Scholar
  10. 10.
    Tanagho EA, Meyers FH, Smith DR. The trigone: anatomical and physiological considerations. I. In relation to the ureterovesical junction. J Urol. 1968;100(5):623–32.PubMedGoogle Scholar
  11. 11.
    Shehata R. A comparative study of the urinary bladder and the intramural portion of the ureter. Acta Anat (Basel). 1977;98(4):380–95.CrossRefGoogle Scholar
  12. 12.
    Politano VA. Ureterovesical junction. J Urol. 1972;107(2):239–42.PubMedGoogle Scholar
  13. 13.
    Elbadawi A. Anatomy and function of the ureteral sheath. J Urol. 1972;107(2):224–9.PubMedGoogle Scholar
  14. 14.
    Tanagho EA, Smith DR. The anatomy and function of the bladder neck. Br J Urol. 1966;38(1):54–71.CrossRefPubMedGoogle Scholar
  15. 15.
    Koss LG. Tumors of the urinary bladder. Fascicle 11. Washington, DC: Armed Forces Institute of Pathology; 1975. pp. 99–102.Google Scholar
  16. 16.
    Fawcett DW. Bloom and Fawcett: a textbook of histology. 11th ed. Philadelphia: WB Saunders; 1986. pp. 787–90.Google Scholar
  17. 17.
    Hicks RM. The function of the golgi complex in transitional epithelium. Synthesis of the thick cell membrane. J Cell Biol. 1966;30(3):623–43.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Battifora H, Eisenstein R, McDonald JH. The human urinary bladder mucosa. An electron microscopic study. Invest Urol. 1964;12:354–61.Google Scholar
  19. 19.
    Fawcett DW, Bloom W, Raviola E. A textbook of histology. 12th ed. New York: Chapman & Hall; 1994. pp. xx, 964.Google Scholar
  20. 20.
    Koss LG. The asymmetric unit membranes of the epithelium of the urinary bladder of the rat. An electron microscopic study of a mechanism of epithelial maturation and function. Lab Invest. 1969;21(2):154–68.PubMedGoogle Scholar
  21. 21.
    Newman J, Antonakopoulos GN. The fine structure of the human fetal urinary bladder. Development and maturation. A light, transmission and scanning electron microscopic study. J Anat. 1989;166:135–50.PubMedCentralPubMedGoogle Scholar
  22. 22.
    Alroy J, Gould VE. Epithelial-stromal interface in normal and neoplastic human bladder epithelium. Ultrastruct Pathol. 1980;1(2):201–10.CrossRefPubMedGoogle Scholar
  23. 23.
    Koss LG. Mapping of the urinary bladder: its impact on the concepts of bladder cancer. Hum Pathol. 1979;10(5):533–48.CrossRefPubMedGoogle Scholar
  24. 24.
    Mostofi FK. Potentialities of bladder epithelium. J Urol. 1954;71:705–14.PubMedGoogle Scholar
  25. 25.
    Morse HD. The etiology and pathology of pyelitis cystica, ureteritis cystica and cystitis cystica. Am J Pathol. 1928;4:33–50.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Goldstein AM, Fauer RB, Chinn M, Kaempf MJ. New concepts on formation of Brunn’s nests and cysts in urinary tract mucosa. Urology. 1978;11(5):513–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Wiener DP, Koss LG, Sablay B, Freed SZ. The prevalence and significance of Brunn’s nests, cystitis cystica and squamous metaplasia in normal bladders. J Urol. 1979;122(3):317–21.PubMedGoogle Scholar
  28. 28.
    Edwards PD, Hurm RA, Jaeschke WH. Conversion of cystitis glandularis to adenocarcinoma. J Urol. 1972;108(4):568–70.PubMedGoogle Scholar
  29. 29.
    Lin JI, Yong HS, Tseng CH, Marsidi PS, Choy C, Pilloff B. Diffuse cystitis glandularis. Associated with adenocarcinomatous change. Urology. 1980;15(4):411–5.CrossRefPubMedGoogle Scholar
  30. 30.
    Tannenbaum M. Inflammatory proliferative lesion of urinary bladder: squamous metaplasia. Urology. 1976;7(4):428–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Engel RM, Wilkinson HA. Bladder exstrophy. J Urol. 1970;104(5):699–704.PubMedGoogle Scholar
  32. 32.
    Nielsen K, Nielsen KK. Adenocarcinoma in exstrophy of the bladder—the last case in Scandinavia? A case report and review of literature. J Urol. 1983;130(6):1180–2.PubMedGoogle Scholar
  33. 33.
    Bhagavan BS, Tiamson EM, Wenk RE, Berger BW, Hamamoto G, Eggleston JC. Nephrogenic adenoma of the urinary bladder and urethra. Hum Pathol. 1981;12(10):907–16.CrossRefPubMedGoogle Scholar
  34. 34.
    Navarre RJ Jr, Loening SA, Platz C, Narayana A, Culp DA. Nephrogenic adenoma: a report of 9 cases and review of the literature. J Urol. 1982;127(4):775–9.PubMedGoogle Scholar
  35. 35.
    Molland EA, Trott PA, Paris AM, Blandy JP. Nephrogenic adenoma: a form of adenomatous metaplasia of the bladder. A clinical and electron microscopical study. Br J Urol. 1976;48(6):453–62.CrossRefPubMedGoogle Scholar
  36. 36.
    Ford TF, Watson GM, Cameron KM. Adenomatous metaplasia (nephrogenic adenoma) of urothelium. An analysis of 70 cases. Br J Urol. 1985;57(4):427–33.CrossRefPubMedGoogle Scholar
  37. 37.
    Satodate R, Koike H, Sasou S, Ohori T, Nagane Y. Nephrogenic adenoma of the ureter. J Urol. 1984;131(2):332–4.PubMedGoogle Scholar
  38. 38.
    Mazal PR, Schaufler R, Altenhuber-Muller R, Haitel A, Watschinger B, Kratzik C, et al. Derivation of nephrogenic adenomas from renal tubular cells in kidney-transplant recipients. N Engl J Med. 2002;347(9):653–9.CrossRefPubMedGoogle Scholar
  39. 39.
    Fromont G, Barcat L, Gaudin J, Irani J. Revisiting the immunophenotype of nephrogenic adenoma. Am J Surg Pathol. 2009;33(11):1654–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Tong GX, Melamed J, Mansukhani M, Memeo L, Hernandez O, Deng FM, et al. PAX2: a reliable marker for nephrogenic adenoma. Mod Pathol. 2006;19(3):356–63.CrossRefPubMedGoogle Scholar
  41. 41.
    DeMeester LJ, Farrow GM, Utz DC. Inverted papillomas of the urinary bladder. Cancer. 1975;36(2):505–13.CrossRefPubMedGoogle Scholar
  42. 42.
    Henderson DW, Allen PW, Bourne AJ. Inverted urinary papilloma: report of five cases and review of the literature. Virchows Arch A Pathol Anat Histol. 1975;366(3):177–86.CrossRefPubMedGoogle Scholar
  43. 43.
    Caro DJ, Tessler A. Inverted papilloma of the bladder: a distinct urological lesion. Cancer. 1978;42(2):708–13.CrossRefPubMedGoogle Scholar
  44. 44.
    Anderstrom C, Johansson S, Pettersson S. Inverted papilloma of the urinary tract. J Urol. 1982;127(6):1132–4.PubMedGoogle Scholar
  45. 45.
    Lazarevic B, Garret R. Inverted papilloma and papillary transitional cell carcinoma of urinary bladder: report of four cases of inverted papilloma, one showing papillary malignant transformation and review of the literature. Cancer. 1978;42(4):1904–11.CrossRefPubMedGoogle Scholar
  46. 46.
    Whitesel JA. Inverted papilloma of the urinary tract: malignant potential. J Urol. 1982;127(3):539–40.PubMedGoogle Scholar
  47. 47.
    Stein BS, Rosen S, Kendall AR. The association of inverted papilloma and transitional cell carcinoma of the urothelium. J Urol. 1984;131(4):751–2.PubMedGoogle Scholar
  48. 48.
    Assor D. Inverted papilloma of the renal pelvis. J Urol. 1976;116(5):654.PubMedGoogle Scholar
  49. 49.
    Lausten GS, Anagnostaki L, Thomsen OF. Inverted papilloma of the upper urinary tract. Eur Urol. 1984;10(1):67–70.PubMedGoogle Scholar
  50. 50.
    Weiss L. Cell and tissue biology: a textbook of histology. 6th ed. Baltimore: Urban & Schwarzenberg; 1988. pp. xii, 1158, [16] of plates p.Google Scholar
  51. 51.
    Paner GP, Ro JY, Wojcik EM, Venkataraman G, Datta MW, Amin MB. Further characterization of the muscle layers and lamina propria of the urinary bladder by systematic histologic mapping: implications for pathologic staging of invasive urothelial carcinoma. Am J Surg Pathol. 2007;31(9):1420–9.CrossRefPubMedGoogle Scholar
  52. 52.
    Dixon JS, Gosling JA. Histology and fine structure of the muscularis mucosae of the human urinary bladder. J Anat. 1983;136(2):265–71.PubMedCentralPubMedGoogle Scholar
  53. 53.
    Ro JY, Ayala AG, el-Naggar A. Muscularis mucosa of urinary bladder. Importance for staging and treatment. Am J Surg Pathol. 1987;11(9):668–73.CrossRefPubMedGoogle Scholar
  54. 54.
    Vakar-Lopez F, Shen SS, Zhang S, Tamboli P, Ayala AG, Ro JY. Muscularis mucosae of the urinary bladder revisited with emphasis on its hyperplastic patterns: a study of a large series of cystectomy specimens. Ann Diagn Pathol. 2007;11(6):395–401.CrossRefPubMedGoogle Scholar
  55. 55.
    Paner GP, Shen SS, Lapetino S, Venkataraman G, Barkan GA, Quek ML, et al. Diagnostic utility of antibody to smoothelin in the distinction of muscularis propria from muscularis mucosae of the urinary bladder: a potential ancillary tool in the pathologic staging of invasive urothelial carcinoma. Am J Surg Pathol. 2009;33(1):91–8.CrossRefPubMedGoogle Scholar
  56. 56.
    Miyamoto H, Sharma RB, Illei PB, Epstein JI. Pitfalls in the use of smoothelin to identify muscularis propria invasion by urothelial carcinoma. Am J Surg Pathol. 2010;34(3):418–22.CrossRefPubMedGoogle Scholar
  57. 57.
    Philip AT, Amin MB, Tamboli P, Lee TJ, Hill CE, Ro JY. Intravesical adipose tissue: a quantitative study of its presence and location with implications for therapy and prognosis. Am J Surg Pathol. 2000;24(9):1286–90.CrossRefPubMedGoogle Scholar
  58. 58.
    Hasui Y, Osada Y, Kitada S, Nishi S. Significance of invasion to the muscularis mucosae on the progression of superficial bladder cancer. Urology. 1994;43(6):782–6.CrossRefPubMedGoogle Scholar
  59. 59.
    Angulo JC, Lopez JI, Grignon DJ, Sanchez-Chapado M. Muscularis mucosa differentiates two populations with different prognosis in stage T1 bladder cancer. Urology. 1995;45(1):47–53.CrossRefPubMedGoogle Scholar
  60. 60.
    Nishiyama N, Kitamura H, Maeda T, Takahashi S, Masumori N, Hasegawa T, et al. Clinicopathological analysis of patients with non-muscle-invasive bladder cancer: prognostic value and clinical reliability of the 2004 WHO classification system. Jpn J Clin Oncol. 2013;43(11):1124–31.CrossRefPubMedGoogle Scholar
  61. 61.
    Hu Z, Mudaliar K, Quek ML, Paner GP, Barkan GA. Measuring the dimension of invasive component in pT1 urothelial carcinoma in transurethral resection specimens can predict time to recurrence. Ann Diagn Pathol 2014;18(2):49–52.CrossRefPubMedGoogle Scholar
  62. 62.
    Al-Hussain T, Carter HB, Epstein JI. Significance of prostate adenocarcinoma perineural invasion on biopsy in patients who are otherwise candidates for active surveillance. J Urol. 2011;186(2):470–3.CrossRefPubMedGoogle Scholar
  63. 63.
    Eble JN, Sauter G, Epstein J, Sesterhenn I, editors. Pathology and genetics of tumours of the urinary system and male genital organs. Lyon: IARC press; 2004.Google Scholar
  64. 64.
    Jequier S, Rousseau O. Sonographic measurements of the normal bladder wall in children. AJR Am J Roentgenol. 1987;149(3):563–6.CrossRefPubMedGoogle Scholar
  65. 65.
    Ananthanarayanan V, Pan Y, Tretiakova M, Amin MB, Cheng L, Epstein JI, et al. Influence of histologic criteria and confounding factors in staging equivocal cases for microscopic perivesical tissue invasion (pT3a): an interobserver study among genitourinary pathologists. Am J Surg Pathol. 2014;38(2):167–75.CrossRefPubMedGoogle Scholar
  66. 66.
    Edge SB, Compton CC. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.CrossRefPubMedGoogle Scholar
  67. 67.
    Miller A. The aetiology and treatment of diverticulum of the bladder. Br J Urol. 1958;30:43–56.CrossRefPubMedGoogle Scholar
  68. 68.
    Kertsschmer HL. Diverticula of the urinary bladder: a clinical study of 236 cases. Surg Gynecol Obstet. 1940;71:491–503.Google Scholar
  69. 69.
    Fox M, Power RF, Bruce AW. Diverticulum of the bladder: presentation and evaluation of treatment of 115 cases. Br J Urol. 1962;34:286–98.CrossRefPubMedGoogle Scholar
  70. 70.
    Barrett DM, Malek RS, Kelalis PP. Observations on vesical diverticulum in childhood. J Urol. 1976;116(2):234–6.PubMedGoogle Scholar
  71. 71.
    Sheldon CA, Clayman RV, Gonzalez R, Williams RD, Fraley EE. Malignant urachal lesions. J Urol. 1984;131(1):1–8.PubMedGoogle Scholar
  72. 72.
    Gopalan A, Sharp DS, Fine SW, Tickoo SK, Herr HW, Reuter VE, et al. Urachal carcinoma: a clinicopathologic analysis of 24 cases with outcome correlation. Am J Surg Pathol. 2009;33(5):659–68.CrossRefPubMedCentralPubMedGoogle Scholar
  73. 73.
    Kong MX, Zhao X, Kheterpal E, Lee P, Taneja S, Lepor H, et al. Histopathologic and clinical features of vesical diverticula. Urology. 2013;82(1):142–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of PathologyMemorial Sloan Kettering Cancer CenterNew YorkUSA

Personalised recommendations