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Cystitis Cystica / Glandularis

Definition

  • Cystic spaces formed in von Brunn nests

Diagnostic Criteria

  • von Brunn nests, cystitis cystica and cystitis glandularis are common
    • When scattered and superficial they are probably normal
      • No need to diagnose such foci
    • When florid they may simulate neoplasm (see Florid von Brunn Nests)
  • Cystitis cystica and cystitis glandularis are defined as lumens formed within von Brunn nests
    • They frequently are intermixed and may form a spectrum
    • Spaces may be encompassed by size of usual nests or be cystically dilated
    • Spaces in cystitis cystica are lined by urothelial cells
    • Spaces in cystitis glandularis are lined by differentiated mucous cells
      • Urothelial cells still form the periphery of the nests
      • If mucin positive goblet cells are present, it can be termed intestinal type
        • If outer urothelial cells are lacking, better terminology may be intestinal metaplasia (Williamson)

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 10/20/12

Supplemental studies

Immunohistology

  • p63 stains the urothelial cells in the nests

Differential Diagnosis

  • Florid von Brunn nests
  • Intestinal metaplasia
  • Nested variant urothelial carcinoma
  • Inverted urothelial carcinoma
  • Invasive usual urothelial carcinoma
  • Fibroepithelial polyp

Florid Cystitis Cystica and/or Glandularis NOS Florid von Brunn Nests
Nests are predominantly cystic Nests are predominantly solid
These form a spectrum and the distinction is not important

Florid Cystitis Cystica and/or Glandularis NOS Intestinal Metaplasia
Glandular differentiated cells are surrounded by multilayered transitional cells Intestinal type epithelium without outer transitional layer

Nested Variant Urothelial Carcinoma Florid von Brunn Nests, Cystitis Cystica/Glandularis
Infiltrative pattern Tend to have uniform depth and/or lobular architecture
Frequently invades muscularis propria Usually confined to superficial submucosa, does not involve muscularis propria
Overall cytologically bland but usually at least focally atypical Cytologically bland
Criteria above apply to both solid and cystic processes
The distinction may be very difficult on superficial biopsies
IPOX for Ki67, p53, p27 and CK20 is not helpful (Volmar)

Urothelial Carcinoma with Inverted Growth Pattern Florid von Brunn Nests, Cystitis Cystica/Glandularis
Usually has a surface papillary component Surface normal
Cytologic features and disorder of carcinoma, appropriate to grade Bland, uniform, orderly cells
Mitotic figures present, appropriate to grade No mitotic figures

Invasive Urothelial Carcinoma Florid von Brunn Nests, Cystitis Cystica/Glandularis
Single cell invasion Intact nests only
Jagged, irregular nests Round regular nests
Mitotic figures and atypia present, appropriate to grade No mitotic figures or atypia
Stroma may be desmoplastic No stromal response

Florid Cystitis Cystica and/or Glandularis NOS Fibroepithelial Polyp (some FEP contain focal or extensive cystitis cystica/glandularis)
Does not form a distinct polyp Well formed, distinct polyp with bulbous, lobulated shape
Multiple or diffuse lesions Solitary lesion, adjacent bladder normal

Grading / Staging

Grading

  • Not applicable

Staging

  • Not applicable

Clinical

  • While irritation has been proposed as a cause, cystitis cystica and glandularis are frequently found incidentally and may represent normal findings
  • No clinical significance
    • (There is some evidence that intestinal metaplasia (as opposed to cystitis glandularis) may be a precursor of carcinoma (Sung))

Classification / Lists

Flat Lesions of the Urinary Bladder

Papillary Lesions of the Urinary Bladder

Subtypes of High Grade Urothelial Carcinoma

Inverted Lesions of the Urinary Bladder

Glandular Lesions of the Urinary Bladder

Bibliography

  • Murphy WM, Grignon DJ, Perlman EJ. Tumors of the Kidney, Bladder and Related Urinary Structures, Atlas of Tumor Pathology, AFIP Fourth Series, Fascicle 1, 2004
  • Eble JN, Sauter G, Epstein JI, Sesterhenn IA eds. World Health Organization Classification of Tumors. Pathology and genetics of tumors of the Urinary System and Male Genital Organs. IARC Press: Lyon 2004.
  • Hodges KB, Lopez-Beltran A, Maclennan GT, Montironi R, Cheng L. Urothelial lesions with inverted growth patterns: histogenesis, molecular genetic findings, differential diagnosis and clinical management. BJU Int. 2011 Feb;107(4):532-7.
  • Williamson SR, Lopez-Beltran A, Montironi R, Cheng L. Glandular lesions of the urinary bladder:clinical significance and differential diagnosis. Histopathology. 2011 May;58(6):811-34.
  • Volmar KE, Chan TY, De Marzo AM, Epstein JI. Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma. Am J Surg Pathol. 2003 Sep;27(9):1243-52.
  • Sung MT, Lopez-Beltran A, Eble JN, MacLennan GT, Tan PH, Montironi R, Jones TD, Ulbright TM, Blair JE, Cheng L. Divergent pathway of intestinal metaplasia and cystitis glandularis of the urinary bladder. Mod Pathol. 2006 Nov;19(11):1395-401.
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