Stanford School of Medicine

Surgical Pathology Criteria

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Florid von Brunn Nests


  • Benign urothelial process composed of markedly increased submucosal von Brunn nests

Diagnostic Criteria

  • Strikingly increased numbers of round epithelial nests in the lamina propria
    • Generally large nests
    • Regular spacing of nests
    • Lacks irregular infiltrative pattern
      • May be lobular or linear
      • Deep border of process shows generally uniform depth of nests
      • May be hard to assess on biopsy specimens
  • Lesions in ureter and pelvis may be composed of crowded smaller and more irregular nests
  • Mild atypia at most
    • May have occasional prominent nucleoli
  • Cystic change may be prominent
    • Cystitis cystica has spaces lined by transitional cells
    • Cystitis glandularis has spaces lined by columnar cells with apical glandular differentiation but retention of urothelial base
    • Frequent overlap and no significant clinical difference between the two and no significance to their presence
    • A glandular variant of inverted papilloma has been described (Kunze)
      • Round urothelial nests with spaces with glandular differentiation
      • This may not be separable from florid von Brunn nests / cystitis glandularis (Picozzi)
  • Moderately atypical lesions may be seen following irradiation or chemotherapy or rarely in their absence (Lane)
    • Features raise the possibility of nested carcinoma
      • Smaller, more irregular nests
      • Infiltrative pattern at base
        • No invasion of muscularis propria
      • Moderate nuclear pleomorphism
        • Nucleoi may be prominent
        • Mitotic figures infrequent
    • Stromal changes indicate reactive nature
      • Acute and chronic inflammation
        • May have ulceration
      • Hemorrhage with fibrin and hemosiderin
      • Ectatic thin walled vessels intimately associated with epithelial nests
      • Edema and fibrosis
      • No desmoplastic response

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

Original posting/updates: 10/20/12, 2/5/13

Supplemental studies


  • MIB1 labels ≤7% of cells

Differential Diagnosis

  • Cystitis cystica/glandularis
  • Nested variant urothelial carcinoma
  • Inverted papilloma
  • Inverted urothelial carcinoma
  • Invasive usual urothelial carcinoma

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

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)

Inverted Papilloma Florid von Brunn Nests, Cystitis Cystica/Glandularis
Regular pattern of anastomosing cords and trabeculae Round nests, may show fusion
Peripheral palisading and central streaming Lacks biphasic palisading/streaming pattern
Criteria above apply to both solid and cystic processes
An older description of inverted papilloma composed of cystic nests (Kunze) may not be separable from florid von Brunn nests

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

Grading / Staging


  • Not applicable


  • Not applicable


  • May occur at any age, either males or females
  • Most common in bladder but may occur anywhere in urinary tract
  • Cystoscopically may appear to be a neoplasm

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


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  • 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.
  • Albores-Saavedra J, Chable-Montero F, Hernández-Rodríguez OX, Montante-Montes de Oca D, Angeles-Angeles A. Inverted urothelial papilloma of the urinary bladder with focal papillary pattern: a previously undescribed feature. Ann Diagn Pathol. 2009 Jun;13(3):158-61.
  • Dhall D, Al-Ahmadie H, Olgac S. Nested variant of urothelial carcinoma. Arch Pathol Lab Med. 2007 Nov;131(11):1725-7.
  • 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.
  • Jones TD, Zhang S, Lopez-Beltran A, Eble JN, Sung MT, MacLennan GT, Montironi R, Tan PH, Zheng S, Baldridge LA, Cheng L. 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 Dec;31(12):1861-7.
  • Lin O, Cardillo M, Dalbagni G, Linkov I, Hutchinson B, Reuter VE. Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 12 cases. Mod Pathol. 2003 Dec;16(12):1289-98
  • Wasco MJ, Daignault S, Bradley D, Shah RB. Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 30 pure and mixed cases. Hum Pathol. 2010 Feb;41(2):163-71.
  • 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.
  • Kunze E, Schauer A, Schmitt M. Histology and histogenesis of two different types of inverted urothelial papillomas. Cancer. 1983 Jan 15;51(2):348-58.
  • Picozzi S, Casellato S, Bozzini G, Ratti D, Macchi A, Rubino B, Pace G, Carmignani L. Inverted papilloma of the bladder: A review and an analysis of the recent literature of 365 patients. Urol Oncol. 2012 Apr 18.
  • Broussard JN, Tan PH, Epstein JI. Atypia in inverted urothelial papillomas: pathology and prognostic significance. Hum Pathol. 2004 Dec;35(12):1499-504.
  • Fine SW, Epstein JI. Inverted urothelial papillomas with foamy or vacuolated cytoplasm. Hum Pathol. 2006 Dec;37(12):1577-82.
  • Asano K, Miki J, Maeda S, Naruoka T, Takahashi H, Oishi Y. Clinical studies on inverted papilloma of the urinary tract: report of 48 cases and review of the literature. J Urol. 2003 Oct;170(4 Pt 1):1209-12
  • 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.
  • Lane Z, Epstein JI. Pseudocarcinomatous epithelial hyperplasia in the bladder unassociated with prior irradiation or chemotherapy. Am J Surg Pathol. 2008 Jan;32(1):92-7.
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