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Nephrogenic Adenoma

Definition

  • Benign tubular and papillary lesion of the urinary tract

Alternate Name

  • Nephrogenic metaplasia

Diagnostic Criteria

  • Most lesions have both a surface papillary and a submucosal tubular component
    • Papillae are simple, with edematous core
    • Tubules may be dilated or tightly packed and compressed
      • May be surrounded by visible basement membrane
      • Cystically dilated tubules may contain eosinophilic colloid like secretion
    • May involve muscularis mucosae
      • Rare description of muscularis propria involvement (Hansel)
  • Papillae and tubules are both lined by a single layer of bland cells with pale to clear cytoplasm
    • Papillary lining may be low columnar, cuboidal or hobnail cells
    • Tubules typically cuboidal
      • Tubule lining may flatten, giving microcystic, pseudovascular and/or signet ring like appearance
    • Mucin stains negative in cells but secretions may stain
  • Lining cells are typically bland, mitotically inactive
    • Rare cases described with focal cytologic atypia (Cheng 1999)
      • Nuclei enlarged, hyperchromatic, may be multinucleate
      • Nucleoli prominent
      • Mitotic figures rare
  • Frequently associated with inflammation clinically and histopathologically
    • Some consider this to be a metaplastic lesion
  • Variant with fibromyxoid stroma can simulate infiltrating adenocarcinoma (Hansel)
    • Epithelial cells compressed with spindle cell appearance
      • Keratin positive
    • Prominent mucin positive fibromyxoid stroma
    • Typical nephrogenic adenoma present at least focally
    • Cells are cytologically bland
    • May be associated with prior treatment for carcinoma

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

  • Racemase, PAX2 positive
  • PSA, p63 and high molecular weight keratin negative
  • Keratin stains spindled cells in fibromyxoid variant

Differential Diagnosis

  • Papillary urothelial neoplasm
  • Polypoid/papillary cystitis
  • Clear cell carcinoma
  • Prostatic adenocarcinoma
  • Cystitis cystica/glandularis
  • Fibroepithelial polyp
  • Chordoid urothelial carcinoma

Nephrogenic Adenoma Urothelial Papilloma
Papillae lined by single layer of cells, frequently hobnailed Papillae lined by normal multilayered transitional epithelium
No umbrella cells Normal umbrella cells present
Usually associated with tubular submucosal component No associated tubular component

Nephrogenic Adenoma Papillary / Polypoid Cystitis
Papillae lined by single layer of cells, frequently hobnailed Papillae lined by normal multilayered transitional epithelium
No umbrella cells Normal umbrella cells present
Usually associated with tubular submucosal component No associated tubular component

Nephrogenic Adenoma Clear Cell Adenocarcinoma
Generally tightly packed uniform acini/tubules Tubules/acini generally more variable in size and distribution
Cytologically quite bland Cytologically atypical
Nucleoli inconspicuous if present Nucleoli may be prominent
No invasion of muscularis propria May invade muscularis propria

Nephrogenic Adenoma Prostatic Adenocarcinoma
Generally tightly packed uniform acini/tubules Tubules/acini generally more variable in size and distribution
Cytologically quite bland Cytologically atypical
Nucleoli inconspicuous if present Nucleoli may be prominent
PSA and PrAP negative Prostate markers positive in virtually all gland forming prostatic adenocarcinomas
Can be a problem especially in the prostatic urethra, or post surgery/TURP (papillae frequently lost) and because both are racemase/AMACR positive and p63 and HMWCK negative

Nephrogenic Adenoma Cystitis Cystica/Glandularis
Tubules lined by single layer of cuboidal cells, frequently hobnailed Cysts lined by normal multilayered transitional epithelium, with or without lumenal glandular differentiation
Usually associated with papillary component No associated papillary component
p63, HMW cytokeratin negative p63, HMWCK positive

Nephrogenic Adenoma Fibroepithelial Polyp
Lined by single layer of cells, frequently hobnailed Lined by normal multilayered transitional epithelium
No umbrella cells Normal umbrella cells present
Usually associated with tubular submucosal component Submucosal component if present is cystitis cystica/glandularis

Nephrogenic Adenoma with Fibromyxoid Stroma Urothelial Carcinoma with Chordoid Features
Areas of typical nephrogenic adenoma (papillae and tubules lined by single layer of cuboidal cells) Areas of usual transitional carcinoma
p63 negative p63 positive
In the fibromyxoid areas these may be identical

Grading / Staging

Grading

  • Not applicable

Staging

  • Not applicable

Clinical

  • Asssociated with chronic irritation, diverticula, prior surgery and renal transplants
    • In cases of transplants, bladder lesions have been shown to be of renal donor origin
  • May recur but does not progress to carcinoma
  • May appear concurrently with carcinoma
    • Generally felt to represent a response to chronic irritation of carcinoma
    • Isolated lesions not considered to have an increased risk of carcinoma

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.
  • Hameed O, Humphrey PA. Pseudoneoplastic mimics of prostate and bladder carcinomas. Arch Pathol Lab Med. 2010 Mar;134(3):427-43.
  • Oliva E, Amin MB, Jimenez R, Young RH. Clear cell carcinoma of the urinary bladder: a report and comparison of four tumors of mullerian origin and nine of probable urothelial origin with discussion of histogenesis and diagnostic problems. Am J Surg Pathol. 2002 Feb;26(2):190-7.
  • 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.
  • Alexiev BA, LeVea CM. Nephrogenic adenoma of the urinary tract: a review. Int J Surg Pathol. 2012 Apr;20(2):123-31.
  • Gupta A, Wang HL, Policarpio-Nicolas ML, Tretiakova MS, Papavero V, Pins MR, Jiang Z, Humphrey PA, Cheng L, Yang XJ. Expression of alpha-methylacyl-coenzyme A racemase in nephrogenic adenoma. Am J Surg Pathol. 2004 Sep;28(9):1224-9.
  • Hansel DE, Nadasdy T, Epstein JI. Fibromyxoid nephrogenic adenoma: a newly recognized variant mimicking mucinous adenocarcinoma. Am J Surg Pathol. 2007 Aug;31(8):1231-7.
  • Cheng L, Cheville JC, Sebo TJ, Eble JN, Bostwick DG. Atypical nephrogenic metaplasia of the urinary tract: a precursor lesion? Cancer. 2000 Feb 15;88(4):853-61.
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