Virchows Archiv

, Volume 463, Issue 6, pp 819–825 | Cite as

Nephrogenic adenoma of the urinary tract: clinical, histological, and immunohistochemical characteristics

  • José I. López
  • Marco Schiavo-Lena
  • Alexandra Corominas-Cishek
  • Adriana Yagüe
  • Kevin Bauleth
  • Rosa Guarch
  • Ondrej Hes
  • Regina Tardanico
Original Article

Abstract

Nephrogenic adenoma is a benign condition of the urinary tract resulting from the displacement and seeding of renal tubular cells from the renal pelvis to the urethra. A retrospective series of 134 cases collected from four hospitals in three different countries was analyzed in this study. Recorded clinical data included age and sex, topography, urological antecedents, coexistent lesions, and follow-up. Cytonuclear and architectural features were reviewed, and PAX-8, p63, PSMA, S100A1, CEA, EMA, CD117, cannabinoid receptor CB1, AMACR, E-cadherin, and CD10 antibodies were included in an immunohistochemical panel. Males predominated (105 M/29 F) with an average age of 66 years (range, 14–96). Urothelial carcinoma was the most frequent clinical antecedent (43.2 %) and also the most common coexisting lesion (14 %). Tubular architecture was the most frequent pattern detected (40 %) although most cases showed a mixed pattern (45.5 %). Deep infiltrative growth into the muscularis propria occurred in two cases. EMA and PAX-8 were expressed in 100 % of nephrogenic adenomas, while E-cadherin reactivity was observed in 66.6 % of cases, cannabinoid receptor CB1 in 25 %, CD10 in 13.6 %, CD117 in 4.1 %, and AMACR in 2.7 %. For the rest of the antigens, no reactivity was found. The average time lapse between the pathological antecedent and the discovery of a nephrogenic adenoma was 32 months. We conclude that nephrogenic adenoma displays a broad spectrum of histological features that may mimic malignancy. In our experience, CB1 immunostaining adds a further argument in favor of a renal origin of this lesion. The combination of PAX-8+, p63−, and EMA + distinguishes nephrogenic adenoma from urothelial and prostate carcinoma, its most frequent malignant look-alikes.

Keywords

Nephrogenic adenoma Urinary tract Renal tubule cell Immunohistochemistry Differential diagnosis 

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Cheng L, Cheville JC, Sebo TJ, Eble JN, Bostwick DG (2000) Atypical nephrogenic metaplasia of the urinary tract: a precursor lesion? Cancer 88:853–861PubMedCrossRefGoogle Scholar
  2. 2.
    Allan CH, Epstein JI (2001) Nephrogenic adenoma of the prostatic urethra. A mimicker of prostate adenocarcinoma. Am J Surg Pathol 25:802–808PubMedCrossRefGoogle Scholar
  3. 3.
    Rahemtullah A, Oliva E (2006) Nephrogenic adenoma: an update on an innocuous but troublesome entity. Adv Anat Pathol 13:247–55PubMedCrossRefGoogle Scholar
  4. 4.
    Xiao GQ, Burstein DE, Miller LK, Unger PD (2006) Nephrogenic adenoma. Immunohistochemical evaluation for its etiology and differentiation from prostatic adenocarcinoma. Arch Pathol Lab Med 130:805–810PubMedGoogle Scholar
  5. 5.
    Alexiev BA, LeVea CM (2012) Nephrogenic adenoma of the urinary tract: a review. Int J Surg Pathol 20:123–131PubMedCrossRefGoogle Scholar
  6. 6.
    Diolombi M, Ross HM, Mercalli F, Sharma R, Epstein JI (2013) Nephrogenic adenoma: a report of 3 unusual cases infiltrating into perinephric adipose tissue. Am J Surg Pathol 37:532–538PubMedCrossRefGoogle Scholar
  7. 7.
    O'Shea PA, Callaghan JF, Lawlor JB, Reddy VC (1981) “Nephrogenic adenoma”: an unusual metaplastic change of urothelium. J Urol 125:249–252PubMedGoogle Scholar
  8. 8.
    Ford TF, Watson GM, Cameron KM (1985) Adenomatous metaplasia (nephrogenic adenoma) of urothelium. An analysis of 70 cases. Br J Urol 57:427–433PubMedCrossRefGoogle Scholar
  9. 9.
    Young RH, Scully RE (1986) Nephrogenic adenoma. A report of 15 cases, review of the literature, and comparison with clear cell adenocarcinoma of the urinary tract. Am J Surg Pathol 10:268–275PubMedCrossRefGoogle Scholar
  10. 10.
    Voss K, Peppas D (2013) Recurrent nephrogenic adenoma: a case report of resolution after treatment with antibiotics and nonsteroidal anti-inflammatory medication. Urology doi:. doi: 10.1016/j.urology.2013.04.024 Google Scholar
  11. 11.
    Kao CS, Kum JB, Fan R, Grignon DJ, Eble JN, Idrees MT (2013) Nephrogenic adenomas in pediatric patients: a morphologic and immunohistochemical study of 21 cases. Pediatr Dev Pathol 16:80–85PubMedCrossRefGoogle Scholar
  12. 12.
    Friedman NB, Kuhlenbeck H (1950) Adenomatoid tumors of the bladder reproducing renal structures (nephrogenic adenoma). J Urol 64:657–670PubMedGoogle Scholar
  13. 13.
    Pierre-Louis ML, Kovi J, Jackson A, Ucci A, Pinn-Wiggins VW (1985) Nephrogenic adenoma a light and electron microscopic and immunohistochemical study. J Natl Med Assoc 77:201–205PubMedGoogle Scholar
  14. 14.
    Mazal PR, Schaufler R, Altenhuber-Muller R, Haitel A, Watschinger B, Kratzik C, Krupitza G, Regele H, Meisl FT, Zechner O, Kerjaschki D, Susani M (2002) Derivation of nephrogenic adenomas from renal tubular cells in kidney transplant recipients. N Engl J Med 347:653–659PubMedCrossRefGoogle Scholar
  15. 15.
    Gupta A, Wang HL, Policarpio-Nicolas ML, Tretiakova MS, Papavero V, Pins MR, Jiang Z, Humphrey PA, Cheng L, Yang XJ (2004) Expression of alpha-methylacyl-coenzyme A racemase in nephrogenic adenoma. Am J Surg Pathol 28:1224–1229PubMedCrossRefGoogle Scholar
  16. 16.
    Skinnider BF, Oliva E, Young RH, Amin MB (2004) Expression of alpha-methylacyl-CoA racemase (P504S) in nephrogenic adenoma: a significant immunohistochemical pitfall compounding the differential diagnosis with prostatic adenocarcinoma. Am J Surg Pathol 28:701–705PubMedCrossRefGoogle Scholar
  17. 17.
    Tong GX, Weeden EM, Hamele-Bena D, Huan Y, Unger P, Memeo L, O'Toole K (2008) Expression of PAX8 in nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract: evidence of related histogenesis? Am J Surg Pathol 32:1380–1387PubMedCrossRefGoogle Scholar
  18. 18.
    Cossu-Rocca P, Contini M, Brunelli M, Festa A, Pili F, Gobbo S, Eccher A, Mura A, Massarelli G, Martignoni G (2009) S-100A1 is a reliable marker in distinguishing nephrogenic adenoma from prostatic adenocarcinoma. Am J Surg Pathol 33:1031–1036PubMedCrossRefGoogle Scholar
  19. 19.
    Fromont G, Barcat L, Gaudin J, Irani J (2009) Revisiting the immunophenotype of nephrogenic adenoma. Am J Surg Pathol 33:1654–1658PubMedCrossRefGoogle Scholar
  20. 20.
    Ortiz-Rey JA, Antón-Badiola I, Pérez-Pedrosa A, Peteiro-Cancelo A, González-Carreró J (2012) Nephrogenic adenoma: an immunohistochemical analysis using biotin-free methods. Appl Immunohistochem Mol Morphol 20:386–391PubMedCrossRefGoogle Scholar
  21. 21.
    Quinones W, Ziober A, Yao Y, Bing Z (2013) Immunohistochemical markers for the differential diagnosis of nephrogenic adenomas. Ann Diagn Pathol 17:41–44PubMedCrossRefGoogle Scholar
  22. 22.
    Gokaslan ST, Krueger JE, Albores-Saavedra J (2002) Symptomatic nephrogenic metaplasia of ureter: a morphologic and immunohistochemical study of four cases. Mod Pathol 15:765–70PubMedCrossRefGoogle Scholar
  23. 23.
    Oliva E, Young RH (1995) Nephrogenic adenoma of the urinary tract: a review of the microscopic appearance of 80 cases with emphasis on unusual features. Mod Pathol 8:722–730PubMedGoogle Scholar
  24. 24.
    Piña-Oviedo S, Shen SS, Truong LD, Ayala AG, Ro JY (2013) Flat pattern of nephrogenic adenoma: previously unrecognized pattern unveiled using PAX2 and PAX8 immunohistochemistry. Mod Pathol 26:792–798PubMedCrossRefGoogle Scholar
  25. 25.
    Hansel DE, Nadasdy T, Epstein JI (2007) Fibromyxoid nephrogenic adenoma: a newly recognized variant mimicking mucinous adenocarcinoma. Am J Surg Pathol 31:1231–1237PubMedCrossRefGoogle Scholar
  26. 26.
    Dahl E, Koseki H, Balling R (1997) Pax genes and organogenesis. Bioessays 19:755–65PubMedCrossRefGoogle Scholar
  27. 27.
    Ozcan A, Shen SS, Hamilton C, Anjana K, Coffey D, Krishnan B, Truong LD (2011) PAX 8 expression in non-neoplastic tissues, primary tumors, and metastatic tumors: a comprehensive immunohistochemical study. Mod Pathol 24:751–64PubMedCrossRefGoogle Scholar
  28. 28.
    Amin W, Parwani AV (2010) Nephrogenic adenoma. Pathol Res Pract 206:659–662PubMedCrossRefGoogle Scholar
  29. 29.
    Herlitz LC, Tong GX, Hamele-Bena D, Greenebaum E (2008) Nephrogenic adenoma identified on urine cytology using PAX-2 immunostaining. Diagn Cytophathol 36:47–49CrossRefGoogle Scholar
  30. 30.
    Ho PL, Kurtova A, Chan KS (2012) Normal and neoplastic urothelial stem cells: getting to the root of the problem. Nat Rev Urol 9:583–594PubMedCrossRefGoogle Scholar
  31. 31.
    Kato N, Honma K, Hojo H, Sasou S, Matsuzaki O, Motoyama T (2005) KIT expression in normal and neoplastic renal tissues: immunohistochemical and molecular genetic analysis. Pathol Int 55:479–483PubMedCrossRefGoogle Scholar
  32. 32.
    Larrinaga G, Varona A, Pérez I, Sainz B, Ugalde A, Cándenas ML, Pinto FM, Gil J, López JI (2010) Expression of cannabinoid receptors in human kidney. Histol Histopathol 25:1133–1138PubMedGoogle Scholar
  33. 33.
    Larrinaga G, Sanz B, Blanco L, Cándenas ML, Pinto FM, Irazusta A, Gil J, López JI (2013) Cannabinoid CB1 receptor is expressed in chromophobe renal cell carcinoma and renal oncocytoma. Clin Biochem 46:638–641PubMedCrossRefGoogle Scholar
  34. 34.
    Herawi M, Drew PA, Pan CC, Epstein JI (2010) Clear cell adenocarcinoma of the bladder and urethra: cases diffusely mimicking nephrogenic adenoma. Hum Pathol 41:594–601PubMedCrossRefGoogle Scholar
  35. 35.
    Amin MB (2009) Histological variants of urothelial carcinoma: diagnostic, therapeutic and prognostic implications. Mod Pathol 22(suppl 2):S96–S118PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • José I. López
    • 1
  • Marco Schiavo-Lena
    • 2
  • Alexandra Corominas-Cishek
    • 1
  • Adriana Yagüe
    • 3
  • Kevin Bauleth
    • 4
  • Rosa Guarch
    • 3
  • Ondrej Hes
    • 4
  • Regina Tardanico
    • 2
  1. 1.Department of Anatomic Pathology, Hospital Universitario CrucesUniversity of the Basque Country (UPV/EHU)BarakaldoSpain
  2. 2.Department of Pathology, Spedali CiviliUniversity of BresciaBresciaItaly
  3. 3.Department of PathologyHospital Virgen del CaminoPamplonaSpain
  4. 4.Department of PathologyCharles University HospitalPlzenCzech Republic

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