Virchows Archiv

, Volume 447, Issue 6, pp 938–946

Can renal oncocytoma be differentiated from its renal mimics? The utility of anti-mitochondrial, caveolin 1, CD63 and cytokeratin 14 antibodies in the differential diagnosis

  • Ozgur Mete
  • Isin Kilicaslan
  • Mine G. Gulluoglu
  • Veli Uysal
Original Article


Among the epithelial renal tumours with eosinophilic cytoplasm, the main differential diagnostic problem arises between renal oncocytomas (ROs) and eosinophilic variants of chromophobe renal cell carcinomas (RCCs). We investigated the possible role of anti-mitochondrial (AMA), anti-caveolin 1 (CAV1), anti-CD63 (CD63) and anti-cytokeratin 14 (CK14) antibodies in the differential diagnosis of eosinophilic epithelial tumours and applied the Muller and Mowry modification of Hale's colloidal iron stain (HCI). Thirty-five ROs and 77 eosinophilic RCCs (27 chromophobe, 28 clear cell and 22 papillary RCCs) were included in this study. Apical and/or polar CD63 immunostaining (94%) and diffuse AMA (91%) and CAV1 (88%) immunostainings were the characteristics of ROs, whereas diffuse CD63 immunostaining (96%) and diffuse-peripheral AMA (96%) and CAV1 (92%) immunostainings were characteristic immunohistochemical features of eosinophilic chromophobe RCCs. We showed CK14 antibody not to be useful in the differential diagnosis of the eosinophilic epithelial renal tumours. The staining localisations with AMA, CAV1 and CD63 antibodies were significantly different between tumour groups. AMA had 96% sensitivity and 94% specificity, whereas CAV1 had 92% sensitivity and 97% specificity in diagnosing chromophobe RCCs. With HCI staining, ROs, showing apical and/or polar staining, could be differentiated from chromophobe RCCs, showing diffuse cytoplasmic staining. HCI had fairly low (69%) sensitivity and 100% specificity, whereas CD63 had 95% sensitivity and 100% specificity to diagnose ROs. We recommend using CD63 as the best marker of choice for distinguishing ROs from eosinophilic chromophobe RCCs when standard diagnostic criteria are not helpful.


Oncocytoma Renal cell carcinoma Immunohistochemistry CD63 Caveolin 1 


  1. 1.
    Abrahams NA, MacLennan GT, Khoury JD et al (2004) Chromophobe renal cell carcinoma: a comparative study of histological, immunohistochemical and ultrastructural features using high throughput tissue microarray. Histopathology 45:593–602CrossRefPubMedGoogle Scholar
  2. 2.
    Akhtar M, Kardar H, Linjawi T et al (1995) Chromophobe cell carcinoma of the kidney: a clinicopathologic study of 21 cases. Am J Surg Pathol 19:1245–1256PubMedGoogle Scholar
  3. 3.
    Amin MB, Amin MB, Tamboli P et al (2002) Prognostic impact of histologic subtyping of adult renal epithelial neoplasms: an experience of 405 cases. Am J Surg Pathol 26:281–291CrossRefPubMedGoogle Scholar
  4. 4.
    Amin MB, Crotty TB, Tickoo SK et al (1997) Renal oncocytoma: a reappraisal of morphologic features with clinicopathologic findings in 80 cases. Am J Surg Pathol 21:1–12CrossRefPubMedGoogle Scholar
  5. 5.
    Avery AK, Beckstead J, Renshaw AA et al (2000) Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasms. Am J Surg Pathol 24:203–210CrossRefPubMedGoogle Scholar
  6. 6.
    Bancroft JD, Gamble M (eds) (2002) Theory and practice of histological techniques, 5th edn. Churchill Livingstone, EdinburghGoogle Scholar
  7. 7.
    Barnes CA, Beckman EN (1983) Renal oncocytoma and its congeners. Am J Clin Pathol 79:312–318PubMedGoogle Scholar
  8. 8.
    Bonsib SM (1996) Renal chromophobe cell carcinoma: the relationship between cytoplasmic vesicles and colloidal iron stain. J Urol Pathol 4:9–14Google Scholar
  9. 9.
    Bonsib SM, Bray C, Timmerman TG (1993) Renal chromophobe cell carcinoma: limitations of paraffin-embedded tissue. Ultrastruct Pathol 17:529–536PubMedCrossRefGoogle Scholar
  10. 10.
    Bonsib SM, Larger D (1990) Chromophobe cell carcinoma: analysis of five cases. Am J Surg Pathol 14:260–267PubMedCrossRefGoogle Scholar
  11. 11.
    Carrion R, Morgan BE, Tannenbaum M et al (2003) Caveolin expression in adult renal tumors. Urol Oncol 21:191–196PubMedGoogle Scholar
  12. 12.
    Cheville JC, Lohse CM, Zincke H et al (2003) Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol 27:612–624CrossRefPubMedGoogle Scholar
  13. 13.
    Chu PG, Lyda MH, Weiss LM (2001) Cytokeratin 14 expression in epithelial neoplasms: a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumours. Histopathology 39:9–16CrossRefPubMedGoogle Scholar
  14. 14.
    Chu PG, Weiss LM (2001) Cytokeratin 14 immunoreactivity distinguishes oncocytic tumour from its renal mimics: an immunohistochemical study of 63 cases. Histopathology 39:455–462CrossRefPubMedGoogle Scholar
  15. 15.
    Chu PG, Weiss LM (2002) Keratin expression in human tissues and neoplasms. Histopathology 40:403–439CrossRefPubMedGoogle Scholar
  16. 16.
    Cochand-Priollet B, Molinie V, Bougaran J et al (1997) Renal chromophobe cell carcinoma and oncocytoma. A comparative morphologic, histochemical, and immunohistochemical study of 124 cases. Arch Pathol Lab Med 121:1081–1086PubMedGoogle Scholar
  17. 17.
    Eble JN, Amin MB, Young RH (1997) Epithelioid angiomyolipoma of the kidney: a report of five cases with a prominent and diagnostically confusing epithelioid smooth muscle component. Am J Surg Pathol 21:1123–1130CrossRefPubMedGoogle Scholar
  18. 18.
    Eble JN, Sauter G, Epstein JI, Sesterhenn IA (eds) (2004) World Health Organization classification of tumours. Pathology and genetics of the urinary system and male genital organs. IARC, LyonGoogle Scholar
  19. 19.
    Erlandson RA, Shek TWH, Reuter VE (1997) Diagnostic significance of mitochondria in four types of renal epithelial neoplasms: an ultrastructural study of 60 tumors. Ultrastruct Pathol 21:409–417PubMedGoogle Scholar
  20. 20.
    Gartner LP, Hiatt JL (eds) (2001) Color textbook of histology, 2nd edn. WB Saunders, PhiladelphiaGoogle Scholar
  21. 21.
    Hagen EC, Vennegoor C, Schlingemann RO et al (1986) Correlation of histopathological characteristics with staining patterns in human melanoma assessed by (monoclonal) antibodies reactive on paraffin sections. Histopathology 10:689–700PubMedCrossRefGoogle Scholar
  22. 22.
    Juhasz M, Chen J, Tulassay Z et al (2003) Expression of caveolin-1 in gastrointestinal and extraintestinal cancers. J Cancer Res Clin Oncol 129:493–497CrossRefPubMedGoogle Scholar
  23. 23.
    Khoury JD, Abrahams NA, Levin HS et al (2002) The utility of epithelial membrane antigen and vimentin in the diagnosis of chromophobe renal cell carcinoma. Ann Diagn Pathol 6:154–158CrossRefPubMedGoogle Scholar
  24. 24.
    Langner C, Wegscheider BJ, Ratschek M et al (2004) Keratin immunohistochemistry in renal cell carcinoma subtypes and renal oncocytomas: a systematic analysis of 233 tumors. Virchows Arch 444:127–134CrossRefPubMedGoogle Scholar
  25. 25.
    Leroy X, Mouskassa D, Copin MC et al (2000) Utility of cytokeratin 7 for distinguishing chromophobe renal cell carcinoma from renal cell carcinoma. Eur Urol 37:484–487CrossRefPubMedGoogle Scholar
  26. 26.
    Li S, Couet J, Lisanti MP (1996) Src tyrosine kinases, G alpha subunits, and H-ras share a common membrane-anchored scaffolding protein caveolin: caveolin binding negatively regulates the auto-activation of Src tyrosine kinases. J Biol Chem 271:29182–29190CrossRefPubMedGoogle Scholar
  27. 27.
    Li WP, Liu P, Anderson RG (2001) Cell-specific targeting of caveolin-1 to caveolae, secretory vesicles, cytoplasm or mitochondria. J Cell Sci 114:1397–1408PubMedGoogle Scholar
  28. 28.
    Liu J, Fanning CV (2001) Can renal oncocytomas be distinguished from renal cell carcinoma on fine-needle aspiration specimens? Cancer 93:390–397CrossRefPubMedGoogle Scholar
  29. 29.
    Mackie RM, Campbell I, Turbitt ML (1984) Use of NK1 C3 monoclonal antibody in the assessment of benign and malignant melanocytic lesions. J Clin Pathol 37:367–372PubMedCrossRefGoogle Scholar
  30. 30.
    Martignoni G, Pea M, Chilosi M et al (2001) Parvalbumin is constantly expressed in chromophobe renal carcinoma. Mod Pathol 14:760–767CrossRefPubMedGoogle Scholar
  31. 31.
    Mathers ME, Pollock AM, Marsh C et al (2002) Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell carcinoma. Histopathology 563–567Google Scholar
  32. 32.
    Metzelaar MJ, Wijngaard PL, Peters PJ et al (1991) A novel lysosomal membrane glycoprotein, cloned by a screening procedure for intracellular antigens in eukaryotic cells. J Biol Chem 266:3239–3245PubMedGoogle Scholar
  33. 33.
    Miettinen M, Ekfors T (1990) Alveolar soft part sarcoma. Immunohistochemical evidence for muscle cell differentiation. Am J Clin Pathol 93:32–38PubMedGoogle Scholar
  34. 34.
    Murphy WM, Beckwith JB, Farrow GM (1994) Tumors of the kidney, bladder and related urinary structures. In: Rosai J (ed) Atlas of Tumor Pathology, 3rd series, fascicle 11. Armed Forces Institute of Pathology, Washington, DCGoogle Scholar
  35. 35.
    Ordonez NG, Rosai J (2004) Urinary tract: kidney, renal pelvis and ureter. In: Rosai J (ed) Rosai and Ackerman's surgical pathology, vol 1, 9th edn. Mosby, Edinburgh, pp 1163–1316Google Scholar
  36. 36.
    Palmer AA, Hall BE, Lew M (1985) A comparison of some methods for identifying melanotic and amelanotic melanoma metastases in paraffin sections. Pathology 17:335–339PubMedCrossRefGoogle Scholar
  37. 37.
    Perez-Ordonez B, Hamed G, Campbell S et al (1997) Renal oncocytoma: a clinicopathologic study of 70 cases. Am J Surg Pathol 21:871–883CrossRefPubMedGoogle Scholar
  38. 38.
    Porena M, Vespasiani G, Rosi P et al (1992) Incidentally detected renal cell carcinoma: role of ultrasonography. J Clin Ultrasound 20:395–400CrossRefGoogle Scholar
  39. 39.
    Renshaw AA (2002) Subclassification of renal cell neoplasms: an update for practising pathologist. Histopathology 41:283–300CrossRefPubMedGoogle Scholar
  40. 40.
    Robenek MJ, Schlattmann K, Zimmer KP et al (2003) Cholesterol transporter caveolin-1 transits the lipid bilayer during intracellular cycling. FASEB J 17:1940–1942PubMedGoogle Scholar
  41. 41.
    Romis L, Cindolo L, Patard JJ et al (2004) Frequency, clinical presentation and evolution of renal oncocytomas: multicentric experience from a European database. Eur Urol 45:53–57CrossRefPubMedGoogle Scholar
  42. 42.
    Rothberg KG, Heuser JE, Donzell WC et al (1992) Caveolin, a protein component of caveolae membrane coats. Cell 68:673–682CrossRefPubMedGoogle Scholar
  43. 43.
    Rous BA, Reaves BJ, Ihrke G et al (2002) Role of adaptor complex AP-3 in targeting wild type and mutated CD63 to lysosomes. Mol Biol Cell 13:1071–1082CrossRefPubMedGoogle Scholar
  44. 44.
    Skinnider BF, Jones EC (1999) Renal oncocytoma and chromophobe renal cell carcinoma. A comparison of colloidal iron staining and electron microscopy. Am J Clin Pathol 111:796–803PubMedGoogle Scholar
  45. 45.
    Stoller ML, Carroll PR (2003) Urology. In: Tierney LM, McPhee SJ, Papadakis MA (eds) Current medical diagnosis & treatment 2003, 42nd edn. Lange Medical Books/McGraw-Hill, New York, pp 903–945Google Scholar
  46. 46.
    Stone CH, Lee MW, Amin MB et al (2001) Renal angiomyolipoma: further immunophenotypic characterization of an expanding morphologic spectrum. Arch Pathol Lab Med 125:751–758PubMedGoogle Scholar
  47. 47.
    Störkel S, Steart PV, Drenckhahn D et al (1989) The human chromophobe cell renal cell carcinoma: its probable relation to intercalated cells of the collecting duct. Virchows Arch B Cell Pathol Incl Mol Pathol 56:237–245PubMedGoogle Scholar
  48. 48.
    Thoenes W, Baum HP, Störkel S et al (1987) Cytoplasmic microvesicles in chromophobe cell renal carcinoma demonstrated by freeze fracture. Short communication. Virchows Arch B Cell Pathol Incl Mol Pathol 54:127–130PubMedGoogle Scholar
  49. 49.
    Thoenes W, Störkel S, Rumpelt HJ (1985) Human chromophobe cell renal carcinoma. Virchows Arch B Pathol 48:207–217CrossRefGoogle Scholar
  50. 50.
    Thoenes W, Störkel S, Rumpelt HJ et al (1988) Chromophobe cell renal carcinoma and its variants: a report on 32 cases. J Pathol 155:277–287CrossRefPubMedGoogle Scholar
  51. 51.
    Tickoo SK, Amin MB, Linden MD et al (1997) Antimitochondrial antibody (113-1) in the differential diagnosis of granular renal cell tumors. Am J Surg Pathol 21:922–930CrossRefPubMedGoogle Scholar
  52. 52.
    Tickoo SK, Amin MB, Zarbo RJ (1998) Colloidal iron staining in renal epithelial neoplasms, including chromophobe renal cell carcinoma. Emphasis on technique and patterns of staining. Am J Surg Pathol 22:419–424CrossRefPubMedGoogle Scholar
  53. 53.
    Tickoo SK, Lee MW, Eble JN et al (2000) Ultrastructural observations on mitochondria and microvesicles in renal oncocytoma, chromophobe renal cell carcinoma and eosinophilic variant of conventional (clear cell) renal cell carcinoma. Am J Surg Pathol 24:1247–1256PubMedCrossRefGoogle Scholar
  54. 54.
    Vennegoor C, Calafat J, Hageman P et al (1985) Biochemical characterization and cellular localization of a formalin-resistant melanoma-associated antigen reacting with monoclonal antibody NKI/C3. Int J Cancer 35:287–295PubMedCrossRefGoogle Scholar
  55. 55.
    Vieillefond A, Paradis V, Bouvier GR et al (1992) Est-il utile d'isoler parmi les carcinomes du rein, une variante a cellules chromophobes? Arch Anat Cytol Pathol 40:250–254PubMedGoogle Scholar
  56. 56.
    Wanaski SP, Glaser BK, Glaser M (2003) Caveolin scaffolding region and the membrane binding region of Src form lateral membrane domains. Biochemistry 42:42–56CrossRefPubMedGoogle Scholar
  57. 57.
    Weiss LM, Gaffey MJ, Warhol MJ (1991) Immunohistochemical characterization of a monoclonal antibody directed against mitochondria reactive in paraffin-embedded sections. Mod Pathol 4:596–601PubMedGoogle Scholar
  58. 58.
    Wu SL, Kothari P, Wheeler TM et al (2002) Cytokeratins 7 and 20 immunoreactivity in chromophobe renal cell carcinomas and oncocytomas. Mod Pathol 15:712–717CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Ozgur Mete
    • 1
  • Isin Kilicaslan
    • 1
  • Mine G. Gulluoglu
    • 1
  • Veli Uysal
    • 1
  1. 1.Department of Pathology, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey

Personalised recommendations