Annals of Surgical Oncology

, Volume 11, Issue 1, pp 71–77 | Cite as

Effect of papillary and chromophobe cell type on disease-free survival after nephrectomy for renal cell carcinoma

  • Stephen D. W. Beck
  • Manish I. Patel
  • Mark E. Snyder
  • Michael W. Kattan
  • Robert J. Motzer
  • Victor E. Reuter
  • Paul RussoEmail author
Original Articles



The clinical staging of renal cortical tumors traditionally has not evaluated the potential effect of histological subtypes on survival. Evidence suggests that conventional clear cell renal cell carcinoma (RCC) and nonconventional clear cell RCC (chromophobe and papillary) have different metastatic potential. Using a large renal tumor database, we examined the effect of tumor histology on the pattern of metastasis and patient survival.


All patients with nonmetastatic renal cortical tumors undergoing partial or radical nephrectomy were identified from a renal tumor database between July 1989 and July 2002. Kaplan-Meier and Cox regression tests were used for statistical analysis.


Analysis revealed 1057 patients: 794 with conventional clear cell RCC, 157 with papillary RCC, and 106 with chromophobe RCC. Metastasis occurred in 95 conventional clear cell RCC, 9 papillary RCC, and 6 chromophobe RCC. Metastasis occurred in 95 conventional clear cell RCC, 9 papillary RCC, and 6 chromophobe RCC with a median follow-up of 34.6, 43.0, and 33.2 months, respectively. Using log-rank analysis, chromophobe and papillary RCC were associated with an improved disease-free survival at 5 years (P=.009 and .015, respectively). Multivariate analysis revealed tumor size, stage, and chromophobe histology as significant variables for disease progression.


Renal cortical tumors have distinct histological subtypes with varying degrees of metastatic potential. Conventional clear cell RCC, which comprises two thirds of renal cortical tumors presenting with localized disease, has a less favorable outcome when compared with papillary and chromophobe RCC. Controlling for size and stage, chromophobe, and not papillary, RCC was a significant variable for disease progression compared with conventional clear cell RCC. Knowledge of renal cortical tumor histological subtype is critical for projecting prognosis, tailoring follow-up strategies, and designing clinical trials.

Key Words

Kidney cancer Histology Metastases Staging 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kovacs G, Akhtar M, Beckwith BJ, et al. The Heidelberg classification of renal cell tumors.J Pathol 1997;183:131–3.PubMedCrossRefGoogle Scholar
  2. 2.
    Amin MB, Crotty TB, Tickoo SK, Farrow GM. Renal oncocytoma: a reappraisal of morphologic features with clinicopathologic findings in 80 cases.Am J Surg Pathol 1997;21:1–12.PubMedCrossRefGoogle Scholar
  3. 3.
    Perez-Ordonez B, Hamed G, Campbell S, et al. Renal oncocytoma: a clinicopathologic study of 70 cases.Am J Surg Pathol 1997;21:871–83.PubMedCrossRefGoogle Scholar
  4. 4.
    Reuter VE, Presti JC Jr. Contemporary approach to the classification of renal epithelial tumors.Semin Oncol 2000;27:124–37.PubMedGoogle Scholar
  5. 5.
    Yoshida MA, Ohyashiki K, Ochi H, et al. Cytogenetic studies of tumor tissue from patients with nonfamilial renal cell carcinoma.Cancer Res 1986;46(4 Pt 2):2139–47.PubMedGoogle Scholar
  6. 6.
    Whaley JM, Naglich J, Gelbert L, et al. Germ-line mutations in the von Hippel-Lindau tumor-suppressor gene are similar to somatic von Hippel-Lindau aberrations in sporadic renal cell carcinoma.Am J Hum Genet 1994;55:1092–102.PubMedGoogle Scholar
  7. 7.
    Gnarra JR, Tory K, Weng Y, et al. Mutations of the VHL tumour suppressor gene in renal carcinoma.Nat Genet 1994;7:85–90.PubMedCrossRefGoogle Scholar
  8. 8.
    Foster K, Prowse A, van den Berg A, et al. Somatic mutations of the von Hippel-Lindau disease tumour suppressor gene in nonfamilial clear cell renal carcinoma.Hum Mol Genet 1994;3:2169–73.PubMedGoogle Scholar
  9. 9.
    Shuin T, Kondo K, Torigoe S, et al. Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas.Cancer Res 1994;54:2852–5.PubMedGoogle Scholar
  10. 10.
    Kovacs G, Fuzesi L, Emanual A, Kung HF. Cytogenetics of papillary renal cell tumors.Genes Chromosomes Cancer 1991;3:249–55.PubMedGoogle Scholar
  11. 11.
    Henn W, Zwergel T, Wullich B, et al. Bilateral multicentric papillary renal tumors with heteroclonal origin based on tissue-specific karyotype instability.Cancer 1993;72:1315–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Kovacs G. Papillary renal cell carcinoma. A morphologic and cytogenetic study of 11 cases.Am J Pathol 1989;134:27–34.PubMedGoogle Scholar
  13. 13.
    Ishikawa I, Kovacs G. High incidence of papillary renal cell tumours in patients on chronic haemodialysis.Histopathology 1993;22:135–9.PubMedGoogle Scholar
  14. 14.
    Renshaw AA, Fletcher JA. Trisomy 3 in renal cell carcinoma.Mod Pathol 1997;10:481–4.PubMedGoogle Scholar
  15. 15.
    Bugert P, Gaul C, Weber K, et al. Specific genetic changes of diagnostic importance in chromophobe renal cell carcinomas.Lab Invest 1997;76:203–8.PubMedGoogle Scholar
  16. 16.
    Schwerdtle RF, Storkel S, Neuhaus C, et al. Allelic losses at chromosomes 1p, 2p, 6p, 10p, 13q, 17p, and 21q significantly correlate with the chromophobe subtype of renal cell carcinoma.Cancer Res 1996;56:2927–30.PubMedGoogle Scholar
  17. 17.
    Kovacs A, Kovacs G. Low chromosome number in chromophobe renal cell carcinomas.Genes Chromospomes Cancer 1992;4:267–8.Google Scholar
  18. 18.
    van den Berg E, van der Hout AH, Oosterhuis JW, et al. Cytogenetic analysis of epithelial renal-cell tumors: relationship with a new histopathological classification.Int J Cancer 1993;55:223–7.PubMedGoogle Scholar
  19. 19.
    Sobin LH, Wittekind C.TNM: Classification of Malignant Tumors. New York: Wiley-Liss, 2002:239.Google Scholar
  20. 20.
    Kattan MW. Judging new markers by their ability to improve predictive accuracy.J Natl Cancer Inst 2003;95:634–5.PubMedGoogle Scholar
  21. 21.
    Zambrano NR, Lubensky IA, Merino MJ, et al. Histopathology and molecular genetics of renal tumors toward unification of a classification system.J Urol 1999;162:1246–58.PubMedCrossRefGoogle Scholar
  22. 22.
    Amin MB, Corless CL, Renshaw AA, et al. Papillary (chromophil) renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 62 cases.Am J Surg Pathol 1997;21:621–35.PubMedCrossRefGoogle Scholar
  23. 23.
    el-Naggar AK, Ro JY, Ensign LG. Papillary renal cell carcinoma: clinical implication of DNA content analysis.Hum Pathol 1993; 24:316–21.PubMedCrossRefGoogle Scholar
  24. 24.
    Lager DJ, Huston BJ, Timmerman TG, Bonsib SM. Papillary renal tumors. Morphologic, cytochemical, and genotypic features.Cancer 1995;76:669–73.PubMedCrossRefGoogle Scholar
  25. 25.
    Ljungberg B, Alamdari FI, Stenling R, Roos G. Prognostic significance of the Heidelberg classification of renal cell carcinoma.Eur Urol 1999;36:565–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Mancilla-Jimenez R, Stanley RJ, Blath RA. Papillary renal cell carcinoma: a clinical, radiologic, and pathologic study of 34 cases.Cancer 1976;38:2469–80.PubMedCrossRefGoogle Scholar
  27. 27.
    Mydlo JH, Bard RH. Analysis of papillary renal adenocarcinoma.Urology 1987;30:529–34.PubMedCrossRefGoogle Scholar
  28. 28.
    Onishi T, Ohishi Y, Goto H, et al. Papillary renal cell carcinoma: clinicopathological characteristics and evaluation of prognosis in 42 patients.BJU Int 1999;83:937–43.PubMedCrossRefGoogle Scholar
  29. 29.
    Akhtar M, Kardar H, Linjawi T, et al. Chromophobe cell carcinoma of the kidney. A clinicopathologic study of 21 cases.Am J Surg Pathol 1995;19:1245–56.PubMedCrossRefGoogle Scholar
  30. 30.
    Crotty TB, Farrow GM, Lieber MM. Chromophobe cell renal carcinoma: clinicopathological features of 50 cases.J Urol 1995; 154:964–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Onishi T, Ohishi Y, Iizuka N, et al. Clinicopathological study on patients with chromophobe cell renal carcinoma (in Japanese).Nippon Hinyokika Gakkai Zasshi 1996;87:1167–74.PubMedGoogle Scholar
  32. 32.
    Renshaw AA, Henske EP, Loughlin KR, et al. Aggressive variants of chromophobe renal cell carcinoma.Cancer 1996;78:1756–61.PubMedCrossRefGoogle Scholar
  33. 33.
    Sanz Perez G, Arocena Garcia-Tapia J, Zudaire Bergera JJ, et al. Chromophobe carcinoma of the kidney (in Spanish).Actas Urol Esp 1999;23:323–6.PubMedGoogle Scholar
  34. 34.
    Taki A, Nakatani Y, Misugi K, et al. Chromophobe renal cell carcinoma: an immunohistochemical study of 21 japanese cases.Mod Pathol 1999;12:310–7.PubMedGoogle Scholar
  35. 35.
    Thoenes W, Storkel S, Rumpelt HJ, et al. Chromophobe cell renal carcinoma and its variants—a report on 32 cases.J Pathol 1988; 155:277–87.PubMedCrossRefGoogle Scholar
  36. 36.
    Lee CT, Katz J, Shi W, et al. Surgical management of renal tumors 4 cm. or less in a contemporary cohort.J Urol 2000;163:730–6.PubMedCrossRefGoogle Scholar
  37. 37.
    McKiernan J, Yossepowitch O, Kattan MW, et al. Partial nephrectomy for renal cortical tumors: pathologic findings and impact on outcome.Urology 2002;60:1003–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Kattan MW, Reuter V, Motzer RJ, et al. A postoperative prognostic nomogram for renal cell carcinoma.J Urol 2001;166:63–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Moch H, Gasser T, Amin MB, et al. Prognostic utility of the recently recommended histologic classification and revised TNM staging system of renal cell carcinoma: a Swiss experience with 588 tumors.Cancer 2000;89:604–14.PubMedCrossRefGoogle Scholar
  40. 40.
    Amin MB, Tamboli P, Javidan J, et al. Prognostic impact of histologic subtyping of adult renal epithelial neoplasms: an experience of 405 cases.Am J Surg Pathol 2002;26:281–91.PubMedCrossRefGoogle Scholar
  41. 41.
    Lau WK, Cheville JC, Blute ML, et al. Prognostic features of pathologic stage T1 renal cell carcinoma after radical nephrectomy.Urology 2002;59:532–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Delahunt B, Eble JN. Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors.Mod Pathol 1997;10:537–44.PubMedGoogle Scholar
  43. 43.
    Delahunt B, Eble JN, McCredie MR, et al. Morphologic typing of papillary renal cell carcinoma: comparison of growth kinetics and patient survival in 66 cases.Hum Pathol 2001;32:590–5.PubMedCrossRefGoogle Scholar
  44. 44.
    Harrell FE Jr, Califf RM, Pryor DB, et al. Evaluating the yield of medical tests.JAMA 1982;247:2543–6.PubMedCrossRefGoogle Scholar
  45. 45.
    Renshaw AA, Richie JP. Subtypes of renal cell carcinoma. Different onset and sites of metastatic disease.Am J Clin Pathol 1999; 111:539–43.PubMedGoogle Scholar
  46. 46.
    Mai KT, Landry DC, Robertson SJ, et al. A comparative study of metastatic renal cell carcinoma with correlation to subtype and primary tumor.Pathol Res Pract 2001;197:671–5.PubMedCrossRefGoogle Scholar
  47. 47.
    Motzer RJ, Bacik J, Mariani T, et al. Treatment outcome and survival associated with metastatic renal cell carcinoma of nonclear-cell histology.J Clin Oncol 2002;20:2376–81.PubMedCrossRefGoogle Scholar
  48. 48.
    Patel MI, Simmons R, Kattan MW, et al. Long-term follow-up of bilateral sporadic renal tumors.Urology 2003;61:921–5.PubMedCrossRefGoogle Scholar

Copyright information

© The Society of Surgical Oncology, Inc 2003

Authors and Affiliations

  • Stephen D. W. Beck
    • 1
  • Manish I. Patel
    • 1
  • Mark E. Snyder
    • 1
  • Michael W. Kattan
    • 2
  • Robert J. Motzer
    • 3
  • Victor E. Reuter
    • 4
  • Paul Russo
    • 1
    Email author
  1. 1.Department of Urology Sidney Kimmel Center for Prostate and Urologic CancersMemorial Sloan-Kettering Cancer CenterNew York
  2. 2.Department of Epidemiology and Biostatistics Sidney Kimmel Center for Prostate and Urologic CancersMemorial Sloan-Kettering Cancer CenterNew York
  3. 3.Department of Medicine Sidney Kimmel Center for Prostate and Urologic CancersMemorial Sloan-Kettering Cancer CenterNew York
  4. 4.Department of Pathology Sidney Kimmel Center for Prostate and Urologic CancersMemorial Sloan-Kettering Cancer CenterNew York

Personalised recommendations