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Volume 58, issue 5, pages e51-e52, November 2010

Kidney Cancer

Peering Through the Microscope Lens Into the Future

Matthew K. Tollefson lowast and R. Houston Thompson

Published online 10 September 2010, pages 669 - 670

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Refers to article:

Prognostic and Therapeutic Impact of the Histopathologic Definition of Parenchymal Epithelial Renal Tumors

Vincenzo Ficarra, Matteo Brunelli, Liang Cheng, Ziya Kirkali, Antonio Lopez-Beltran, Guido Martignoni, Rodolfo Montironi, Giacomo Novara and Hein Van Poppel

Accepted 2 August 2010

November 2010 (Vol. 58, Issue 5, pages 655 - 668)

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Article Outline

In this comprehensive review, Ficarra et al assemble a team of expert urologic oncologists and genitourinary pathologists who succinctly lay out the current state of pathologic review of renal cell carcinoma [1]. The authors appropriately identify key issues and current controversies in the prediction of the disease based on its histologic features. Several key issues stand out and deserve emphasis.

First, it is imperative that clinicians and pathologists maintain an active working relationship. Pathologists depend on clinicians for specimens that maintain structure and enable a robust histologic review of the material. Techniques such as morcellation [2] or inadequate biopsy samples make histologic interpretation more difficult and should be discouraged. In turn, clinicians depend on pathologists to perform an accurate review of the submitted material. Indeed, even in our own experience, when reviewing patients who unexpectedly progressed despite having low-risk histologic features, two thirds were found to be understaged histologically [3]. These patients were found to have an unrecognized invasion of the renal sinus, a critical highway of blood vessels and lymphatics that may facilitate metastasis from the kidney [4].

Second, accurate disease prediction is important for counseling patients regarding their risk of recurrence. But perhaps more importantly, such studies facilitate trials of adjuvant or salvage therapies by ensuring equal risk of disease progression among treatment groups. At the Mayo Clinic, we have strived to improve the outcome prediction that is obtained through routine hematoxylin and eosin staining by clarifying the role of pathologic stage, tumor size, nuclear grade, and histologic coagulative necrosis, to form the SSIGN score, a simple predictive model that has been independently validated [5]. We also support the authors’ assertion that histologic subtype in renal cell carcinoma represents a vital feature for both prognostication [6] and for selecting an appropriate systemic therapy for those patients with metastatic disease.

Finally, the authors correctly point out that although further refinements in the histologic review of renal cell carcinoma are possible, significant advances in disease prediction are likely to be based on immunohistochemical studies for features that are simply not visible with routine hematoxylin and eosin staining [7] and [8]. Immunohistochemical studies have yielded seminal observations in renal cell carcinoma and have formed hypotheses regarding treatment targets for those with advanced disease. For example, observations that renal cell carcinoma may evade host immunity through the overexpression of immunosuppressive coregulatory molecules have led to the development of therapeutic approaches to thwart immunosuppressive efforts within the tumor microenvironment [9].

In summary, reviews such as the one presented in this issue of European Urology[1] enable clinicians and pathologists to come together and agree on which features are important to predict outcome from this potentially deadly disease. We hope ongoing improvements in disease prediction will help identify patients that may benefit from adjuvant therapy, exclude those patients that will not, and identify future treatment strategies. With these advances, one may finally look through the lens of the microscope to predict what will happen. Further advances will permit us to change that future.

Conflicts of interest

The authors have nothing to disclose.

References

  • [1] V. Ficarra, M. Brunelli, L. Cheng, et al. Prognostic and therapeutic impact of histopathological definition of parenchymal epithelial renal tumors. Eur Urol. 2010;58:655-668 Abstract, Full-text, PDF, Crossref.
  • [2] C.F. Granberg, A.E. Krambeck, B.C. Leibovich, et al. Potential underdetection of pT(3a) renal-cell carcinoma with laparoscopic morcellation. J Endourol. 2007;21:1183-1186 Crossref.
  • [3] R.H. Thompson, M.L. Blute, A.E. Krambeck, et al. Patients with pT1 renal cell carcinoma who die from disease after nephrectomy may have unrecognized renal sinus fat invasion. Am J Surg Pathol. 2007;31:1089-1093
  • [4] S.M. Bonsib. The renal sinus is the principal invasive pathway: a prospective study of 100 renal cell carcinomas. Am J Surg Pathol. 2004;28:1594-1600 Crossref.
  • [5] I. Frank, M.L. Blute, J.C. Cheville, C.M. Lohse, A.L. Weaver, H. Zincke. An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J Urol. 2002;168:2395-2400
  • [6] B.C. Leibovich, C.M. Lohse, P.L. Crispen, et al. Histological subtype is an independent predictor of outcome for patients with renal cell carcinoma. J Urol. 2010;183:1309-1315
  • [7] M.K. Tollefson, R.H. Thompson, Y. Sheinin, et al. Ki-67 and coagulative tumor necrosis are independent predictors of poor outcome for patients with clear cell renal cell carcinoma and not surrogates for each other. Cancer. 2007;110:783-790 Crossref.
  • [8] N.E. Hoffmann, Y. Sheinin, C.M. Lohse, et al. External validation of IMP3 expression as an independent prognostic marker for metastatic progression and death for patients with clear cell renal cell carcinoma. Cancer. 2008;112:1471-1479 Crossref.
  • [9] R.H. Thompson, M.D. Gillett, J.C. Cheville, et al. Costimulatory B7-H1 in renal cell carcinoma patients: indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci U S A. 2004;101:17174-17179 Crossref.
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Footnotes

Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, MN, USA

lowast Corresponding author. Department of Urology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA. Tel. +1 507 284 3982; Fax: +1 507 284 4951.

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