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European UrologyVolume 58, issue 5, pages e51-e52, November 2010
Peering Through the Microscope Lens Into the Future
Published online 10 September 2010, pages 669 - 670
Refers to article:
Prognostic and Therapeutic Impact of the Histopathologic Definition of Parenchymal Epithelial Renal Tumors
Accepted 2 August 2010
November 2010 (Vol. 58, Issue 5, pages 655 - 668)
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 . 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  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 . 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 .
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 . We also support the authors’ assertion that histologic subtype in renal cell carcinoma represents a vital feature for both prognostication  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  and . 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 .
In summary, reviews such as the one presented in this issue of European Urology 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.
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Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, MN, USA
© 2010 European Association of Urology, Published by Elsevier B.V.
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