Perspectives in pathology Molecular and cytogenetic insights into the pathogenesis, classification, differential diagnosis, and prognosis of renal epithelial neoplasms Liang Cheng MD a,b, ⁎ , Shaobo Zhang MD a , Gregory T. MacLennan MD c , Antonio Lopez-Beltran MD d , Rodolfo Montironi MD e a Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA b Department of Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA c Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA d Department of Pathology, Cordoba University, 14071 Cordoba, Spain e Institute of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, 60121 Ancona, Italy Received 5 August 2008; revised 10 September 2008; accepted 12 September 2008 Keywords: Kidney; Renal neoplasms; Molecular genetics; Molecular pathology; Gene expression profiling differential diagnosis; Tumor origin; Classifications Summary Renal cell carcinomas comprise a heterogeneous group of epithelial neoplasms with diverse biologic potential and variable clinical outcomes. The application of molecular and cytogenetic techniques to the study of renal neoplasms has improved our understanding of the molecular mechanisms responsible for tumor initiation and progression. Molecular classification of renal cell carcinomas has also provided new avenues for diagnosis, clinical outcome, and therapy response prediction. In this article, we review the molecular markers for various renal epithelial neoplasms and discuss the mechanisms underlying the development of these neoplasms. We also evaluate the use of molecular and cytogenetic techniques in establishing an accurate diagnosis in difficult cases and their potential usefulness in accurately classifying renal neoplasms, assessing prognosis, and selecting appropriate therapy. © 2009 Elsevier Inc. All rights reserved. 1. Introduction Renal cell carcinoma subtypes share some common histologic characteristics, but they also exhibit distinctly different biologic behavior and response to therapy. The varying carcinogenic pathways underlying their develop- ment may account for these differences. Accurate histo- pathologic classification has historically been of great practical value in the clinical management of renal cell neoplasms, but in recent years, the discovery of new molecular and cytogenetic markers has led to the recognition and classification of several novel subtypes of renal cell neoplasms [1-3]. The cytogenetic and molecular properties of a particular renal neoplasm are related to its carcinogenetic pathway, cellular origin, and inherent biologic properties. Strong correlations exist between the cytogenetic makeup and ⁎ Corresponding author. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. E-mail address: liang_cheng@yahoo.com (L. Cheng). www.elsevier.com/locate/humpath 0046-8177/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2008.09.009 Human Pathology (2009) 40, 10–29