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Genitourinary tumor pathology: introductory comments.

This special issue of the Archives of Pathology & Laboratory Medicine is dedicated to genitourinary tumor pathology. The insights and controversies in this field are extensively dealt with and reviewed in 8 articles, whose main features are briefly summarized below.

Fadi Brimo, MD, and Jonathan I. Epstein, MD, review 3 of the most common differential diagnoses encountered in a large consultation service in genitourinary pathology: partial atrophy versus prostatic acinar adenocarcinoma, oncocytoma versus chromophobe renal cell carcinoma (RCC), and urothelial carcinoma in situ versus normal urothelium and reactive atypia. They discuss the detailed, morphologic, distinctive features and the usefulness of immunohistochemistry. Careful morphologic assessment and awareness of the diagnostic pitfalls are keys to reaching a definitive diagnosis in most cases. Immunohistochemistry is useful but should be used strictly in conjunction with the morphologic impression.

The review by George J. Netto, MD, and Liang Cheng, MD, deals with the critical role of molecular testing in diagnostic genitourinary pathology. They focus on promising candidate biomarkers that may soon make the transition to the realm of clinical management of genitourologic malignancies. In particular, the authors discuss 4 major areas of interest. Unprecedented advances in cancer genetics and genomics are rapidly affecting clinical management and diagnostics in solid tumor oncology. Molecular diagnostics is now an integral part of routine clinical management in patients with lung, colon, and breast cancer. In sharp contrast, molecular biomarkers have been largely excluded from current management algorithms for urologic malignancies. The need for new treatment alternatives that can improve on the so-far modest outcome is evident in several types of urologic cancer. Well-validated, prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management are lacking.

Identifying robust, predictive biomarkers that will stratify response to emerging targeted therapeutics is another crucially needed development.

The contribution by Hillary Ross, MD, Guido Martignoni, MD, and Pedram Argani, MD, deals with RCC that have clear cell and papillary features. The 4 main neoplasms in the differential are clear cell RCC, papillary RCC, clear cell papillary RCC, and Xp11 translocation RCC. The authors highlight the helpful cytomorphologic, immunohistochemical, and cytogenetic features of each of these entities to enable reproducible classification. Key morphologic clues and a focused immunohistochemical panel, including CK7, [alpha]-methylacyl coenzyme A racemase (AMACR), TFE3, cathepsin K, and CAIX, now allow most resected RCCs with papillary architecture and clear cells to be accurately classified. In other cases, cytogenetic and molecular findings can establish the diagnosis. Despite these tools, some RCCs with papillary architecture and clear cells do not fit into any of the described entities and currently remain unclassified. Accurate diagnosis has both prognostic and therapeutic implications.

Ying Bei Chen, MD, PhD, and Satish K. Tickoo, MD, review the clinicopathologic characteristics of common entities in the spectrum of neoplastic and potential, preneoplastic cystic kidney lesions encountered in adults, with emphasis on renal cystic diseases associated with tumor development and renal neoplasms with predominantly cystic morphology. The presence of multiple renal cysts, both acquired and syndromic, can be associated with a variety of renal tumors. The morphology of the cysts and associated tumor types can help predict the genetic or acquired basis of the lesions. Particularly in specimens with no accompanying pertinent clinical history, such potential associations should be suggested in surgical pathology reports. In the adult population, neoplasms occurring in the background of renal cystic diseases and cystic renal neoplasms frequently pose diagnostic challenges given their many overlapping features.

According to Steven S. Shen, MD, PhD, Luan D. Truong, MD, Marina Scarpelli, MD, and Antonio Lopez-Beltran, MD, PhD, immunohistochemical techniques using a variety of markers have been applied to the diagnosis of RCC, and, in some situations, such techniques have become indispensable. The common diagnostic situations that call for immunohistochemical staining are the differential diagnoses of renal versus nonrenal neoplasms, histologic subtyping of renal cell carcinoma, diagnosis of possible metastatic renal carcinomas, and, less frequently, molecular prognostication. With the refinement of molecular and histologic classification of renal neoplasms and the availability of more-effective molecular targeted therapy for specific renal neoplasms, immunohistochemical techniques are increasingly important in their diagnosis. During the past few decades, many markers have been evaluated for their role in the diagnosis, prognosis, and treatment of renal neoplasms. The numbers of markers that are useful in routine practice continue to increase. The challenge will be to choose among the markers and to decide in which situations immunohistochemistry will be truly useful.

The article by Brian Robinson, MD, Cristina Magi Galluzzi, MD, PhD, and Ming Zhou, MD, PhD, deals with intraductal carcinoma of the prostate (IDC-P), that is, a proliferation of secretory cells within the prostate ducts and acini with marked architectural and cytologic atypia that is more pronounced than that found in high-grade prostatic intraductal neoplasia. The authors review the following 4 major areas of interest: the historic perspectives, the diagnostic criteria, the molecular genetics of IDC-P, and the clinical significance of finding IDC-P in both radical prostatectomy and prostate biopsy and its reporting. In most cases, IDC-P is caused by intraductal spread of prostate carcinoma cells because IDC-P is usually associated with high-grade and high-volume prostate carcinoma. Rarely, IDC-P can be an isolated finding without a concomitant prostate carcinoma and may represent a stage of intraductal spread during prostate carcinogenesis beyond what is recognized as high-grade prostatic intraductal neoplasia but before invasive prostate carcinoma develops. Intraductal carcinoma of the prostate is an adverse histologic parameter, and patients with IDC-P have a significantly worse prognosis than do those without such a component.

A consensus conference was organized in 2005 by the International Society of Urological Pathology (ISUP) to standardize the reporting of histologic patterns and the compiling and reporting of grading information. The article by Lars Egevad, MD, Roberta Mazzucchelli, MD, PhD, and Rodolfo Montironi, MD, FRCPath, deals with the implications of the ISUP modified Gleason grading system. The authors cover major areas of interest. In particular, the recommendations regarding pattern interpretation and reporting are summarized and discussed, the practical consequences of the ISUP modification of the Gleason grading system are described, and the prognostic importance of the Gleason score, its reproducibility, and preoperative assessment are explained.

Huihui Ye, MD, and Thomas M. Ulbright, MD, discuss difficult differential diagnoses in testicular pathology. In particular, they summarize key diagnostic features and useful ancillary tools for the most frequently encountered problems in testicular tumor pathology, including the differential diagnoses between seminoma and nonseminomatous germ cell tumors, germ cell tumors and nongerm cell tumors, intratubular germ cell neoplasia and atypical germ cells with maturation arrest, pseudovascular invasion and real lymphovascular invasion in germ cell tumors, and macroscopic Sertoli cell nodules and Sertoli cell tumors. In almost all cases, awareness of the differential diagnostic possibilities, based on routine light microscopic features, permits application of either additional, directed observations or immunohistochemical studies that lead to an accurate diagnosis. Pathologists must, therefore, be familiar with important diagnostic pitfalls in testicular pathology, particularly for those diagnoses that result in different treatments or prognoses.

As Guest Editors, we would like to congratulate the authors of all the articles in this special issue for their excellent contributions. We would like to thank them for their enthusiasm in collecting the material needed to write the papers and for their successful effort in writing their contributions. We would like also to thank Helmut Popper, MD, for choosing us as Guest Editors and the Editor-in-Chief of the Archives of Pathology & Laboratory Medicine, Philip T. Cagle, MD, and the Archives staff, in particular Katie Giesen, for fully supporting us in the process of handling and reviewing the papers, including their publication.

Accepted for publication December 7, 2011.

From the Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy (Dr Montironi); and the Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland (Dr Epstein).

The authors have no relevant financial interest in the products or companies described in this article.

doi: 10.5858/arpa.2011-0498-ED

Reprints: Rodolfo Montironi, MD, FRCPath, Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Via Conca 71, I-60126 Torrette, Ancona, Italy (e-mail:

Rodolfo Montironi, MD, FRCPath; Jonathan I. Epstein, MD

Rodolfo Montironi, MD, FRCPath, IFCAP, obtained his medical degree at the Medical School of the University of Ancona, Italy, in 1976; his board certificate in pathology and laboratory medicine at the University of Parma, Italy, in 1979; and his board certificate in clinical oncology at the University of Ancona in 1982. He received his advanced training in pathology in several British institutions under the supervision of world leaders in pathology, in particular at Hammersmith Hospital, London, UK, with John G. Azzopardi, MD, FRCPath, in 1979. He is a Fellow of the Royal College of Pathologists and an International Fellow of the College of American Pathologists. He is a Professor of Pathology at the Medical School of the Polytechnic University of the Marche Region; Director of the Uropathology Program, United Hospitals, Ancona; and Associate Member at the Arizona Cancer Center, College of Medicine, University of Arizona, Tucson. He is the president of the International Society of Urological Pathology. He is a member of different international societies of pathology and of urology, including the European Society of Pathology and the European Association of Urology. Dr Montironi's work is centered in genitourinary tumor pathology. He is an author or coauthor of more than 500 publications in peer-reviewed international journals and of more than 20 chapters in books in the field of genitourinary tumor pathology. He has been a regular invited speaker at all major national and international pathology meetings. He organized and co-organized several international courses on genitourinary tumor pathology. Dr Montironi serves on the editorial boards of several international pathology and urology journals, including European Urology.

Jonathan I. Epstein, MD, obtained a combined BA-MD degree from Boston University's 6-Year Medical Program (1975-1981). Following his residency in anatomic pathology at Johns Hopkins Hospital in Baltimore, Maryland (1981-1983; 1984-1985) and a fellowship in oncologic pathology at Memorial Sloan Kettering Cancer Center in New York, New York (1983-1984), he joined the staff at Johns Hopkins Hospital and has been there his entire career. At the Johns Hopkins Medical Institutions, he is professor of Pathology, Urology, and Oncology; the recipient of the Reinhard Chair of Urological Pathology; and director of Surgical Pathology.

Dr Epstein is on 9 editorial boards in the fields of pathology, urology, oncology, and medicine. He has been invited outside his institution for 273 lectures in 36 different countries. Dr Epstein has devoted his career to the study of urologic pathology. He is the past president of the International Society of Urological Pathology and has been active in the United States and Canadian Academy of Pathology, including serving on the Education Committee and the Council and is currently the chair of the Development Committee. Dr Epstein has 646 publications in the peer-reviewed literature and has authored 47 book chapters. His most-frequently cited first or last authored publications are "Pathological and Clinical Findings to Predict Tumor Extent of Nonpalpable (stage T1c) Prostate Cancer," published in JAMA, which establishes the criteria for active surveillance (851 citations); the WHO Consensus Conference on Classification of Urothelial Neoplasia (580 citations); and 2 articles on prognosis following radical prostatectomy (>500 citations each). More recently, he was the organizer and leader of a consensus conference that updated the Gleason grading system, published in 2005. Dr Epstein's most notable chapters are "Disorders of the Prostate Gland," in Sternberg's Diagnostic Surgical Pathology; "Pathology of Prostatic Neoplasia, " in Campbell's Urology; and "Diseases of The Lower Urinary System and Male Genitourinary System" in Robbins Pathology Textbook. He is the author or coauthor of 5 books and the series editor of the "Biopsy Interpretation Series." Interpretation of Prostate Biopsies is in its fourth edition, and Bladder Biopsy Interpretation is in its second edition. He is 1 of 4 editors of the Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs in volume 6 of the World Health Organization Classification of Tumours (2004), and recently published, with Drs Humphrey and Cubilla, Tumors of the Prostate Gland, Seminal Vesicles, Male Urethra, and Penis in the Armed Forces Institute of Pathology, fourth series, of the Atlas of Tumor Pathology (2011). Dr Epstein has one of the largest surgical pathology consulting services in the world with approximately 16 000 cases per year, covering the full range of urologic pathology. Dr Epstein uses these consultations to train 4 genitourinary pathology fellows each year, along with many visiting pathologists. To date, 42 genitourinary pathology fellows have been trained through his service for academic and private practice throughout the United States and in multiple other countries.
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Title Annotation:Special Issue--Insights and Controversies in Urologic Pathology
Author:Montironi, Rodolfo; Epstein, Jonathan I.
Publication:Archives of Pathology & Laboratory Medicine
Date:Apr 1, 2012
Previous Article:Implications of the International Society of Urological Pathology modified Gleason grading system.
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