Table Of ContentUrologic Surgical Pathology
T h i r d E d i t i o n
Urologic
Surgical
Pathology
David G. Bostwick, MD, MBA
Chief Medical Officer
Bostwick Laboratories
Glen Allen, Virginia
United States
Liang Cheng, MD
Professor of Pathology and Urology
Chief of Genitourinary Pathology Division
Director of Fellowship in Urologic Pathology
Director of Molecular Diagnostics Service
Department of Pathology and Laboratory Medicine
Indiana University School of Medicine
Indianapolis, Indiana
United States
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
UROLOGIC SURGICAL PATHOLOGY ISBN: 978-1-4557-4327-8
Copyright © 2014, 2006, 1998 by Saunders, an imprint of Elsevier Inc.
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Notices
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical
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ISBN: 978-1-4557-4327-8
Executive Content Strategist: William Schmitt
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Publishing Services Manager: Anne Altepeter
Senior Project Manager: Doug Turner
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Printed in the United States of America
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Contributors
Mahul B. Amin, MD Robert E. Emerson, MD
Professor and Chairman Associate Professor
Department of Pathology and Laboratory Medicine Department of Pathology and Laboratory Medicine
Cedars-Sinai Medical Center Indiana University School of Medicine
Los Angeles, California Indianapolis, Indiana
United States United States
Alberto G. Ayala, MD Pilar González-Peramato, MD, PhD
Professor of Pathology Associate Professor of Pathology
Weill Medical College of Cornell University Department of Pathology
Department of Pathology and Genomic Medicine University Autonoma de Madrid School of Medicine
Houston Methodist Hospital Section of Genitourinary Pathology
Ashbel-Smith Professor Emeritus of Pathology Staff Pathologist
The University of Texas MD Anderson Cancer Center Department of Pathology
Houston, Texas Hospital La Paz
United States Madrid, Spain
Stephen M. Bonsib Deloar Hossain, MD
Nephropathologist Director of Cytopathology and Molecular Diagnostics
Nephropath Bostwick Laboratories
Little Rock, Arkansas Glen Allen, Virginia
United States United States
David G. Bostwick, MD, MBA David Hull, MD
Chief Medical Officer Medical Director
Bostwick Laboratories Bostwick Laboratories
Glen Allen, Virginia Glen Allen, Virginia
United States United States
Liang Cheng, MD Kyu-Rae Kim, MD, PhD
Professor of Pathology and Urology Professor of Pathology
Chief of Genitourinary Pathology Division Department of Pathology
Director of Fellowship in Urologic Pathology The University of Ulsan College of Medicine
Director of Molecular Diagnostics Service Asian Medical Center
Department of Pathology and Laboratory Medicine Seoul, South Korea
Indiana University School of Medicine
Indianapolis, Indiana Ernest E. Lack, MD
United States Senior Consulting Pathologist
Joint Pathology Center
Mukul Divatia, MD Silver Spring, Maryland
Department of Pathology and Genomic Medicine United States
Houston Methodist Hospital
Weill Medical College of Cornell University Antonio Lopez-Beltran, MD, PhD
Houston, Texas Professor of Pathology
United States Cordoba University School of Medicine
Cordoba, Spain
v
Jun Ma, MD Ricardo Paniagua, MD, PhD
Associate Medical Director Professor of Cell Biology
Bostwick Laboratories Department of Biomedicine and Biotechnology
Glen Allen, Virginia University of Alcalá
United States Alcalá de Henares, Madrid
Spain
Gregory T. MacLennan, MD
Professor of Pathology, Urology, and Oncology Andrew A. Renshaw, MD
Division Chief of Anatomic Pathology Staff Pathologist
Case Western Reserve University School of Medicine Department of Pathology
University Hospitals Case Medical Center Baptist Hospital of Miami
Cleveland, Ohio Miami, Florida
United States United States
Isabelle Meiers, MD Victor E. Reuter, MD
Medical Director Professor of Pathology
Bostwick Laboratories Weill Medical College of Cornell University
London, United Kingdom Attending Pathologist and Vice-Chair
Memorial Sloan-Kettering Cancer Center
Rodolfo Montironi, MD New York, New York
Professor of Pathology United States
Head of Genitourinary Cancer Program
Section of Pathological Anatomy Jae Y. Ro, MD, PhD
Department of Biomedical Sciences and Public Health Professor
Polytechnic University of the Marche Region (Ancona) Weill Medical College of Cornell University
Torrette, Ancona New York, New York
Italy Director of Surgical Pathology
Department of Pathology and Genomic Medicine
Manuel Nistal, MD, PhD Houston Methodist Hospital
Professor of Histology Houston, Texas
Department of Anatomy, Histology, and Neuroscience United States
University Autonoma de Madrid School of Medicine
Head of Service of Pathology Thomas M. Ulbright, MD
Department of Pathology Lawrence M. Roth Professor of Pathology and Laboratory
Hospital La Paz Medicine
Madrid, Spain Department of Pathology and Laboratory Medicine
Indiana University School of Medicine
Edina Paal, MD Pathologist
Assistant Professor Department of Pathology and Laboratory Medicine
The George Washington University Indiana University Health Pathology Laboratory
Staff Pathologist Indianapolis, Indiana
Pathology and Laboratory Medicine Service United States
Veterans Administration Medical Center
Washington, District of Columbia Robert H. Young, MD
United States Robert E. Scully Professor of Pathology
Harvard Medical School
Pathologist
James Homer Wright Pathology Laboratories
Massachusetts General Hospital
Boston, Massachusetts
United States
vi
Preface
The third edition of Urologic Surgical Pathology represents a new biomarkers for prostate cancer are gaining clinical
substantial revision, with color images, new contributors, acceptance, including PCA3, sarcosine, pro-PSA, mitochon-
and major updates in knowledge that reflect recent advances drial DNA testing, and gene expression profiles derived from
in urologic pathology. Retained is the original core team of genomic studies. Classification of testicular tumors and
participating world-class urologic pathologists who have related disorders increasingly relies on select biomarkers.
made this the best-selling text in the field from its inception. Arguably, the past few years have been the most exciting and
Also retained is the commitment to providing the most orga- productive period ever for biomarker discovery in support of
nized, complete, and practical information for the practicing tissue diagnosis, and these advances are included in the
pathologist. Our text is aimed primarily at practicing surgical current text, with an emphasis on practical applications.
pathologists, but it also should be valuable to medical stu- The editors are deeply grateful to Tracey Bender at Indiana
dents, internists, urologists, oncologists, and other medical University for her outstanding assistance in every step of the
specialists. editorial process. We are also indebted to the dedicated and
Significant progress has been made in urologic pathology critical team from Elsevier who assisted in every aspect of the
since the release of the previous edition. Genetic informa- creation of this text, including William Schmitt, Lisa Barnes,
tion has transformed virtually all aspects of pathology, Doug Turner, and Rebecca Gruliow.
including the evaluation of the four main organs in urologic Our contributing pathology colleagues were invaluable in
pathology (i.e., kidney, bladder, prostate, and testis). The the creation of the third edition. These authors, many of
classification of renal tumors has undergone a renaissance whom returned from previous editions to update and refine
in a few short years, resulting in genetic validation of mul- their chapters, represent a veritable who’s who of urologic
tiple new and clinically important subtypes, including pathologists. Each of these authors, both returning and new,
the category of clear cell papillary renal cell carcinoma, deserves significant credit for the quality of the text. Finally,
tubulocystic renal cell carcinoma, acquired cystic disease– we are grateful to our colleagues and readers for their con-
associated renal cell carcinoma, and others. Prediction of structive criticism and advice regarding past editions.
outcome after definitive treatment of bladder cancer increas-
ingly relies on molecular signatures. TMPRSS2-ERG gene David G. Bostwick, MD, MBA
fusion is now employed for analysis of select prostate cancers; Liang Cheng, MD
this remarkable family of gene fusions, discovered less than October 2013
a decade ago, is now routinely used. Similarly, a number of
vii
Tubulointerstitial disease 46
CHAPTER OUTLINE
Acute and chronic renal failure 47
Embryologic development and normal structure 3
Acute tubular injury (necrosis) 47
Pronephros 3
Acute tubulointerstitial nephritis 48
Mesonephros 3
Herbal remedies and slimming agents and aristocholic acid
Metanephros 4 nephropathy 50
Nephron differentiation 6 Immunoglobulin G4–related sclerosing tubulointerstitial nephritis 50
Gross anatomy 7 Analgesic nephropathy 51
Microscopic anatomy 10 Bacterial infection–associated tubulointerstitial disease 52
Parenchymal maldevelopment and cystic kidney Viral infections 55
diseases 11
Granulomatous tubulointerstitial disease 56
Abnormalities in form and position 12
Metabolic abnormalities, heavy metals, and crystal-
Abnormalities in mass and number 14 associated tubulointerstitial diseases 59
Renal dysplasia 19 Heavy metals 59
Polycystic kidney disease 23 Hypercalcemic nephropathy 59
Cystic diseases (without dysplasia) in hereditary syndromes 26 Nephrolithiasis 60
Miscellaneous diseases 31 Oxalate-associated renal disease 60
Vascular diseases 33 Cystinosis 62
Hypertension-associated renal disease 33 Uric acid–associated renal disease 63
Thrombotic microangiopathy 35 Amyloidosis and paraprotein-associated
Renal artery stenosis 36 tubulointerstitial disease 64
Renal artery dissection 40 Amyloidosis 64
Renal artery aneurysm 40 Light chain cast nephropathy 66
Arteriovenous malformation and fistula 41 Immunoglobulin and light chain deposition disease 66
Renal emboli and infarcts 41 Light chain proximal tubulopathy 67
Renal cortical necrosis 42 Crystal-storing histiocytosis 68
Renal papillary necrosis 43 Renal transplantation 68
Renal cholesterol microembolism syndrome 43 Rejection 68
Renal artery thrombosis 44 T-cell–mediated rejection 68
Renal vein and renal venous thrombosis 44 Calcineurin inhibitor nephrotoxicity 72
Bartter syndrome 45
Vasculitis 45
CHAPTER 1
Nonneoplastic diseases of the kidney
Stephen M. Bonsib
Study with me, then, a few things in the spirit of
truth alone so we may establish the manner of
Nature’s operation. For this essay which I plan, will
shed light upon the structure of the kidney. Do not
stop to question whether these ideas are new or old,
but ask, more properly, whether they harmonize with
Nature. I never reached my idea of the structure of
the kidney by the aid of books, but by the long and
varied use of the microscope. I have gotten the rest by
the deductions of reason, slowly, and with an open
mind, as is my custom.1
Marcello Malpighi, 1666
CHAPTER 1: Nonneoplastic diseases of the kidney
In keeping with the spirit of Marcello Malpighi, this chapter
also aspires to reveal “the manner of Nature’s operations” as
it affects the kidney.1 However, unlike Malpighi, today’s
knowledge draws extensively upon the labors, discoveries,
and insights of investigators of the past 4 centuries.
Knowledge of the normal structure and function of the
kidney has been acquired over centuries of scholarly effort.
We have come a long way since Aristotle taught that urine
was formed by the bladder and that kidneys were present
“not of actual necessity, but as matters of greater finish and
perfection.”1 The foundation of urology was established in
the sixteenth century by Leonardo da Vinci and Vesalius,
who provided the first accurate and detailed drawings of the
female and male genitourinary tracts (Fig. 1-1).2,3 More than
300 years passed before William Bowman, in 1842, coupled
intravascular dye injection with microscopic examination to
demonstrate the structural organization of the nephron and
its vascular supply (Fig. 1-2).4,5 Bowman’s observations pro-
vided morphologic support for Malpighi’s seventeenth-
century speculation of a filtration function for the malpighian
Fig. 1-1 Vesalius’ anatomic illustration of the male genitourinary tract
published in 1543. Note that the left kidney is incorrectly placed lower than
the right. (From Murphy LJT [ed]. The history of urology. Springfield, Ill:
Charles C Thomas, 1972; with permission.)
A B
Fig. 1-2 A and B, William Bowman’s illustration of the vascular supply to glomeruli and the relationship of the efferent arteriole to the convoluted tubules.
(From Bowman W. On the structure and use of the malpighian bodies of the kidney, with observations on the circulation through that gland. Philos Trans R
Soc Lond Biol 1842;132:57; with permission.)
2
