Urologic Surgical Pathology, 2nd Edition

1032 Pages·2008·149.9 MB·English

by  David G. Bostwick MD MBA FCAP

Preface to Second Edition of
Urologic Surgical Pathology
In the 12 years since the publication of the fi rst edition of Throughout this renaissance in the classifi cation and diag-
Urologic Surgical Pathology, great strides have been made in nosis of urologic diseases and in the prediction of individual
our understanding of urologic diseases. Many clinically patient outcome, the histopathologic examination of tissue
important new histopathologic entities have been described and cells remains the gold standard. Today’s surgical pathol-
or more fully defi ned in virtually every genitourinary organ. ogist in any part of the world fi nds urologic specimens to be
Numerous clinically important diagnostic and prognostic an increasingly important part of everyday sign-out. The
markers have entered routine practice, including alpha- expectation for excellence in diagnosis remains very high. It
methylacyl-CoA racemase, the most widely discussed bio- is with this understanding that we have produced our second
marker in surgical pathology in this century. Genetic testing edition.
for the early detection of bladder and prostate cancer and This book is intended chiefl y for use by surgical patholo-
the molecular classifi cation of renal cell carcinomas has gists in their daily practice. The numerous comments and
become increasingly important. This is an age of enlighten- suggestions from readers of the fi rst edition have been care-
ment in urologic surgical pathology, and we have attempted fully considered and incorporated into the current effort. The
to capture the sense of excitement herein. text has expanded more than 30%, and the number of full-
Our specialty of surgical pathology continues to evolve. color illustrations now exceeds 1200. Two new chapters have
The emergence of personalized medicine has created a para- been added (Urine Cytology and Fine Needle Aspiration of
digm shift in diagnostic and prognostic biomarker analysis. the Kidney) to refl ect increasing emphasis on cellular diag-
Diagnostic tests are now linked to individualized treatments. nosis in urologic pathology. We have remained true to our
The dream of digital imaging is slowly being realized; high purpose of providing a framework for comparison, evalua-
resolution images are now routinely captured and transmit- tion, and integration into clinical practice of the evolving
ted across the internet for multiple purposes. Central pathol- urologic diagnosis. The emphasis remains on the practical
ogy review of clinical trial cases has become common aspects of diagnostic pathology.
practice, and central review protocols will likely be standard- We are exceedingly grateful to our contributing colleagues
ized in the near future. The accuracy of predictive outcome for sharing their knowledge and experience. We continue to
models for individual patients continues to be improved. solicit constructive criticism to ensure greater usability in
New algorithms, nomograms, neural networks, and other future editions.
models emerge virtually every month. Further, evidence-
based practice with an emphasis on levels of scientifi c evi- David G. Bostwick, MD, MBA
dence is replacing the “intuitive” practice of medicine, Liang Cheng, MD
resulting in more consistent outcomes. March, 2008
Contributors List
Urologic Surgical Pathology, 2nd Edition
Mahul B. Amin, M.D. Kyu-Rae Kim, M.D., Ph.D.
Professor and Chairman Professor of Pathology
Department of Pathology and Laboratory Medicine Asan Medical Center
Cedars-Sinai Medical Center The University of Ulsan College of Medicine
Los Angeles, CA Seoul
USA Korea
Alberto G. Ayala, M.D. Ernest E. Lack, M.D.
Professor of Pathology Director of Anatomic Pathology
Weill Medical College of Cornell University Washington Hospital Center
Deputy Chairman, Department of Pathology Washington, DC
The Methodist Hospital USA
Ashbel-Smith Professor Emeritus of Pathology
The University of Texas M.D. Anderson Cancer Center Antonio Lopez-Beltran, M.D., Ph.D.
Houston, TX Professor of Anatomic Pathology
USA Unit of Anatomic Pathology
Department of Surgery
Stephen M. Bonsib, M.D. Cordoba University School of Medicine
Albert G. and Harriet G. Smith Endowed Professor and Chair Cordoba
Department of Pathology Spain
Louisiana State University Heath Sciences Center
Shreveport, LA Gregory T. MacLennan, M.D.
USA Professor of Pathology, Urology and Oncology
University Hospitals of Cleveland
David G. Bostwick, M.D., MBA Institute of Pathology, Case Western Reserve University
Chief Medical Offi cer Cleveland, OH
Bostwick Laboratories USA
Glen Allen, VA
USA Isabelle Meiers, M.D.
Chief of Histopathology Department
Liang Cheng, M.D. University Hospital Lewisham
Professor of Pathology and Urology London
Chief of Genitourinary Pathology Division UK
Director of Molecular Pathology Laboratory
Department of Pathology and Laboratory Medicine and Rodolfo Montironi, M.D.
Clarian Pathology Laboratory Professor of Pathology
Indiana University School of Medicine Section of Pathological Anatomy
Indianapolis, IN School of Medicine, Polytechnic University of the Marche
USA Region
United Hospitals
Deloar Hossain, M.D. Ancona
Associate Medical Director Italy
Bostwick Laboratories
Glen Allen, VA John F. Morrow, M.D.
USA Associate Medical Director
Bostwick Laboratories
Janet L. Johnston, B.A., CT (ASCP) Glen Allen, VA
Director of Advanced Cytodiagnostics USA
Bostwick Laboratories
Glen Allen, VA
USA
Manuel Nistal, M.D., Ph.D. Jae Y. Ro, M.D., Ph.D.
Head of Service of Pathology, Hospital La Paz Professor of Pathology
Professor of Histology, Departamento de Morfología Director of Surgical Pathology
Universidad Autómoma de Madrid Department of Pathology
Madrid The Methodist Hospital
Spain Weill Medical College of Cornell University
Houston, TX
Ricardo Paniagua, M.D., Ph.D. USA
Professor of Cell Biology
Department of Cell Biology and Genetics Thomas M. Ulbright, M.D.
University of Alcalá Lawrence M. Roth Professor of Pathology
Madrid Director of Anatomic Pathology
Spain Department of Pathology and Laboratory Medicine and
Clarian Pathology Laboratory
Junqi Qian, M.D. Indiana University School of Medicine
Director of Molecular Diagnostics Indianapolis, IN
Bostwick Laboratories USA
Glen Allen, VA
USA Jacqueline A. Wieneke, M.D.
Chief, Division of Otorhinolaryngic-Head &
Andrew A. Renshaw, M.D. Neck Pathology
Staff Pathologist Staff Pathologist
Department of Pathology Department of Endocrine and Otorhinolaryngic-Head &
Baptist Hospital of Miami Neck Pathology
Miami, FL Armed Forces Institute of Pathology
USA Washington, DC
USA
Victor Reuter, M.D.
Professor of Pathology Robert H. Young, M.D.
Weil Medical College of Cornell University Robert E. Scully Professor of Pathology
Attending Pathologist and Vice-Chair Harvard Medical School
Memorial Sloan-Kettering Cancer Center Pathologist, James Homer Wright Pathology Laboratories
New York, NY Massachusetts General Hospital
USA Boston, MA
USA
Embryologic development and normal structure 2 Renal emboli and infarct 40
Pronephros 2 Renal cortical necrosis 40
Mesonephros 2 Renal cholesterol microembolism syndrome 41
Metanephros 3 Renal artery thrombosis 43
Nephron differentiation 4 Renal vein and renal venous thrombosis 43
Gross anatomy 6 Bartter’s syndrome 43
Microscopic anatomy 11 Vasculitis 43
Parenchymal maldevelopment and cystic diseases 11 Tubulointerstitial diseases 45
Abnormalities in form and position 12 Infection-related tubulointerstitial nephritis 46
Abnormalities in mass and number 14 Chronic pyelonephritis 49
Renal dysplasia 19 Acute tubulointerstitial disease 54
Multicystic and aplastic dysplasia 19 Acute tubular necrosis 54
Segmental dysplasia 21 Acute interstitial nephritis 56
Dysplasia associated with lower tract obstruction 21 Chronic interstitial nephritis 58
Dysplasia associated with malformation syndrome 22 Drugs and heavy metals 58
Hereditary renal adysplasia and urogenital adysplasia 22 Analgesic nephropathy 58
Polycystic kidney diseases 22 Metabolic abnormalities and tubulointerstitial diseases 58
Cysts (without dysplasia) in hereditary syndromes 26 Hypercalcemic nephropathy 58
Miscellaneous conditions 29 Uric acid-associated renal disease 60
Vascular diseases 30 Renal transplantation 61
Hypertension-associated renal disease 30 Ciclosporin and FK 506 nephrotoxicity 63
Benign nephrosclerosis 31 Miscellaneous conditions 64
Malignant nephrosclerosis 32 Sarcoidosis 64
Thrombotic microangiopathy 33 Amyloidosis and paraprotein-associated tubulointerstitial disease 64
Renal artery stenosis 35 Light-chain cast nephropathy (myeloma kidney) 66
Renal artery aneurysm 39
Arteriovenous malformation and fi stula 40

CHAPTER 1
Non-neoplastic 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 ONE: Non-neoplastic diseases of the kidney
In keeping with the spirit of Marcello Malpighi, this chapter The ultrastructural features and immunohistochemical
aspires to reveal ‘the manner of Nature’s operations’ as it profi les of the normal kidney and many diseases were eluci-
affects the kidney.1 However, unlike Malpighi, today’s knowl- dated in the 1970s and 1980s following refi nement of the
edge draws extensively upon the labors, discoveries, and percutaneous biopsy technique and advances in morpho-
insights of investigators over the last four centuries. logic analysis. Today, we are on the threshold of discovering
Our knowledge of the normal structure and function of the genetic basis of many mechanisms that mediate normal
the kidney has been acquired over centuries of scholarly and abnormal renal development and physiology.
effort. We have come a long way since Aristotle taught that
urine was formed by the bladder and that kidneys were
Embryologic development and
present ‘not of actual necessity, but as matters of greater
normal structure
fi nish and perfection.’1 The foundations of urology were
established in the 16th century by Leonardo da Vinci and
Vesalius, who provided the fi rst accurate and detailed draw- This chapter begins with a brief review of the embryology
ings of the female and male genitourinary tracts (Fig. 1-1).2,3 and normal gross and microscopic structure of the kidney.
Over 300 years passed before William Bowman, in 1842, For more in-depth coverage of these topics several excellent
coupled intravascular dye injection with microscopic exami- resources are available.12–15
nation to demonstrate the structural organization of the The development of the urinary and genital tracts is
nephron and its vascular supply (Fig. 1-2).4,5 Bowman’s closely related (Fig. 1-4). Both develop from paired longitu-
observations provided morphologic support for Malpighi’s dinal cords of tissue lateral to the aorta, known as the inter-
17th-century speculation of a fi ltration function for the mal- mediate mesoderm.12,13 From the portion caudal to the
pighian body (the glomerulus).1 Sixty years later, embryo- seventh somite, known as the nephrogenic mesoderm (or
logic development of the nephron was demonstrated nephrogenic cord), three nephronic structures develop in
by Huber in a thin-section serial reconstruction study quick succession: the pronephros, the mesonephros, and the
of embryos (Fig. 1-3). Huber’s observations were refi ned metanephros. Although the pronephros and the mesoneph-
and elegantly illustrated by Brödel in 1907.6,7 Potter ros are transient organs, they are crucial for proper develop-
and Osathanondh8–11 validated the fi ndings in a series of ment of the urinary and reproductive tracts.
microdissection studies of developing kidneys that were
published in the 1960s. Pronephros
The fi rst embryologic derivative of the nephrogenic cord is
the pronephros, a structure that is functional only in the
lowest forms of fi sh. It arises from the cranial portion of the
mesonephric cord during the third week of gestation (1.7 mm
stage). Approximately seven pairs of tubules form, only to
regress 2 weeks later (Fig. 1-4). The pronephros is important
because the pronephric tubules grow caudally and fuse with
the next pronephric unit, giving rise to the pronephric duct,
now called the mesonephric duct.
Mesonephros
Cells of the mesonephric duct continue to proliferate caudally
(Fig. 1-4) and begin to form the mesonephric kidney during
the fourth week of gestation (4 mm). The mesonephros is a
highly differentiated structure and is the functional kidney of
higher fi sh and amphibians. Portions of the mesonephric
kidney can be easily identifi ed in small embryos (1–3 cm in
size) that are occasionally encountered in surgical specimens
such as those from ectopic pregnancies (Fig. 1-5).
The mesonephric kidney consists of approximately
40 pairs of nephrons. The cranial nephrons regress sequen-
tially while caudal nephrons form, with 7–15 nephrons
being functional at all times (Fig. 1-4). The nephrons
are induced in a fashion analogous to that of their meta-
nephric counterparts. A fully developed mesonephric
nephron consists of a glomerulus connected to the meso-
nephric duct by a convoluted proximal tubule (Fig. 1-6A).
Fig. 1-1 Vesalius’ anatomic illustration of the male genitourinary tract
The glomerulus is vascularized by capillaries that branch
published in 1543. Note that the left kidney is placed lower than the right.
from small arterioles originating from the aorta, and its effer-
(From Murphy LJT. The history of urology, Springfi eld, MA: Charles C.
Thomas, 1972; with permission.) ent arteriole empties into the posterior cardinal vein. The
2
Embryologic development and normal structure
A B
Fig. 1-2 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 Roy Soc
Lond Biol 1842; 132: 57; with permission.)
glomerulus appears to fi lter plasma. Its tubule possesses a the müllerian ducts form the fallopian tubes, uterus, and
brush border and appears capable of nutrient resorption, proximal vagina while the mesonephric ducts largely regress,
and concentration and dilution of urine. The mesonephric although several embryologic remnant structures persist,
kidney remains functional until the end of the fourth month including the epoöphoron, paroöphoron, and Gartner’s
of gestation. ducts.
Formation of the adult metanephric kidney begins during
Metanephros the fi fth and sixth weeks of gestation (4–5 mm), after the
mesonephric duct has established communication with the
The metanephric kidney is the product of a complex orches- urogenital sinus. A diverticulum, known as the ampullary
tration of embryologic processes. While the collecting system (or ureteric) bud, forms on its posterior medial aspect
and renal pyramids are forming there is simultaneous induc- (Fig. 1-4), establishing contact with the sacral portion of
tion of thousands of nephrons, and neurovascular and the nephrogenic mesoderm, the nephrogenic blastema. A
lymphatic components ramify in a carefully organized archi- complex reciprocal inductive process occurs, resulting in
tecture throughout the cortex and medulla. dichotomous ampullary bud branching and nephron induc-
While the metanephric kidney is forming, substantial tion, eventually culminating in the adult metanephric
changes also are occurring in the adjacent müllerian and kidney. The metanephros is therefore a product of two
mesonephric ducts (Fig. 1-4) proximal to the origin of the embryonic derivatives: the nephrons are of blastemal origin
ampullary bud.12 Following degeneration of mesonephric whereas the ureter, pelvis, calyces, cortical, and medullary
nephrons in males, the persisting mesonephric duct devel- collecting ducts are derived from the ampullary bud.
ops into male genital secretory structures: epididymis, vas Upon contact with metanephric blastema, the ampullary
deferens, seminal vesicle, and ejaculatory duct. In females, bud undergoes a rapid sequence of dichotomous branching
3
CHAPTER ONE: Non-neoplastic diseases of the kidney
Fig. 1-4 Diagram illustrating the relationship between reproductive tract
and urinary tract development. (From Patton BM. Human embryology.
New York: McGraw Hill, 1968; with permission.)
collecting duct by a connecting tubule (Fig. 1-12). Addi-
tional groups of three to seven nephrons then form, each
Fig. 1-3 Wax model serial reconstruction of nephron differentiation by attached directly to a collecting duct without a connecting
Huber. (From Huber GC. On the development and shape of uriniferous
tubule. Therefore, each cortical collecting duct has 10–14
tubules of certain of the higher mammals. Am J Anat 1905; 4: 29; with
generations of nephrons attached, with the most recently
permission.)
formed and least mature nephrons located beneath the renal
capsule.
and fusion, forming the renal collecting system by the
14th week.8 The initial two branches form the renal
pelvis, the third to sixth branches form the major and minor Nephron differentiation
calyces, and the sixth to 11th branches form the papillary
ducts (Fig. 1-7). Ampullary bud branching is more rapid in The formation of individual nephrons begins as early as 7
the upper and lower poles, resulting in more numerous weeks of gestation, resulting in a limited degree of ‘renal
calyces and papillae in those regions. function’ by 9 weeks. In the subcapsular nephrogenic zone
While the collecting system is forming, nephron induc- of the immature kidney (Fig. 1-13), the sequence of nephron
tion has already begun (Fig. 1-5). The kidneys move into the induction can be observed in its various stages of comple-
fl anks owing to a combination of migration out of the pelvis tion. Wax models made by Huber and the drawing by Brödel
and rapid caudal growth of the embryo (Fig. 1-8). The kidney (Figs 1-3, 1-14) provide a three-dimensional perspective for
also rotates from its original position with the pelvis ante- understanding the cellular events visible in Figure 1-13.
rior, to its fi nal position with the pelvis medial.7 By week 13 An individual nephron begins to form when the meta-
or 14, the minor calyces and renal pyramids are well formed nephric blastema aggregates adjacent to the ampullary bud
and the lobar architecture can be appreciated grossly (Figs to form a hollow vesicle.9–11 The molecular basis for this
1-9, 1-10). At this time, the cortex contains several genera- event is complex and appears to involve growth factors,
tions of nephrons and the lateral portions of adjacent lobes adhesion molecules, matrix components, and other regula-
begin to merge to form the columns of Bertin. tory proteins.16–19 The cells within the vesicle grow differen-
By weeks 20–22, the renal lobes are well formed and the tially, resulting in elongation and the formation of two
kidney is a miniature of the adult kidney (Fig. 1-11). The indentations creating an S-shaped structure with three seg-
ampullae (or collecting ducts at this time) cease branching ments. The upper and middle segments are destined to
but continue to lengthen.9,10 As they lengthen, they induce become the proximal and distal tubules. They form tubular
arcades of four to seven nephrons that are connected to the structures and establish communication with each other and
4