Bladder Pathology

740 Pages·2012·78.2 MB·English

by  Liang Cheng

BLADDER PATHOLOGY
BLADDER PATHOLOGY
LIANG CHENG, MD
Professor of Pathology and Urology
Chief of Genitourinary Pathology Division
Director of Fellowship in Urologic Pathology
Director of Molecular Pathology Laboratory
Indiana University School of Medicine
Indianapolis, Indiana, USA
ANTONIO LOPEZ-BELTRAN, MD, PHD
Professor of Anatomic Pathology
Department of Surgery
Cordoba University School of Medicine
Cordoba, Spain
DAVID G. BOSTWICK, MD, MBA
Medical Director
Bostwick Laboratories
Glen Allen, Virginia, USA
A JOHN WILEY & SONS, INC., PUBLICATION
Copyright©2012byWiley-Blackwell.Allrightsreserved.
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LibraryofCongressCataloging-in-PublicationData:
Cheng,Liang.
Bladderpathology/LiangCheng,AntonioLopez-Beltran,DavidG.Bostwick.
p.;cm.
Includesbibliographicalreferences.
ISBN978-0-470-57108-8(cloth)
I.Lopez-Beltran,Antonio.II.Bostwick,DavidG.III.Title.
[DNLM:1. UrinaryBladder—pathology. 2. NeoplasmStaging. 3. UrinaryBladderDiseases—
pathology. 4. UrinaryBladderNeoplasms—pathology. WJ500]
616.6(cid:2)2071—dc23
2011044251
PrintedinSingapore
10 9 8 7 6 5 4 3 2 1
Contents
Preface vii
1 Normal Anatomy and Histology 1 18 Congenital Disorders and
Pediatric Neoplasms 399
2 Inflammatory and Infectious
Conditions 17 19 Soft Tissue Tumors 423
3 Urothelial Metaplasia and 20 Lymphoid and Hematopoietic
Hyperplasia 45 Tumors 461
4 Polyps and Other Nonneoplastic 21 Urothelial Carcinoma Following
Benign Conditions 71 Augmentation Cystoplasty 471
5 Benign Epithelial Tumors 85 22 Other Rare Tumors 485
6 Flat Urothelial Lesions with 23 Secondary Tumors 497
Atypia and Urothelial Dysplasia 99
24 Treatment Effects 507
7 Urothelial Carcinoma in Situ 113
25 Handling and Reporting of
8 Bladder Cancer: General Features 137 Bladder Specimens 525
9 Grading of Bladder Cancer 161 26 Diagnostic
Immunohistochemistry 545
10 Stage pT1 Urothelial Carcinoma 193
27 Pathology of the Urachus 567
11 Staging of Bladder Cancer 217
28 Pathology of Renal Pelvis, Ureter,
12 Histologic Variants of Urothelial
and Urethra 581
Carcinoma 239
29 Molecular Determinants of
13 Adenocarcinoma and Its Putative
Tumor Recurrence 609
Precursors and Variants 283
30 Urinary Cytology 623
14 Squamous Cell Carcinoma and
Other Squamous Lesions 305 31 Evaluation of Hematuria and
Urinalysis 645
15 Neuroendocrine Tumors 323
32 Urine-based Biomarkers 655
16 Sarcomatoid Carcinoma
(Carcinosarcoma) 355 33 Tissue-based Biomarkers 679
17 Bladder Tumors with Inverted 34 Molecular Pathology of Bladder
Growth 383 Cancer 707
Index 735
v
Preface
The urinary bladder is subject to a unique and field can lessen the impact of these burdens on both
extraordinarily diverse array of congenital, inflamma- practitioners and patients.
tory, metaplastic, and neoplastic abnormalities. The In the text we strive to provide a comprehensive
objective of BladderPathology is to provide contem- resource for practicing surgical pathologists and their
porary, comprehensive, and evidence-based practice clinical colleagues so that they may better meet the
information for pathologists, urologists, and medical daily demands and challenges of this ever-evolving
oncologists. A full spectrum of pathologic conditions field.Wehopethatthisvolumehascapturedoursense
that afflict the bladder and urothelium are described of excitement as we strive to stay on the cutting edge
and illustrated. The book is aimed especially at of these advances in medical practice. We have incor-
the practicing pathologist, with an emphasis on porated recent advances in molecular genetics of the
diagnostic criteria and differential diagnoses. It is our urinary bladder with discussion of their current or
hope that this very comprehensive book, consisting potential impact on patient care. It is our intent to
of 34 chapters, 754 pages, 112 tables, and 1741 provide a framework by which diagnostic criteria can
full color photographs, will aid in the pathologist’s becompared,evaluated,andintegratedwithmolecular
recognition, understanding, and accurate interpre- and other ancillary test data.
tation of the light microscopic findings in bladder We are indebted to many people who have been
specimens. involvedinthepreparationofthisbook.Wearegrate-
This is an age of enlightenment in surgical pathol- ful to our mentors, colleagues, and trainees who have
ogy. The emergence of personalized medicine with challenged and inspired us. They include Drs. George
new understandings of cancer genetics has created a M. Farrow, John N. Eble, David G. Grignon, Thomas
paradigm shift in our practice. Greater weight con- M. Ulbright, Michael O. Koch, Gregory T. MacLen-
tinues to be placed on an evidence-based approach nan, John F. Gaeta, Rodolfo Montironi, and many
to diagnosis and patient management. This includes others. Our special thanks go to Ryan P. Christy from
an emphasis on the scientific validation of our diag- the Multimedia EducationDivisionof the Department
nostic methods and their meaningful application in of Pathology at Indiana University, who edited the
practice. This is especially true in the management illustrations, and to Tracey Bender for her assidu-
of patients with medical conditions involving the uri- ous assistance in the editorial process. We also thank
nary bladder. Cancer of the bladder represents the the staff at Wiley-Blackwell, including Thomas H.
fifth most common cancer in the human body, with Moore, Ian Collins, Angioline Loredo, and Sheeba
more than 60,000 new carcinoma diagnoses annually Karthikeyan for their invaluable support throughout
in the United States. Many patients with bladder can- the project. Finally, we earnestly solicit feedback and
cerhaveaprolongedsurvival,necessitatinglong-term constructive criticism from readers so that the book
followup,includingtheprocurementofnumeroussub- may be improved in future editions.
sequent cystoscopic biopsies and urine samples for
histologicandcytopathologicevaluation.This,inturn, Liang Cheng
hasgeneratedaconsiderablediagnosticburdenforthe Antonio Lopez-Beltran
pathologistandcosttothehealthcaresystem.Itisour David G. Bostwick
hope that continuing advances in the urinary bladder March 2012
vii
Chapter 1
Normal Anatomy and Histology
Embryology 2 BladderWall 6
Anatomy 2 ParaganglionicTissue 10
GrossAnatomy 2 TheUrachus 10
BloodSupplyandLymphaticDrainage 2 TheRenalPelvisandUreters 10
NerveSupply 2 TheUrethra 11
NormalHistology 3 ImmunohistochemicalFindings 14
Urothelium 3 References 14
BladderPathology,FirstEdition.LiangCheng,AntonioLopez-Beltran,DavidG.Bostwick.
©2012Wiley-Blackwell.Published2012byJohnWiley&Sons,Inc.
1
Normal Anatomy and Histology
Embryology in acute and chronic urinary retention, it may cause the
lowerabdomentobulgevisiblyandiseasilypalpableinthe
suprapubic region. The empty bladder has an apex (supe-
Early in fetal life, when cloacal dilation first appears and rior surface), two infralateral or anterolateral surfaces, a
the hindgut ends in a blind sac, an ectodermal depression base (posterior surface), and a neck. The apex extends a
developsundertherootofthetail.1 Thisdepression,known short distance above the pubic bone and ends as a fibrous
as the proctoderm, deepens until only a thin layer of tis- cord derivative of the urachus. This fibrous cord extends
sue, the cloacal membrane, remains between the gut and from the apex of the bladder to the umbilicus between the
the outside of the body. The division of the cloaca results peritoneum and the transversalis fascia. It raises a ridge of
fromdevelopmentoftheurorectalfoldthatclosescaudally peritoneum called the median umbilical ligament. There is
toward the cloacal membrane. As the urorectal fold cuts a peritoneal covering at the apex in both sexes that also
progressively deeper into the cloaca, a wedge-shaped mass covers a small part of the base in men.2,3
of mesenchyme accompanies it and forms a dense septum The apex of the bladder is apposed to the uterus and
betweentheurogenitalsinusanteriorlyandtherectumpos- ileum in the female and to the ileum and pelvic portion of
teriorly. This separation of the cloaca is completed before the colon in the male. The base of the bladder faces pos-
the cloacal membrane ruptures, so that its two parts open teriorly and is separated from the rectum by the uterus and
independently. When it first opens to the outside, the uro- vagina in the female, and by the vasa deferentia, seminal
genital sinus, which is the ventral division of the cloaca, is vesicles, and ureters in the male. The anterolateral sur-
tubular and continuous with the allantois. At this stage, it face on each side of the bladder is apposed to the pubic
can be divided into a ventral or pelvic portion, which will bone, levator ani, and obturator internus muscles, but the
become the bladder proper, and a urethral portion, which central anterior bladder is separated from the pubic bone
receives the mesonephric and fused mu¨llerian ducts and by the retropubic space, which contains abundant fat and
later becomes the prostatic and membranous urethra in the venous plexuses. The neck of the bladder, its most inferior
male and the entire urethra in the female.2 part, connects with the urethra. When the bladder is dis-
After 8 weeks, the ventral part of the urogenital sinus tended with urine, the neck remains fixed and stationary,
expands to form an epithelial sac, the apex of which tapers whereas the dome rises above the pelvic cavity into the
into an elongated narrowed urachus. The splanchnic meso- lower abdomen, touching the posterior aspect of the lower
derm surrounding both segments differentiates as interlac- anterior abdominal wall and the small and large bowels.3
Beneaththeurothelialliningoftheinnerbladder,thereis
ing bands of smooth muscle fibers and an outer fibrocon-
looseconnectivetissuethatpermitsconsiderablestretching
nective tissue coat. By 12 weeks, the layers of the adult
of the mucosa. As a result, the urothelial mucosal lining
urethra and bladder can be recognized. This sequence of
is wrinkled when the bladder is empty but smooth and
events indicates that the detrusor muscle and the urethral
flatwhendistended.Thisarrangementexiststhroughoutthe
musculature have the same origin, constituting one unin-
terruptedstructure.2 Thisarrangementiseasilyobservedin bladderexceptatthetrigone,wherethemucousmembrane
adheres firmly to the underlying muscle; consequently, the
the female, in that the bladder and urethra form one tubu-
trigone is always smooth, regardless of the level of disten-
lar unit with expansion of the upper part. However, in the
sion (Figs. 1-1 and 1-2).
male, the structure is complicated by simultaneous devel-
opment of the prostate gland. The developmental sequence
isthesameinbothgenders, andthestructuralarrangement BloodSupplyandLymphaticDrainage
in the male is only slightly more complex than that in the
Thebladderissuppliedbythesuperior,middle,andinferior
female.2
vesical arteries, all of which are branches of the anterior
divisionofthehypogastricartery.Betweenthebladderwall
properandtheouteradventitiallayer,thereisarichplexus
Anatomy of veins that ultimately terminate in the hypogastric veins
after converging in several main trunks.
The bladder lymphatics drain into the external iliac,
GrossAnatomy hypogastric, and common iliac lymph nodes. There are
rich lymphatic anastomoses between the pelvic and genital
The bladder is a hollow muscular organ whose main func- organs.4–6
tionisthatofareservoir.Whenempty,theadultbladderlies
behind the symphysis pubis and is largely a pelvic organ.
NerveSupply
In infants and children, it is more cephalad than in adults.
When full, the bladder rises above the symphysis and can The bladder is richly innervated by divisions of the
readily be palpated or percussed. When overdistended, as autonomicnervoussystem.2,7 Sympatheticnervesoriginate
2
Normal Anatomy and Histology
AA AA
BB BB
Figure1-1 Normaltrigone(AandB). Figure1-2 Normaltrigoneinawomanduringthe
reproductiveyears.Notethesquamousmucosaandclosely
packedunderlyingmuscle(AandB).
fromthelowerthoracicandupperlumbarsegments,mainly
T11–T12 and L1–L2. These sympathetic fibers descend
into the sympathetic trunk and the lumbar splanchnic
nerves,connectingwiththesuperiorhypogastricplexus,an
inferior extension of the aortic plexus. The latter separates
into the right and left hypogastric nerves, and these
extend inferiorly to join the pelvic plexus of the pelvic
parasympathetic nerves. Parasympathetic nerves arise from
sacral segments S2–S4, and these form the rich pelvic
parasympathetic plexus. This plexus joins the sympathetic
hypogastric plexus, and vesical branches emerge from this
plexus toward the bladder base, innervating the bladder
and urethra.7,8
Normal Histology
Urothelium
Figure1-3 Normalurothelium.Thethicknessofurothelium
The urothelium is a unique stratified epithelium of vari- isvariable,uptosevencelllayersinnormalurothelium.Note
ablethickness(Figs.1-3to1-6).Thenumberofcelllayers theprominentsuperficialumbrellacells.
3
Normal Anatomy and Histology
AA
Figure1-5 Normalurothelium.Notetheorderly
arrangementoftheurothelialcells.Thelongaxisofurothelial
cellsisoftenperpendiculartothemucosalsurface.The
superficialcellsarelessdistinct.Prominentnucleargrooves
arenotedinsomecells.
BB
Figure1-4 Normalurothelium(AandB).Cytoplasmic
vacuolizationisobserved.Inthispreparation,theurothelium
isuptosevencellsinthickness(B).
Figure1-6 Normalurothelium.Notethevariablethickness
ofurotheliuminthispreparation.Thesuperficialcellshave
prominentcytoplasmicvacuolization.
depends on the degree of distension of the bladder, usually
varying from three to seven layers. When distended, the
bladderisthreetosixcelllayersthick,althoughthetypical
biopsy contains about five layers; in the contracted state,
it consists of six to eight layers.9 For practical purposes,
urotheliumcomposedofmorethansevencelllayersiscon-
sidered abnormal unless this finding can be attributed to
tangential cutting of tissue.10,11 In addition, the urothelium
is thought to be monoclonal in origin, with some features
of mosaicism.12
Thenormalurotheliumcontainsalayeroflargesuperfi-
cial cells that are frequently multinucleated, often referred
to as umbrella cell thickness (Figs. 1-7 to 1-9). These cells
have abundant eosinophilic cytoplasm, with large nuclei
Figure1-7 Normalurothelium.Notetheprominent
whose long axes are perpendicular to those of the smaller
superficialcells.Nuclearvacuolizationisoccasionallyseenin
cells of the underlying basal and intermediate cell lay-
intermediatecells.Somevariationofcellsizeandshapecan
ers. The superficial cells vary in size and configuration
beobservedinnormalurotheliumandshouldnotbe
according to the degree of bladder distension and angle
interpretedasdysplasia.
4
Normal Anatomy and Histology
potential importance in pathologic grading of bladder can-
cer (see also Chapter 9).
Basal and intermediate cells are located between the
basal lamina and the superficial cells (Figs. 1-8 to 1-10).
Thesecellsaremorphologicallyidenticaltoeachother,and
are distinguished only by their position in the mucosa.13
They are regularly arranged, with distinct cell boundaries
and oval, round, or fusiform nuclei with occasional promi-
nent nuclear grooves. The nuclei are located centrally in
the cells and contain finely granular chromatin that often
accentuates the nuclear borders. Nucleoli are usually small
and difficult to detect. Mitotic figures are rare in the nor-
malurothelium.Thebasallayerofepithelialcellsexpresses
Bcl-2, while the intermediate cells express RB1 and PTEN
at varying intensities. HER2 and p53 are not expressed
Figure1-8 Normalurothelium.Notetheprominent by normal urothelial cells. Ki67, indicating proliferation,
superficialcells. may not be expressed in a single field. The long axis of
the basal and intermediate cells is perpendicular to the
basement membrane. The basement membrane is usually
not visible in routine hematoxylin and eosin or periodic
acid–Schiff stained sections, but appears as a razor-thin
layer beneath the mucosa when present. Basement mem-
brane markers such as laminin and type IV collagen may
be useful diagnostically in select cases to define the base-
mentmembrane,butarenotemployedroutinely.15 Delicate
capillaries of the muscularis mucosae are in intimate asso-
ciation with the basement membrane, and invaginations or
tangential cutting may create the factitious appearance of
intraepithelial extension.
The urothelium is able to respond to thermal, mechan-
ical, and chemical stimuli (“sensor functions”) and has
the ability to release chemicals (“transducer functions”).16
Urothelial basal cells express certain receptors and ion
channels (e.g., vanilloid receptor-1), similar to afferent
Figure1-9 Normalurothelium.Basalandintermediatecells
arelocatedbetweenthebasallaminaandthesuperficialcells.
Occasionalprominentnucleargroovesmaybeseen.Notethe
binucleatedsuperficialumbrellacells.
of tissue section; they may appear cuboidal in the dis-
tended bladder, but are often flattened. In addition, superfi-
cialcellsarelooselyattachedtotheunderlyingcellsdespite
being interconnected with each other by extensive junc-
tional complexes13 and may be absent from otherwise nor-
mal urothelium in routine biopsies. Superficial umbrella
cells express uroplakins and cytokeratin 20 with immuno-
histochemistry.Theapicalplasmalemmaisthickened,with
stiff plaques, unlike the short microvilli seen in the under-
lyingintermediatecells.13 However,thetrigonalsuperficial
cells of women during the reproductive years have a cob-
blestone pattern with long clubbed microvilli.14 Superficial
Figure1-10 Normalurothelium.Basalandintermediate
cells may persist on the surface of papillary urothelial car- cellsaremoredenselypackedwithahighernuclear
cinoma, particularly low grade carcinomas—a finding of cytoplasmicratiothanthatofsuperficialcells.
5