Urinary Cytology: Manual and Atlas

206 Pages·1993·21.371 MB·English

by  Prof. Dr. Peter Rathert, Dr. Stephan Roth, Prof. Mark S. Soloway M.D. (auth.)

P. Rathert S. Roth M. S. Soloway
URINARY
CYTOLOGY
Manual and Atlas
Second Edition, Fully Revised and Expanded
In Collaboration with
A. Backing, R. Friedrichs, F. HofsHidter, 1.-D. Hoppe,
E. Huland, H. Huland, C. Hunold, R. N afe, S. Peter,
P. Rottger, H. Riibben, and B. 1. Schmitz-Drager
Translated by Terry C. Telger
With 196 Figures in 279 Separate Illustrations,
Mostly in Color
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Hong Kong Barcelona
Budapest
Prof. Dr. PETER RATHERT Prof. MARK S. SOLOWAY, M. D.
Klinik fUr Urologie und Kinderurologie University of Miami
Krankenhaus Duren Department of Urology M-814
Akademisches Lehrkrankenhaus p. O. Box 016960
Roonstrasse 30 Miami, FL 33101, USA
W-5160 Duren, FRO
Dr. STEPHAN ROTH
Klinik und Poliklinik fUr Urologie Translator:
WesWilische Wilhelms-UniversiUit Munster TERRY C. TELGER
Albert-Schweitzer-Strasse 33 6112 Waco Way
W-4400 Munster, FRO Fort Worth, TX 76133, USA
Title of the German Edition
P. Rathert· St. Roth. Urinzytologie -Praxis und Atlas
© Springer-Verlag Berlin Heidelberg 1991
Library of Congress Cataloging/in/Publication Data. Rathert, Peter. [Urinzytologie. English] Urinary cytol
ogy: manual and atlas / P.Rathert, S.Roth, M.S. Soloway; in collaboration with A. Bocking ... let al.] :
translated by Terry C. Telger. -2nd ed., fully rev. and expanded. p. cm. Rev. ed. of: Urinary cytology / H. J. de
Voogt, P. Rathert, M. E. Beyer-Boon. 1977. Includes bibliographical references and index.
ISBN-13: 978-3-642-76186-7 e-ISBN-13: 978-3-642-76184-3
001: 10.1007/978-3-642-76184-3
1. Urine -Examination -Atlases. 2. Diagnosis, Cytologic-Atlases. 3. Urine-Examination -Handbooks,
manuals, etc. 4. Diagnosis, Cytologic -Handbooks, manuals, etc. I.Roth, S.(Stephan), 1957- . II. Soloway,
Mark S. III. Voogt, H.J. de, 1925 - Urinary cytology. IV, Title. [DNLM: l. Bladder Neoplasms -
diagnosis -atlases. 2. Cytodiagnosis -methods -atlases. 3. Urine -cytology -atlases. WJ 17 R234u] RB53.
R.3713 1993
616.99 '262'07582-dc20 DNLM/DLC
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Contributors
Professor Dr. A. BOCKING
Institut fUr Pathologie der Medizinischen Fakultat der Rheinisch-Westfalischen
Technischen Hochschule, Pauwelsstr. 30, W-5100 Aachen, FRG
Dr. R FRIEDRICHS
Urologische Klinik, Universitatsklinikum RudolfVirchow, Standort
Chariottenburg, Spandauer Damm 130, W-1000'Beriin 19, FRG
Professor Dr. F. HOFSTADTER
Institut fUr Pathologie der Universitat Regensburg, Universitatsstr. 31,
W-8400 Regensburg, FRG
Dr. l.-D. HOPPE
Institut fUr Pathologie, Krankenhaus Duren, Akademisches Lehrkrankenhaus,
Roonstr. 30, W-5160 Duren, FRG
Dr. E. HULAND
Urologische Klinik und Poliklinik, Universitatsklinik, Martinistr. 52,
W-2000 Hamburg 20, FRG
Professor Dr. H. HULAND
Direktor der Urologischen Klinik und Poliklinik, Universitatsklinik,
Martinistr. 52, W-2000 Hamburg 20, FRG
Dr. C. HUNOLD
Urologische Klinik und Poliklinik der Medizinischen Einrichtungen der
Universitat, Gesamthochschule Essen, Hufelandstr. 55, W-4300 Essen 1, FRG
Dr. RNAFE
Institut fUr Pathologie, Medizinische Hochschule Hannover, Konstanty
Gutschow-Str. 8, W-3000 Hannover 61, FRG
Professor Dr. S. PETER
Urologische Klinik Darmstadt, Grafenstr. 9, W-6100 Darmstadt, FRG
Professor Dr. P. ROTTGER
Institut fUr Pathologie, Krankenhaus Duren, Akademisches Lehrkrankenhaus,
Roonstr.30, W-5160 Duren, FRG
Professor Dr. H. ROBBEN
Urologische Klinik und Poliklinik der Medizinischen Einrichtungen der
Universitat, Gesamthochschule Essen, Hufelandstr. 55, W-4300 Essen 1, FRG
Privatdozent Dr. B.l. SCHMITZ-DRAGER
Urologische Klinik der Universitat, Moorenstr. 5, W-4000 Dusseldorf 1, FRG
Preface to the Second Edition
"Urine cytology, no doubt, deserves a much more
central position in urologic diagnosis. "
L. ANDERSON, 1978
After an initial period of relative stagnation following the work of V. D. Lambl
(1854), oncologic urinary cytology has evolved at an explosive pace since the
work of G. V. Papanicolaou and V. F. Marshall (1945). This led the
cytopathologist L. G.Koss to state in 1979 that urinary cytology should be made
an essential diagnostic tool of the urologist.
The first edition of this book, written in collaboration with Drs. H. 1. de Voogt
and M. E. Boon, already combined the disciplines of pathology and urology in
recognition of the fact that both the clinical and pathologic features of urothelial
tumors must be understood in order to select patients for urinary cytology and
comprehend its limitations and especially its interpretive criteria.
Since the first edition was published, basic research has given us new insights
into the ultrastructure of the urothelium, and many new preparatory techniques
have been developed for the collection, concentration, fixation, staining, and
analysis of cellular material. Not all of them could be included in this book (i.e.
thin layer prep.). In particular, the scientific accuracy of urinary cytology has
been enhanced by DNA single-cell cytometry, flow cytophotometry, and
immunocytology. Terminology, moreover, has been refined and standardized.
Besides oncologic urothelial cellular analysis, urinary erythrocyte morphol
ogy also has assumed clinical importance.
We could not do justice to these developments simply by reworking the 1979
text. We are grateful to Springer-Verlag for preparation of the new edition and
especially to Dr. U. HEILMANN and Mrs. I. C. LEGNER for their competent advice
and to E. KIRCHNER, 1. SCHAUBEL, and W. BISCHOFF for their meticulous
production work. Through their help we were able to add numerous authorities
from the fields of pathology and urology to our list of contributors. We are
grateful to these colleagues for their spontaneous willingness to assist in the
creation of this monograph and atlas. Their authoritative input was essential for
providing up-to-date, comprehensive coverage of our subject matter. Special
emphasis has been placed on conveying reproducible, practice-oriented
methods while also presenting basic scientific principles in a comprehensible
form. We hope that the book will stimulate interest in urinary tract cytology
among cytophatologists and urologists, deepen their awareness of its importance
and limitations, and assist them in the preparation and analysis of cytologic
material.
In the practice of urinary cytology, close cooperation between the pathologist
and urologist leads to progress in the early diagnosis and follow-up 'of patients
with urothelial malignancies. Besides cystoscopy, sonography, and urography,
exfoliative oncologic urinary cytology is an essential component in the
management of these patients.
PETER RATHERT, Duren
STEPHAN ROTH, Munster
MARK S. SOLOWAY, Miami
Foreword to the First Edition
The cytologic diagnosis of cancer has its roots in clinical microscopy as it was
shaped during the first half of the nineteenth century. In reviewing some of the
early writing on this subject, one is amazed at the accuracy of the descriptions and
soundness of the observations. Cytology of the urine is no exception: In 1864
Sanders described fragments of cancerous tissue in the urine of a patient with
bladder cancer (Edinburgh Medical Journal 111, 273). This observation was
confirmed by Dickinson in 1869 (Transactions of the Pathological Society
London 20, 233). It is a source of special pride to me that in 1892 a New York
pathologist, FRANK FERGUSON, advocated the examination of the urinary
sediment as the best means of diagnosing bladder cancer, short of cystoscopy.
PAPANICOLAOU freely acknowledged these contributions while establishing
sound scientific bases for continuation and spread of this work. PAPANICOLAOU'S
work in the area of the urinary tract did not fall on deaf ears. He documented to
several urologists who were within his sphere of personal influence, mainly Dr.
VICTOR MARSHALL, Professor of Urology at Cornell University Medical School,
that urinary tract cytology was a reliable tool in the diagnosis of urothelial
carcinoma. Some of us who have attempted to spread the master's word had their
share of success in institutions with which we were associated. Perhaps the most
important contribution of urinary tract cytology has been in the identification of
nonpapillary carcinoma in situ, a key lesion in the assessment or prognosis of
urothelial neoplasia. Yet, the authors of this fine book on urinary cytology are
quite right when they imply that the vast majority of urologists are either
unaware or skeptical of this method of diagnosis. There are many reasons for
this, perhaps the most important of which are its limitations. Well-differentiated
papillary lesions of the bladder, such as papilloma and grade 1 papillary
carcinoma, are unlikely to yield diagnostic cells. Thus, the expectation of the
urologists that any bladder tumor will be reliably diagnosed by cytology is false.
Similar mistakes are committed by pathologists and cytopathologists who fail to
recognize the limitations of the method and, in attempting to diagnose too much,
make major errors of judgment that arouse the mistrust of their clinical
colleagues. Urinary tract cytology is difficult and is full of pitfalls and distressing
sources of diagnostic mistakes. It cannot be learned casually but requires many
years of experience and close cooperation between the pathologist and the
urologist. This atlas should contribute to the popularization of this important
method of diagnosis, which admirably complements but does not replace clinical
judgment and the biopsy. The goal of these efforts is a relatively simple one: to
offer the patient with cancer of the lower urinary tract the best possible chance
for an early diagnosis reSUlting in a cure or at least containment ofthe disease and
as comfortable a life as possible if a cure is not attainable. Urinary cytology can
contribute significantly to this goal by identifying the patients at very high risk for
invasive cancer whose urinary sediment contains obvious cancer cells. For such
patients, radical treatment of the diseased urothelium prior to the development
of metastases may be the best and sometimes only chance of salvation.
x Foreword to the First Edition
Drs. BEYER-BoON, DE VOOGT, and RATHERT should be congratulated on this
fine atlas. It should contribute substantially to the clarification and education of
both urologists and pathologists who are interested in cancer of the lower urinary
tract.
LEOPOLD G. Koss
Professor and Chairman
Department of Pathology
Albert Einstein College of Medicine
at Montefiore Hospital and Medical Center
Bronx, New York 10467
Contents
1 History of Urinary Cytology
P. RATHERT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2 Indications of Urinary Cytology
P. RATHERT and S. ROTH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
3 Nonneoplastic Transitional Epithelium of the Urinary Tract
1.-D. HOPPE and P. ROTIGER . . . . . . . . . . . . . . . . . . . . . . . . . . .. 15
4 Ultrastructure ofthe Urothelium
S.PETER. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 23
5 Epidemiology, Etiology, and Classification ofUrothelial Tumors
H. ROBBEN and C. HUNOLD . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 35
6 Urothelial Atypia and Dysplasia
F. HOFSTADTER. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 47
7 Cytologic Grading of U rothelial Tumors
S. ROTH, R. FRIEDRICHS, and P. RATHERT. . . . . . . . . . . . . . . . . . . .. 53
8 Working Techniques in Urinary Cytology
S.ROTH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 61
9 Atlas Section
S. ROTH and P. RATHERT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 83
10 Diagnostic DNA Cytometry of the Urothelium
A. BOCKING. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 147
11 Immunocytology of Urothelial Tumors
B.1.SCHMITZ-DRAGER. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 165
12 Quantitative Immunocytology with Monoclonal Antibody (MAB)
486 P 3/12: Clinical Application
H. HULAND and E. HULAND. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 177
13 Urinary Erythrocyte Morphology and Diagnosis of Hematuria
S.ROTH ......................................... 187
14 An Expert System for Analysis and Standardization
of Bladder Carcinoma Grading
R. NAFE, S. ROTH, and P. RATHERT. . . . . . . . . . . . . . . . . . . . . . . .. 205
Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 209
1 History of Urinary Cytology
P. RATHERT
CONTENTS tury later as exfoliative cytoLogy (Grunze and
Spriggs 1983). This method, which predated the
1.1 Introduction .............................. .
histologic examination of tissue, involved the
1.2 History of Oncologic Urinary Cytology ....... .
microscopic examination of cells desquamated
1.3 Landmark Technical Developments. . . . . . . . . . . 2 from tissue surfaces. In one patient with a palpa
1.4 Innovations in Urinary Cytology. . . . . . . . . . . . . . 6 ble mass in the mandibular angle region and a
1.4.1 Automated Image Analysis. . . . . . . . . . . . . . . . . . 6 draining retroauricular sinus tract, the cytologic
examination of exfoliated cells in the discharge
1.4.2 Immunocytology. . . . . . . . . . . . . . . . . . . . . . . . . . . 6
raised suspicion of a malignant process, which was
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
confirmed by the subsequent course of the di
sease.
V D. Lambl (Fig. 1.4) was the first, in 1856, to ap
1.1 Introduction ply this technique to the detection of cancer cells in
urine. We must credit Grunze and Spriggs (1983)
Even today the "matula", a flask for inspection of with identifying Lambl as the inaugurator of onco
the urine, is depicted in the official emblems of the logic urinary cytology. It was previously thought
American Urological Association, the German that Sanders (1864) was the first to detect bladder
Society for Urology, and the Professional Associa cancer cells microscopically in urine; Ferguson
tion of German Urologists. It symbolizes the cen (1892) also has been incorrectly named as the foun
tral importance of urinalysis as a medical and espe der of urine cytology.
cially a urologic method of investigation. The color Vilem Dusan Lambl, born in Letina (near Pil
and odor of urine were of keen diagnostic interest sen) in 1824, became known for a species of infec
to the physicians of the Middle Ages (Figs.l.1, 1.2). tious protozoan that he discovered and was subse
But due to lack of alternative diagnostic methods, quently named for him, Giardia Lamblia (formerly
uroscopy soon evolved into a mystical uromancy in known as Lamblia intestinalis). His historic paper
which the color of a urine specimen was subject to on the cytologic diagnosis of bladder cancer
fantastic interpretations (Fig. 1.3). Urinalysis was (Fig. 1.5a,b) stands alone in his general body of
not taken seriously as a diagnostic tool until the work and was not pursued by other authors. This
nineteenth century, when chemical and micro was probably due to the lack of therapeutic options
scopic techniques were applied scientifically to the at that time in patients diagnosed with bladder can
examination of the urine. cer (Rathert 1987).
Lambl's publication is interesting not only be
cause it establishes his precedence in the field
1.2 History of Oncologic Urinary of oncologic urinary cytology but also because
it includes a reference to "bedside diagnosis"
Cytology
(Fig. 1.5 a), a concept that would become impor
tant many years later. Lambl also notes various
The general acceptance and evolution of urinary methods of specimen collection, most notably
cytology, like that of many other sUbjective bladder washing, and the possibility of preserving
diagnostic methods, has taken place over a long pe urine by acidification and cooling. Lambl's work
riod of time (Rathert 1986). Nearly a century pas was also prophetic in its acknowledgement of the
sed before urinary cytology became established as importance of microscopy: "The microscope is
a diagnostic technique. founding a science that is not necessary for the cli
In 1843 Dr. Julius Vogel of Gottingen first nician in all its details; but if ever the assistance of a
reported on a method that became popular a cen- microscope were urgently needed, it is in the area
2 P. Rathert
Fig. 1.2. "Uroscopy" as portrayed in a German painting
from the eighteenth century (Museo Nat. Art Sanitaria,
Rome)
Fig.I.1. Page from a medieval manuscript (1580) on the
physical examination of urine in a flask (matnla). (J. A. Ben
jamin Collection. Medical Library, University of California,
Los Angeles)
of urinalysis, where a confident diagnosis must pre strumental foundation in the form of the micro
cede the selection of an appropriate therapy" scope.
(LambI1856). Although Francesco Fontana claimed in 1646 to
The decisive breakthrough in oncologic urinary have built the first microscope in 1618 (Singer
cytology came later with the 1945 publication by 1914), today this distinction is generally credited to
Papanicolaou and Marshall, which led to a pro the lens grinder Hans Hanssen and his son Zacha
gressive integration of urinary cytology into rou rias of Middelburg (Turner 1980; Grunze and
tine urologic diagnosis. Spriggs 1983). Their instrument, which followed
the basic design of Galileo's telescope, had a bicon
cave eyepiece a biconvex objective lens that pro
vided a magnification of 60 diameters. According
1.3 Landmark Technical to Dittrich (1971), the term microscopium was
Developments coined by Demesianos, a member of the Accade
mia dei Lincei in Rome.
Besides optical magnification, another impor
Clinical cytology and urinary cytology were intro tant prerequisite for effective visual cellular analy
duced to medicine in the mid-1800s. This had been sis is sufficient contrast of the object being examin
preceded by more than 200 years of scientific in ed. This led very early to the use of stains to bring
quiry and innovation, which laid the necessary in- out structural details. Anthony van Leeuwenhoek