Comprehensive cytopathology

1104 Pages·2008·214.04 MB·English

by  Marluce Bibbo

SAUNDERS(cid:2)an(cid:2)imprint(cid:2)of(cid:2)Elsevier(cid:2)Inc.
© 2008, Elsevier Inc. All rights reserved.
First edition 1991
Second edition 1997
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ISBN: 978-1-4160-4208-2
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Notice
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Contributors
Fadi W Abdul-Karim MD Alicia L Carter MD
Associate Professor of Pathology and Orthopedics Fellow Cytopathology
Department of Pathology Duke University Medical Center
University Hospitals of Cleveland Burlington, NC, USA
Cleveland, OH, USA
Mamatha Chivukula MD
Tahseen Al-Saleem MD Assistant Professor of Pathology
Director of Hematopathology and Flow Cytometry Magee-Womens Hospital of UPMC
Senior Member Pittsburg, PA, USA
Division of Medical Science
Luiz M Collaço MD
Fox Chase Cancer Center
Professor of Pathology
Philadelphia, PA, USA
Federal University of Parana
Anniek JM van Aspert – van Erp PhD CFIAC Evangelica Faculty of Parana
Research Associate Bigorrilho, Curitiba, Brazil
Department of Pathology
Terence J Colgan MD
University of Nijmegen
Professor of Laboratory Medicine and Pathobiology
Ravenstein, The Netherlands
Mount Sinai Hospital
Peter H Bartels PhD Toronto, ON, Canada
Professor Emeritus of Optical Sciences
David J Dabbs MD
Department of Optical Sciences
Professor and Chief of Pathology
University of Arizona
Department of Pathology
Tucson, AZ, USA
Magee-Womens Hospital of UPMC
Simon Bergman MD Pittsburgh, PA, USA
Associate Professor of Pathology
Magnus von Knebel Doeberitz MD
Department of Pathology
Professor of Pathology
Wake Forest University Health Sciences
Department of Applied Tumor Biology
Winston-Salem, NC, USA
Institute of Pathology
Marluce Bibbo MD ScD FIAC FASCP University of Heidelberg
Professor of Pathology and Cell Biology Heidelberg, Germany
Department of Pathology, Anatomy and Cell Biology
Craig E Elson MD FCAP
Jefferson Medical College, TJU
Director of Cytopathology
Director of Cytopathology
Department of Pathology
Thomas Jefferson University Hospital
Research Medical Center
Philadelphia, PA, USA
HCA Midwest Division
Sandra H Bigner MD Kansas City, MO, USA
Medical Director
Michael S Facik MPA CT(ASCP)
Laboratory Corporation of America
Cytopathology Laboratory Supervisor
Burlington, NC, USA
Department of Cytopathology
Lukas Bubendorf MD University of Rochester Medical Center
Professor of Pathology Rochester, NY, USA
Institute for Pathology
Brendan T Fitzpatrick MD
Division of Cytology
Attending Pathologist
University Hospital Basel
Our Lady of Lourdes Medical Center
Basel, Switzerland
Camden, NJ, USA
Johan Bulten MD PhD MIAC
William J Frable MD
Assistant Professor of Pathology
Professor of Pathology
Department of Pathology
Virginia Commonwealth University
Radboud University Nijmegen Medical Center
Richmond, VA, USA
Nijmegen, The Netherlands
iixx
Contributors
Hugo Galera-Davidson MD FIAC William H Kern MD FIAC
Professor of Pathology Clinical Professor Emeritus of Pathology
Faculty of Medicine Department of Pathology
University of Seville LAC/USC Medical Center
Hospital Universitario Virgen Macarena Pasadena, CA, USA
Seville, Spain
Larry F Kluskens MD PhD
Kim R Geisinger MD FCAP Assistant Professor
Professor of Pathology Director of Cytology
Department of Pathology Department of Pathology
Wake Forest University School of Medicine Rush University Medical Center
Winston-Salem, NC, USA Chicago, IL, USA
Ben J Glasgow MD Savitri Krishnamurthy MD
Associate Professor of Ophthalmology and Pathology Associate Professor
Department of Pathology Department of Cytopathology
UCLA Center for Health Sciences MD Anderson Cancer Center
Los Angeles, CA, USA University of Texas
Houston, TX, USA
Katharina Glatz-Krieger MD
Professor of Pathology Oscar Lin MD PhD
University Hospital of Basel Associate Attending
Basel, Switzerland Memorial Sloan-Kettering Cancer Center
New York, NY, USA
Ricardo González-Cámpora MD FIAC
Professor of Pathology Diane B Mandell CT (ASCP) CFIAC
Faculty of Medicine Supervisor, Cytology Service
University of Seville Center for the Health Sciences
Hospital Universitario Virgen Macarena University of California at Los Angeles
Seville, Spain Los Angeles, CA, USA
Hans Jurgen Grote MD Cindy McGrath MD
Assistant Professor Assistant Professor of Pathology and Laboratory Medicine
Institute of Cytopathology Cytopathology Section
Heinrich-Heine University University of Pennsylvania Medical Center
Dusseldorf, Germany Philadelphia, PA, USA
Prabodh K Gupta MD FIAC C Meg McLachlin MD
Professor, Pathology and Laboratory Medicine Associate Professor, Pathology and OBGYN
Cytopathology and Cytometry Section University of Western Ontario,
Department of Pathology and Laboratory Medicine Medical Leader, Surgical Pathology
Hospital of the University of Pennsylvania London Health Sciences Centre
Philadelphia, PA, USA London, ON, Canada
Pierre Heimann MD PhD Christopher RB Merritt MD
Pathologist Professor of Radiology
Service d’Anatomie Pathologique Thomas Jefferson University Hospital
Cytologie, Cytogénétique Philadelphia, PA, USA
Institut Jules Bordet
Kiran F Narsinh MD
Brussels, Belgium
Fellow Eye Pathology
William W Johnston MD FIAC Department of Pathology
Professor Emeritus of Pathology JSEI,UCLA Medical Center
Duke University Los Angeles, CA, USA
Durham, NC, USA
Joseph F Nasuti MD
Ruth L Katz MD Attending Pathologist
Professor of Pathology Dianon Systems, Division of LabCorp
Director, Image Analysis and Research Cytopathology Bridgeport, CT, USA
Department of Pathology
Ritu Nayar MD
MD Anderson Hospital
Associate Professor of Pathology
Houston, TX, USA
Northwestern University
Catherine M Keebler ScD(hon) CFIAC Feinberg School of Medicine
Registrar Northwestern Memorial Hospital
International Academy of Cytology Chicago, IL, USA
Chicago, IL, USA
xx
Contributors
Bernard Naylor MB ChB FIAC Alain Verhest MD PhD FIAC
Professor Emeritus of Pathology Professor of Pathology (retired)
The University of Michigan Brussels, Belgium
Ann Arbor, MI, USA
G Peter Vooijs MD PhD FIAC
Wai-Kuen Ng MBBS FRCPA Professor of Pathology
FHKCPath FHKAM(Pathology) FIAC Scientific Director
Honorary Clinical Associate Professor Technological Medicine
Department of Pathology University of Twente
Queen Mary Hospital Enschede, The Netherlands
The University of Hong Kong
Nicolas Wentzensen MD
Hong Kong SAR, China
Department of Applied Tumor Biology
José Schalper Perez MD MIAC Institute of Pathology
Professor of Pathology University of Heidelberg
San Sebastian University School of Medicine Heidelberg, Germany
Chief, Division of Anatomical Pathology and Cytopathology
David C Wilbur MD
Concepcion, Chile
Associate Professor of Pathology
Reda S Saad MD PhD Harvard Medical School
Associate Professor Director, Cytopathology
Department of Pathology and Laboratory Medicine Massachusetts General Hospital
Allegheny General Hospital Boston, MA, USA
Pittsburgh, PA, USA
Moira D Wood MD
Jan F Silverman MD FCAP Assistant Professor of Pathology,
Professor and Chairman Department of Pathology, Anatomy and Cell Biology
Department of Pathology and Laboratory Medicine Thomas Jefferson University
Allegheny General Hospital Philadelphia, PA, USA
Pittsburgh, PA, USA
Bin Yang MD PhD
Lambert Skoog MD PhD Assistant Professor
Professor of Clinical Cytology Department of Pathology
Department of Pathology and Clinical Cytology The Cleveland Clinic Foundation
Karolinska University Hospital Solna Cleveland, OH, USA
Stockholm, Sweden
Grace CH Yang MD FIAC
Diane Solomon MD Professor of Clinical Pathology and Laboratory Medicine
Division of Cancer Prevention Papanicolaou Cytology Laboratory
National Cancer Institute Department of Pathology and Laboratory Medicine
National Institutes of Health New York Presbyterian Hospital-Weill Cornell Medical Center
Bethesda, MD, USA New York, NY, USA
Theresa M Somrak JD CT(ASCP) CFIAC Nancy A Young MD
Director Director, Outpatient Laboratory
Cytopathology Education Consortium Activities Senior Member
Chicago, IL, USA Division of Medical Science
Fox Chase Cancer Center
Kari Syrjanen MD PhD FIAC
Philadelphia, PA, USA
Professor
Department of Oncology & Radiotherapy Maureen F Zakowski MD FCAP
Turku University Hospital Professor of Pathology
Turku, Finland Memorial Sloan-Kettering Cancer Center
Department of Pathology and Cytology
Edneia M Tani MD PhD
New York, NY, USA
Associate Professor Clinical Cytology
Department of Pathology and Cytology Lucilia Zardo MD
Karolinska University Hospital Solna Director, Section for Technology in Cytopathology
Stockholm, Sweden Division of Pathology
National Cancer Institute
Liang-Che Tao MD FRCPC
Rio de Janeiro, Brazil
Professor Emeritus of Pathology and Laboratory Medicine
Department of Pathology
Indiana University
Camano Island, WA, USA
xi
Preface
Since the publication of the second edition of Comprehensive joined the distinguished roster of authors not only to write new
Cytopathology in 1997 new trends in the practice of gynecologic and chapters but also to rewrite them.
non gynecologic cytology have emerged. Liquid based preparations I would like to thank Dr David Wilbur for editing the chapters
and HPV testing have been introduced in gynecologic cytology, in the FGT section of CC3E and for his valuable input. Thanks to
immunocytochemistry, clinical cytogenetics and molecular tech- all contributors for their efforts and outstanding contributions.
niques have seen expanded applications to non gynecologic Special thanks to Nani Clansey, Development Editor, for her
cytology, and fine needle aspiration under sonographic, computer enormous help in the development of this work and William
tomographic or fluoroscopic guidance for cytologic diagnosis R Schmitt, Editor, for his support and also to Rory MacDonald,
has become an indispensable component of the workup of body Project Manager, Stewart Larking, Designer and to Gillian
lesions ,with more FNA’s being performed by radiologists, and Richards, Illustration Manager in Elsevier Ltd.
endoscopists in close cooperation with cytologists. In this third edition of Comprehensive Cytopathology we have
The table of contents reflects additions and changes in topics attempted, through an international group of experts to present
to provide detailed discussions of the significant advances a state of the art work. Again we placed in a single comprehensive
in the field. Examples include New concepts on molecular book discussions on general cytology, diagnostic exfoliative
basis of neoplasia (chapter 1), The role of genetics in cancer cytology of all body sites, entities and diagnostic challenges in
development (chapter 2), Evaluation of the sample in smears fine needle aspiration of various organs, effects of therapy on
and liquid based preparations (chapter 5), FNA of Mediastinum cytologic specimens and special methodologies and technologies
(chapter 26), FNA of Pediatric Tumors (chapter 29), Virtual in cytology. We hope that our attempt to incorporate advances
Microscopy (chapter 33), Automation of Cervical Cytology in the field while keeping emphasis on cytomorphology will be
(chapter 34), Molecular Techniques (chapter 36). Among the valuable to all professionals interested in cytopathology.
unique features of this edition is the large number of more than
1700 color illustrations depicting the main diagnostic entities Marluce Bibbo MD
with applications of adjunct techniques to cytopathology. New
contributors from institutions around the world (chapters 1, 2,
3, 6, 9, 10, 18, 21, 24, 25, 26, 28, 29, 33, 34, 35 & 36) have
xiii
Dedication
To George L Wied and Stanley F. Patten,
our great mentors and friends,
and our families for encouragement and
support.
Marluce Bibbo & David Wilbur
xxiivv
Acknowledgments
Some of the material in the third edition is derived from chapters
in the second edition. The editors acknowledge the contributions
of the following authors to the previous edition.
George L Wied
Karen H van Hoeven
Dorothy Rosenthal
Torsten Lowhagen
Hi Young Hong
Lisa M Bibb
Specific acknowledgment is made for permission to use the
following figures:
Ch 19, Fig 66: Courtesy of Ms Jamie L Covell, Charlottesville, VA,
Ch 2, Figs 5 & 6: Courtesy of Applied Imaging Corporation USA
Ch 5, Fig 12: Courtesy of Dr Zubair W Balloch, Philadelphia, PA, Ch 19, Fig 67: Courtesy of Dr Cesar V Reyes, Mines, IL, USA
USA Ch 19, Fig 69: Courtesy of Ms Sharon Hicks, Martinez, CA, USA
Ch 5, Fig 14: Courtesy of Dr Yener Erozan, Baltimore, MD, USA Ch 19, Fig 72: Courtesy of the late Dr James N Landers, Detroit,
Ch 5, Figs 18 & 19: Courtesy of Dr Corrado Minimo, MI, USA
Philadelphia, PA, USA Ch 19, Fig 94: Courtesy of Dr Andrew A Renshaw, Miami, FL,
Ch 7, Fig 11: Courtesy of Dr Belur Bhagavan, Baltimore, MD, USA
USA Ch 19, Fig 126: Courtesy of Mr. Tarring A Seidel, Danville, PA,
Ch 7, Figs 23 & 75: Courtesy of Dr S Bhambhani, New Delhi, USA
India Ch 19, Fig 137: Courtesy of Dr Dorothy L Rosenthal, Baltimore,
Ch 7, Fig 25: Courtesy of Dr K Kapila and K Verma, New Delhi, MD, USA
India Ch 19, Fig 139: Courtesy of Dr Bella Maly, Jerusalem, Israel
Ch 9, Fig 16a: Courtesy of Robert H Young, Boston, MA, USA Ch 19, Fig 140: Courtesy of Dr Maria C Gamarra, Buffalo, NY,
Ch 10, Figs 18, 19, 37 & 38: Courtesy of K. Shimizu, Japan USA
Ch 10, Figs 20, 21, 39 & 40: Courtesy of Y Norimatsu, Japan Ch 24, Figs 9 & 10: Courtesy of Dr Janet F Stastny, Outpatient
Cytopathology Center, Johnson City, TN, USA
Ch 14, Fig 13: Courtesy of Dr Jan Silverman, Pittsburg, PA, USA
Ch 24, Figs 14 & 16: Courtesy of Dr Nivaldo Medeiros, Emeritus
Ch 14, Fig 16: Courtesy of Dr Robert Petras, Cleveland, OH, USA
Attending, Clinical Hospital of the University of Sao
Ch 14, Fig 22: Courtesy of Josh Sickel MD, Mountain View, CA, Paulo, Brasil
USA
Ch 27, Fig 9: Courtesy of Dr Ritu Nayar, Northwestern University,
Ch 15, Figs 3, 9 & 14: Courtesy of Dr PT Chandrasoma, Los Chicago, IL. USA
Angeles, CA, USA
Ch 27, Fig 15A: Courtesy of Gary Rust, MD, Humble, TX, USA
Ch 15, Fig 16: Courtesy of Dr Yener Erozan, Baltimore, MD, USA
Ch 27, Fig 36B: Courtesy of Dr Stephen Somerville, Longview, TX,
Ch 15, Fig 44: Courtesy of Dr Demetrius Bagley, Philadelphia, PA, USA
USA
Ch 27, Fig 45: Courtesy of Dr Alan Heimann, Stony Brook
Ch 16, Figs 2, 4, 7, 10 & 16 Courtesy of Dr Keith Volmar, Chapel University, NY, USA
Hill, NC, USA
Ch 27, Fig 56: Courtesy of Dr Bruce MacKay, MD Anderson
Ch 18, Fig 49: Courtesy of Dr Syed Z Ali, Baltimore, MD, USA Cancer Center, Houston, TX, USA
Ch 19, Fig 31: Courtesy of Dr Sudha R Kini, Detroit, MI, USA Ch 28, Fig 100: Courtesy of Dr Syed Z Ali of Johns Hopkins
Ch 19, Fig 36: Courtesy of Dr Suzanne M Selvaggi, Madison, WI, Hospital, Baltimore, MD, USA
USA Ch 31, Fig 10 (right): Courtesy of Dr J Reagan, Case Western
Ch 19, Fig 64: Courtesy of Dr Praboth K Gupta, Philadelphia, PA, Reserve Cytopathology Laboratory, Cleveland, OH,
USA USA
xx
Acknowledgments
Ch 34, Figs 4AB, 5 & 17: Courtesy of James Linder MD, Cytyc Ch 35, The authors would like to acknowledge Jeff Richmond, MD,
Corporation Cytology Fellow, University of Pittsburgh Medical Center
Ch 34, Figs 10AB: Courtesy of Dr Mathilde Boon, Leiden, (UPMC), Marluce Bibbo, MD, and Mary Blumberg, MD,
Netherlands Surgical Pathology Fellow, UPMC, for their kind
contribution of some of the figures; and Sean Toddy, CT,
American Society for Clinical Pathology (ASCP), and Peter
Atanasoff, CT, ASCP, Product Manager, Cytyc Corp, for
providing the Cellient Automated cell block system pictures.
xi
1
C h a p t e r
The Cell: Basic Structure and Function
Magnus von Knebel Doeberitz and Nicolas Wentzensen
Contents
PART I: BASIC STRUCTURE AND FUNCTION OF MAMMALIAN CELLS Cell Membrane, Receptors, and Signal Transduction
Overview Cell Junctions
Nucleus Cell Growth and Division
Contents of the Nucleus
PART II: THE MOLECULAR BASIS OF NEOPLASIA
Nuclear Morphology
hematoxylin Overview
Nucleoli
Principles of Malignant Transformation
Nuclear envelope and Nuclear Shape
Cytoplasm and Plasmalemma Cancer-related Genes
Cytoplasmic Stain The Major Pathways of Carcinogenesis
Endoplasmic Reticulum Carcinogenesis induced by Papillomavirus Infections
Golgi Apparatus Basic Structure of the Virus and Its Genome
epidemiology of hpV Infections
Mitochondria
the role of the hr-hpV e6 and e7 Genes
Lysosomes progression of hpV-Infected epithelial Cells to Invasive Cancer Cells
Cytoskeleton, Centrosome Concluding Remarks
PART I: BASIC STRUCTURE AND FUNCTION OF MAMMALIAN CELLS
Overview
Apart from the loss of the spatial information, cells can have
Cells are the basic structural and functional units of all liv- considerably altered morphology when taken out of the united
ing organisms. The estimations about the total cell count of a structures. Cell–cell contacts are important features that build
human body vary widely; a number as large as 1014 seems con- the shape of a cell. Many structural elements within a cell are
ceivable. Although the principal components of all cells are very connected to proteins that are attached to other cells or the
similar, the differentiation of cells results in a wide variation of basal membrane. This must be taken into account when cells
cellular morphology and function. are compared in histological and cytological assessments.
The smallest human cells by diameter are spermatozoa Another important difference between histology and cytol-
with a size of ~3 μm, followed by the anucleate erythrocytes ogy is based on the fact that in histology, plain two-dimensional
(8 μm). The largest cells are female oocytes that can be as large tissue sections are assessed, while in most cytology applications,
as 35–40 μm and are visible to the naked eye. Motor neurons are complete cells that still have some three-dimensional features,
extremely long cells, with their axons reaching from the spine to although they might appear flat in the microscope, are analyzed.
the distal extremities (up to 1.4 m length). Based on these facts, the transfer of histological morphology to
Most cells can only be functional in large united structures, the picture seen in cytology is limited.
such as organs or suborganic structures. Other cells, mainly In this section, an overview of the most important cellular
of hemato- or lymphopoietic origin, are mobile and active structures and functions relevant for cytopathology are pre-
as single cells, although in many cases, their functionality is sented (Fig. 1.1). We have assembled the most important infor-
dependent on interaction with other cells. mation on cellular structures by describing the regular function
Cytopathology studies diseases on the cellular level. While in in brief, the relevance for cytopathology, and the morphology
histopathology, cells are assessed in the spatial context, in vir- in normal and abnormal cells. For more detailed information
tually all cytological applications, they are removed from their about cellular structures and functions, a cell biology textbook
spatial context and must be assessed isolated or as cell sheets. is recommended.