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Vinod B Shidham
Barbara F Atkinson
Shidham Atkinson

Diagnosis of
Serous Fluids
Vinod B Shidham MD FIAC FRCPath
Director of FNAB Service and Cytopathology Fellowship Training Program
Medical College of Wisconsin
Milwaukee, WI

Barbara F Atkinson MD
Executive Vice-Chancellor, Kansas University Medical Center and
Executive Dean, University of Kansas School of Medicine
Kansas City, KS


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An imprint of Elsevier Inc
© 2007, Elsevier Inc. All rights reserved.

First published 2007

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ISBN: 978-1-4160-0145-4

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Medical knowledge is constantly changing. Standard safety precautions must be followed,
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Contributors vii
Foreword ix
Preface xi
Acknowledgments xii
Dedication xiii
List of abbreviations xv

1 Introduction 1
Vinod B Shidham
2 The panorama of different faces of mesothelial cells 19
Vinod B Shidham
3 Approach to diagnostic cytopathology of serous effusions 31
Vinod B Shidham and Barbara F Atkinson
4 Diagnostic pitfalls in effusion fluid cytology 43
Vinod B Shidham
5 Immunocytochemistry of effusion fluids: introduction to SCIP approach 55
Vinod B Shidham and Barbara F Atkinson
6 Reactive conditions 79
Nirag C Jhala, Darshana N Jhala and David C Chhieng
7 Diagnostic cytopathology of peritoneal washing 91
Rosemary E Zuna
8 Mesothelioma 107
R Nagarjun Rao
9 Metastatic carcinoma in effusions 115
Vinod B Shidham
10 Metastatic sarcomas, melanoma, and other non-epithelial neoplasms 147
Mamatha Chivukula and Reda Saad
11 Where do they come from? Evaluation of unknown primary site of
origin 157
David C Chhieng and Nirag Jhala
12 Hematolyphoid disorders 171
Steven R Sanchez and Chung-Che (Jeff) Chang
13 Flow cytometry, molecular analysis, and other special techniques 195
Choladda Vejabhuti and Chung-Che (Jeff) Chang
14 Appendix I: Collection and processing of effusion fluids for cytopathologic
evaluation 207
Vinod B Shidham and John Epple
15 Appendix II: Immunocytochemistry of effusions— processing and
commonly used immunomarkers 237
Vinod B Shidham

Index 259

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Barbara F Atkinson MD R Nagarjun Rao MD, FRCPath

Executive Vice-Chancellor, Kansas University Medical Center and Assistant Professor of Pathology
Executive Dean, University of Kansas School of Medicine Department of Pathology
Kansas City, KS Medical College of Wisconsin
USA Milwaukee, WI
Chung-Che (Jeff) Chang MD
Associate Professor of Pathology Reda S Saad MD, PhD
Director of Hematopathology Associate Professor of Pathology
The Methodist Hospital Department of Pathology and Laboratory Medicine
Houston, TX Drexel University College of Medicine
USA Allegheny General Hospital
Pittsburgh PA
David C Chhieng MD, MBA, MSHI
Professor of Pathology
Director, Immunohistochemistry Lab Vinod B Shidham MD, FIAC, FRCPath
Department of Pathology Professor
University of Alabama at Birmingham Director of FNAB Service and Cytopathology Fellowship Training
Birmingham, AL Program
USA Medical College of Wisconsin
Milwaukee, WI
Mamatha Chivukula MD
Assistant Professor
Department of Pathology Steven R Sanchez MD
Magee Womens Hospital of UPMC Associate Pathologist
Pittsburgh, PA Pathology Associates of Tyler
USA Tyler, TX
John Epple SCT(ASCP)
Cytology Supervisor Choladda Vejabhuti MD
Dynacare Laboratory—Cytology Hematopathology/Cytopathology Fellow
Milwaukee, WI Department of Pathology
USA Baylor College of Medicine
Houston, TX
Darshana N Jhala MD, BMus
Associate Professor, Anatomic Pathology
Division of Anatomic Pathology Rosemary E Zuna MD
University of Alabama at Birmingham Associate Professor of Pathology
Birmingham, AL Department of Pathology
Medical Director, Cytotechnology Program University of Oklahoma Health Sciences Center
Auburn University Montgomery Oklahoma City, OK
Montgomery, AL USA
Nirag C Jhala MD, MIAC
Associate Professor of Pathology
Division of Anatomic Pathology
University of Alabama at Birmingham
Birmingham, AL

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This book is a most comprehensive account of the cytopa- trointestinal tract. This section is profusely illustrated by pho-
thology of serous effusions and peritoneal washings. It tographs of cells from these organs. It is usually possible with
opens with an introductory chapter on the histology of the a fair degree of accuracy to predict the primary site of neoplas-
serous cavities and the blood-derived constituents that may tic cells found in a serous effusion if the clinical circumstances
be found in them, the complementary roles of the Papanico- are known. However, the prediction of unknown primary sites
laou and Romanowsky stains, the types of serous effusions of origin of neoplastic cells in serous effusions could be facil-
and a list of the human and non-human entities that may itated by the two interesting tables on the cytologic features,
be found in them, and an analysis of the morphology of the differential diagnosis, ultrastructural features, and possible
mesothelial cell. This is followed by a ‘panorama of different primary sites of origin that this chapter contains.
faces’ of mesothelial cells, which illustrates just about every Hematolymphoid disorders are thoroughly dealt with.
variant of the cell that is likely to be encountered, both in its Each of the disorders is accompanied by an explanatory para-
solitary form and in clusters. Since it is hard to imagine that graph about the entity and often by photographs of relevant
there is any seasoned cytopathologist who has not stumbled cells. This section contains a large table on immunopheno-
into making a false-positive report initiated by the sight of typic comparison of fifteen lymphomas and leukemias. Flow
‘reactive’ mesothelial cells, this is a worthy choice of subject, cytometry, molecular techniques, and other special tech-
one that would be especially important for the newcomer to niques are now being more used in an adjunctive manner for
the cytology of serous effusions. the evaluation of serous effusions. The uniqueness of surface
The chapter on the approach to diagnostic cytopathology marker flow cytometric studies of hematopoietic neoplasms
is systematically and logically presented. A helpful feature in serous effusions is such that the authors conclude that they
in this section consists of two algorithms clearly intended to may provide a valuable way to confirm the primary diagnosis
lead the way to correct diagnoses. This chapter, as do many of of lymphoid cancer. This section also includes tables on the
the chapters, contains a helpful listing of various features and major molecular genetic abnormalities of lymphomas, acute
techniques relevant to the subject. Diagnostic pitfalls in effu- leukemias, and soft tissue tumors.
sion cytology, a subject of paramount importance, are fully Finally, two appendices are provided that deal with the col-
dealt with and serve as a warning to those about to undertake lection of serous effusions for cytopathologic examination,
this important aspect of cytopathology. including processing and commonly used immunomarkers.
The section on the immunocytochemical approach to Both of these sections are replete with valuable, practical
cytologic diagnosis in serous effusions introduces the term information.
‘subtractive coordinate immunoreactivity pattern’ to high- In summary, this is an outstanding monograph which
light what are and what are not neoplastic cells by using a makes full use of the older techniques for the cytologic eval-
variety of immunomarkers to provide a contrast between dif- uation of serous effusions, but which also demonstrates
ferent types of cells, neoplastic and non-neoplastic. The sec- how the modern techniques, particularly of flow cytometry,
tion on ‘reactive conditions’ deals with conditions that have genetic evaluation, and immunocytochemistry, may be put
characteristic cellular features that could mimic carcinoma. to good use.
Although most of the conditions are a manifestation of the Bernard Naylor MD
ever-present reactive mesothelial cell, included amongst University of Michigan
them are systemic lupus erythematosus and rheumatoid effu-
sions. The section on peritoneal washings includes a large
variety of non-neoplastic and neoplastic entities. The chap-
ter on the cytopathology of diffuse malignant mesothelioma
of epithelial type is dealt with in a conventional manner by
identifying its cells in effusions as being of mesothelial lin-
eage and observing their excessive number and tendency to
form numerous cellular clusters, thereafter corroborating the
diagnosis by immunocytochemistry.
A large chapter is devoted to the cytopathology of neoplasms
of various organs, predominantly lung, breast, ovary, and gas-

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Because of its complexity, cytopathologic evaluation of effu- chapters. To summarize the theory with a practical touch,
sion fluids can be challenging. However, because effusion some of the chapters are concluded with study cases.
fluids are relatively easy to collect, any pathology laboratory The layout of the pages attempts to simplify the process
may be confronted with such specimens, regardless of its level of finding important points that are periodically highlighted
of expertise. In comparison to other common specimens, in italic type, as teaching points. The additional details are
effusion fluids need special and unique approaches for explained as a preamble to the book in Chapter 1. Similarly,
cytopathologic evaluation. the chapters are color-coded to be identifiable from the side
This book was planned and written with the following of the book as different color bars for quick chapter reference
major goals in mind: after a reasonable grasp of the general pattern of the book has
been obtained.
• to highlight effusion fluid processing methodology
A significant proportion of problems associated with cyto-
• to simplify the interpretation approach based on
pathologic evaluation of effusion fluids are related to spec-
imen collection and processing. Chapter 14 is dedicated to
• To emphasize a special approach for evaluation of
addressing this, along with recommended approaches based
effusion fluid immunocytochemistry
on our experience.
• to introduce other ancillary tests.
For pathology laboratories possessing optimal immunohis-
The readership we have in mind includes beginners such tochemistry support, the immunocytochemical evaluation of
as pathology residents, fellows, and cytotechnology students, cell block sections of effusion fluids is invaluable as an objec-
and also those who have experience in cytopathology but are tive ancillary tool. However, the lack of a proper approach
faced with a difficult diagnostic dilemma. to immunocytochemical evaluation may lead to equivocal
Each chapter begins with a general outline. We anticipate results. A special chapter is devoted to explain the SCIP (sub-
that many readers may not read the book from beginning to tractive coordinate immunoreactivity pattern) approach to
end and may prefer to focus on topics of specific concern. facilitate easy immunocytochemical interpretation.
Although the chapters are interrelated, the contributors of Although washing the serous cavity with saline or balanced
each have attempted to cover their topic as an independent salt solution may be expected to yield a cell sample similar
entity. Due to the overlap of related areas, there will be some to effusion fluid, there are differences that must be taken into
repetition of certain themes. account. To highlight and address some of the differences
A picture is worth a thousand words. Emphasis is given between cytopathologic evaluation of washings and effusion
to the inclusion of as many images and sketches as possible, fluids, periodic references are made to this variation and a
with a broad range of stains and magnifications highlighting separate chapter is included to discuss peritoneal washing.
multiple images of the same phenomenon. The figures and We believe that Cytopathologic Diagnosis of Serous Fluids
legends have been designed so that they can stand by them- provides a comprehensive source that will help students learn
selves or be used in addition to the text of a chapter. Thus, about the cytopathologic interpretation of these challeng-
there is some repetition of information in the text and the ing specimens as well as providing a practical reference for
figure legends, which reinforces the material, but the pictures busy practicing pathologists and cytotechnologists to evalu-
on their own are instructive. ate their difficult cases.
Many readers, especially in their early phase of training, Vinod B Shidham MD
would benefit from the algorithms presented in some Barbara F Atkinson MD


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A project such as this cannot be embarked upon without encouragement and help from the Chair of Pathology at
help. Although this acknowledgment may not be sufficient in the Medical College of Wisconsin, Dr Carl Becker, has been
expressing the depths of our appreciation, it is an attempt to invaluable. In addition, the timely supply of material and
address this important component of book writing. Specific critical reviews of various chapters by Dr Bernard Naylor and
acknowledgments at the end of some of the chapters should Dr David Dabbs is highly appreciated.
also be noted. The contributions and encouragement from our family
Many excellent, hard-working cytopathologists, patholo- members was also invaluable. Anjani Shidham, Anushree
gists, and cytotechnologists have contributed to this project. Shidham, Sushrut Shidham, and Abhijeet Kolpekwar have
Their patience, consideration, and enthusiasm have fueled helped with various aspects of the books production, includ-
the progress leading to its completion. Their high level of ing typing, copyediting, and searching. We are deeply grate-
expertise and dedication has been integral to the production ful to Mrs Paz B. Naylor, PhD for coordinating many steps
of this book. As editors, we sincerely appreciate the insight, involved with forwarding and reviewing various chapters by
help, and expertise of all of our contributing authors and Dr Naylor. We would like to recognize the efforts of Michael
their supporters. Houston, Elizabeth MacSween, Alan Nicholson, Louise Cook,
Many faculty members, staff members, residents, and fel- Claire Bonnett, Natasha Andjelkovic, and Belinda Kuhn at
lows at the Medical College of Wisconsin, Milwaukee, WI, Elsevier during various stages of this project.
have put forth significant efforts at various levels. We thank We would especially like to thank all the people who have
Dr Richard Komorowski, Dr Anthony Cafaro, Dr Natalia worked with us over the years as our teachers, colleagues,
Markelova, Dr Behnaz Behmaram, Dr Zainab Basir, Dr James cytotechnologists, fellows, residents, students, friends, and
Keating, Dr Steven Kroft, Dr Petio Kotov, Dr Vincent Graffeo, mentors. Their contributions may not be obvious, but they
Dr Jordi Rowe, Dr Krista D'Amore, and Dr Louis Novoa-Takara have played critical roles, and each has been an inspiration
for their critical review and input. We are grateful for the coor- in their own way.
dination and secretarial help of Ms Patsy Gill and Ms Barbara Vinod B Shidham MD
Petersen. We also acknowledge the periodic copyediting Barbara F Atkinson MD
support of Ms Jeanette Bjerke and Mr Glen Dawson. The


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Vinod B. Shidham
In fond memory of:
My father-in-law (late Bhaskar Paranjape) and
my mother-in-law (late Pratibha Paranjape)

My dad (Baburao Shidham MD) and my mom (Sunanda Shidham MA);
brothers (Pramod Siddham MD and Ganesh Shidham MD);
sisters (Chhaya Raghoji MD MS and Maya Pathikonda MD);
loving wife—Anjani;
friends, students, residents, fellows, readers, and all well wishers;
whose affection keeps projects such as this book happening.

Barbara F Atkinson
G. William Atkinson MD
Rhoda and Walter Frajola
Julie McCollum and George Atkinson
Will, Sydney, and Raven Nancy and Charles Perkins


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