Bone Marrow Biopsy Pathology: A Practical Guide

544 Pages·2020·209.028 MB·English

by  Christine Beham-Schmid, Annette Schmitt-Graeff

Essentials of Diagnostic Pathology
Series Editor: Farid Moinfar
Christine Beham-Schmid
Annette Schmitt-Graeff
Bone Marrow Biopsy
Pathology
A Practical Guide
Essentials of Diagnostic Pathology
More information about this series at: http://www.springer.com/series/8171
Christine Beham-Schmid
Annette Schmitt-Graeff
Bone Marrow Biopsy
Pathology
A Practical Guide
Christine Beham-Schmid Annette Schmitt-Graeff
Institute of Pathology Albert-Ludwigs-University of Freiburg
Medical University Graz Freiburg
Graz Germany
Austria
Series Editor 
Farid Moinfar
Department of Pathology, Ordensklinikum Linz/Hospital of the Sisters of Charity
Department of Pathology, Medical University of Graz
Graz, Austria
ISSN 2194-6256 ISSN 2194-6264 (electronic)
Essentials of Diagnostic Pathology
ISBN 978-3-662-60307-9 ISBN 978-3-662-60309-3 (eBook)
https://doi.org/10.1007/978-3-662-60309-3
© Springer-Verlag GmbH Germany, part of Springer Nature 2020
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Preface
When I (C.B-S) was asked by Prof. F. Moinfar to write a book on bone marrow pathology, I
was hesitant in view of the abundance of excellent textbooks on this topic. However, the fact
that this book should be intended as a practical guide dominated rather by illustrations than by
text, and the promise of Prof. Annette Schmitt-Graeff to act as a coauthor, at least encouraged
me to start this project.
As a young internship doctor in the small public hospital in Oberndorf/Salzburg, I (C.B-S)
was stimulated by Primarius Dr. K. Mittermayer to have a look on bone marrow aspirates. This
resulted in my interest in hematology, which was deepened when I consecutively started a
training in pathology with focus on hematopathology at the Institute of Pathology, Faculty of
Medicine, University of Graz. During this time, I received intensive training in bone marrow
biopsy pathology in Munich (Prof. Burkhardt) and Tel Aviv (Bertha Frisch) and in lymphoma
diagnostics in London (P.G. Isaacson). Up to now, I have seen ten thousands of bone marrow
biopsies and gained a lot of experience. Since the knowledge of clinical data is essential for
exact pathohistological diagnosis of bone marrow biopsies, a close cooperation with the clini-
cal colleagues is mandatory.
My (A.S-G) enthusiasm for bone marrow (BM) diagnostics dates back to my residency in
hematology/oncology at the Departments of Internal Medicine, University Hospitals of
Cologne and Essen, Germany. I was keen on evaluating blood and BM cytology. I also realized
the impact of BM and lymph node biopsies on therapeutic strategies for our patients suffering
from myeloid or lymphoproliferative neoplasms. This appreciation was the rationale to pursue
a residency and a fellowship in anatomical pathology at the University Hospital Düsseldorf,
Germany, where I established histologic BM assessment. My research activities were on the
cytoskeleton including BM stroma with Prof. Dr. Dr. h.c. Giulio Gabbiani, University Hospital
Geneva, Switzerland, where I assumed the position as consultant. There and at the Berlin
Reference Center for Lymph Node Pathology of Prof. Dr. Dr. h.c. Harald Stein I was princi-
pally in charge of BM pathology including supervising residents in this field.
Later, I joined the faculty at the Medical Center, University Freiburg, Germany, where I was
appointed Professor of Hematopathology and GI Pathology. My activities were focused on
integrating morphological, immunophenotypic, and molecular aspects of hematological neo-
plasms and primary immunodeficiency disorders with the late Prof. Dr. Paul Fisch in close
clinico-pathologic cooperation.
As previous president of the German Division of the IAP (GDIAP) and actual member of
the General IAP and GDIAP Education committees, I have taught and directed numerous
hematopathology courses of the IAP nationally and internationally. In the context of my active
involvement in education and teaching, I am delighted to contribute to this textbook with a mix
of basic information and challenging diagnostic cases.
This book is intended as a practical guide in the complex field of bone marrow pathology.
We hope it will turn out helpful in the daily diagnostic work.
June 2020
Graz, Austria Christine Beham-Schmid
Freiburg, Germany Annette Schmitt-Graeff
v
Acknowledgments
I would like to thank my coauthor and friend Annette Schmitt-Graeff, without her support, my
own contributions for this book would not have been possible.
Moreover, I am deeply indebted to Prof. Farid Moinfar for giving me the opportunity to
write this book with my coauthor.
My special acknowledgment is also attributed to my teachers in hematology and hematopa-
thology Prim. Dr. K. Mittermayer, Oberndorf/Salzburg, Prof. Dr. R. Burkhardt, Munich/
Germany, Prof. Dr. B. Frisch, Tel Aviv/Israel, Prof. P.G. Isaacson, London/G.B., and Prof. Dr.
J. Thiele, Cologne/Germany.
In addition, I would like to recognize the excellent work of the team of the laboratory of
hematopathology and the photographers, Institute of Pathology, Medical University of Graz,
Austria.
Last but not least, I am most grateful to my husband Alfred and my son Clemens for their
never-ending patience and support during this project.
Christine Beham-Schmid
First, I would like to acknowledge the great dedication of my coauthor Prof. Dr. Christine
Beham-Schmid, Graz, and the series Editor Prof. Dr. Farid Moinfar, Linz, Austria, to the proj-
ect of our book.
I express my deep appreciation to many experts who inspired me with their devotion to
hematopathology and hematology. In particular, I want to mention Prof. Dr. Dr.hc Harald
Stein, Berlin, and Prof. Dr. Juergen Thiele, Cologne/Hannover, Germany, and Prof. Dr. Kristin
Henry, London, G.B. Special thanks go to Prof. Dr. Rüdiger Hehlmann who founded the
European LeukemiaNet (ELN). I would also like to acknowledge Prof. Dr. Attilio Orazi, El
Paso, and Prof. Dr. Daniel A. Arber, Chicago, USA, for their exciting investigations and teach-
ing in hematopathology.
I am especially indebted to Prof. Dr. Robert Zeiser, Dr. Dietmar Pfeifer, Dr. Milena Pantic,
and Dr. Justina Rawluk, Department of Hematology and Oncology, Medical Center, University
Freiburg, Germany, for their support and helpful contribution to molecular analyses, cytoge-
netics, and cytology of myeloid neoplasms.
Lastly, I would like to thank my mother Margret Gräff, my husband Eberhard Schmitt, our
son Rafael J. P. Schmitt, and my daughter-in-law Zelda Othenin for their patience and love.
Annette Schmitt-Graeff
vii
Contents
1 Normal Bone Marrow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Christine Beham-Schmid
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1.1 Bone Components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 Cellularity of the Marrow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.2.1 Topography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.3 Cellular Components of the Bone Marrow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.3.1 Hematopoiesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.3.2 Erythrocytopoiesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.3.3 Granulocytopoiesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.3.4 Monocytopoiesis and Macrophages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.3.5 Megakaryocytopoiesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
1.3.6 Lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
1.3.7 Plasma Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
1.3.8 Mast Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
1.3.9 Bone Marrow Stroma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2 Non-neoplastic Conditions with Quantitative and Qualitative
Changes in Hematopoiesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Christine Beham-Schmid
2.1 Common Non-neoplastic Erythroid Lineage Disorders . . . . . . . . . . . . . . . . . . . 27
2.1.1 Common Examples of Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.2 Acquired Anemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.2.1 Anemia of Chronic Disease (ACD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.2.1.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.2.2 Iron Deficiency Anemias (IDA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
2.2.2.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
2.2.3 Megaloblastic Anemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
2.2.3.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
2.2.4 Hemolytic Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.2.4.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.2.5 Aplastic Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
2.2.5.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
2.3 Bone Marrow Biopsy in Collagen Vascular Diseases (CVD),
Especially in Systemic Lupus Erythematosus (SLE) . . . . . . . . . . . . . . . . . . . . . . 40
2.3.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
2.4 Bone Marrow Involvement in Castleman’s Disease . . . . . . . . . . . . . . . . . . . . . . 44
2.4.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
2.5 Non-neoplastic Conditions with Quantitative and Qualitative
Changes in Granulopoiesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
2.5.1 Severe (Acquired) Neutropenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
2.5.1.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
ix
x Contents
2.6 Kostmann Disease (Infantile Genetic Agranulocytosis,
Severe Congenital Neutropenia) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
2.6.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
2.7 Leukemoid Reaction (LR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
2.7.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
2.8 Granulopoiesis with Increased Eosinophils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
2.8.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
2.9 Quantitative and Qualitative Changes in Megakaryocytopoiesis . . . . . . . . . . . . . 57
2.9.1 Morphologic Abnormalities of Megakaryocytes . . . . . . . . . . . . . . . . . . . 57
2.9.2 Megakaryocytic Emperipolesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
2.10 Micromegakaryocytes and Hypolobulated/Nonlobulated
Megakaryocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
2.11 Enlarged Megakaryocytes with Hyperlobulated Nuclei . . . . . . . . . . . . . . . . . . . 61
2.12 Megakaryocytes with Naked Nuclei . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
2.13 Clustering of Megakaryocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
2.13.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
2.14 Intrasinusoidal Megakaryocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
2.15 Paratrabecular Location of Megakaryocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
2.16 Gray Platelet Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
2.17 Bone Marrow Alterations After Chemotherapy/Stem
Cell Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
2.17.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
2.18 Monoclonal Antibody Treatment (Rituximab). . . . . . . . . . . . . . . . . . . . . . . . . . . 76
2.18.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
2.19 Bone Marrow Alterations after Bone Marrow Transplantation . . . . . . . . . . . . . . 77
2.19.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
3 Bone Changes Found in Bone Marrow Biopsies . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Christine Beham-Schmid
3.1 Osteodystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
3.1.1 Renal Osteodystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
3.1.1.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
3.1.2 Hyperparathyroid Osteodystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
3.1.2.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
3.1.3 Osteopenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
3.1.3.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
3.1.4 Osteomalacia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
3.1.4.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
3.1.5 Osteopetrosis (Marble Bone Disease) . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
3.1.5.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
3.1.6 Paget’s Disease of Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
3.1.6.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
4 Non-hematological Malignancies in the Bone Marrow . . . . . . . . . . . . . . . . . . . . . . 91
Christine Beham-Schmid
4.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .102
5 Increase of Plasma Cells, Reactive and Neoplastic . . . . . . . . . . . . . . . . . . . . . . . . .103
Christine Beham-Schmid
5.1 Reactive Plasmacytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .103
5.1.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .103
Contents xi
5.2 Monoclonal Gammopathy of Undetermined Significance (MGUS) . . . . . . . . . .105
5.2.1 Plasma Cell Myeloma (MM) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .105
5.2.2 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .105
5.2.3 Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .105
5.2.4 Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .110
5.2.5 Genetic Abnormalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .110
5.2.6 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .110
5.3 Plasma Cell Myeloma with Amyloid Deposition . . . . . . . . . . . . . . . . . . . . . . . .111
5.3.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .113
6 Inflammatory and Infectious Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .115
Christine Beham-Schmid
6.1 Infectious Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .120
6.1.1 Hemophagocytic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .120
6.1.1.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123
6.2 Visceral Leishmaniasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .124
6.2.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .125
6.3 Parvovirus B19 Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .126
6.3.1 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .127
6.4 Infection with Mycobacterium Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . .128
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .130
7 Malignant Lymphomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .131
Christine Beham-Schmid
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .131
7.2 Chronic Lymphocytic Leukemia (CLL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .134
7.2.1 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .134
7.2.2 Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .134
7.2.3 Transformation of CLL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .134
7.2.4 Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .134
7.2.5 Cytogenetic Abnormalities and Molecular Characteristics . . . . . . . . . . .134
7.2.6 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .143
7.3 B-Cell Prolymphocytic Leukemia (B-PLL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . .144
7.3.1 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .144
7.3.2 Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .144
7.3.3 Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .144
7.3.4 Cytogenetic Abnormalities and Molecular Characteristics . . . . . . . . . . .144
7.3.5 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .147
7.4 Lymphoplasmacytic Lymphoma (LPL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .148
7.4.1 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .148
7.4.2 Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .148
7.4.3 Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .148
7.4.4 Cytogenetic Abnormalities and Molecular Characteristics . . . . . . . . . . .148
7.4.5 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .155
7.5 Mantle Cell Lymphoma (MCL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .156
7.5.1 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .156
7.5.2 Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .156
7.5.3 Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .156
7.5.4 Cytogenetic Abnormalities and Molecular Characteristics . . . . . . . . . . .156
7.5.5 Caution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .159
7.6 Hairy Cell Leukemia (HCL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .162
7.6.1 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .162
7.6.2 Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .162