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H. Begemann J. Rastetter
Atlas of Clinical Hematology Initiated by L. Heilmeyer and H. Begemann
With Contributions by D. Huhn, B.R. Kranz, and W. Mohr
Translated by T. C. Telger
Fourth, Completely Revised Edition
With 205 Figures in Color and 35 in Black and White
Springer-Verlag Berlin Heidelberg New York London Paris Tokyo HongKong
English editions
© Springer-Verlag Berlin Heidelberg 1st ed.1955
Editions published under license
Spanish edition
2nd ed. 1972 3rd ed. 1979 4th ed.1989
German editions
Atlas der klinischen Hamatologie © Springer-Verlag Berlin Heidelberg 1st ed.1955 2nd ed. 1972 3rd ed. 1978 4th ed. 1987
Japanese edition
Rinsho Ketsuekigaku Atlas © Springer-Verlag Tokyo 1989
published by Editorial Cientifico-Medica Barcelona, 1973
Italian edition published by PICCIN Editore S.A.S. Padova, 1973, 1980
Japanese edition published by Igaku Shoin Ltd. Tokyo, 1975
ISBN-13: 978-3-642-97157-0 e-ISBN-13: 978-3-642-97155-6 DOl: 10.1007/978-3-642-97155-6
Library of Congress Cataloging-in-Publication Data. Begemann, Herbert. [Atlas der klinischen Hiimatologie. English] Atlas of clinical hematology 1 H. Begemann, J. Rastetter; initiated by L. Heilmeyer and H. Begemann ; with contributions by D. Huhn, B.R. Kranz, and W. Mohr; translated by T.C. Telger. -4th completely rev. ed. p. em. Translation of: Atlas der klinischen Hiimatologie. Includes index. ISBN-13: 978-3-642-97157-0 1. B1ood-Examination-Atlases. 2. Blood-Diseases-Diagnosis-Atla-ses. 3. Hematology-Atlases. I. Rastetter, Johann. II. Heilmeyer, Ludwig. III. Title. [DNLM: 1. Hematologyatlases. WH 17 H466a] RB145.B41313 1989. 616.1'5075'022--{fc20. DNLM/DCL for Library of Congress. 89-19659 CIP
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© Springer-Verlag Berlin Heidelberg 1955,1972,1979,1989 Softcover reprint of the hardcover 4th edition 1989
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6
Addresses
HERBERT BEGEMANN, Prof. Dr. med. emerit. Chefarzt der I. Medizinischen Abteilung des SUidtischen Krankenhauses Munchen-Schwabing, Munchen, Federal Republic of Germany
JOHANN RASTETTER, Prof. Dr. med. Leiter der Abteilung fUr Hiimatologie und Onkologie, I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universitiit Munchen, Federal Republic of Germany
DIETER HUHN, Prof. Dr. med. Leiter der Abteilung Hiimatologie und Onkologie, Freie Universitiit Berlin, Universitiitsklinikum Charlottenburg, Medizinische Klinik und Poliklinik, Berlin, Federal Republic of Germany
BERND R. KRANZ, Dr. med. Institut fUr Immunologie, Hiimatologikum, Gesellschaft fur Strahlen- und Umweltforschung mbH, Munchen, Federal Republic of Germany
WERNER MOHR, Prof. Dr. med. emerit. Chefarzt der klinischen Abteilung des Bernhard-Nocht-Instituts fUr Schiffs- und Tropenkrankheiten, Hamburg, Federal Republic of Germany
Translator:
TERRY C. TELGER Fort Worth, Texas, USA
v
Preface to the Fourth Edition
Hematology, the study of the blood and its disorders, has existed as a science for about one hundred years. During that period it has remained true to its goals. Despite many advances in the submicroscopic and biochemical realm, hematology has clung to its basic postulate that the majority of blood disorders are expressed in morphologically distinct cell changes. Even modern hematology relies largely on the morphologic examination of cells, and the microscope continues to be its main diagnostic tool. Today we may describe hematology as the only morphologically oriented clinical science. It owes its existence chiefly to the development of staining methods which make it possible to assign morphologic structures to specific cellular functions and thus to specific pathologic states. The first step in this direction was the brilliant discovery of panoptic stains in the early part of this century by Pappenheim, Wright, and others. This was followed in the 1950s and 1960s by the development of numerous cytochemical procedures for the differentiation of diverse biochemical reactions and cell types. In the last decade, immunologic methods have been employed to identify cell type-specific antigens as a means of classifying lymphoid and other cells more precisely and more objectively. This has aided in the differentiation of many important hematologic diseases.
In this fourth edition of the Atlas of Clinical Hematology, we have attempted to update the text and bring it in line with recent developments. As before, the book is subdivided into a theoretical part and a pictorial part which illustrates the morphologic features of specific disorders using a combination of photomicrographs and watercolor paintings created by Hans and Thea Dettelbacher. The paintings convey a sense of depth to the microscopic image that will aid the student in the differentiation of morphologic details. We have retained the chapter on electron microscopy, which we regard as a kind of connecting link between cell structures that are visible with the light microscope and the functional significance of those structures. Tropical medicine has become a subject of growing interest to hematologists and internists in our increasingly mobile population, so the section on tropical medicine has been revised and expanded. Also, we have added new photomicrographs and have replaced a number of old ones with photos of greater clarity.
The present edition features a new, comprehensive chapter on the light-microscopic demonstration of immunologic cell markers. It is divided into a methodologic and a cytologic section and deals extensively with the sub typing of normal and malignant lymphoid cells. This new and difficult chapter was authored by Bernd R. Kranz, who proved to be not only an expert in his field but also a cooperative, constructive coworker who offered many helpful suggestions
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going beyond his area of specialization. We express our sincere thanks for his contributions. We are also deeply indebted to our coauthors Dieter Huhn and Werner Mohr, who worked with us on earlier editions and extensively revised and updated their chapters.
We thank our colleagues Heimpel of Ulm, Kaiserling of Tiibingen, Lopes-Cardozo of Leiden, Miiller-Hermelink ofWiirzburg, and Sepp of Munich for supplying specimens and photomicrographs of rare disorders or special cell forms. We are grateful to Mr. Jorg Kiihn, who mastered the difficult task of supplementing the watercolor illustrations done for the first edition by Hans and Thea Dettelbacher. Mr. Kiihn proved to be a talented and sensitive artist, and his contribution is gratefully acknowledged.
Despite her other professional obligations, Dr. Gudula Wernekke-Rastetter has again provided an outstanding subject index. We thank her for turning our atlas into a useful reference work.
If this book recaptures the visual impact of the earlier editions, the credit belongs to Springer-Verlag and its staff as well as to the Dreher Reproduction Service in Stuttgart and Stiirtz Printers in Wiirzburg. All contributed to the success of our book, and all demonstrated great technical expertise and understanding. Everyone with whom we worked took pains to implement our wishes as regards the finished appearance of the volume. Working with them was always a pleasant and satisfying experience. We express our sincere thanks to Dr. H. Gotze, Mrs. T. Deigmoller, Mrs. U. Pfaff, Dr. J. Wieczorek, and Mr. K. SolI, to name but a few of the many persons who contributed to the success of this book. Finally we would like to express our deep gratitude to our translator, T.C. Telger.
It is the hope of the editors and authors that this fourth edition of our atlas will enjoy the same enthusiastic critical and consumer response which greeted the first three editions.
Munich, Summer 1989 HERBERT BEGEMANN' JOHANN RASTETTER
VIII
Preface to the First Edition
So far the diagnostic advances of smear cytology have found only limited applications in medical practice. This is due largely to the fact that available illustrative materials have been too stylized to give the novice a realistic introduction to the field. In the present atlas we attempt to correct this situation by portraying the great morphologic variety that can exist in individual cells and in pathologic conditions. In so doing, we rely mainly on artist's depictions rather than photographs. On the one hand the "objectivity" of color photos, though much praised, is inherently questionable and is further degraded by the process of chemographic reproduction. An even greater drawback of photomicrographs is their inability to depict more than one plane of section in sharp detail. By contrast, a person looking through a microscope will tend to make continual fine adjustments to focus through multiple planes and thus gain an impression of depth. A drawing can recreate this impression much better than a photograph and so more closely approximates the subjective observation. We have avoided depicting cells in black and white; while there is merit in the recommendation of histologists that students' attention be directed toward structure rather than color, this is rarely practicable in the cytologic examination of smears. The staining methods adopted from hematology still form the basis for staining in smear cytology. For this reason most of the preparations shown in this atlas were stained with Pappenheim's panoptic stain. Where necessary, various special stains were additionally used. For clarity we have placed positional drawings alongside plates that illustrate many different cell types, and we have used arrows to point out particular cells in films that are more cytologically uniform.
We were most fortunate to have our color plates drawn by an artist, Hans Dettelbacher, in whom the faculties of scientific observation, technical precision, and artistic grasp are combined in brilliant fashion. We express our thanks to him and to his equally talented daughter Thea, who assisted her father in his work. Without their contribution it is doubtful that the atlas could have been created.
We are also grateful to a number of researchers for providing scientific help and specimens, especially Prof. Dr. Henning and Dr. Witte of Erlangen, Dr. Langreder of Mainz, Prof. Dr. Mohr of the Tropical Institute of Hamburg, Dr. Moeschlin of Zurich, Dr. Undritz of Basel, and Dr. Kuhn of our Freiburg Clinic. We also thank our translators, specifically Dr. Henry Wilde of our Freiburg Clinic for the English text, Dr. Rene Prevot of Mulhouse for the French text, and Dr. Eva FeIner-Kraus of Santiago de Chile for the Spanish text. We must not fail to acknowledge the help provided by the scientific and technical
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colleagues at our hematology laboratory, especially Mrs. Hildegard Trappe and Mrs. Waltraud Wolf-Lamer. Finally, we express our appreciation to SpringerVerlag, who first proposed that this atlas be created and took the steps necessary to ensure its technical excellence.
Freiburg, Spring 1955 LUDWIG HEILMEYER· HERBERT BEGEMANN
x
Contents
Methodology
A. Techniques of Specimen Collection and Preparation.
Blood Smear. . . . . . . . . . . . Bone Marrow . . . . . . . . . . . Puncture of Lymph Nodes and Tumors Splenic Puncture . . . . . . . . . . Concentration of Leukocytes from Peripheral Blood in Leukocytopenia Isolation of Mononuclear Cells by Density Gradient Centrifugation Lupus Erythematosus (LE) Cell Test Detection of Sickle Cells. . . . . . . . . . . . . . . . . . .
B. Light Microscopic Procedures. . . . . . . . . . . . . . . . . . . .
1. Staining Methods for the Morphologic and Cytochemical Differentiation of Cells. . . . . . . . . . . .
Pappenheim's Stain (Panoptic Stain) Wright Stain. . . . . Hemacolor Fast Stain. . . . . . . Sangodiff G Stain . . . . . . . . Undritz Toluidine Blue Stain for Basophils . Mayer's Acid Hemalum Nuclear Stain . Reticulocyte Stain . . Heinz Body Test . . . . . . . . . . Nile Blue Sulfate Stain . . . . . . . Stain for Demonstrating Hemoglobin F in Red Blood Cells. Stain for Demonstrating Methemoglobin-Containing Cells in Blood Smears. Iron Stain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cytochemical Detection of Glycogen in Blood Cells Using the Periodic Acid
Schiff Reaction and Diastase Test (PAS Reaction) . . . . . . . . . . Cytochemical Detection of Peroxidase. . . . . . . . . . . . . . . . . Cytochemical Detection and Semiquantitative Assay of Leukocyte Alkaline
Phosphatase (LAP) in the Blood Smear . . Cytochemical Detection of Acid Phosphatase. . . . . . . . . . . . . .
. .... 3
3 3 5 6 7 8 8 9
11
11
11 11 11 11 12 12 12 12 13 13 14 14
15 17
17 18
XI
Cytochemical Detection of Nonspecific Esterases . . . . . . . a-Naphthyl Acetate Esterase. . . . . . . . . . . . . . . Inhibition of a-Naphthyl Acetate Esterase by Sodium Fluoride Naphthol-AS-Acetate Esterase. . . . Naphthol-AS-D-Chloracetate Esterase . . . . . . . . . .
2. Immunocytochemical Detection of Cell-Surface and Intracellular Antigens
3. Staining Methods for the Demonstration of Blood Parasites
Thick Smear Method . . . . . . . . . . . . . . . . Examination of Blood for Bartonella . . . . . . . . . Examination of Bone Marrow Smears for Blood Parasites Examination for Toxoplasma. . . . . Examination of the Blood for Filariae . Examination for Mycobacterium leprae
C. Electron Microscopy
Introduction. Methodology
lliustrations
A. Overview of Cells in the Blood, Bone Marrow, and Lymph Nodes Illustrative Overview . . . . . . . . . . . . . . . . . .
B. Blood and Bone Marrow .
1. Individual Cells . . . .
a) Light Microscopic Morphology and Cytochemistry
Cells of Erythropoiesis. . . . . . . . Erythrocytes . . . . . . . . . . . . Erythropoiesis in Megaloblastic Anemias Myeloblasts and Promyelocytes . . . .
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The Neutrophils: Myelocytes, Metamyelocytes, Band and Segmented Forms . . . . . . . .
Degenerate Forms and Toxic Granulation. . Eosinophils, Basophils, and Mast Cells . . . Congenital Anomalies of Granulocytopoiesis Granulocytopoiesis in Megaloblastic Anemias Cells of the Reticulohistiocytic System . . . Storage Cells, Epithelial Cells, Endothelial Cells
Fig.
1
2 3,4
5 6
7 8 9
10 11 12 13
....
19 19 20 20 22
23
28
28 28 28 28 28 29
31
31 31
Page
34 36,37
38
38
38
38 40,42
44 46
48 50 50 52 52 54 56
Fig. Page
Reticulum Cells of Blood-Forming Organs 14 58 Osteoblasts and Osteoclasts . 15 58 Megakaryocytes . 16-18 62 Lymphocytes and Plasma Cells 19 64 Cytochemistry of Leukocytes and Megakaryocytes 20-22 66-68
b) Immunocytologic Differentiation of Normal Lymphoid Cells. 69
Stages of B-Cell Maturation and Activation 70 B Lymphocytopoiesis 23 72 Band Pre-B Cells in Bone Marrow. 24 73 B Lymphocytes in Peripheral Blood 25 73 Stages of Plasma Cell Development, CSF in Viral Meningitis. 26 73
Stages of T-Cell Maturation and Activation 74 T Lymphocytopoiesis, Thymus 27 75 Mature T Lymphocytes in Peripheral Blood. 28 76 Activated T Cells 29 76
c) Electron Microscopic Cell Morphologies 77
Ultrastructure of Cells 77 Special Ultrastructural Features 77
Marrow Sinus and Megakaryocyte . 30 79 Platelets . 31,32 81 Plasma Cells 33,34 81 Mast Cells 35,36 83 Normoblasts and Reticulum Cell 37 83 Oxyphilic Normoblast 38 85 Reticulocyte 39 85 Myeloblast . 40 85 Promyelocyte . 41 85 Neutrophilic Granulocyte. 42 87 Monocyte 43 87 Basophilic Granulocyte 44 87 Granule of a Basophilic Granulocyte . 45 89 Granule of an Eosinophilic Leukocyte 46 89 Eosinophilic Granulocyte. 47,48 89 Lymphocytes . 49-52 91-93 Erythrocyte Containing Numerous Heinz Bodies . 53 93 Sickle Cell 54 95 Polychromatic Normoblast with Hemosiderin-Containing
Mitochondria (" Ringed Sideroblast") 55 95 Mitochondria of a Normoblast in Sideroachrestic Anemia. 56 95 Normoblast in Sideroachrestic Anemia . 57,58 95 Normoblast in Dyserythropoietic Anemia Type I and II . 59,60 97 Leukemic Cell in Promyelocytic Leukemia 61 97 Leukemic Cells in Hairy Cell Leukemia . 62 98 Detail of a Hairy Cell 63 98 Sezary Cell . 64 99 Detail of a Leukemic Cell in Immunocytoma 65 99
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2. Normal and Pathologic Bone Marrow .
Composition of Normal Bone Marrow
Hypochromic Anemias
Iron Deficiency . Infectious Anemias Sideroachrestic Anemia
Hemolytic Anemias.
Megaloblastic Anemias
Congenital Dyserythropoietic Anemias
Chronic Erythroblastophthisis (Pure Red Cell Aplasia) .
Erythremias .
Reactive Bone Marrow Changes
Toxic Reaction of Bone Marrow. Hypereosinophilia .
Agranulocytosis
Thrombocytopenias and Thrombocytopathies
Panmyelopathy (Panmyelophthisis) .
Myelodysplastic Syndromes (MDS) .
Multiple Myeloma (Plasmacytoma, Kahler's Disease)
Gaucher's Disease
Myeloproliferative Syndrome.
Chronic Myeloid Leukemia (CML)
Eosinophilic Leukemia
Basophilic Leukemia
Mastocytoma
Acute Leukemia (AML, ALL)
Undifferentiated Leukemia Lymphoblastic Leukemia.
Myeloblastic Leukemia. Promyelocytic Leukemia . Myelomonocytic Leukemia Monocytic Leukemia
Acute Erythroleukemia
C. Lymph Nodes and Spleen
Cytology of Lymph Node and Splenic Aspirates.
Normal Lymph Node Cytology Normal Spleen Cytology . . . . . . . .
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Fig.
66-69
70, 71 72 73
74-79
80-86
87
88
89-92
93-95 96,97
98,99
100-103
105
104
106-110
111-113
114,115
116-121
122
123
124
125, 126 127,128 137-139
129 130-132, 140 133,141,142 134,135, 143
144-146
147-151 152,153
Page
100
100-105
106
107, 108 108 109
110-117
118-126
127, 129
127, 130
128,131-134
135
137-139 140,141
142-144
145-148
149, 153
150-152
154-158
159-161
162-164
165-173
174
174
174
175
179 180
186-188 . 181
182,183, 188 183,189,190
184, 191
192-194
195
196
198-201 .. 202
Reactive Lymph Node Hyperplasia . . .
Normal and Hyperergic Hyperplasia Toxoplasmosis . . . . . . Tuberculosis . . . . . . . Sarcoidosis (Boeck's Disease) Branchiogenic Cyst
Infectious Mononucleosis . . . .
Hodgkin's Disease (Lymphogranulomatosis)
Malignant Non-Hodgkin's Lymphomas . .
Fig.
154--157 · . 158
159-161, 163 · . 162 · . 164
165-168
169-177
a) Low-Grade and Intermediate-Grade Malignant Non-Hodgkin's Lymphomas
Chronic Lymphocytic Leukemia. . . . . . Immunocytoma and Waldenstr6m's Disease. Pro lymphocytic Leukemia . . . . . . . . Centrocytic Lymphoma . . . . . . . . . Centroblastic-Centrocytic Lymphoma (Giant
Follicular Lymphoblastoma, Brill-Symmers Disease) Sezary Syndrome . . Hairy Cell Leukemia. . . . . . . . . . . . .
b) High-Grade Malignant Non-Hodgkin's Lymphomas
Lymphoblastic Malignant Lymphomas . Immunoblastic Malignant Lymphomas. Various Highly Malignant Lymphomas .
Malignant Histiocytosis. . . . . . . . . .
178-182 183, 184
185 186
187 188 189
190 191
192,193
194, 195
D. Immunocytologic Identification and Classification of Lymphoid Malignancies
Distinction of Malignant from Benign Lymphoid Cells Classification of Malignant Lymphoid Cells . . . . .
C(ommon) ALL. .............. . Lymphoblastic B-Ce11 Lymphoma, Burkitt Phenotype,
CSF in Meningeal Involvement . . . . . . . . . Lymphoplasmacytoid Immunocytoma, CSF in Meningeal
Involvement . . . . . . . . . . . . . . . . Multiple Myeloma, CSF in Meningeal Involvement. . . . T-ALL, CSF in Meningeal Involvement. . . . . . . . . Primary CNS Lymphoma of T-Precursor Phenotype, CSF .
E. Tumor Aspirates . . . . . . . . . .
Ewing's Sarcoma, Bone Marrow. Chloroma, Tumor Aspirate . . .
196
197
198 199 200 201
202 203
Page
. 203
204--207 · . 208 209-211 · . 210 · . 211
212-216
217-224
225
227
227-230 231-233 231,233 234,235
234,236 237,238 237,239
240
241 242
243,244
245-247
.... 248
248 249
252
253
253 254 255 255
256
258 258
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Prostatic Carcinoma, Bone Marrow . . Bronchogenic Carcinoma, Lymph Node Thyroid Carcinoma, Tumor Aspirate . Mucinous Carcinoma, Bone Marrow . Breast Carcinoma, Lymph Node. . Chondrosarcoma, Tumor Aspirate. . Melanosarcoma, Lymph Node . . . Soft-Tissue-Sarcoma; Tumor Aspirate Seminoma, Lymph Node . Various Tumor Cells. . . . . . . .
F. Appendix . . . .
Herpes Zoster. . . . . . . . . . . . . . . . . Smear from an Epithelial Vesicle in Herpes Zoster
Lupus Erythematosus
G. Blood Parasites. Principal Causative Organisms of Tropical Diseases
Malaria .................. .
African Sleeping Sickness (Trypanosoma Gambiense)
Chagas' Disease (South American Trypanosomiasis)
Toxoplasmosis.
Leprosy ...
Leishmaniasis .
Cutaneous Leishmaniasis (Oriental Sore)
Relapsing Fever . . . . .
Bartonellosis (Oroya Fever)
Dipetalonema Perstans . .
Loa Loa ....... .
Wucheria Bancrofti and Brugia Malayi
Fig.
204 205 206 207 208 209
210,211 · . 212 · . 213 214-217
218,219
· . 220
· . . .
221-225
· . 226
227,228
229,230
· . 231
232,233
234
235
236
237,240
238,240
239,240
Page
259 259 260 260 261 261 262 263 263
264-267
268
268 269,270
268,271
.. 272
272-281
282,283
282-284
284-286
.. 287
288,289
290,291
292,293
292,293
294,295,298
294,295,298
.. 296-298
Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
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