1. Penchansky Pediatric Bone Marrow
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1 1. Penchansky Pediatric Bone Marrow
2 Springer-Verlag Berlin Heidelberg GmbH
3 Lila Penchansky Pe Bo la rle e Marrow With 356 Figures in 530 Separate Illustrations, Mostly in Color " Springer
4 Professor LI LA PENCHANSKY, MD Department of Pathology BST S495 School of Medicine University of Pittsburgh Pittsburgh, PA USA ISBN Library of Congress Cataloging-in-Publication Data Penchansky, Lila. Pediatric bone marrow I Lila Penchansky. p.;cm. Includes bibliographical references and index. ISBN ISBN (ebook) DOI / Bone marrow-diseases-diagnosis. 2. Children-Diseases-Diagnosis. 3. Leukemia in children Diagnosis. 4. Pediatrics. l. Title. [DNLM: 1. Bone Marrow Diseases-diagnosis-Child. WH 380 P397P 2004J RC645 7.P '41- dc This work is subject to copyright. Ali rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, re citation, broadcasting, reproduction on microfilms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permis sion for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. springeronline. com Springer-Verlag Berlin Heidelberg 2004 Originally published by Springer-Verlag Berlin Heidelberg New York in 2004 Softcover reprint of the hardcover 1st edition 2004 The use of general descriptive names, registered names, trademarks, etc. in this publicat ion does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about the application of operative techniques and medications contained in this book. In every individual case the user must check such information by consulting the relevant literature. Cover design: Erich Kirchner, Heidelberg Typesetting and reproduction of the figures: AM-productions GmbH, Wiesloch Printed on acid-free paper
5 To ALL THE CHILDREN WHO TAUGHT ME ALL I KNOW ABOUT THEIR BONE MARROW
6 Preface As a medical student I found Pediatrics to be one of the most enjoyable courses. The ability of the children to heal and the speed of the process fascinated me. On the other hand, blood disorders were particularly puzzling for me. The possibility of studying both subjects by concentrating on the pathology of the bone marrow in children led me to specialize in that area. This Text Atlas summarizes my 35years of experience in the field. It does not pretend to cover every disorder of the bone marrow in children, but provides a guide to the diagnosis of hematologic disorders that require examination of the bone marrow in common disorders and their morphological variations, as well as rare disorders. It is commonly said that "a picture is worth a thousand words;' but for pictures to have a meaning they need to be interpreted. The numerous illustrations presented here, often together with the clinical information and hematologic data, are intended to provide images representing specific disorders in a given setting. They are all examples from my personal experience in the field at the Children's Hospital of Pittsburgh and my consultations files, except for a few examples generously provided by colleagues in the field of Pediatric Pathology. Digital images obtained from the original slides have been edited to emphasize the points of interest or to summarizeinformation in a single image. The references provided at the end of each chapter do not necessarily include every reference in the field. In these computerized days, additional references are found easily,but the ones selected include the most recent or classical references in a specific area. Often, when the author's experience is similar to the findings of numerous publications in the area, no reference is provided, and the findings are taken to be common knowledge. The explosion of new diagnostic methods in recent years has increased our diagnostic capacity as well as our understanding of the mechanisms of a large number of hematologic disorders. Technological advances make us think at times that our eyes cannot go as far as technology. However,our clinical and morphological diagnostic skills have improved by correlating the results of highly sophisticated tests with clinical data and morphology. The existing links between technological information and the shape and structure of cells has been a great source of interest to me and has stimulated my return to the observation of morphological details. Special thanks are given to my husband Daniel Russell PhD, for his patience and support during difficult times and his critical reading of my manuscript, making him the most pathology-knowledgeable of French teachers, and to my parents Jaime Penchansky and Vera 1. de Penchansky, for their love that gave me the strength to "follow a star;' as my mother used to say.my thanks also go out to Virginia Pirrota MT for helping me at all times and for
7 VIII Preface her hard work throughout our years together at the Children's Hospital of Pittsburgh, to Dr Ronald Jaffe for his critical review of some of the chapters and for providing me with all the archival material I needed to review for this project, and to Dr Guillermo Gallo, who also reviewed some of the chapters. I am particularly grateful to Michael E. Sendek, Senior Systems Engineer in the Clinical Pathology Informatics Division of the Department of Pathology at the University of Pittsburgh, for teaching me all I know about obtaining images and editing them to obtain the desired effect in the computer. I appreciate his patience for all my demands and response to my calls. He is also responsible for the final standard format to the multiple images. Finally,I am grateful to Dr George Michalopoulos, chairman of the Department of Pathology at the University of Pittsburgh; without his help and support this book would not have been possible, and to Patricia Arndt for all her secretarial help. I cannot thank by name all the colleagues, technicians,and support personnel who helped me during the years because the list would be too long, but I thank you all for your collaboration with me at the Department of Pathology, University of Pittsburgh, for making this book possible. LILA PENCHANSKY
8 Contents CHAPTER I Normal Bone Marrow. References CHAPTER 2 Inherited Bone Marrow Failure Introduction Inherited Hematopoietic Syndromes Associated with Pancytopenia 15 Fanconi Anemia Q Laboratory Findings Dyskeratosis Congenita Q Laboratory Findings Shwachman-Diamond Syndrome Q Laboratory Findings Congenital Amegaka ryocytic Thrombocytopenia Q Labora tory Findings Rare Familial Marrow Failure Syndromes Inherited Hema topoieti c Syndromes Associated with Single Cytopenia Diamond-Blackfan Anemia Q Laboratory Findings Congenital Dyserythropoietic Anemias Severe Congenital Neutropenia 24 Q Laboratory Findings Cyclic Neutropenia Q Laboratory Findings Chronic Benign Neutropenia Thrombocytopenia with Absent Radii Q Laboratory Findings Inherited Disorders of the Leukocytes Associated with Change in their Morphology Pelger-Hiiet Anomaly May-Hegglin Anomaly Chediak-Higashi Syndrome 30 Alder-Reilly Anomaly Other Morphological Abnormalities Inherited Immunodeficiency Reticular Dysgenesis (Alymphocytic Neutropenia) 34 Q Laboratory Findings X-Linked Agammaglobulinemia (Bruton Agammaglobulinemia) Q Laboratory Findings Cartilage-Hair Hypoplasia :::) Laboratory Findings Wiskott-Aldrich Syndrome Q Laboratory Findings Omenn Syndrome Q Laboratory Findings Inherited Sideroblastic Anemias 36 Q Laboratory Findings Aminolevulinate Synthase (ALAS2) Deficiency Pearso n Syndrome 38 Osteopetrosis Q Laboratory Findi ngs References CHAPTER 3 Macrophage- and Dendritic-Cell-Related Disorders Including the Lysosomal Storage Disorders Introduction Storage Disorders 48 Gaucher Disease 48 Q Laboratory Findings Niemann-Pick Disease Q Laboratory Findings
9 X Contents Wolman Disease 52 Fabry Disease 52 Sialidoses 52 Gangliosidosis GMt and G M Fucosidosis U-Mannosidosis Glycogen Storage Diseases Mucopolysaccharidosis 54 Cystinosis Primary Hyperoxaluria 55 Sea-blue Histiocytosis 55 Histiocytosis 57 Langerhans Cell Histiocytosis 59 c ) Laboratory Findings Xanthoma Disseminatum 62 Macrophage-Related Disorders Hemophagocytic Syndrome c) Laboratory Findings References CHAPTER 5 Bone Marrow Metastases Introduction c) Laboratory Findings Neuroblastoma 104 c) Laboratory Findings Rhabdomyosarcoma c) Laboratory Findings Ewing Family of Tumors 119 c) Laboratory Findings Desmoplastic Small Round-Cell Tumor Central Nervous System c) Laboratory Findings Other Metastatic Tumors References CHAPTER 4 Bone Marrow Infections 71 Introduction Infection-Associated Hemophagocytic Syndrome Granulomas. Bacterial Infections. Mycobacteria. Ehrlichiosis Fungus Viruses Human Parvovirus B Epstein-Barr-Virus Cytomegalovirus Human Immune Deficiency Virus 89 Human Herpesvirus Type Other Viruses Parasites Malaria Other Parasites 96 References CHAPTER 6 Hematologic Manifestations oftrisomy Introduction c) Laboratory Findings Acute Megakaryoblastic Leukemia (FAB M7) Introduction 139 c) Laboratory Findings Cytochemistry and Immunocytochemistry Electron Microscopy Cytogenetic and Molecular Genetics References CHAPTER 7 Myelodysplastic Syndromes 151 Myelodysplastic and Myeloproliferative Disorders Introduction Myelodysplastic Syndromes 152 Juvenile Myelomonocytic Leukemia 152 c) Laboratory Findings Monosomy 7 Syndrome Unclassifiable Myelodysplastic Syndromes.. 158
10 Contents XI MDSs that Fit the FAB Classification in Children 159 c:> Laboratory Findings Myeloproliferative Disorders 162 Chronic Myelogenous Leukemi a 162 c:> Laboratory Findings Chronic Neutrophilic Leukemia Polycythemia Disorders Polycythemia Vera 168 c:> Laboratory Findings Essential Thrombocythemia c:> Laboratory Findings Hypereosinophilic Syndrome I Chronic Eosinophilic Leukemia c:> Laboratory Find ings Systemic Mastocytosis c:) Laboratory Findings References CHAPTER 9 Acute Lymphoblastic Leukemia and Lymphoma 215 Introduction Acute Lymphocytic Leukemia I Lymphoblastic Lymphoma 216 c:> Laboratory Findings Minimal Residual Disea se 237 Lymphomas Non-Hodgkin Lymphomas 238 Large-Cell Lymphomas 238 Anaplastic Large- Cell Lymph om a 239 c:> Laborator y Findings Hodgkin Lymphoma 241 c:> Laboratory Findings Reference s CHAPTER 8 Acute Myeloid Leukemia Introduction Acute Myelogenous Leukemia c:> Laboratory Findings Acute Myeloid Leukemi a with Minimal Differentiation (FAB Mo) 182 Acute Myeloid Leukemia without Matu ration (FAB M1) Acute Myeloid Leukemi a with Maturation (FAB M2) Acute Promyelocytic Leukemia (FAB M3) 189 Acute Myelomonocytic Leukemia (FAB M4) Acute Monoblastic Leukemi a (M5) Acute Ery throleukemia (M6) 201 Acute Megakar yobla stic Leukem ia (M7) 203 Acute Basophilic Leukemia Minimal Residual Disease Therapy-Related Acute Leukem ia 205 Congenital Leukemia Recur rent Chromosomal Abnormalit ies Acute Leukemia of Ambiguous Lineage References CHAPTER 10 Anemias Int roduction 247 Microcytic Anemias 249 Iron Deficiency Anemia c:> Laboratory Findings 249 Macrocytic Anemias B12 and Folic Deficiency c:> Laborato ry Findings Normocytic Anemias Hemolytic Anemias 255 Hereditary Hemolytic Anemias 258 Red Blood Cell Memb rane Disorders Hereditary Spherocytosis 258 c:> Laboratory Findings Hereditary Elliptocytosis Synd romes 261 c:> Laboratory Findings Other Inherited Disorders of the Red-Cell Membrane 264 Hereditary Anemias Due to Hemoglobin Abnormalities 264 Sickle Cell Anemia 264 c:> Laboratory Find ings Thalassemia Syndromes 266 ~-Thal assemias c:> Laboratory Findings (X - Thalassemias
11 XII Contents Acquired Hemolytic Anemia Hemolytic Disease of Newborn, 269 c:) Laboratory Findings Autoimmune Hemolytic Anemia c:) Laboratory Findings Transient Erythroblastopenia of Childhood Aplastic Anemia 273 c:) Laboratory Findings References Acquired Non-Immune Hemolytic Anemias Paroxysmal Nocturnal Hemoglobinuria Subject Index
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