Table Of Content1.Penchansky Pediatric BoneMarrow
Springer-Verlag Berlin Heidelberg GmbH
Lila Penchansky
• •
Pe la rle
Bo
e Marrow
With 356 Figures in 530 Separate Illustrations,
Mostly in Color
" Springer
Professor
LI LA PENCHANSKY, MD
Department of Pathology
BST S495
School of Medicine
University of Pittsburgh
Pittsburgh, PA 15261
USA
ISBN 978-3-642-62296-0
Library of Congress Cataloging-in-Publication Data
Penchansky, Lila.
Pediatric bone marrow I Lila Penchansky.
p.;cm.
Includes bibliographical references and index.
ISBN 978-3-642-62296-0 ISBN 978-3-642-18799-5 (eBook)
DOI 10.1007/978-3-642-18799-5
1. Bone marrow-Diseases-Diagnosis. 2. Children-Diseases-Diagnosis. 3. Leukemia in children
Diagnosis. 4.P ediatrics. l. Title.
[DNLM: 1. Bone Marrow Diseases-diagnosis-Child. WH 380 P397P 2004J
RC645·7.P4652004 618.92'41-dc22 2003057314
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© Springer-Verlag Berlin Heidelberg 2004
Originally published by Springer-Verlag Berlin Heidelberg New York in 2004
Softcover reprint of the hardcover 1st edition 2004
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Printed on acid-free paper 543210
To ALL THE CHILDREN
WHO TAUGHT ME ALL I KNOW
ABOUT THEIR BONE MARROW
Preface
As a medical student I found Pediatrics to be one of the most enjoyable
courses.Theability ofthe childrentohealandthe speed ofthe process fasci
nated me.Onthe otherhand,blooddisorders wereparticularlypuzzlingfor
me.Thepossibilityofstudyingbothsubjects byconcentratingonthepathol
ogy of the bone marrow in children led me to specialize in that area. This
TextAtlassummarizesmy35years ofexperienceinthe field.Itdoes not pre
tend to coverevery disorder ofthe bone marrowin children,but provides a
guide to the diagnosis ofhematologicdisorders that requireexamination of
the bone marrowin common disorders and their morphological variations,
aswellasrare disorders.
It is commonly said that "a picture is worth a thousand words;' but for
picturestohaveameaningthey need tobe interpreted.The numerous illus
trations presented here, often together with the clinical information and
hematologic data, are intended to provide images representing specific dis
ordersinagivensetting. Theyareallexamples from mypersonalexperience
in the field at the Children's Hospital of Pittsburgh and my consultations
files,exceptforafewexamples generouslyprovidedbycolleagues inthe field
ofPediatricPathology.
Digital images obtainedfrom the original slides havebeen edited to em
phasize thepointsofinterestortosummarizeinformationinasingleimage.
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 specificarea. Often,when the author's experience is
similarto the findings ofnumerous publications in the area, no reference is
provided,and the findings aretaken tobecommonknowledge.
The explosion of new diagnostic methods in recent years has increased
our diagnosticcapacityaswellasourunderstandingofthe mechanismsofa
large number of hematologic disorders. Technological advances make us
thinkattimes that oureyescannotgoasfarastechnology.However,ourclin
ical and morphological diagnostic skills have improved by correlating the
results ofhighly sophisticated tests with clinical data and morphology.The
existing links between technological information and the shape and struc
ture ofcellshas been agreat source ofinterestto me and has stimulatedmy
return tothe observationofmorphologicaldetails.
Special thanks are given to my husband Daniel Russell PhD,for his pa
tience and supportduringdifficulttimes and hiscriticalreadingofmyman
uscript,makinghim the most pathology-knowledgeable ofFrench teachers,
and to my parents Jaime Penchansky and Vera1. de Penchansky,for their
lovethat gavemethe strengthto"followastar;'asmymotherused tosay.My
thanks alsogoout toVirginia PirrotaMTfor helping me atalltimes and for
VIII Preface
her hard work throughout our years together at the Children's Hospital of
Pittsburgh,to Dr Ronald Jaffefor his critical review ofsome ofthe chapters
and forprovidingmewith allthearchival materialIneededtoreviewforthis
project, and to Dr Guillermo Gallo,who also reviewed some ofthe chapters.
Iam particularlygrateful to Michael E.Sendek, Senior Systems Engineerin
the Clinical PathologyInformatics Division ofthe DepartmentofPathology
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 ap
preciatehis patienceforallmydemandsandresponse tomycalls.Heisalso
responsibleforthe finalstandardformattothe multipleimages.Finally,Iam
gratefultoDrGeorgeMichalopoulos,chairmanofthe DepartmentofPathol
ogy 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.Icannotthankbyname allthecolleagues,technicians,and supportper
sonnelwho 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 ofPittsburgh,formakingthis bookpossible.
LILA PENCHANSKY
Contents
May-Hegglin Anomaly. ......... 29
CHAPTER I
Chediak-HigashiSyndrome 30
NormalBoneMarrow .
Alder-ReillyAnomaly.................... 32
OtherMorphologicalAbnormalities ....... 32
References................................. 13
Inherited Immunodeficiency................. 34
ReticularDysgenesis
CHAPTER2 (AlymphocyticNeutropenia) 34
InheritedBoneMarrowFailure ............. 15 Q LaboratoryFindings. ................. 34
X-LinkedAgammaglobulinemia
Introduction............................... 15 (BrutonAgammaglobulinemia) ... 35
LaboratoryFindings. ................. 35
InheritedHematopoieticSyndromes Q
Cartilage-HairHypoplasia. ............... 35
Associatedwith Pancytopenia 15
:::) LaboratoryFindings.................. 35
Fanconi Anemia. ........................ 15
Wiskott-AldrichSyndrome ............... 35
LaboratoryFindings.................. 16
Q LaboratoryFindings.................. 36
Q
DyskeratosisCongenita .................. 18
OmennSyndrome. ...................... 36
LaboratoryFindings. ................. 18
Q LaboratoryFindings .................. 36
Shwachman-DiamondSyndrome.......... 18 Q
LaboratoryFindings. ................. 18 InheritedSideroblasticAnemias 36
Q
CongenitalAmegakaryocytic Q LaboratoryFindings. ................. 37
Thrombocytopenia. ..................... 19 8-AminolevulinateSynthase (ALAS2)
LaboratoryFindings. ................. 19 Deficiency.............................. 38
Q
Rare FamilialMarrowFailure Syndromes... 19 PearsonSyndrome 38
Osteopetrosis ........................... 38
InheritedHematopoieticSyndromes
LaboratoryFindings.................. 39
Associated with Single Cytopenia. ............ 19 Q
Diamond-Blackfan Anemia..... .......... 19 References. ................................ 41
LaboratoryFindings .................. 19
Q
CongenitalDyserythropoieticAnemias. ....... 20
CHAPTER3
SevereCongenital Neutropenia 24
Macrophage-and Dendritic-Cell-Related
LaboratoryFindings.................. 24
Q DisordersIncludingthe Lysosomal
CyclicNeutropenia ...................... 27
StorageDisorders......................... 47
LaboratoryFindings .................. 27
Q
ChronicBenign Neutropenia.............. 28
Introduction............................... 47
Thrombocytopeniawith Absent Radii. ..... 28
LaboratoryFindings. ................. 28 Storage Disorders 48
Q
GaucherDisease 48
InheritedDisorders ofthe Leukocytes
LaboratoryFindings. ................. 48
Q
Associatedwith Change in theirMorphology... 29
Niemann-PickDisease. .................. 50
Pelger-Hiiet Anomaly. ................... 29
LaboratoryFindings.................. 50
Q
X Contents
Wolman Disease 52
FabryDisease 52 CHAPTER5
BoneMarrowMetastases.................. 101
Sialidoses 52
GangliosidosisGMtandGM2............... 53
Introduction............................... 101
Fucosidosis............................. 53
LaboratoryFindings. ................. 102
U-Mannosidosis. ........................ 53 c)
Glycogen StorageDiseases................ 54 Neuroblastoma 104
Mucopolysaccharidosis 54 LaboratoryFindings. ................. 112
c)
Cystinosis. ............................. 55
Rhabdomyosarcoma. ....................... 115
PrimaryHyperoxaluria 55
LaboratoryFindings. ................. 118
Sea-blueHistiocytosis 55 c)
Ewing FamilyofTumors 119
Histiocytosis 57
LaboratoryFindings. ................. 119
LangerhansCellHistiocytosis 59 c)
c) LaboratoryFindings. ................. 61 DesmoplasticSmall Round-Cell Tumor. ....... 121
Xanthoma Disseminatum 62
CentralNervousSystem..................... 123
Macrophage-RelatedDisorders. .............. 64 LaboratoryFindings. ................. 123
c)
HemophagocyticSyndrome .... .......... 64
OtherMetastaticTumors .................... 125
LaboratoryFindings. ................. 68
c)
References. ................................ 129
References................................. 68
CHAPTER6
CHAPTER4
HematologicManifestationsofTrisomy21 .. 133
BoneMarrowInfections 71
Introduction. .............................. 133
Introduction. .............................. 71
LaboratoryFindings. ................. 133
c)
Infection-Associated
Acute MegakaryoblasticLeukemia (FABM7) ... 139
HemophagocyticSyndrome 72
Introduction 139
Granulomas . 72 LaboratoryFindings.................. 139
c)
Cytochemistry
BacterialInfections . 72
and Immunocytochemistry............... 142
Mycobacteria . 75
ElectronMicroscopy. .................... 145
Ehrlichiosis . 77
CytogeneticandMolecularGenetics. ...... 145
Fungus ................................... 77
References. ................................ 147
Viruses. ............ 80
HumanParvovirusB19................... 81
Epstein-Barr-Virus. ..................... 85 CHAPTER7
Cytomegalovirus........................ 88 MyelodysplasticSyndromes 151
HumanImmuneDeficiencyVirus 89
HumanHerpesvirusType 6. .............. 92 Myelodysplastic
OtherViruses........................... 94 andMyeloproliferativeDisorders. ............ 151
Parasites. ................................. 95 Introduction............................... 151
Malaria................................ 95
MyelodysplasticSyndromes 152
OtherParasites 96
JuvenileMyelomonocyticLeukemia 152
References................................. 97
LaboratoryFindings. ................. 153
c)
Monosomy7Syndrome .................. 156
UnclassifiableMyelodysplasticSyndromes.. 158
Contents XI
MDSsthat Fitthe FAB Classification
in Children 159 CHAPTER 9
AcuteLymphoblasticLeukemia
c:> LaboratoryFindings. ................. 161
and Lymphoma 215
MyeloproliferativeDisorders 162
ChronicMyelogenousLeukemia 162 Introduction. .............................. 215
c:> LaboratoryFindings. ................. 163
Acute Lymphocytic LeukemiaI
ChronicNeutrophilicLeukemia ........... 167
LymphoblasticLymphoma 216
PolycythemiaDisorders.................. 168
c:> LaboratoryFindings. ................. 216
PolycythemiaVera 168
c:> LaboratoryFindings. ................. 168 Minimal ResidualDisease 237
EssentialThrombocythemia .............. 169
Lymphomas ............................... 237
c:> LaboratoryFindings. ................. 169
Non-Hodgkin Lymphomas 238
HypereosinophilicSyndromeI
Large-CellLymphomas 238
ChronicEosinophilicLeukemia ........... 170
Anaplastic Large-CellLymphoma 239
c:> LaboratoryFindings .................. 172
c:> LaboratoryFindings. ................. 239
Systemic Mastocytosis ................... 173
HodgkinLymphoma 241
Laboratory Findings.................. 174
c:)
c:> LaboratoryFindings.................. 241
References................................. 176
References................................. 243
CHAPTER8
AcuteMyeloidLeukemia................... 179 CHAPTER 10
Anemias.................................. 247
Introduction. .............................. 179
Introduction 247
AcuteMyelogenousLeukemia. ............... 180
MicrocyticAnemias 249
c:> LaboratoryFindings. ................. 180
IronDeficiencyAnemia .................. 249
AcuteMyeloid Leukemia c:> LaboratoryFindings 249
with MinimalDifferentiation (FAB Mo) 182
MacrocyticAnemias........................ 252
AcuteMyeloid Leukemia B12andFolicDeficiency.................. 252
withoutMaturation (FAB M1)................ 184 c:> LaboratoryFindings.................. 252
Acute Myeloid Leukemiawith Maturation NormocyticAnemias. ...................... 254
(FAB M2). ................................. 185
HemolyticAnemias 255
AcutePromyelocyticLeukemia(FAB M3) 189
HereditaryHemolyticAnemias 258
Acute MyelomonocyticLeukemia (FAB M4).... 195 Red Blood CellMembrane Disorders. ...... 258
HereditarySpherocytosis 258
Acute MonoblasticLeukemia(M5)............ 198
c:> LaboratoryFindings.................. 259
AcuteErythroleukemia(M6) 201 HereditaryElliptocytosisSyndromes 261
c:> LaboratoryFindings. ................. 262
AcuteMegakaryoblastic Leukemia (M7) 203
OtherInheritedDisorders
Acute BasophilicLeukemia .................. 203 ofthe Red-Cell Membrane 264
Minimal Residual Disease ........ 205 Hereditary Anemias
Due to HemoglobinAbnormalities 264
Therapy-RelatedAcute Leukemia 205
SickleCellAnemia 264
CongenitalLeukemia ............. 207 c:> Laboratory Findings .................. 264
ThalassemiaSyndromes 266
Recurrent ChromosomalAbnormalities ....... 210
~-Thalassemias ......................... 268
AcuteLeukemiaofAmbiguous Lineage........ 211 c:> LaboratoryFindings. ................. 268
Thalassemias ......................... 268
References. ................................ 211 (X-
