Atlas of Clinical Hematology

434 Pages·2005·29.201 MB·English

by  Professor Dr. med. Helmut Löffler, Professor Dr. med. Johann Rastetter, Professor Dr. med. Dr. phil. T. Haferlach (auth.)

H. Lo¨ffler(cid:1)J. Rastetter(cid:1)T. Haferlach
Atlas of Clinical Hematology
(cid:1) (cid:1)
H. Lo¨ffler J. Rastetter T. Haferlach
Atlas of
Clinical
Hematology
Initiated by L. Heilmeyer
and H. Begemann
Sixth Revised Edition
With 199 Figures, in 1056 separate Illustrations,
Mostly in Color, and 17 Tables
ProfessorDr. med. Helmut Lo¨ffler
Ehem. Direktor der II. Medizinischen Klinik und Poliklinik
der Universita¨t Kiel im Sta¨dtischen Krankenhaus
Seelgutweg 7, 79271 St. Peter, Germany
ProfessorDr. med. JohannRastetter
Ehem. Leiter der Abteilung fu¨r Ha¨matologie und Onkologie
1. Medizinische Klinik und Poliklinik
Klinikum rechts der Isar der Technischen Universita¨t Mu¨nchen
Westpreußenstraße 71, 81927 Mu¨nchen, Germany
ProfessorDr. med. Dr. phil. T. Haferlach
Labor fu¨r Leuka¨mie-Diagnostik
Medizinische Klinik III
Ludwig-Maximilians-Universita¨t Großhadern
Marchioninistraße 15
81377 Mu¨nchen
Editions published under license
English editions
ª Springer-Verlag Berlin Heidelberg Spanish edition
published by
1st ed. 1955
Editorial Cientifico-Me´dica
2nd ed. 1972
Barcelona, 1973
3rd ed. 1979
4th ed. 1989
Italien edition
5th ed. 2000
published by
German editions PICCIN Editore S.A.S.
Atlas der klinischen Ha¨matologie Padova, 1973, 1980
ª Springer-Verlag Berlin Heidelberg
1st ed. 1955 Japanese edition
2nd ed. 1972 published by
3rd ed. 1978 Igaku Shoin Ltd.
4th ed. 1987 Tokyo,1975
5th ed. 1999
Brazilian edition
Japanese edition published by
Rinsho Ketsuekigaku Atlas Revinter Ltd.
ª Springer-Verlag Tokyo,1989 Rio de Janeiro, 2002
Translated by: Terry C. Telger, Fort Worth, Texas, USA
ISBN 3-540-21013-X Springer Berlin Heidelberg New York
ISBN3-540-65085-15thEdition SpringerBerlinHeidelbergNewYork
LibraryofCongressCataloging-in-PublicationData
BibliographicinformationpublishedbyDieDeutscheBibliothek
DieDeutscheBibliothekliststhispublicationintheDeutscheNationalbibliografie;detailedbibliographicdataisavailable
intheInternetathttp://dnb.ddb.de
Thisworkissubjecttocopyright.Allrightsarereserved,whetherthewholeorpartofthematerialisconcerned,spe-
cificallytherightsoftranslation,reprinting,reuseofillustrations,recitation,broadcasting,reproductiononmicrofilmor
inanyotherway,andstorageindatabanks.Duplicationofthispublicationorpartsthereofispermittedonlyunderthe
provisionsoftheGermanCopyrightLawofSeptember9,1965,initscurrentversion,andpermissionforusemustalways
beobtainedfromSpringer-Verlag.ViolationsareliableforprosecutionundertheGermanCopyrightLaw.
SpringerisapartofSpringerScience+BusinessMedia
springeronline.com
ªSpringer-VerlagBerlinHeidelberg1955,1972,1979,1989,2000and2005
PrintedinGermany
Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.inthispublicationdoesnotimply,eveninthe
absenceofaspecificstatement,thatsuchnamesareexemptfromtherelevantprotectivelawsandregulationsandthe-
reforefreeforgeneraluse.
Productliability:Thepublisherscannotguaranteetheaccuracyofanyinformationaboutdosageandapplicationcon-
tainedinthisbook.Ineveryindividualcasetheusermustchecksuchinformationbyconsultingtherelevantliterature.
Coverdesign:FridoSteinen-Broo,eStudioCalamar,Spain
Production:PROEDITGmbH,69126Heidelberg,Germany
Typesetting:Mitterweger&PartnerKommunikationsgesellschaftmbH,68723Plankstadt,Germany
Printedonacid-freepaper 24/3150/ML–543210
V
Preface to the Sixth Edition
Soonafterthe5theditionofthisvolumeappeared,theWHOpublishedde-
tailsonthepathologyandgeneticsofthehematopoieticandlymphatictis-
sues.Workinprogressfoundinshortjournalarticleshadalreadybeenin-
tegrated into the last edition. Now it was possible to incorporate the new
proposalsforclassificationanddiagnosisandtoincludefiguresofnewtypes
of leukemia and lymphoma. These include leukemias of dendritic cells, in-
travascularlargeB-celllymphoma,theliver-spleenT-celllymphomaaswell
as persistent polyclonal B-cell lymphocytosis, which is placed between be-
nign and malignant.
Thepresentvolumecompletesandextendsthecytogeneticandmolecu-
lar-genetic characterization of the different diseases and incorporates new
figures.AtthispointwewouldliketothankPDDr.ClaudiaSchoch,Munich,
forhervaluablehelpandforgraciouslyprovidingnewzytogeneticandFISH
figures.Inaddition,severalfiguresandtableswerereplaced,andaschematic
drawingofthetopographyoflymphomainfiltrationinbonemarrow(cour-
tesyofProf.Dr.H.E.Schaefer,Freiburg)wasaddedtothelymphomachap-
ter.
Even in 2004, diagnosis in hematology and lymphomas starts, as a rule,
with the morphological examination of blood, bone marrow or lymphatic
tissues. It can direct the subsequent use of immunophenotyping, cytoge-
netics and molecular genetics, in this way demonstrating ways of saving
money and avoiding unnecessary investigations.
Gene expression profiling and, in the future, proteomics still represent
veryexpensivemethodsthatmustfindtheirplaceindiagnosisandprognos-
ticevaluation.Geneprofilingstudieshavealreadyconfirmedmorphological
subtypes in AML, e.g., M3 and M3V, which cannot be distinguished into
strictly separate groups by cytogenetic and molecular-genetic methods.
Newtherapeuticmeasures(especiallyimmunotherapy)havebroughtinter-
esting progress into the MDS group. For example, the biological entity 5q
minussyndrome,whichiswelldefinedbymorphologyandcytogenetics,re-
spondsverywelltotreatmentwiththethalidomidederivativeCC5013.The
fusion gene BCR-ABL, which was originally detected by cytogenesis and is
todayroutinelydetectedbyFISHorPCRinCML,wasthefirstexampleofa
specificallytailoredmoleculartherapyinatumor;certainlyotherexamples
willfollow.CasesofALLinvolvingt(9;22),t(4;11)andt(8;14)havealsobeen
establishedasseparateprognosticgroupswithspecialtherapeuticproblems.
Alloftheseexamplesdemonstratethatacomprehensivearsenalofdiag-
nosticmethodshastobeusedtodayfordiagnosticandprognosticdecisions
and individualized therapeutic planning.
WeareagaingratefultoProf.Dr.R.DiskoofMunichwhoagreedtorevise
andupdatethechapterontheprincipalcausativeagentsoftropicaldiseases.
FinallywewishtothankMrs.StephanieBenkoandtheentirestaffofSpring-
er-VerlaginHeidelbergaswellasMs.MarinaLittereratProEditGmbHfor
their thoughtful and effective support.
VII
Preface to the Fifth Edition
ThefirsteditionoftheAtlasofClinicalHematologywaspublishedover40
years ago. The first four editions were coauthored by Herbert Begemann,
whodiedunexpectedlyinAprilof1994.Wewishtodedicatethefifthedition
as a memorial to this dedicated physician and hematologist.
Sincethefourtheditionwaspublishedin1987,hematologyhasundergone
profoundchanges.Newmethodssuchascytochemistryandimmunopheno-
typing have been joined by cytogenetics and, more recently, molecular ge-
netictechniques,whichhaveassumedamajorroleinroutinediagnosticpro-
cedures. This has been due in part to significant advances in methodology
and new tools in molecular biology. When used in standardized protocols,
thesetoolscanfurnishswiftresultsthatarerelevanttopatientcare.Sincethe
adventofcytogeneticsandmoleculargenetics,wehaveformulatednewde-
finitionsforclinicalandbiologicalentities.Anexampleispromyelocyticleu-
kemiawithitstwovariants(M3andM3v),the(15;17)translocation,andthe
PML/RARAfusiongene,whichhasbeensuccessfullytreatedforthefirsttime
withdifferentiationtherapy.Anotherexampleisacutemyelomonocyticleu-
kemia with abnormal eosinophiles (M4Eo), inversion 16, and the MYH/11/
CBFB fusion gene, which has a very good prognosis. The transmission of
morphologicfindingsbyelectronicdatatransferisalsogainingimportance
in hematology, as it permits the immediate review of difficult findings by
specialists. Several colleagues seated at their own desks and microscopes
can communicate with one another instantaneously by computer monitor.
These advances do not alter the fact that hematologists must still have a
sound grasp of morphologic principles. Diagnostic problems often arise
when modern counting devices and cell sorters, with their impressive cap-
abilities,areusedwithoutregardforcellularmorphology.Thereisnoques-
tion that classical morphology has gained much from its competition and
comparison with the new techniques, leading to significant diagnostic
and prognostic advances.
While retaining the basic concept of the previous editions, we found it
necessarytoeliminateseveralchapters.Nowthatmanyhematologiccenters
and laboratories are equipped with fluorescence-activated cell sorters
(FACS)forimmunotyping,andgiventheavailabilityofreliablecommercial
kitsandprecisestaininginstructionsforimmunocytochemistry,thechapter
by B. R. Kranz has been omitted from the present edition. We have also
droppedthemethodologysectionandmostoftheelectronmicrographssup-
pliedbyProf.D.Huhn.Bothcolleaguesmeritoursincerethanks.Eversince
the first edition, Prof. W. Mohr of Hamburg has authored the chapter on
blood parasites as the principal causative agents of tropical diseases, and
we gratefully acknowledge his contribution. Following the death of Prof.
Mohr, we have chosen to include this chapter owing to the special impor-
tance of tropical diseases in the modern world. We are grateful to Prof. R.
Disko of Munich, who agreed to revise and update the chapter.
Thechaptersonchronicmyeloproliferativediseases,andespeciallythose
dealing with myelodysplasias, acute leukemias, malignant lymphomas, and
malignantmastocytoses,hadtobeextensivelyrevisedorrewritten.Wehave
added new sections and illustrations on therapy-induced bone marrow
changes,cytologicchangesinthecerebrospinalfluidduetoleukemicorlym-
VVIIIIII PrefacetotheFifthEdition
phomatous meningeal involvement, and NK cell neoplasias. We have also
endeavored to give due attention to issues in pediatric hematology.
Incompilingthisrevisedfifthedition,inwhichover90%oftheillustra-
tionsarenew,webenefitedgreatlyfromourtwodecadesofcentralmorpho-
logicaldiagnosticsfortheALLandAMLstudiesinadultsandthemorpho-
logical consulting of the BFM treatment study on AML in children (H. L.).
Wethankthedirectorsofthesestudies,ProfessorsD.Hoelzer,T.Bu¨chner,U.
Creutzig,andJ.Ritter,fortheirconsistentlyfinecooperation.Wealsothank
theInstituteofPathologyoftheUniversityofKiel,headedbyProf.KarlLen-
nert, and the current head of the Department of Hematologic Pathology,
Prof. Reza Parwaresch, for preparing histologic sections of the tissue cores
that we submitted.
Acknowledgements
WeareindebtedtoProf.BrigitteSchlegelberger,Prof.WernerGrote(direc-
toroftheInstituteofHumanGenetics,UniversityofKiel),Dr.Harder,and
Mr. Blohm for providing the cytogenetic findings and schematic drawings.
Welimitedourattentiontoimportantfindingsthathavebearingonthedia-
gnosis or confirmation of a particular entity.
A work of this magnitude cannot be completed without assistance. My
secretaryofmanyyears,Mrs.UteRosburg,oftenfreedmefromdistracting
tasks so that I could gain essential time. Mrs. Margot Ulrich efficiently or-
ganizedtheprocessingofthephotographicmaterials,whileMrs.Ramm-Pe-
tersen,Mrs.Meder,andMrs.Tetzlaffweremeticulousintheirperformance
ofcytologic,cytochemical,andimmunocytochemicalmethodologies.Myse-
nior staff members in Kiel, Prof. Winfried Gassmann and Dr. Torsten Ha-
ferlach, helped with the examination and evaluation of many of the speci-
menspicturedintheAtlas.MycolleagueDr.Haferlachcollaboratedwiththe
study group of Prof. Schlegelberger to introduce the FISH technique into
routineclinicaluse.Finally,wethankMrs.MonikaSchrimpfandtheentire
staff at Springer-Verlag in Heidelberg as well as Ms. Judith Diemer at PRO
EDIT GmbH for their thoughtful and effective support.
St. Peter and Munich Helmut Lo¨ffler · Johann Rastetter
Summer 1999
IX
Preface to the First Edition
So far the diagnostic advances of smear cytology have found only limited
applicationsinmedicalpractice.Thisisduelargelytothefactthatavailable
illustrativematerialshavebeentoostylizedtogivethenovicearealisticin-
troductiontothefield.Inthepresentatlasweattempttocorrectthissitua-
tionbyportrayingthegreatmorphologicvarietythatcanexistinindividual
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
colorphotos,thoughmuchpraised,isinherentlyquestionableandisfurther
degraded by the process of chemographic reproduction. An even greater
drawback of photomicrographs is their inability to depict more than one
planeofsectioninsharpdetail.Bycontrast,apersonlookingthroughami-
croscopewilltendtomakecontinualfineadjustmentstofocusthroughmul-
tiple planes and thus gain an impression of depth. A drawing can recreate
thisimpressionmuchbetterthanaphotographandsomorecloselyapprox-
imatesthesubjectiveobservation.Wehaveavoideddepictingcellsinblack
and white; while there is merit in the recommendation of histologists that
students’ attention be directed toward structure rather than color, this is
rarelypracticableinthecytologicexaminationofsmears.Thestainingmeth-
ods adopted from hematology still form the basis for staining in smear cy-
tology. For this reason most of the preparations shown in this atlas were
stainedwithPappenheim’spanopticstain.Wherenecessary,variousspecial
stainswereadditionallyused.Forclaritywehaveplacedpositionaldrawings
alongside plates that illustrate many different cell types, and we have used
arrowstopointoutparticularcellsinfilmsthataremorecytologicallyuni-
form.
Weweremostfortunatetohaveourcolorplatesdrawnbyanartist,Hans
Dettelbacher,in whom thefacultiesof scientificobservation,technical pre-
cision,andartistic grasparecombinedinbrilliant fashion.Weexpressour
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
helpandspecimens,especiallyProf.Dr.HenningandDr.WitteofErlangen,
Dr.LangrederofMainz,Prof.Dr.MohroftheTropicalInstituteofHamburg,
Dr.MoeschlinofZurich,Dr.UndritzofBasel,andDr.KuhnofourFreiburg
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 Felner-Kraus of Santiago de Chile for the Spanish
text.Wemustnotfailtoacknowledgethehelpprovidedbythescientificand
technicalcolleaguesatourhematologylaboratory,especiallyMrs.Hildegard
TrappeandMrs.WaltraudWolf-Loffler.Finally,weexpressourappreciation
toSpringerVerlag,whofirstproposedthatthisatlasbecreatedandtookthe
steps necessary to ensure its technical excellence.
Freiburg, Spring 1955 Ludwig Heilmayer · Herbert Begemann
XI
Contents
Methodology
I Techniques of Specimen Collection and Preparation 3
Blood Smear 4
Bone Marrow 4
Fine-Needle Aspiration of Lymph Nodes and Tumors 5
Splenic Aspiration 6
ConcentratingLeukocytesfromPeripheralBloodinLeukocytopenia 6
Demonstration of Sickle Cells 6
II Light Microscopic Procedures 7
1 Staining Methods for the Morphologic and Cytochemical
Differentiation of Cells 8
1.1 Pappenheim’s Stain (Panoptic Stain) 8
1.2 Undritz Toluidine Blue Stain for Basophils 8
1.3 Mayer’s Acid Hemalum Nuclear Stain 8
1.4 Heilmeyer’s Reticulocyte Stain 8
1.5 Heinz Body Test of Beutler 8
1.6 Nile Blue Sulfate Stain 9
1.7 Kleihauer-Betke Stain for Demonstrating Fetal Hemoglobin
in Red Blood Cells 9
1.8 Kleihauer-Betke Stain for Demonstrating Methemoglobin-
Containing Cells in Blood Smears 10
1.9 Berlin Blue Iron Stain 10
1.10 Cytochemical Determination of Glycogen in Blood Cells
by the Periodic Acid Schiff Reaction and Diastase Test
(PAS Reaction) 11
1.11 Sudan Black B Stain 13
1.12 Cytochemical Determination of Peroxidase 13
1.13 Hydrolases 13
1.14 Appendix 16
XXIIII Contents
2 Immunocytochemical Detection of Cell-Surface and Intracellular
Antigens 18
3 Staining Methods for the Detection of Blood Parasites 19
3.1 “Thick Smear” Method 19
3.2 Bartonellosis 19
3.3 Detection of Blood Parasites in Bone Marrow Smears 19
3.4 Toxoplasmosis 19
3.5 Microfiliariasis 19
3.6 Mycobacterium Species (M. tuberculosis, M. leprae) 19
Illustrations
III Overview of Cells in the Blood, Bone Marrow,
and Lymph Nodes 23
IV Blood and Bone Marrow 27
4 Individual Cells 28
4.1 Light Microscopic Morphology and Cytochemistry 28
5 Bone Marrow 67
5.1 Composition of Normal Bone Marrow 69
5.2 Disturbances of Erythropoiesis 80
5.3 Reactive Blood and Bone Marrow Changes 107
5.4 Bone Marrow Aplasias (Panmyelopathies) 118
5.5 Storage Diseases 122
5.6 Hemophagocytic Syndromes 129
5.7 Histiocytosis X 132
5.8 Chronic Myeloproliferative Disorders (CMPD) 134
5.9 Myelodysplastic Syndromes (MDS) 158
5.10 Acute Leukemias 170
5.11 Neoplasias of Tissue Mast Cells (Malignant Mastocytoses) 286
V Lymph Nodes and Spleen 293
6. Cytology of Lymph Node and Splenic Aspirates 294
6.1 Reactive Lymph Node Hyperplasia 295
6.2 Infectious Mononucleosis 304
6.3 Persistent Polyclonal B Lymphocytosis 307
6.4 Malignant Non-Hodgkin Lymphomas
and Hodgkin Lymphoma 308