Practical Diagnosis of Hematologic Disorders. Vol 2 Malignant Disorders

Transcription

1 5 th ed Practical Diagnosis of Hematologic Disorders Vol 2 Malignant Disorders Vol2_FrontMatter_v03_0804 final.indd i 8/6/ :00:11 PM

2 Authors Carl R Kjeldsberg, MD Professor of Pathology, University of Utah Health Sciences Center Chairman of the Board, ARUP Laboratories, Inc Sherrie L Perkins, MD, PhD Professor of Pathology, University of Utah Health Sciences Center Chief Medical Officer, Director of Laboratories, Medical Director of Hematopathology, ARUP Laboratories, In John Anastasi, MD Associate Professor, Associate Director Hematopathology Department of Pathology University of Chicago Medical Center Daniel A Arber, MD Professor and Associate Chair of Pathology for Clinical Services Stanford University David W Bahler, MD, PhD Associate Professor of Pathology, University of Utah Director, Hematologic Flow Cytometry Laboratory, ARUP Laboratories, Inc Robert C Blaylock, MD Professor of Pathology, Medical Director of University Hospital Transfusion Services and ARUP Blood Services Medical Director of the Immunohematology Reference Laboratory, ARUP Laboratories, Inc Co-Director of University Hospital Clinical Laboratories Kojo S J Elenitoba-Johnson, MD Professor of Pathology, Director of Division of Translational Research Director of Molecular Diagnostics Laboratory Director, Molecular Genetic Pathology Program University of Michigan Kathryn Foucar, MD Professor of Pathology, Vice Chair for Clinical Affairs University of New Mexico Health Sciences Center and TriCore Reference Laboratories Clinical Assistant Professor, Department of Pathology Stanford University Megan S Lim, MD, PhD Associate Professor of Pathology, Director of Hematopathology Director, Hematopathology Fellowship Training Program University of Michigan Robert W McKenna, MD Professor and Vice Chair for Academic Affairs Senior Consultant in Hematopathology, Department of Laboratory Medicine and Pathology Richard D Brunning Professor of Laboratory Medicine and Pathology University of Minnesota LoAnn C Peterson, MD Paul E Steiner Research Professor of Pathology, Feinberg Medical School Northwestern University, Northwestern Memorial Hospital George M Rodgers, MD, PhD Professor of Medicine and Pathology, University of Utah Health Sciences Center Medical Director, Coagulation Laboratory, ARUP Laboratories, Inc Mohamed E Salama, MD Assistant Professor of Pathology, University of Utah Health Sciences Center Assistant Medical Director, Hematopathology, ARUP Laboratories, Inc James W Vardiman, MD Professor of Pathology University of Chicago Medical Center Vol2_FrontMatter_v03_0804 final.indd ii 8/6/ :00:18 PM

3 Practical Diagnosis of Hematologic Disorders 5th Edition Vol 2 Malignant Disorders Carl R Kjeldsberg, MD Sherrie L Perkins, MD, PhD Editors et xiii alia ASCP Press American Society for Clinical Pathology Chicago, IL Vol2_FrontMatter_v03_0804 final.indd iii 8/6/ :00:19 PM

4 Publishing Team Erik Tanck (production/designer) Joshua Weikersheimer (publishing direction) Notice Trade names and equipment and supplies described herein are included as suggestions only. In no way does their inclusion constitute an endorsement or preferences by the American Society for Clinical Pathology. The ASCP did not test the equipment, supplies, or procedures and, therefore, urges all readers to read and follow all manufacturers instructions and package insert warnings concerning the proper and safe use of products. Copyright 2010 by the American Society for Clinical Pathology. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher. Printed in Singapore Vol2_FrontMatter_v03_0804 final.indd iv 8/6/ :00:19 PM

5 CONTENTS Vol 2 Malignant Disorders Preface xiii Acknowledgments xiv Part IX Myeloid Neoplasms MYELOPROLIFERATIVE NEOPLASMS 35. Chronic Myelogenous Leukemia, BCR-ABL John Anastasi, MD 36. Chronic Neutrophilic Leukemia 443 John Anastasi, MD 37. Polycythemia Vera 449 John Anastasi, MD 38. Primary Myelofibrosis 467 John Anastasi, MD 39. Essential Thrombocythemia 487 John Anastasi, MD 40. Chronic Eosinophilic Leukemia, NOS 501 Sherrie Perkins, MD, PhD Mohamed Salama, MD 41. Mastocytosis 509 Megan S Lim, MD, PhD 42. Myeloproliferative Neoplasms, Unclassifiable 521 John Anastasi, MD v Vol2_FrontMatter_v03_0804 final.indd v 8/6/ :00:19 PM

6 Practical Diagnosis of Hematologic Disorders MYELOID AND LYMPHOID NEOPLASMS WITH EOSINOPHILIA AND ABNORMALITIES OF PDGFRA, PDGFRB OR FGFR1 43. Myeloid and Lymphoid Neoplasms With Eosinophilia and Abnormalities of PDGFRA, PDGFRB or FGFR1 Mohamed Salama, MD Sherrie Perkins, MD, PhD 44. Myelodysplastic/Myeloproliferative Neoplasms 535 Sherrie Perkins, MD, PhD MYELODYSPLASTIC SYNDROMES 45. Myelodysplastic Syndromes 547 Sherrie L Perkins, MD, PhD Robert W McKenna, MD Part X Acute Myeloid Leukemias ACUTE MYELOID LEUKEMIA AND RELATED PRECURSOR NEOPLASMS 46. Acute Myeloid Leukemia With Recurrent Genetic Abnormalities 585 Daniel A. Arber, MD 47. Acute Myeloid Leukemia With Myelodysplasia-Related Changes and Therapy-Related Myeloid Neoplasms 615 Daniel A Arber, MD 48. Acute Myeloid Leukemia, NOS 621 Daniel A Arber, MD 49. Myeloid Sarcoma 633 Daniel A Arber, MD 50. Myeloid Proliferations Related to Down Syndrome 639 Daniel A Arber, MD 51. Blastic Plasmacytoid Dendritic Cell Neoplasm 645 Daniel A Arber, MD vi Vol2_FrontMatter_v03_0804 final.indd vi 8/6/ :00:19 PM

7 Contents 52. Acute Leukemias of Ambiguous Lineage 653 Daniel A Arber, MD Part XI Lymphoid Neoplasms 53. Introduction to Non-Hodgkin Lymphoma 661 Kojo SJ Elenitoba-Johnson, MD Megan S Lim, MD, PhD Carl Kjeldsberg, MD Part XII Precursor Lymphoid Neoplasms 54. Precursor Lymphoid Neoplasms 691 Sherrie L Perkins MD, PhD Robert McKenna, MD Part XIII Mature B-Cell, T-Cell and Histiocytic Neoplasms MATURE B-CELL NEOPLASMS 55. Mature B-Cell Neoplasms With Leukemic Manifestations 723 LoAnn Peterson, MD 56. Mature B-Cell Neoplasms With Plasma Cell or Plasmacytoid Differentiation 747 LoAnn Peterson, MD 57. Mature B-Cell Neoplasms With Primary Tissue Manifestations 769 Kojo S J Elenitoba-Johnson, MD Megan S Lim, MD Carl Kjeldsberg, MD MATURE T-CELL AND NK-CELL NEOPLASMS 58. Mature T-Cell and NK-Cell Neoplasms 805 Kojo S J Elenitoba-Johnson, MD Megan S Lim, MD Carl Kjeldsberg, MD vii Vol2_FrontMatter_v03_0804 final.indd vii 8/6/ :00:20 PM

8 Practical Diagnosis of Hematologic Disorders HODGKIN LYMPHOMA 59. Hodgkin Lymphoma 835 Carl Kjeldsberg, MD Kojo S J Elenitoba-Johnson, MD HISTIOCYTIC AND DENDRITIC CELL NEOPLASMS 60. Histiocytic and Dendritic Cell Neoplasms 853 Megan S Lim, MD, PhD POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS 61. Post-Transplant Lymphoproliferative Disorders 865 Megan S Lim, MD, PhD Part XIV Part XIV Special Techniques 62. Molecular Techniques in the Diagnosis of Hematologic Malignancies 879 Kojo S J Elenitoba-Johnson, MD 63. Flow Cytometric Analysis 899 David Bahler, MD, PhD Appendix Appendix: Hematology Reference Values 919 Index p index 2.1 and following viii Vol2_FrontMatter_v03_0804 final.indd viii 8/6/ :00:20 PM

9 Contents List of Tables Ch 35. Chronic Myelogenous Leukemia, BCR-ABL1+ t35.1 Features of Chronic Myelogenous Leukemia BCR-ABL1+, Chronic Phase 424 t35.2 WHO Critieria for Chronic Myelogeneous Leukemia, Accelerated Phase 428 t35.3 CML, Blast Phase 428 t35.4 Distinguishing Features Among the Chronic Myeloid Leukemias 436 t35.5 Summary of Features of Chronic Neutrophilic Leukemia (CNL) 437 Ch 37. Polycythemia Vera t37.1 Stages and Associated Features in Polycythemia Vera 449 t37.2 Classification of Polycythemia 452 t37.3 WHO Recommended Criteria for the Diagnosis of Polycythemia Vera 456 t37.4 Comparison of Findings in Polycythemia Vera and Secondary Erythrocytosis 457 Ch 38. Primary Myelofibrosis t38.1 Causes of Bone Marrow Fibrosis 468 t38.2 Major Clinical and Laboratory Features in PMF 470 t38.3 WHO Diagnostic Criteria for Primary Myelofibrosis 471 t38.4 Myeloid Disorders With Myelofibrosis 482 t38.5 Comparison of Usual Findings in Polycythemia Vera-Polycythemic Phase, PMF-Prefibrotic Stage, and Essential Thrombocythemia 482 Ch 39. Essential Thrombocythemia t39.1 Causes of Marked Thrombocytosis 487 t39.2 Features Helpful in Distinguishing Essential Thrombocythemia 489 and Secondary Thrombocytosis t39.3 Revised WHO (2008) Diagnostic Criteria for the Diagnosis 490 of Essential Thrombocythemia t39.4 Morphologic Features of ET 491 t39.5 Comparison of Features of Essential Thrombocythemia With Other Chronic Myeloproliferative Disorders 495 Ch 40. Chronic Eosinophilic Leukemia, NOS t40.1 Diagnostic Criteria of Chronic Eosinophilic Leukemia, NOS 502 t40.2 Systemic Involvement by Chronic Eosinophilic Leukemia, NOS 503 t40.3 Differential Diagnostic Consideration for Persistent Eosinophilia 506 Ch 41. Mastocytosis t41.1 Classification of Mast Cell Disease 510 (Adapted From World Health Organization Criteria) t41.2 Major and Minor Diagnostic Criteria for Systemic Mastocytosis 514 t41.3 Comparison of Immunophenotypes of Mast Cells and Closely Related Cell Types 519 Ch 42. Myeloproliferative Neoplasms, Unclassifiable t42.1 Situations in Which a Diagnosis of Myeloproliferative Neoplasm-Unclassifiable Can Be Considered 522 Ch 43. Myeloid and Lymphoid Neoplasms With Eosinophilia and Abnormalities of PDGFRA, PDGFRB or FGFR1 t43.1 Fusion Partners of PDGFRB and Related Cytogenetic Defects 530 Occurring in Myeloid Neoplasms Presenting With Eosinophilia t43.2 FGFR1 Gene Fusion Partners 533 ix Vol2_FrontMatter_v03_0804 final.indd ix 8/6/ :00:21 PM

10 Practical Diagnosis of Hematologic Disorders Ch 44. Myelodysplastic/Myeloproliferative Neoplasms t44.1 Features Distinguishing Myelodysplastic Syndrome (MDS) 535 from Myeloproliferative Neoplasms (MPN) t44.2 WHO Classification of Myelodysplastic/Myeloproliferative Neoplasms 535 t44.3 Diagnostic Criteria for Chronic Myelomonocytic Leukemia 536 t44.4 Diagnostic Criteria for Atypical Chronic Myeloid Leukemia, BCR-ABL1 (acml) 540 t44.5 Comparison of Chronic Myelogenous Leukemia (CML) and Atypical Chronic Myelogenous Leukemia (acml) 541 t44.6 Diagnostic Criteria of Juvenile Myelomonocytic Leukemia 543 t44.7 Diagnostic Criteria for Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable (MDS/MPN, U) 545 Ch 45. Myelodysplastic Syndromes t45.1 International Prognostic Scoring System (IPSS) Thresholds 548 for Cytopenias in the Diagnosis of Myelodysplastic Syndromes t45.2 WHO Classification of MDS 549 t45.3 Hematologic Findings in Myelodysplastic Syndromes 549 t45.4 Morphologic Abnormalities in Myelodysplastic Syndromes 551 t45.5 Recurrent Cytogenetic Abnormalities in Myelodysplastic Syndromes 559 t45.6 International Prognostic Scoring System (IPSS) for Myelodysplastic Syndromes 561 t45.7 Chromosome Abnormalities Seen in MDS and Candidate Genes Affected 561 t45.8 Immunophenotypic Abnormalities Observed in Myelodysplastic Syndromes 562 t45.9 Peripheral Blood and Bone Marrow Findings in Myelodysplastic Syndromes 564 t45.10 Refractory Anemia (RA) 566 t45.11 Refractory Anemia With Ringed Sideroblasts (RARS) 569 t45.12 Refractory Cytopenia With Multilineage Dysplasia (RCMD) 570 t45.13 Refractory Anemia With Excess Blasts (RAEB) 572 t45.14 Myelodysplastic Syndrome With Isolated del(5q) 573 t45.15 Pediatric MDS 574 t45.16 WHO Minimal Diagnostic Criteria for Refractory Cytopenia of Childhood 575 t45.17 Comparison of Morphological Criteria of Hypoplastic Refractory Cytopenia 576 of Childhood and Aplastic Anemia t45.18 Differential Diagnostic Considerations in Myelodysplastic Syndromes 577 t45.19 Survival, Prognosis and Evolution to AML in Adult Patients with MDS 579 t45.20 Indicators of Good and Poor Prognosis in Myelodysplastic Syndromes 580 Ch 46. Acute Myeloid Leukemia (AML) With Recurrent Genetic Abnormalities t46.1 French-American-British (FAB) Classification Morphologic Categories of AML 586 t46.2 WHO 2008 Classification of Acute Myeloid Leukemia 586 t46.3 Cytologic Features of Blasts in Acute Myeloid and Acute Lymphoblastic Leukemias 587 t46.4 Cytochemical Stains and Their Utility 588 t46.5 Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group 590 for Clinical Cancer Research Composite Prognostic Index for Adult AML (age <60) t46.6 Common Variant Translocations of APL 600 t46.7 Common MLL Fusion Transcripts in AML 602 Ch 47. AML With Myelodysplasia-Related Changes and Therapy-Related Myeloid Neoplasms t47.1 Criteria for Diagnosis of AML With Myelodysplasia-Related Changes 616 Ch 48. AML, NOS t48.1 Differential Diagnosis of Acute Basophilic Leukemia (ABL) 630 Ch 49. Myeloid Sarcoma t49.1 Characteristics of Adult vs Pediatric Myeloid Sarcoma 635 x Vol2_FrontMatter_v03_0804 final.indd x 8/6/ :00:21 PM

11 Contents Ch 51. Blastic Plasmacytoid Dendritic Cell Neoplasm t51.1 Immunophenotypic Overlap Between Blastic Plasmacytoid Dendritic Cell Neoplasm 650 and Cases of Cutaneous Involvement by Acute Myeloid Leukemia t51.2 Distinguishing Blastic Plasmacytoid Dendritic Cell Neoplasm From CD56+ True NK-Cell, NK/T-Cell and γ/δ T-Cell Lymphoma/Leukemias 651 Ch 53. Introduction to Non-Hodgkin Lymphoma t53.1 Cytogenetic and Molecular Abnormalities in Non-Hodgkin Lymphoma 662 t53.2 Predisposing Conditions and Factors in the Development 663 of Non-Hodgkin Lymphoma t53.3 Comparison of Non-Hodgkin and Hodgkin Lymphomas 664 t53.4 Stages of Lymphoma 664 t53.5 National Cancer Institute Modified Staging for Intermediate- 664 and High-Grade Lymphomas t53.6 Staging Procedures for Non-Hodgkin Lymphoma 665 t53.7 Principles of Classification of Non-Hodgkin Lymphoma 666 t53.8 Mature Neoplasms 667 t53.9 Major Antibodies Used in Immunophenotyping of Malignant Lymphomas in Paraffin Sections t53.10 Application of Immunophenotypic Analysis 679 t53.11 Undifferentiated Large Neoplasm Antibody Panel for Paraffin Sections 679 t53.12 Immunophenotyping of Non-Hodgkin and Hodgkin Lymphomas 679 in Paraffin Sections t53.13 Comparison of Non-Hodgkin Lymphoma Features in Children and Adults 681 t53.14 Classification of Non-Hodgkin Lymphoma in Children 681 t53.15 Comparison of Morphologic and Immunophenotypic Features 682 in Childhood Non-Hodgkin Lymphomas t53.16 Causes of Lymph Node Enlargement Simulating Malignant Lymphoma 682 t53.17 International Prognostic Index of Parameters and Relative Risk 683 t53.18 International Prognostic Index: The International Index and Age-Adjusted Index 683 t53.19 Histopathology and Prognosis in Non-Hodgkin Lymphomas 684 t53.20 Cellular Prognostic in Non-Hodgkin Lymphomas 684 t53.21 Checklist for the Reporting of Lymphoid Neoplasms 685 t53.22 New Therapeutic Agents in Malignant Lymphoma 687 Ch 54. Precursor Lymphoid Neoplasms t54.1 WHO Classification of Acute Lymphoblastic Leukemia/Lymphoma 692 t54.2 Frequency of Clinical and Laboratory Findings at Diagnosis 693 in Children and Adults with ALL t54.3 Characteristic Clinical Features of Precursor T-ALL 693 t54.4 Distribution of White Cell Counts at Diagnosis 694 t54.5 FAB Morphologic Classification of Lymphoblasts 696 t54.6 Common Antigen Expression Patterns of Acute Lymphoblastic Leukemias/ Lymphoblastic Lymphomas 703 t54.7 Distribution of Immunophenotypic Subtypes in Acute Lymphoblastic Leukemia 703 t54.8 Correlation of Prognosis with Bone Marrow Cytogenetic Findings in ALL 707 t54.9 Cytogenetic Translocations Associated With Specific Molecular Genetic Abnormalities in ALL 711 t54.10 Most Significant Prognostic Indicators in Pediatric ALL 717 t54.11 Adverse Prognostic Factors in Adult and Pediatric ALL 717 Ch 55. Mature B-Cell Neoplasms With Leukemic Manifestations t55.1 Mature B-Cell Neoplasms With Leukemic Manifestations 723 t55.2 Rai Clinical Staging System for Chronic Lymphocytic Leukemia 724 t55.3 Binet Staging System for Chronic Lymphocytic Leukemia 724 t55.4 Typical Phenotypes of B-Cell Chronic Lymphoid Leukemias and Lymphomas 730 xi Vol2_FrontMatter_v03_0804 final.indd xi 8/6/ :00:22 PM

12 Practical Diagnosis of Hematologic Disorders Ch 56. Mature B-Cell Neoplasms With Plasma Cell or Plasmacytoid Differentiation t56.1 Mature B-Cell Neoplasms With Plasma Cell or Plasmacytoid Differentiation 747 t56.2 Monoclonal Immunoglobulins in Mature B-Cell Neoplasms 748 With Plasma Cell Differentiation t56.3 Approximate Incidence of Monoclonal Gammopathies in the United States 749 t56.4 Diagnostic Criteria for Monoclonal Gammopathy of Undetermined Significance 749 t56.5 Course of 241 Patients With Monoclonal Gammopathy 750 of Undetermined Significance t56.6 Diagnostic Criteria for Plasma Cell Myeloma 751 Ch 57. Mature B-Cell Neoplasms With Primary Tissue Manifestations t57.1 Mature B-Cell Neoplasms With Primary Tissue Manifestations 769 t57.2 Small Lymphocytic B-Cell Neoplasms: Characteristic Morphologic Features 770 t57.3 Small Lymphocytic B-Cell Neoplasms: Immunophenotypic Features 770 t57.4 Useful Features in the Differential Diagnosis of Mediastinal Lymphomas 794 Ch 58. Mature T-Cell and NK-Cell Neoplasms t58.1 Mature T-Cell and NK-Cell Neoplasms 805 t58.2 Differential Diagnosis of Neoplasms Expressing T-Cell and NK-Cell Markers 810 With Frequent Leukemic Presentation t58.3 Differential Diagnosis of Neoplasms Expressing T-Cell and NK-Cell Markers 825 With Frequent Cutaneous Involvement t58.4 Differential Diagnosis of Nodal Peripheral T-Cell Lymphoma, 827 Not Otherwise Specified t58.5 Characteristics of Variant ALK Translocations 832 Ch 59. Hodgkin Lymphoma t59.1 Staging Procedures in Hodgkin Lymphoma 837 t59.2 The Cotswald Modification of the Ann Arbor Staging Classification 837 for Hodgkin Lymphoma t59.3 World Health Organization (WHO) Classification of Hodgkin Lymphoma 837 t59.4 Immunophenotype Features of RS Cells and L&H Cells 839 t59.5 Differential Diagnosis of Hodgkin Lymphoma 839 t59.6 Immunophenotypic Distinction of Hodgkin Lymphoma From Non-Hodgkin Lymphoma 851 Ch 60. Histiocytic and Dendritic Cell Neoplasms t60.1 Immunophenotypic Features Useful in the Distinction of Macrophages, 854 Langerhans Cells, Dendritic Cells and Lymphocytes t60.2 Clinical Variants of Langerhans Cell Histiocytosis 856 t60.3 Differential Diagnosis of Langerhans Cell Histiocytosis 860 Ch 61. Post-Transplant Lymphoproliferative Disorders t61.1 Comparison of Post-Transplant Lymphoproliferative Disorders 866 Occurring in Solid Organ and Bone Marrow Transplant Patients t61.2 Evaluation for Diagnosis of PTLDs 867 t61.3 General Categories of Post-Transplantation Lymphoproliferative Disorders 868 Ch 62. Molecular Techniques in the Diagnosis of Hematologic Malignancies t62.1 Comparison of Molecular Methods Used in Diagnostic Hematopathology 880 t62.2 Genetic Alterations in Hematologic Malignancies Ch 63. Flow Cytometric Analysis t63.1 Fluorochromes Often Used With 488-nm Wavelength Excitation 900 t63.2 Common Hematopoietic Cell Antigens Evaluated With Flow Immunophenotyping 903 t63.3 Common Antigens Used to Assess Acute Leukemia Blast Lineage by Flow Cytometry 907 t63.4 Characteristic Phenotypic Features Associated with Specific Acute Leukemias 907 t63.5 Typical Immunophenotypes of Mature B-Cell Neoplasms 910 t63.6 Phenotypic Features Associated With Specific Mature T-Cell Neoplasms 913 xii Vol2_FrontMatter_v03_0804 final.indd xii 8/6/ :00:23 PM

13 Preface The goal of this book, beginning with the first edition in 1989, has been to provide an up-todate, concise source of guidelines to the selection, use and interpretation of laboratory tests, while at the same time providing an overview of the pathogenesis and clinical features of the most common hematologic disorders. Though the size and scope of this book have increased considerably, keeping pace with the expansion of the knowledge and diagnostic complexity in hematopathology, the focus on providing practical information has not changed. Each chapter follows a practical format to make finding specific information easy. This fifth edition contains substantial new information, particularly with regard to molecular modalities and utilization of ancillary testing in the diagnosis of hematologic disorders. The new edition uses the framework of the 2008 WHO classification for malignancies, and provides up-to-date diagnostic approaches, correct usage of laboratory testing, and algorithms for diagnosis of both benign and malignant disorders. We hope that this newest edition will be an even more valuable tool and resource for a broad audience, including pathologists, residents and fellows in pathology and medicine, hematologists/ oncologists, internists, pediatricians, medical students and medical technologists, as well as for those preparing for board examinations in pathology and internal medicine. We welcome your comments or suggestions for future editions and trust that this book will provide the quality information and education you ve come to expect. xiii Vol2_FrontMatter_v03_0804 final.indd xiii 8/6/ :00:23 PM

14 Acknowledgements We wish to express our appreciation to Joshua Weikersheimer of the ASCP Press, for his assistance in all aspects of publication, and to Susan Flinders for administrative assistance. We want to also thank our colleagues in the Department of Pathology at the University of Utah, and the staff at ARUP Laboratories for their support. Present and former hematopathology fellows have provided much inspiration Most of all, we are grateful for the support and love from our families, Gillean, Tanya, Kristina, Don, Rachel and Jessica. xiv Vol2_FrontMatter_v03_0804 final.indd xiv 8/6/ :00:23 PM