Pocket Guide to Diagnostic

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S. David Hudnall
Melissa A. Much
Alexa J. Siddon

Pocket Guide
to Diagnostic
Hematopathology

123
Pocket Guide to Diagnostic
Hematopathology
S. David Hudnall • Melissa A. Much
Alexa J. Siddon

Pocket Guide
to Diagnostic
Hematopathology
S. David Hudnall Melissa A. Much
Professor of Pathology and Department of Pathology
Laboratory Medicine Yale School of Medicine
Yale School of Medicine New Haven, CT
New Haven, CT USA
USA
Alexa J. Siddon
Department of Laboratory
Medicine
Yale School of Medicine
New Haven, CT
USA

ISBN 978-3-030-10628-7    ISBN 978-3-030-10630-0 (eBook)

https://doi.org/10.1007/978-3-030-10630-0

© Springer Nature Switzerland AG 2019

This work is subject to copyright. All rights are reserved by the Publisher, whether
the whole or part of the material is concerned, specifically the rights of transla-
tion, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on
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and retrieval, electronic adaptation, computer software, or by similar or dissimi-
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The use of general descriptive names, registered names, trademarks, service
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statement, that such names are exempt from the relevant protective laws and
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regard to jurisdictional claims in published maps and institutional affiliations.

This Springer imprint is published by the registered company Springer

Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Preface

With the rapid advances in molecular diagnosis, the field of

diagnostic hematopathology has become increasingly com-
plex. This complexity is reflected in the increasing girth of the
standard WHO classification Blue Book. Over a 10-year
period (2007–2017), the WHO Blue Book1 has grown from
335 to 452 pages of text—an increase of 117 pages. This com-
plexity has made it all the more challenging to apply this vast
wealth of information to our cases in a timely fashion. To
address this issue, three hematopathology faculty at Yale
School of Medicine have collaborated in preparing this
pocket guide to diagnostic hematopathology.
The Pocket Guide to Diagnostic Hematopathology is
designed not as a comprehensive textbook, but instead as a
short practical guide to the diagnosis of neoplastic and non-­
neoplastic diseases of blood, bone marrow, and lymphoid
tissues.
Major diagnostic features of each disease entity are out-
lined in a single page of text and accompanied by a single
figure page. This simple format was chosen to provide essen-
tial information that may quickly be reviewed at the micro-
scope. Each entry begins with a one-line Snapshot description,
followed by short descriptions of clinical, morphologic,
immunohistochemical, and genetic features, and ending with
Caveats and Pearls and Differential Diagnosis.

1
Swerdlow SH; International Agency for Research on Cancer; World
Health Organization; et al. WHO classification of tumours of haemato-
poietic and lymphoid tissues. Lyon: International Agency for Research
on Cancer; 2017.
v
vi Preface

For more in-depth reading, several excellent comprehen-

sive texts and recently published review articles are listed in
the reference section.

New Haven, CT, USA S. David Hudnall

 Melissa A. Much
Alexa J. Siddon
Contents

1 Chronic Myeloid Neoplasms. . . . . . . . . . . . . . . . . . . . . . . 1

Chronic Myeloproliferative Neoplasms . . . . . . . . . . . .  1
Chronic Myeloid Leukemia . . . . . . . . . . . . . . . . . . . .  1
Chronic Neutrophilic Leukemia . . . . . . . . . . . . . . . . 7
Polycythemia Vera . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Primary Myelofibrosis . . . . . . . . . . . . . . . . . . . . . . . . 12
Essential Thrombocythemia . . . . . . . . . . . . . . . . . . . 15
Chronic Eosinophilic Leukemia . . . . . . . . . . . . . . . . 19
Myeloproliferative Neoplasm, Unclassifiable . . . . . 21
Myelodysplastic/Myeloproliferative Neoplasms . . . . . 23
Chronic Myelomonocytic Leukemia . . . . . . . . . . . . 23
 Atypical Chronic Myeloid Leukemia,
BCR-ABL1-­Negative . . . . . . . . . . . . . . . . . . . . . . . . . 27
Juvenile Myelomonocytic Leukemia . . . . . . . . . . . . 29
 Myelodysplastic/Myeloproliferative Neoplasm
with Ring Sideroblasts and Thrombocytosis . . . . . . 31
 Myelodysplastic/Myeloproliferative Neoplasm,
Unclassifiable . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Myelodysplastic Syndromes . . . . . . . . . . . . . . . . . . . . . . . 34
 Myelodysplastic Syndrome with Single Lineage
Dysplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
 Myelodysplastic Syndrome with Ring
Sideroblasts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
 Myelodysplastic Syndrome with Multilineage
Dysplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Myelodysplastic Syndrome with Excess Blasts . . . . 42
Myelodysplastic Syndrome with Isolated del(5q) . . 45
Myelodysplastic Syndrome, Unclassifiable . . . . . . . 47
Childhood Myelodysplastic Syndrome . . . . . . . . . . . 48
vii
viii Contents

2 Myeloid Neoplasms with Germline Predisposition. . . . 49

3 Acute Myeloid Leukemia and Related Precursor

Neoplasms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Acute Myeloid Leukemia with Recurrent
Genetic Abnormalities . . . . . . . . . . . . . . . . . . . . . . . . . . .  51
Acute Promyelocytic Leukemia . . . . . . . . . . . . . . . . . . .  53
Acute Myeloid Leukemia with Gene Mutations . . . . .  56
Acute Myeloid Leukemia with
Myelodysplasia-Related Changes . . . . . . . . . . . . . . . . . .  58
Therapy-Related Myeloid Neoplasms . . . . . . . . . . . . . .  60
Acute Myeloid Leukemia with Minimal
Differentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  61
Acute Myeloid Leukemia Without Maturation . . . . . .  62
Acute Myeloid Leukemia with Maturation . . . . . . . . .  64
Acute Myelomonocytic Leukemia . . . . . . . . . . . . . . . . .  65
Acute Monocytic/Monoblastic Leukemia . . . . . . . . . . .  67
Pure Erythroid Leukemia . . . . . . . . . . . . . . . . . . . . . . . .  70
Acute Megakaryoblastic Leukemia . . . . . . . . . . . . . . . .  73
Acute Basophilic Leukemia . . . . . . . . . . . . . . . . . . . . . .  75
Acute Panmyelosis with Myelofibrosis . . . . . . . . . . . . .  76
Myeloid Sarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  78
Myeloid Proliferations Associated
with Down Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . .  80

4 Mastocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Cutaneous Mastocytosis . . . . . . . . . . . . . . . . . . . . . . . . . .  83
Systemic Mastocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . .  85

5 Blastic Plasmacytoid Dendritic Cell Neoplasm . . . . . . . 89

6 Myeloid/Lymphoid Neoplasms with Eosinophilia

and Rearrangement of PDGFRA, PDGFRB,
FGFR1, or with ­PCM1-­JAK2 . . . . . . . . . . . . . . . . . . . . . 93

7 Acute Leukemias of Ambiguous Lineage. . . . . . . . . . . . 97

8 Precursor Lymphoid Neoplasms. . . . . . . . . . . . . . . . . . . . 99

B-Lymphoblastic Leukemia/Lymphoma, NOS . . . . . .  99
B-Lymphoblastic Leukemia/Lymphoma with
Recurrent Genetic Abnormalities . . . . . . . . . . . . . . . . . 102
 Contents ix

BCR-ABL1 Translocation . . . . . . . . . . . . . . . . . . . . . 102

KMT2A Rearrangement . . . . . . . . . . . . . . . . . . . . . . 102
ETV6-RUNX1 Translocation . . . . . . . . . . . . . . . . . . . 102
Hyperdiploidy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
T(5;14) Rearrangement . . . . . . . . . . . . . . . . . . . . . . . 103
T(1;19) Rearrangement . . . . . . . . . . . . . . . . . . . . . . . 103
T-Lymphoblastic Leukemia/Lymphoma . . . . . . . . . . . . 104
NK-Lymphoblastic Leukemia/Lymphoma . . . . . . . . . . 108

9 Mature B-Cell Neoplasms. . . . . . . . . . . . . . . . . . . . . . . . 109

Chronic Lymphocytic Leukemia/Small Lymphocytic
Lymphoma/Monoclonal B-Cell Lymphocytosis . . . . . . 109
B-Cell Prolymphocytic Leukemia . . . . . . . . . . . . . . . . . . 115
Splenic Marginal Zone B-Cell Lymphoma . . . . . . . . . . 117
Hairy Cell Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Primary Splenic B-Cell Lymphoma/Leukemia
(Nonmarginal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
 Splenic Diffuse Red Pulp Small B-Cell
Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
Hairy Cell Leukemia Variant . . . . . . . . . . . . . . . . . . 122
Lymphoplasmacytic Lymphoma . . . . . . . . . . . . . . . . . . . 124
IgM Monoclonal Gammopathy of Undetermined
Significance (IgM MGUS) . . . . . . . . . . . . . . . . . . . . . . . . 127
Non-IgM Monoclonal Gammopathy
of Undetermined Significance . . . . . . . . . . . . . . . . . . . . . 128
Plasma Cell Myeloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Plasmacytoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
Monoclonal Immunoglobulin Deposition Diseases . . . . 135
Plasma Cell Neoplasms with Paraneoplastic
Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
 Plasma Cell Neoplasms with POEMS
Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
 Plasma Cell Neoplasms with TEMPI
Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Extranodal Marginal Zone Lymphoma
of Mucosa-Associated Lymphoid Tissue
(Malt Lymphoma) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Nodal Marginal Zone Lymphoma . . . . . . . . . . . . . . . . . 144
Follicular Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
Large B-Cell Lymphoma with IRF4
Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
x Contents

Primary Cutaneous Follicle Center Lymphoma . . . . . . 153

Mantle Cell Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . 154
Diffuse Large B-Cell Lymphoma (DLBCL), NOS . . . 159
T-Cell/Histiocyte-Rich Large B-Cell Lymphoma . . . . . 164
EBV-Positive Mucocutaneous Ulcer . . . . . . . . . . . . . . . 166
Lymphomatoid Granulomatosis . . . . . . . . . . . . . . . . . . . 167
Primary Mediastinal (Thymic) Large B-Cell
Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Intravascular Large B-Cell Lymphoma . . . . . . . . . . . . . 171
ALK-Positive Large B-Cell Lymphoma . . . . . . . . . . . . 173
Plasmablastic Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . 174
Primary Effusion Lymphoma . . . . . . . . . . . . . . . . . . . . . 177
HHV8-Associated Lymphoproliferative Disorders . . . 179
 Primary Effusion Lymphoma
(see separate entry) . . . . . . . . . . . . . . . . . . . . . . . 179
Burkitt Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
Burkitt-Like Lymphoma with 11q Aberration . . . . . . . 185
High-Grade B-Cell Lymphoma with MYC
and BCL2 and/or BCL6 Rearrangement . . . . . . . . . . . 186
High-Grade B-Cell Lymphoma, NOS . . . . . . . . . . . . . . 188
B-Cell Lymphoma, Unclassifiable, with Features
Intermediate Between DLBCL and Classic
Hodgkin Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189

10 Immunodeficiency-­Associated
Lymphoproliferative Disorders. . . . . . . . . . . . . . . . . . . . 191
Lymphoproliferative Disorders Associated
with Primary Immune Disorders . . . . . . . . . . . . . . . . . . 191
HIV-Associated Lymphomas . . . . . . . . . . . . . . . . . . . . . 193
Post-Transplant Lymphoproliferative
Disorders (PTLD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
Other Iatrogenic Immunodeficiency-­Associated
Lymphoproliferative Disorders . . . . . . . . . . . . . . . . . . . . 197

11 Mature T- and NK-Cell Neoplasms . . . . . . . . . . . . . . . . 199

T-Cell Prolymphocytic Leukemia (T-PLL) . . . . . . . . . . 199
T-Cell Large Granular Lymphocytic Leukemia
(T-LGLL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
Chronic Lymphoproliferative
Disorder of NK-Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
 Contents xi

Aggressive NK-Cell Leukemia . . . . . . . . . . . . . . . . . . . . 208

EBV-Positive T-Cell and NK-Cell
Lymphoproliferative Diseases of Childhood . . . . . . . . . 210
Adult T-Cell Leukemia/Lymphoma (ATLL) . . . . . . . . 213
Extranodal NK-/T-Cell Lymphoma, Nasal Type . . . . . . 215
Intestinal T-Cell Lymphoma . . . . . . . . . . . . . . . . . . . . . . 220
 Enteropathy-Associated
T-Cell Lymphoma (EATL) . . . . . . . . . . . . . . . . . . . . . 220
 Monomorphic Epitheliotropic Intestinal T-Cell
Lymphoma (MEITL) . . . . . . . . . . . . . . . . . . . . . . . . . . 223
Hepatosplenic T-Cell Lymphoma (HSTL) . . . . . . . . . . 225
Subcutaneous Panniculitis-Like T-Cell Lymphoma
(SPTCL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
Mycosis Fungoides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
Sezary Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Primary Cutaneous CD30-Positive T-Cell
Lymphoproliferative Disorders . . . . . . . . . . . . . . . . . . . . 237
Primary Cutaneous T-Cell Lymphomas,
Rare Subtypes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Peripheral T-Cell Lymphoma, NOS (PTCL, NOS) . . . 248
Angioimmunoblastic T-Cell Lymphoma (AITL) . . . . . 252
Anaplastic Large Cell Lymphoma, ALK Positive
(ALCL, ALK+) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
Anaplastic Large Cell Lymphoma, ALK Negative
(ALCL, ALK−) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260
Breast Implant-Associated Anaplastic Large Cell
Lymphoma (iALCL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262

12 Hodgkin Lymphomas. . . . . . . . . . . . . . . . . . . . . . . . . . . . 265

Nodular Lymphocyte Predominant Hodgkin
Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
Classic Hodgkin Lymphoma, Nodular Sclerosis
Variant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
Classic Hodgkin Lymphoma, Lymphocyte-­Rich
Variant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
Classic Hodgkin Lymphoma, Mixed-­Cellularity
Variant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
Classic Hodgkin Lymphoma,
Lymphocyte-­Depleted Variant . . . . . . . . . . . . . . . . . . . . 286
xii Contents

13 Histiocytic and Dendritic Cell Neoplasms. . . . . . . . . . 289

Histiocytic Sarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
Tumors Derived from Langerhans Cells . . . . . . . . . . . . 293
Rare Dendritic Cell Tumors . . . . . . . . . . . . . . . . . . . . . . 297
Follicular Dendritic Cell Sarcoma . . . . . . . . . . . . . . . . . 298
Disseminated Juvenile Xanthogranuloma . . . . . . . . . . . 302
Erdheim-Chester Disease . . . . . . . . . . . . . . . . . . . . . . . . 304

14 Non-neoplastic Marrow Findings����������������������������������� 307

Parvovirus Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307
Cryptococcus Infection . . . . . . . . . . . . . . . . . . . . . . . . . . 309
Histoplasma Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . 312
Leishmania Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
Gaucher Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317
Aplastic Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
Hemophagocytic Lymphohistiocytosis . . . . . . . . . . . . . . 321

15 Non-neoplastic Lymph Node and Spleen Lesions������� 325

Reactive Lymphoid Hyperplasia . . . . . . . . . . . . . . . . . . . 325
Progressive Transformation of Germinal Centers . . . . 326
Sarcoidosis Lymphadenopathy . . . . . . . . . . . . . . . . . . . . 328
Sinus Histiocytosis with Massive Lymphadenopathy
(Rosai-Dorfman Disease) . . . . . . . . . . . . . . . . . . . . . . . . 331
Kikuchi Lymphadenopathy . . . . . . . . . . . . . . . . . . . . . . . 335
Kimura Lymphadenopathy . . . . . . . . . . . . . . . . . . . . . . . 337
Castleman Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
Human Immunodeficiency Virus Lymphadenitis . . . . . 342
Kaposi Lymphadenopathy . . . . . . . . . . . . . . . . . . . . . . . . 344
Epstein-Barr Virus Lymphadenitis . . . . . . . . . . . . . . . . . 346
Cat-Scratch Lymphadenitis . . . . . . . . . . . . . . . . . . . . . . . 349
Toxoplasma Lymphadenitis . . . . . . . . . . . . . . . . . . . . . . . 352
Mycobacterial Lymphadenitis . . . . . . . . . . . . . . . . . . . . . 355
Syphilis Lymphadenitis . . . . . . . . . . . . . . . . . . . . . . . . . . . 357
Lymphogranuloma Venereum Lymphadenitis . . . . . . . 359
Herpes Simplex Virus Lymphadenitis . . . . . . . . . . . . . . 360
Lupus (SLE) Lymphadenopathy . . . . . . . . . . . . . . . . . . 362

Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  363

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
Contributors

S. David Hudnall Professor of Pathology and Laboratory

Medicine, Yale School of Medicine, New Haven, CT, USA
Melissa A. Much Department of Pathology, Yale School of
Medicine, New Haven, CT, USA
Alexa J. Siddon Department of Laboratory Medicine, Yale
School of Medicine, New Haven, CT, USA
Center for Biomedical Data Science, Yale School of Medicine,
New Haven, CT, USA

xiii
Abbreviations

ABC Activated B-cell

ACE Angiotensin converting enzyme
AFB Acid-fast bacilli
AITL Angioimmunoblastic T-cell lymphoma
ALCL Anaplastic large cell lymphoma
ALK Anaplastic lymphoma kinase
ALL Acute lymphoblastic leukemia
AML Acute myeloid leukemia
AMML Acute myelomonocytic leukemia
ANBE Alpha-naphthyl butyrate esterase
APML Acute promyelocytic leukemia
B-ALL B-acute lymphoblastic leukemia
BL Burkitt lymphoma
B-LBL B-lymphoblastic lymphoma
BPDCN Blastic plasmacytoid dendritic cell
neoplasm
CAE Chloroacetate esterase
CHL Classic Hodgkin lymphoma
CLL Chronic lymphocytic leukemia
CM Cutaneous mastocytosis
CML Chronic myeloid leukemia
CMML Chronic myelomonocytic leukemia
CNS Central nervous system
DIC Disseminated intravascular coagulation
DLBCL Diffuse large B-cell lymphoma
EBER ISH EBV-encoded RNA (ribonucleic acid) in
situ hybridization
EBV Epstein-Barr virus (or HHV-4)
EMA Epithelial membrane antigen
xv
xvi Abbreviations

EP Extraosseous plasmacytoma
EPO Erythropoietin
ESR Erythrocyte sedimentation rate
ET Essential thrombocythemia
FDC Follicular dendritic cell
FL Follicular lymphoma
GC Germinal center
G-CSF Granulocyte-colony stimulating factor
GI Gastrointestinal
GMS Grocott-Gomori’s (or Gömöri) methena-
mine silver stain
GSE Gluten-sensitive enteropathy
H&E Hematoxylin and eosin stain
HHV-4 Human herpesvirus-4 (EBV)
HHV-8 Human herpesvirus-8
HL Hodgkin lymphoma
HLH Hemophagocytic lymphohistiocytosis
HPF High power field
HRS Hodgkin/Reed-Sternberg
HSV Herpes simplex virus
HTLV-1 Human T-cell lymphotropic virus type 1
iALCL Breast implant-associated anaplastic large
cell lymphoma
ICUS Idiopathic cytopenia of undetermined
significance
Ig Immunoglobulin
IgE Immunoglobulin E
IGH Immunoglobulin heavy chain
IHC Immunohistochemistry
IPSID Immunoproliferative small intestinal
disease
ISH In situ hybridization
JMML Juvenile myelomonocytic leukemia
KIR Killer-cell immunoglobin-like receptor
LCDD/HCDD Light chain/heavy chain deposition disease
LCH Langerhans cell histiocytosis
LCS Langerhans cell sarcoma
LDH Lactate dehydrogenase
 Abbreviations xvii

LDHL Lymphocyte-depleted Hodgkin lymphoma

LGL Large granular lymphocyte
LP Lymphocyte predominant
LPD Lymphoproliferative disorder
LPL Lymphoplasmacytic lymphoma
MALT Mucosa-associated lymphoid tissue
MBL Monoclonal B-cell lymphocytosis
MCL Mantle cell lymphoma
MDS Myelodysplastic syndrome
MGUS Monoclonal gammopathy of undetermined
significance
MLD Multilineage dysplasia
MPN Myeloproliferative neoplasm
MPO Myeloperoxidase
MRC Myelodysplasia-related changes
NLPHL Nodular lymphocyte predominant Hodgkin
lymphoma
NOS Not otherwise specified
NSE Nonspecific esterase
NSHL Nodular sclerosis Hodgkin lymphoma
PAS Periodic acid-Schiff stain
PCR Polymerase chain reaction
PEL Primary effusion lymphoma
PLAP Placental alkaline phosphatase
PMBL Primary mediastinal large B-cell
lymphoma
PMF Primary myelofibrosis
PNH Paroxysmal nocturnal hemoglobinuria
POEMS Polyneuropathy, organomegaly (liver,
spleen), endocrinopathy (hypogonadal,
thyroid), monoclonal gammopathy, and
skin changes (hyperpigmentation, hypertri-
chosis) syndrome
PTCL Peripheral T-cell lymphoma
PTLD Post-transplant lymphoproliferative
disorder
PV Polycythemia vera
RAEB Refractory anemia with excess blasts
xviii Abbreviations

RAEB-F Refractory anemia with excess blasts and

fibrosis
RS Ring sideroblast
SBP Solitary plasmacytoma of bone
SLE Systemic lupus erythematosus
SLL Small lymphocytic lymphoma
SMA Smooth muscle actin
T/NK T/natural killer
T-ALL T-cell acute lymphoblastic leukemia
TCR T-cell receptor
TdT Terminal deoxynucleotidyl transferase
TEMPI Telangiectasia, erythrocytosis with high
erythropoietin, monoclonal gammopathy,
perinephric fluid collection, and intrapul-
monary shunting
TFH T follicular helper cell
T-LBL T-cell lymphoblastic lymphoma
T-LGL T-cell large granular lymphocyte
T-LGLL T-cell large granular lymphocytic leukemia
T-PLL T-cell prolymphocytic leukemia
TRAP Tartrate-resistant acid phosphatase
VEGF Vascular endothelial growth factor
WBC White blood cell
Chapter 1
Chronic Myeloid
Neoplasms

Chronic Myeloproliferative Neoplasms

Chronic Myeloid Leukemia

Snapshot
• Clonal myeloid neoplasm with left-shifted (most cases)
neutrophilic leukocytosis and BCR/ABL1 translocation
[t(9;22)], infrequently presents with increased blasts (accel-
erated or blast phase)

Clinical Features
• WBC ≥12 × 109/L with granulocytic left shift (neutrophilia
in p230+ neutrophilic variant)
• Basophilia and eosinophilia commonly seen
• Absolute monocytosis may be seen in BCR/ABL p190+
disease
• No increase in circulating blasts (<2%)
• Blood, marrow, spleen, and liver involvement seen in
chronic phase
• Extramedullary disease (skin, nodes, soft tissues) may be
seen in blast phase

© Springer Nature Switzerland AG 2019 1

S. D. Hudnall et al., Pocket Guide to Diagnostic
Hematopathology, https://doi.org/10.1007/978-3-030-10630-0_1
2 Chapter 1. Chronic Myeloid Neoplasms

Marrow Morphology
• Hypercellular markedly myeloid predominant marrow
with left-shifted maturation
• Small hypolobated megakaryocytes
• Reticulin fibrosis ranges from minimal to marked
• Marked marrow fibrosis with clusters/sheets of small
abnormal megakaryocytes seen in accelerated phase

Diagnostic Criteria for Progressive Disease1

Accelerated phase
At least one of the following:
• Increased blasts (10–19%) in blood or marrow
• Persistent splenomegaly, unresponsive to therapy
• Persistent leukocytosis or thrombocytosis, unresponsive to
therapy
• Persistent thrombocytopenia, unrelated to therapy
• Basophilia (≥20% basophils in blood)
• Additional cytogenetic defect at diagnosis or during
therapy

Blast phase
At least one of the following:
• ≥20% blasts in blood or marrow
• Discrete extramedullary blastic infiltrate
• Large sheets of blasts in marrow biopsy

Immunophenotype
• Myeloblasts in myeloid blast crisis may express myeloid,
monocytic, erythroid, and/or megakaryocytic markers, e.g.,
MPO, CD14, e-cadherin, CD61
• Lymphoblasts in lymphoid blast crisis usually express
B-lymphoblast markers (CD19, PAX5, TdT), sometimes
express T lymphoblast markers (cCD3, TdT)

1
Note: Adapted from Table 2.01 from Swerdlow SH; International
Agency for Research on Cancer; World Health Organization; et al.
WHO classification of tumours of haematopoietic and lymphoid tissues.
Lyon: International Agency for Research on Cancer; 2017.
 Chronic Myeloproliferative Neoplasms 3

Genetics
• Classic BCR/ABL1 translocation [t(9;22)(q34.1;q11.2)]
• BCR/ABL fusion protein isoforms: p210 (major), p190
(minor), p230 (rare)
• Negative for other MPD-related mutations/translocations
(JAK2, CALR, MPL, PDGFRA/B, FGFR1)

Caveats and Pearls

• Absolute monocytosis mimicking CMML may be
seen in p190+ CML
• Marked thrombocytosis may mimic essential
thrombocythemia
• Marked neutrophilia in neutrophilic variant of CML
(BCR/ABL p230+) may mimic chronic neutrophilic
leukemia
• CML with reticulin fibrosis may mimic primary
myelofibrosis

Differential Diagnosis
• Leukemoid reaction (toxic granulation, absence of baso-
philia, high LAP [leukocyte alkaline phosphatase] score,
BCR-ABL-negative)
• Atypical CML (thrombocytopenia, trilineage dysplasia,
BCR-ABL-negative)
• Chronic myelomonocytic leukemia (absolute and relative
monocytosis, dysplasia, BCR/ABL-negative)
• Essential thrombocythemia (numerous enlarged hyperlo-
bated megakaryocytes, BCR/ABL-negative, variably posi-
tive for JAK2, CALR, or MPL mutation)
• Polycythemia vera (increased hemoglobin/hematocrit,
panmyelosis (trilineage proliferation), JAK2
mutation-positive)
• Primary myelofibrosis (leukoerythroblastosis [nucleated
red cells, dacrocytes, and myeloid left shift on peripheral
smear] moderate to marked fibrosis, osteosclerosis, numer-
ous abnormal megakaryocytes with irregular hyperchro-
4 Chapter 1. Chronic Myeloid Neoplasms

matic nuclei, BCR/ABL-negative, variably positive for

JAK2, CALR, or MPL mutation)
• Chronic neutrophilic leukemia (neutrophilia with minimal
left shift, BCR/ABL-negative, CSF3R mutation-­positive)

Chronic myeloid leukemia. Leukocytosis with increased basophils

(peripheral blood smear)
 Chronic Myeloproliferative Neoplasms 5

Chronic myeloid leukemia. Increased basophils and eosinophils

(peripheral blood smear)
6 Chapter 1. Chronic Myeloid Neoplasms

Chronic myeloid leukemia. Hypercellular myeloid marrow (core

biopsy)

Chronic myeloid leukemia. Increased small hypolobated mega-

karyocytes
 Chronic Myeloproliferative Neoplasms 7

Chronic Neutrophilic Leukemia2

Snapshot
• Persistent nonreactive neutrophilia with hypercellular
neutrophil-rich bone marrow and CSF3R1 mutation

Clinical Features
• Absolute neutrophilia (≥25 × 109/L)
• ≥80% segmented neutrophils and bands (WBC count)
• Hepatosplenomegaly
• Mucosal bleeding (some cases)

Marrow Morphology
• Neutrophil-rich marrow without myeloid left shift (<5%
blasts)
• No dysplasia and no reticulin fibrosis (most cases)

Genetics
• POSITIVE: CSF3R mutation, often with SETBP1 or
ASXL1 mutation
• NEGATIVE: (9;22) BCR/ABL translocation

Differential Diagnosis
• Chronic myeloid leukemia, neutrophilic variant (positive
for p230 fusion protein)
• Reactive neutrophilia (acute infection, acute inflammation,
drug effect [G-CSF, corticosteroids, others], underlying
neoplasm [including plasma cell neoplasm], stress, toxin
exposure)

2
Note: Adapted from Table 2.02 from Swerdlow SH; International
Agency for Research on Cancer; World Health Organization; et al.
WHO classification of tumours of haematopoietic and lymphoid tissues.
Lyon: International Agency for Research on Cancer; 2017.
8 Chapter 1. Chronic Myeloid Neoplasms

Caveats and Pearls

• Development of myelodysplasia may herald progres-
sion to acute myeloid leukemia

Chronic neutrophilic leukemia. Hypercellular neutrophil-­rich marrow

 Chronic Myeloproliferative Neoplasms 9

Polycythemia Vera
Snapshot
• Persistent nonreactive JAK2-positive polycythemia (ele-
vated hemoglobin or hematocrit) with panmyelosis

Clinical Features
• Symptoms may include thrombosis, headache, blurred
vision, dizziness, pruritis, splenomegaly

Morphology
• Hypercellular marrow with trilineage proliferation (pan-
myelosis), increased pleomorphic (not atypical) mega-
karyocytes, absent stainable iron, and absent-minimal
reticulin fibrosis (in most cases)

Diagnostic Criteria

Polycythemia vera
1. Elevated hemoglobin (>16.5 g/dL males, >16 g/dL females)
or hematocrit (>49% males, >48% females)
2. Hypercellular marrow with panmyelosis and pleomorphic
megakaryocytes
3. JAK2 mutation or low serum EPO level
NOTE: If hemoglobin or hematocrit is markedly elevated
(HGB: >18.5 g/dL males, >16.5 g/dL females; HCT: >55.5%
males, 49.5% females), and criteria 3 and 4 are met, criterion
2 may not be required
Post-PV myelofibrosis
1. Prior history of PV
2. Myelofibrosis (moderate to severe)
10 Chapter 1. Chronic Myeloid Neoplasms

3. At least two of the following: anemia, leukoerythroblasto-

sis, increasing splenomegaly, constitutional symptoms
(fever, weight loss, night sweats)
Genetics
• JAK2 V617F or JAK2 exon 12 mutation (nearly all cases)
Differential Diagnosis
• Prefibrotic myelofibrosis (abnormal megakaryocytes with
irregular hyperchromatic nuclei)

Polycythemia vera. Hypercellular erythroid-predominant marrow

with numerous pleomorphic megakaryocytes
 Chronic Myeloproliferative Neoplasms 11

Polycythemia vera (PV). Post-PV myelofibrosis

12 Chapter 1. Chronic Myeloid Neoplasms

Primary Myelofibrosis

Snapshot
• Hypercellular marrow with increased abnormal mega-
karyocytes in clusters, fibrosis, osteosclerosis, and spleno-
megaly with extramedullary hematopoiesis

Clinical Features
• Blood smear with leukocytosis, left shift, nucleated red
cells, and dacrocytes (leukoerythroblastosis), thrombocy-
tosis, splenomegaly

Diagnosis
Must have all of the following:
1. Increased abnormal megakaryocytes (large irregular
hyperlobated forms in clusters)
2. Moderate to marked reticulin fibrosis with or without col-
lagen fibrosis
3. Does not meet criteria for another myeloproliferative
neoplasm
4. Presence of a mutation in JAK2, CALR, or MPL (if not
detected, search for abnormal karyotype or another
mutation)
5. At least one of the following: leukocytosis (≥11 × 109/L),
anemia (not attributable to an unrelated condition), sple-
nomegaly, leukoerythroblastosis, elevated lactate dehydro-
genase (LDH)
Prefibrotic Myelofibrosis
• Early stage of disease with no significant fibrosis (absent
to mild)
• Leukoerythroblastosis and splenomegaly may be absent
Another random document with
no related content on Scribd:
 This manner of asceticism is not particularly common nowadays,
and we need not fear that it will be too generally practiced. I am
calling attention to it in order to show that selfishness may take on
the mask of purity or of respectability, a selfishness that springs from
pure moral motives and a longing for the elevation of character.
But there is another type of respectable selfishness that is far
more common, possibly more common in America than in any other
country. It is not usually recognised as selfishness, but regarded as
one of the greatest—perhaps the greatest—of the virtues. It is seen
chiefly among earnest and ambitious young men, who assume that
life is not a holiday, but a serious affair, a struggle, a strictly
competitive race, where if you stop a moment, even for reflexion, you
are left behind.
We are bound to respect these men. They have at all events
found out half the secret of life. They have set before themselves
some goal, in politics, in business, in literature, and they are
determined to reach it. They are equally determined to gain the prize
by no dishonourable means. Their minds are full of the lessons
learned from their predecessors, men who by the sacrifice of
temporary pleasures, by the refusal to indulge in recreation or
relaxation, have surpassed their competitors and reached the top.
We are constantly told that it is only by intense concentration, by
terrific efforts day and night, and by keeping the end constantly in
view that one can attain success. Surely these young men are to be
admired, surely they are models, examples worthy of emulation?
Well, they are better than criminals, they are better than
parasites, they are better than drones. But their driving motive is
selfishness. Tennyson wrote The Palace of Art, Browning wrote
Paracelsus, because each of these poets knew that his individual
danger was not what is usually known as “temptation.” They knew
that they would never go to hell by the crowded highway of
dissipation, for they were above the mere call of the blood. Their
danger lay in a high and noble ambition, which has wrecked many
first-rate minds.
 Modern life tends to encourage this respectable selfishness. The
central law of the so-called science of Economics is selfishness. A
whole science is built on one foundation—that every man in the
world will get all he can for himself. The subject is naturally studied
not from an ethical, but from a scientific standpoint. Life is a race.
Now I believe that Efficiency—mere practical success in the
world—is as false an ideal as asceticism. If the morality of
withdrawal is not good enough, neither is the morality of success.
Those deserve the highest admiration and the most profound
respect who have actually aided their human brethren, who have left
the world better than they found it.
This is by no means a hopeless ideal of character. It is not
necessary to crush a tyrant or to organise a revolution or to
reconstruct society or to be a professional reformer. There are plenty
of professional reformers who have tremendous enthusiasm for
humanity and who have never helped an individual. Those who by
unselfish lives and consideration for others elevate the tone of the
community in which they live and who by their presence make others
happier, these are the salt of the earth. Their daily existence is more
eloquent than a sermon.
American young men and women in our High Schools and
universities are not often face to face with the mystery of life. They
have no conception of the amount of suffering in the world. Their
own lives are comparatively free from it, in many cases free even
from anxiety. These boys and girls are for the most part sensible,
alert, quick-witted, and practical; what I should like to see would be a
change in their ideals from mere Success to something nobler. I
should like to see them devoting their intelligence and energy to the
alleviation of suffering and to the elevation of human thought and life.
If one still believes that the highest happiness and satisfaction
come from the attainment of any selfish ambition, no matter how
worthy in itself, it is well to remember the significance of the fact that
Goethe, acknowledged to be one of the wisest of men, made Faust
happy only when he was unselfishly interested in the welfare of
others; and to remember that Benjamin Franklin, perhaps the
shrewdest of all shrewd Americans, found the greatest pleasure of
his long life in two things—public service and individual acts of
kindness.
 XX
BIRDS AND STATESMEN

When, in the Spring of 1910, Theodore Roosevelt was on his

way to England from his African explorations, he wrote a strange
letter to the British Foreign Office in London. I call it a strange letter,
because it is the kind of epistle one would not expect to be sent by
an ex-executive of one country to the Foreign Office of another. He
wrote that during his stay in England he would like to make an
excursion into the woods, hear the English songbirds and learn their
names; in order that he might do this satisfactorily and intelligently,
would the Foreign Office please select some naturalist who knew the
note of every bird in England and request him to accompany Mr.
Roosevelt on this expedition?
Well, the head of the British Foreign Office was Sir Edward Grey
and he himself knew the note of every singing bird in England—a
remarkable accomplishment for one of the busiest statesmen in the
world. He therefore appointed himself as bird-guide for the ex-
President of the United States.
The two distinguished men stood on a railway platform one day
in May and were surrounded by reporters, who supposed that a new
world-problem of the first magnitude was on the carpet. But the two
men told the reporters that they were going away into the country for
two days, did not wish to be disturbed, and asked the journalists to
leave them alone. Accordingly, it was generally believed that
Roosevelt and Grey were absorbed in the discussion of international
affairs, and as the great war broke out a few years later, some went
so far as to believe then that it had its origin in this sinister interview.
 Now, as a matter of fact, the two men did not mention either war
or politics; they went a-walking in the New Forest and every time
they heard the voice of a bird, Grey told Roosevelt the singer’s
name. They both agreed (and so do I) that the English blackbird is
the best soloist in Great Britain.
It is a curious fact that the four most famous birds in English
literature are none of them native in America. The Big Four are the
Nightingale, the Skylark, the Blackbird and the Cuckoo. From
Chaucer to Kipling the British poets have chanted the praise of the
Nightingale. And of all the verses in his honour, it is perhaps the
tribute by Keats that is most worthy of the theme.

Thou was not born for death, immortal Bird!

No hungry generations tread thee down;
The voice I hear this passing night was heard
In ancient days by emperor and clown:
Perhaps the self-same song that found a path
Through the sad heart of Ruth, when, sick for home,
She stood in tears amid the alien corn;
The same that oftimes hath
Charmed magic casements, opening on the foam
Of perilous seas, in faery lands forlorn.

We never had nightingales in the United States until Edward W.

Bok imported them into his Bird Paradise in Florida. Previous
attempts to bring them over had failed; the birds invariably died.
Some investigators declared that this tragedy was owing to the
change of diet; but of course the real reason for their death was
American poetry. After the nightingales had listened for centuries to
Chaucer, Shakespeare, Milton, Wordsworth, Keats, etc., the change
to the level of American verse was too much for them, and they died
of shock.
The English skylark leaves the grass and soars aloft, singing his
heart out, so that after he has disappeared in the sky, we hear his
voice coming down out of the blue, like a revelation. One of the
poets calls it a “sightless song.”
Shakespeare sends the skylark to the gate of heaven.
And Shelley’s poem on the skylark expresses the ethereal nature
of the soaring voice of this bird:

Higher still and higher

From the earth thou springest,
Like a cloud of fire;
The blue deep thou wingest,
And singing still dost soar, and
Soaring ever singest.

American blackbirds do not sing well; the so-called crow-

blackbird, so common in flocks in autumn, makes a noise like
tonsillitis, or as if he had a boy’s voice in process of changing, or as
if he were a hinge that needed oiling. Our redwing blackbird, with his
scarlet epaulets, has a good-natured and perky wheeze, which can
hardly be called singing. But the English and Continental blackbird
pours out of his throat the most heavenly melody. One Winter day in
Munich, in the midst of a snowstorm, I saw a blackbird perched on a
tree directly in front of the University building. He was “hove to,” that
is, he had his beak turned directly into the wind, and as the
snowflakes beat against his little face, he sent straight into the gale
the loveliest music. Tennyson has observed how the voice of the
blackbird loses its beauty in the hot Summer days.

A golden bill! the silver tongue,

Cold February loved, is dry:
Plenty corrupts the melody
That made thee famous once, when young;
 And in the sultry garden-squares,
Now thy flute-notes are changed to coarse,
I hear thee not at all, or hoarse
As when a hawker hawks his wares.

The nearest we Americans can get to the English cuckoo is the

abominable cuckoo clock. The voice of the English cuckoo sounds
exactly like the clock, only of course you can’t train him to strike
right. In addition to his regular accomplishment, he is a ventriloquist
and can throw his voice a tremendous distance. One day, crossing a
field in Sussex, I heard the loud double note of the cuckoo,
apparently directly behind me. He was in reality a furlong away.
Wordsworth says:

O blithe New-comer! I have heard,

I hear thee and rejoice.
O Cuckoo! shall I call thee Bird,
Or but a wandering Voice?

While I am lying on the grass

Thy twofold shout I hear,
From hill to hill it seems to pass,
At once far off and near.

Concerning the all too common crimes of shooting, snaring, and

eating little singing birds, the English poet, Ralph Hodgson, has
expressed himself in words that ought to be everywhere read:

I saw with open eyes

Singing birds sweet
Sold in the shops
For the people to eat,
Sold in the shops of
Stupidity Street.

I saw in a vision
The worm in the wheat
And in the shops nothing
For people to eat:
Nothing for sale in
Stupidity Street.
 XXI
RUSSIA BEFORE THE REVOLUTION

The best way to invade Russia is by sea; and I advise those who
plan to visit the Soviet Republic to go via Stockholm. Copenhagen,
Christiania, Stockholm are three interesting cities and should be
seen in that order. Stockholm, the “Venice of the North,” is one of the
most beautiful, most picturesque, and most attractive places in the
world.
It is surprising that the short sea voyage from Stockholm to Saint
Petersburg (now Leningrad) is not better known; it is enchantingly
beautiful. We left Stockholm at six o’clock in the evening of a fine
September day, and as our tiny steamer drew away, the sunset light
over the fair city hung a new picture on the walls of my mind. It took
some five hours to reach the Baltic, five hours of constantly changing
scenery, one view melting into another like a succession of
dissolving panoramas. Hundreds of miniature islands dotted with
châteaux and country houses; winking lighthouse towers; “the grey
sea and the long black land.”
An impossible half-moon lent the last touch of glory to the scene.
We stood on the top deck and beheld the spacious firmament on
high, thick inlaid with patines of bright gold; while the long level light
of the crazy moon fell across the darkening water and the myriad
islands.
In the middle of the night we crossed the Baltic, and in the
whitening dawn entered the gulf of Finland. The air was nipping and
eager, but the sun rose in a cloudless sky. All day long the steamer
nosed her way through the blue sea, twisting and turning among the
countless points of the earth’s surface that were just able to keep
their heads above water. A few of these were covered with green
grass, and supported white farm buildings where laughing children
accompanied by dignified dogs ran out to see our transit; but for the
most part these elevations were bald, with a tall lighthouse as sole
decoration.
At five in the afternoon we reached Helsingfors (still my farthest
north) and stepped ashore to spend six hours in seeing the town, the
boat not proceeding toward Russia until late in the night. The
clouded sky was low and harsh the next morning, and the sea was
surly. Toward noon it cleared, and early in the afternoon we saw the
gilded domes and spires of Holy Russia. After a long delay with
passports, we drove across one of the bridges over the Neva to our
hotel at a corner of the Nevski Prospekt. Although it was only
September, the temperature was under fifty, and seemed colder.
I had a severe cold, which had its origin in a chill I had caught in
rashly touching a piece of toast that a waiter brought me in a London
hotel. But I was right in style. Accustomed as I was to see on the
streets of any American city the healthy, cheerful, well-clad and well-
shod men and women, I was appalled by the faces and the clothes
of the Russians. What they look like today I know not, but a more
unhappy looking crowd than I saw every day on the streets of
Russian cities I have never seen outside of pictures of Hell. Many of
the people had their ears and mouths bandaged and on their feet
were (if they could afford it) enormous knee-boots. All seemed to be
suffering from the foot and mouth disease.
Never shall I forget the boots and overcoats and uniforms on the
Nevski Prospekt. The question of leg-clothes would have interested
the author of Sartor Resartus. In Edinburgh all the men and some of
the women wore knickers, with stockings that seemed an inch thick.
Compared with Europeans, Americans are tropically clad. In order to
avoid the glare of publicity, I bought in Scotland a homespun golf
suit.
I tried these abbreviated trousers just once on the Nevski
Prospekt. Everybody stopped to stare. Had I worn a flowing purple
robe, I should not have attracted such attention. Military officers
gazed at me in cold amazement, as though I had leprosy; while the
more naïve passers made audible comment, which fortunately I
could not translate. Then I tried the experiment of conventional
clothing, but wore low shoes. Everyone gazed at my feet, some in
wonder, some in admiration, some in terror. I felt as I did many years
ago when I wore a striped cap in Brussels. A stranger looked at me
earnestly and then said in an almost reverent tone, and he said it
three times: Nom de Dieu!
In America our citizens show much the same interest in strange
clothing. Professor E. B. Wilson, a distinguished mathematician,
bought a suit of clothes in Paris. He wore it only once in America. A
citizen gazed at him steadfastly, and said “J——!”
The faces of the common people in Russian cities were sad to
behold, whether one saw them on the street or in church. Not only
was there no hilarity, such as one sees everywhere in American
towns; those faces indicated a total lack of illuminating intelligence.
They were blank, dull, apathetic, helpless. Gorki said that the people
in Russia had so little to look forward to that they were glad when
their own houses burned down, as it made a break in the dull routine
of life.
One afternoon I walked the entire length of the Nevski Prospekt,
no mean achievement in a heavy overcoat. I began at the banks of
the restless, blustering Neva, passed the extraordinary statue of
Peter the Great, came through the garden by the statue of Gogol,
and with the thin gold spire of the Admiralty at my back, entered the
long avenue.
I followed the immense extension of the Nevski, clear to the
cemetery, and stood reverently before the tomb of Dostoevski. Here
in January, 1881, the body of the great novelist was laid in the grave,
in the presence of forty thousand mourners.
In a corner of the enclosure I found the tomb of the composer
Chaikovski; I gazed on the last resting-place of Glinka, father of
Russian music. On account of the marshy soil, the graves are built
above instead of below the surface of the ground, exactly as they are
in New Orleans. It is in reality a city of the dead, the only place
where a Russian finds peace. I passed out on the other side of the
cemetery, walked through the grounds of the convent, and found
myself abruptly clear from the city, on the edge of a vast plain.
 XXII
THE DEVIL

It is rather a pity that the Devil has vanished with Santa Claus
and other delectable myths; the universe is more theatrical with a
“personal devil” roaming at large, seeking whom he may devour. In
the book of Job the Devil played the part of the return of the native,
coming along in the best society in the cosmos to appear before the
Presence. And when he was asked where he came from, he replied
in a devilishly debonair manner, “From going to and fro in the earth,
and from walking up and down in it.”
There are so many things in this world that seem to be the
Devil’s handiwork, and there are so many people who look like the
devil, that it seems as if he could not be extinct. His chief service to
the universal scene was to keep virtue from becoming monotonous;
to warn even saints that they must mind their step; to prove that
eternal vigilance is the price of safety. The Enemy of Mankind never
took a holiday. Homer might nod, but not he. In fact, on human
holidays he was, if possible, unusually efficient. The idleness of man
was the opportunity of Satan.
The principle of evil is so active, so tireless, so penetrating that
the simplest way to account for it is to suppose that men and things
receive constantly the personal attention of the Devil. Weeds, and
not vegetables, grow naturally; illness, not health, is contagious;
children and day-labourers are not instinctively industrious;
champagne tastes better than cocoa.
Throughout the Middle Ages, although every one believed
steadfastly in the reality of the Devil and that he was the most
unscrupulous of all foes, there was a certain friendliness with him,
born, I suppose, of daily intimacy. It was like the way in which hostile
sentries will hobnob with one another, swap tobacco, etc., in the less
tense moments of war. The Devil was always just around the corner
and would be glad of an invitation to drop in.
Thus in the mediæval mystery plays, the forerunners of our
modern theatres, the Devil was always the Clown. He supplied
“comic relief” and was usually the most popular personage in the
performance. He appeared in the conventional makeup, a horrible
mask, horns, cloven hoofs and prehensile tail, with smoke issuing
from mouth, ears and posterior. He did all kinds of acrobatic feats,
and his appearance was greeted with shouts of joy. In front of that
part of the stage representing Hellmouth he was sometimes
accompanied with “damned souls,” persons wearing black tights with
yellow stripes. On an examination at Yale I set the question,
“Describe the costume of the characters in the mystery plays.” One
of the students wrote: “The damned souls wore Princeton colours.”
The modern circus clown comes straight from the Devil. When
you see him stumble and fall all over himself, whirl his cap aloft and
catch it on his head, distract the attention of the spectators away
from the gymnasts to his own antics, he is doing exactly what his
ancestor the Devil did in the mediæval plays.
It is at first thought singular that those audiences, who believed
implicitly in a literal hell of burning flame, should have taken the Devil
as the chief comic character. I suppose the only way to account for
this is to remember how essential a feature of romantic art is the
element of the grotesque, which is a mingling of horror and humour,
like our modern spook plays. If you pretend that you are a hobgoblin
and chase a child, the child will flee in real terror, but the moment
you stop, the child will say, “Do that again.”
There are many legends of compacts with the Devil, where some
individual has sold his soul to gain the whole world. The most
famous of these stories is, of course, Faust, but there are
innumerable others. Here is a story I read in an American magazine
some fifty years ago.
 A man, threatened with financial ruin, was sitting in his library
when the maid brought in a visiting card and announced that a
gentleman would like to be admitted. On the card was engraved
Mr. Apollo Lyon.
As the man looked at it his eyes blurred, the two words ran
together, so they seemed to form the one word
Apollyon.
The gentleman was shown in; he was exquisitely dressed and
was evidently a suave man of the world. He proposed that the one
receiving him should have prosperity and happiness for twenty
years. Then Mr. Lyon would call again and be asked three questions.
If he failed to answer any of the three the man should keep his
wealth and prosperity. If all three were correctly answered the man
must accompany Mr. Lyon.
The terms were accepted; all went well for twenty years. At the
appointed time appeared Mr. Lyon, who had not aged in the least; he
was the same smiling, polished gentleman. He was asked a question
that had floored all the theologians. Mr. Lyon answered it without
hesitation. The second question had stumped all the philosophers,
but it had no difficulties for Mr. Lyon.
Then there was a pause, and the sweat stood out on the
questioner’s face. At that moment his wife came in from shopping.
She was rosy and cheerful. After being introduced to Mr. Lyon she
noticed her husband was nervous. He denied this, but said that he
and Mr. Lyon were playing a little game of three questions and he did
not want to lose. She asked permission to put the third question and
in desperation her husband consented. She held out her new hat
and asked: “Mr. Lyon, which is the front end of this hat?” Mr. Lyon
turned it around and around, and then with a strange exclamation
went straight through the ceiling, leaving behind him a strong smell
of sulphur.
 XXIII
THE FORSYTE SAGA

It is impossible to say what books of our time will be read at the

close of this century; it is probable that many of the poems and tales
of Kipling, the lyrics of Housman, dramatic narratives by Masefield,
some plays by Shaw and Barrie, will for a long time survive their
authors.
Among the novels, I do not know of any that has or ought to
have a better chance for the future than the books written about the
family of the Forsytes by John Galsworthy. They at present hold
about the same place in contemporary English literature as is held in
France by Romain Rolland’s Jean Christophe. Both are works of
great length which reflect with remarkable accuracy the political,
social, commercial, artistic life and activity of the twentieth century,
the one in England, the other on the Continent.
Entirely apart from their appeal as good novels, that is to say,
apart from one’s natural interest in the plot and in the characters,
both are social documents of great value. If the future historian
wishes to know English and Continental society in the first quarter of
the twentieth century, he will do well to give attention and reflexion to
these two works of “fiction.”
John Galsworthy was just under forty when in 1906 he published
a novel called The Man of Property. He had produced very little
before this, but it took no especial critical penetration to discover that
the new book was a masterpiece. The family of the Forsytes bore a
striking resemblance to one another in basic traits and ways of
thinking, yet each was sharply individualised. A new group of
persons had been added to British fiction. The word “Property,” as in
Tennyson’s Northern Farmer, was the keynote, and before long it
began to appear that one of the most dramatic of contrasts was to be
used as the subject. This is the struggle between the idea of
Property and the idea of Beauty—between the commercial,
acquisitive temperament and the more detached, but equally
passionate artistic temperament.
Even in the pursuit of beauty Mr. Soames Forsyte never forgot
the idea of property. He was a first-class business man in the city,
but he was also an expert judge of paintings, which he added to his
collection. Oil and canvas do not completely satisfy any healthy
business man; so Soames added to his collection, as the
masterpiece in his gallery, an exquisitely beautiful woman whom he
made his wife.
The philosophy of love comes in here. What is love? Is it
exclusively the idea of possession, which often is no more dignified
than the predatory instinct or is it the unalloyed wish that the object
of one’s love should be as happy and secure as possible? No one
can truly and sincerely love Beauty either in the abstract or in the
concrete if one’s eyes are clouded by predatory desire. One must
look at beauty without the wish to possess it if one is really to
appreciate beauty. A first-class French chef would look into the big
front window of a confectioner’s shop and fully appreciate the art and
taste that created those delectable edibles; but a hungry boy who
looked at the same objects would not appreciate them critically at all.
The wife of Soames finds him odious, so odious that we cannot
altogether acquit her of guilt in marrying him; and Soames, who as a
Man of Property expected her to fulfill her contract, did not make
himself more physically attractive by insisting on his rights. She left
him for a man of exactly the opposite temperament.
When Mr. Galsworthy finished this fine novel, he had no intention
of going on with the history of the family. He wrote many other novels
and some remarkable plays, but nothing made the impression on
readers that had been produced by the Forsyte family. Nearly twenty
years later he returned to the theme, and at once his power as a
novelist seemed to rise; there is something in this family that calls
out his highest powers. When he discovered that he had written five
works of fiction on the Forsytes, three long novels and two short
stories, of which the brief interlude called Indian Summer of a
Forsyte is an impeccable and I hope imperishable work of art, he hit
upon the happy idea of assembling them into one prose epic, and
calling the whole thing by the ironical title of The Forsyte Saga. It is
my belief that for many years to come the name of John Galsworthy
will be associated with this work, in what I fervently hope will be its
expanded form.
For since the assembling of the five pieces Mr. Galsworthy has
published several other novels dealing with the family—The White
Monkey, The Silver Spoon and in 1928 he wrote FINIS with Swan
Song. Here he kills Soames, and while he probably does not feel
quite so sad as Thackeray felt when he killed Colonel Newcome, I
venture to say that he does not gaze on the corpse of Soames with
indifferent eyes. For to my mind the most interesting single feature of
this whole mighty epic is the development of the character of this
man.
Clyde Fitch used to say something that is no doubt true of many
works of the imagination; he said that he would carefully plan a play,
write his first act, and definitely decide what the leading characters
should say and do in the subsequent portions of the work. Then
these provokingly independent characters seemed to acquire, not
only an independent existence, but a power of will so strong that
they insisted on doing and saying all kinds of things which he tried in
vain to prevent.
In The Man of Property Soames Forsyte is a repulsive character;
he is hated by his wife, by the reader, and by the author. But in these
later books Soames becomes almost an admirable person, and we
may say of him at the end in reviewing his life, that nothing became
him like the leaving of it—for he died nobly. Long before this
catastrophe, however, we have learned to admire, respect, and
almost to love Soames. Is it possible that Mr. Galsworthy had any
notion of this spiritual progress when he wrote The Man of Property,
or is it that in living so long with Soames he began to see his good
points?
 Dickens was a master in this kind of development. When we first
meet Mr. Pickwick, he seems like the president of a service club as
conceived by Sinclair Lewis; he is the butt of the whole company.
Later Mr. Pickwick develops into a noble and magnanimous
gentleman, whom every right-minded person loves. Look at Dick
Swiveller—when we first see him, he is no more than a guttersnipe.
He develops into a true knight.
 XXIV
PROFESSION AND PRACTICE

Beautiful lines which show that the man who wrote them had a
clear conception of true religion are these:

Thus to relieve the wretched was his pride,

And even his failings leaned to virtue’s side;
But in his duty prompt at every call,
He watched and wept, he prayed and felt for all;
And, as a bird each fond endearment tries
To tempt its new-fledged offspring to the skies,
He tried each art, reproved each dull delay,
Allured to brighter worlds, and led the way.

The man who wrote them is thus described by James Boswell:

“Those who were in any way distinguished excited envy in him to so
ridiculous an excess that the instances of it are hardly credible.
When accompanying two beautiful young ladies with their mother on
a tour of France, he was seriously angry that more attention was
paid to them than to him.” Goldsmith wrote of virtue, modesty, sweet
unselfishness in the most convincing manner; his words were more
convincing than his behaviour. He allured to brighter worlds, but did
not lead the way.
Schopenhauer, the great philosopher of pessimism, taught that
absolute asceticism was the only true religion and method of escape
from the ills of life; but he never practiced it, and told his disciples to
mind his precepts and not his example. Unfortunately, whenever any
one gives advice in the field of morality or religion, the first person on