Aggressive Lymphomas

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Editors
Georg Lenz Gilles Salles
Department of Translational Oncology Department of Hematology
University-Hospital Münster University Claude Bernard Lyon 1
Münster Pierre-Benite cedex
Germany France

ISSN 2197-9766     ISSN 2197-9774 (electronic)

Hematologic Malignancies
ISBN 978-3-030-00361-6    ISBN 978-3-030-00362-3 (eBook)
https://doi.org/10.1007/978-3-030-00362-3

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Contents

Part I Epidemiology, Pathology and Molecular Pathogenesis

1 Epidemiology of Aggressive Lymphomas��������������������������������������   3

James R. Cerhan
2 Pathology and Molecular Pathogenesis of DLBCL
and Related Entities������������������������������������������������������������������������ 41
Laura Pasqualucci and German Ott
3 Pathology and Molecular Pathogenesis of Burkitt
Lymphoma and Lymphoblastic Lymphoma���������������������������������� 75
Hélène A. Poirel, Maria Raffaella Ambrosio, Pier Paolo
Piccaluga, and Lorenzo Leoncini
4 Pathology and Molecular Pathogenesis
of T-Cell Lymphoma������������������������������������������������������������������������ 95
Javeed Iqbal and Laurence de Leval

Part II Standard of Care of Aggressive Lymphomas

5 Standard of Care in First-Line Therapy of DLBCL�������������������� 145

Greg Nowakowski, Fabian Frontzek, and Norbert Schmitz
6 Standard of Care Relapsed DLBCL���������������������������������������������� 157
Kayane Mheidly, Roch Houot, Michael Scordo,
and Craig Moskowitz
7 Burkitt Lymphoma�������������������������������������������������������������������������� 167
Kieron Dunleavy and Martine Chamuleau
8 Human Immunodeficiency Virus-­Related Lymphomas �������������� 177
Josep-Maria Ribera and Richard F. Little
9 Primary CNS Lymphoma���������������������������������������������������������������� 189
Agnieszka Korfel
10 Extranodal Localization of Aggressive Lymphoma���������������������� 201
Jeremy S. Abramson and Armando López-Guillermo
11 CD20-Negative Aggressive Lymphomas���������������������������������������� 213
Jorge J. Castillo

v
vi Contents

12 Standard of Care in T-Cell Lymphoma������������������������������������������ 227

Alessandro Broccoli, Dai Chihara, Michelle A. Fanale,
and Pier Luigi Zinzani
13 Aggressive Lymphoma in Children and Adolescents�������������������� 245
Birte Wistinghausen and Birgit Burkhardt

Part III Future Directions in Aggressive Lymphomas

14 Role of Modern Imaging with FDG-­PET/CT

in Aggressive Lymphoma���������������������������������������������������������������� 285
Judith Trotman and Michel Meignan
15 Kinase Inhibitors in Large Cell Lymphoma���������������������������������� 297
Franck Morschhauser, Salomon Manier, and Nathan Fowler
16 Immunological Approaches������������������������������������������������������������ 307
Guillaume Cartron, F. Frontzek, and N. Schmitz
17 Therapeutic Modulators of Apoptosis and Epigenetics
in Aggressive Lymphoma���������������������������������������������������������������� 325
Michael J. Dickinson and John F. Seymour
18 Targeted Therapeutics for Lymphoma: Using Biology
to Inform Treatment������������������������������������������������������������������������ 343
T. E. C. Cummin, M. S. Cragg, J. W. Friedberg,
and P. W. M. Johnson
Introduction

In the last several years, the understanding of the biology and the molecular
pathogenesis of aggressive lymphomas has substantially improved. This sig-
nificantly changed diagnostic and therapeutic algorithms. As a result, a vari-
ety of novel molecular lymphoma subtypes and patient risk groups have
recently been identified, and various novel and very specific compounds as
well as new immunologic approaches have shown impressive efficacy in clin-
ical trials. These therapeutic improvements will soon translate into standard
of care and will further improve the prognosis of affected patients.
Our textbook summarizes the current knowledge on the epidemiology,
pathology, and biology of the major aggressive lymphoma subtypes. In the
main section, we provide an up-to-date overview of the standard of care ther-
apeutic approaches of patients affected by these diseases. In the last part, we
describe how we believe that the field will develop and how future diagnostic
and therapeutic strategies will look like. Thus, our textbook provides an up-­
to-­date compendium on the recent developments in the field of aggressive
lymphomas.
At last, we would like to thank all of the authors whose expertise and tre-
mendous efforts made the completion of this textbook possible. Finally, we
are very grateful to the Springer publisher and especially to Ejaz Ahmad, who
continuously supported the development of this textbook.

September 2018
Münster, Germany Georg Lenz
Pierre-Benite cedex, France Gilles Salles

vii
 Part I
Epidemiology, Pathology
and Molecular Pathogenesis
 Epidemiology of Aggressive
Lymphomas 1
James R. Cerhan

1.1 Introduction and Scope precursor lymphoid neoplasm (B- and T-cell),
mature B-cell neoplasms, mature T/NK-cell neo-
Lymphomas are a heterogeneous group of nearly plasms, Hodgkin lymphoma (HL), and histio-
100 variants of lymphoid malignancy that arise cytic and dendritic cell neoplasms. Acute and
from lymphocytes and produce tumors in the chronic lymphocytic leukemia (ALL and CLL,
lymph nodes, lymphatic organs, and extranodal respectively) and multiple myeloma (MM) are
lymphatic tissue (i.e., lymphoma), as well as the classified as a B-cell neoplasms [6]. The 2016
bone marrow (i.e., multiple myeloma) or periph- revision of the fourth edition of the WHO classi-
eral blood (i.e., leukemia) [1]. Collectively, lym- fication of lymphoid malignancies [1] was
phoid neoplasms are the fourth most common recently released, and although it did not allow
cancers in the USA, with an estimated 136,960 for any new definitive entities, it incorporated
cases in 2016 [2]. Lymphomas are considered to new genetic/molecular and clinical data into cur-
be clonal tumors of immature or mature B-cells, rent disease entities and added a limited number
T-cells, or natural killer (NK) cells arrested at of new provisional entities.
various stages of differentiation [3]. B-cell neo- While there are multiple B-cell [7, 8] and
plasms appear to recapitulate the normal stages T-cell [9] subtypes that are considered to be
of B-cell differentiation, and many B-cell lym- aggressive lymphomas (with some entities
phomas can be linked to a presumed normal cell changing or being added across editions of the
counterpart. The normal counterparts of T-cells WHO Classification in 2001 [6], 2008 [4], and
and NK-cells are not as well characterized as 2016 [1]), in this chapter, the focus is on three
B-cells, but they do share many immunopheno- broadly defined groups: diffuse large B-cell lym-
typic and functional properties and are currently phoma (DLBCL), Burkitt lymphoma/leukemia
grouped together. Based on this understanding, (BL), and peripheral T-cell lymphoma (PTCL).
the current World Health Organization (WHO) Table 1.1 provides an overview of the major lym-
classification system [4], which has been incor- phoid malignancy subtypes by version of the
porated into the International Classification of WHO Classification, with more detail provided
Diseases for Oncology (ICD-O) [5], recognizes for the aggressive subtypes. Based on national
US data, of the estimated 136,960 newly diag-
nosed lymphoid neoplasms in 2016, there were
J. R. Cerhan (*)
8500 HL (6.2%), 117,470 B-cell lymphoid
Department of Health Sciences Research, Mayo Clinic
College of Medicine, Rochester, MN, USA malignancies (85.8%), and 8380 T/NK-cell lym-
e-mail: [email protected] phoid malignancies (6.1%). In Table 1.1, we have

© Springer Nature Switzerland AG 2019 3

G. Lenz, G. Salles (eds.), Agressive Lymphomas, Hematologic Malignancies,
https://doi.org/10.1007/978-3-030-00362-3_1
4 J. R. Cerhan

Table 1.1 Expected number of incident lymphoid neoplasms in 2016, USA, according to the WHO classification of
lymphoid malignanciesa
WHO version New % of
cases, lymphoid
Subtypeb ICD-O-3 codes 2001 2008 2016 2016 neo-plasms
Lymphoid neoplasms, total 136,960 100
 1. Hodgkin lymphoma (HL) 9650–9655,9659,9661– X X X 8500 6.2
9667
 2. Non-Hodgkin lymphoid neoplasms 125,850 91.9
  2(a) Non-Hodgkin lymphoid 117,470 85.8
neoplasms, B-cell
   1. Precursor B-cell lymphoblastic 9727(B), 9728, X X X 4930 3.6
leukemia/lymphoma 9811–9818, 9835(B),
9836
    1.1.  Precursor B-cell 9727(B), 9728, 9811, X X 4570 3.3
lymphoblastic leukemia/ 9835(B), 9836
lymphoma, NOS
    1.2.  Precursor B-cell 9812–9818 X X 360 0.3
lymphoblastic leukemia/
lymphoma, with recurrent
genetic abnormalities
    2. Mature non-Hodgkin lymphoma, 105,190 76.8
B-cell
    2.1.1.  Chronic lymphocytic 9670, 9823 X X X 20,980 15.3
leukemia/small
lymphocytic leukemia
(CLL/SLL)
    2.1.2.  Prolymphocytic leukemia, 9832(B), 9833 X X X 120 0.1
B-cell
    2.1.3. Mantle cell lymphoma 9673 X X X 3320 2.4
    2.2.1.  Lymphoplasmacytic 9671 X X X 1060 0.8
lymphoma
    2.2.2.  Waldenstrom 9761 X X X 1270 0.9
macroglobulinemia
    2.3. Diffuse large B-cell 9678–9679, 9684(B), 27,650 20.2
lymphoma (DLBCL) 9680, 9687–9688, 9712,
9735, 9737–9738
      2.3.1. DLBCL-NOS 9684(B), 9680 X X X 25,380 18.5
(excluding C44.0–44.9,
C49.9, C71.0–71.9)
      2.3.2. Primary DLBCL of 9680 (C71.0–71.9) X X 1100 0.8
the CNS (PCNSL)
      2.3.3. Primary cutaneous 9680 (C44.0–44.9) X X 400 0.3
DLBCL, leg type
      2.3.4. T-cell/histiocyte-rich 9688 X X 200 0.1
large B-cell
lymphoma
      2.3.5. Intravascular large 9712, 9680 (C49.9) X X X 60 0.04
B-cell lymphoma
      2.3.6. ALK positive large 9737 X X <50 <0.04
B-cell lymphoma
      2.3.7. Plasmablastic 9735 X X 180 0.1
lymphoma
1 Epidemiology of Aggressive Lymphomas 5

Table 1.1 (continued)

WHO version New % of
cases, lymphoid
Subtypeb ICD-O-3 codes 2001 2008 2016 2016 neo-plasms
       2.3.8. Large B-cell 9738 X <50 <0.04
(plasmablastic)
lymphoma arising
from HHV-8
associated
multicentric
Castleman disease
       2.3.9. Primary effusion 9678 X X X <50 <0.04
lymphoma (PEL)
     2.3.10. Primary mediastinal 9679 X X X 240 0.2
(thymic) large B-cell
lymphoma (MLBCL)
       EBV+ DLBCL of the X
elderly
      EBV+ DLBCL, NOS X
       DLBCL associated X X
with chronic
inflammation
       Primary cutaneous X X
DLBCL, leg type
       Lymphoid 9766 X X X
granulomatosis
      Large B-cell X
lymphoma with IRF4
rearrangement
      EBV+ mucocutaneous X
ulcer
      HHV8+ DLBCL, NOS X
    2.4. Burkitt lymphoma/ 9687, 9826 X X X 1480 1.1
leukemia (BL)
       Burkitt-like lymphoma with X
chromosomal 11q
aberrations
      High-grade B-cell X
lymphoma, with MYC and
BCL2 and/or BCL6
rearrangements
      High-grade B-cell X
lymphoma, NOS
       B-cell lymphoma, 9596 X X
classifiable, with feature
intermediate between
DLBCL and HL
    2.5. Marginal zone lymphomas 9689, 9699 X X X 7460 5.4
    2.6. Follicular lymphoma 9597,9690– X X X 13,960 10.2
9691,9695,9698
    2.7. Hairy cell leukemia 9940 X X X 1100 0.8
     2.8. Hairy cell leukemia variant 9591 (C42.1–42.2) X X 810 0.6
    2.9. Plasma cell neoplasms 9731–9734 X X X 25,980 19.0
    2.10. Heavy chain diseases 9762 X X X <50 <0.04
    3. B-cell lymphoid neoplasms, 9590(B), 9591(B) X X X 7350 5.4
NOS (excluding C42.1–42.2),
9675(B), 9820(B)
(continued)
6 J. R. Cerhan

Table 1.1 (continued)

WHO version New % of
cases, lymphoid
Subtypeb ICD-O-3 codes 2001 2008 2016 2016 neo-plasms
  2(b) Non-Hodgkin lymphoid 8380 6.1
neoplasms, T/NK-cell
   1.  Precursor T/NK-cell 9727(T, NK), 9729, X X X 1070 0.8
lymphoblastic leukemia/ 9835(T, NK), 9837
lymphoma, NOS
    2. Mature non-Hodgkin lymphoid 7190 5.2
neoplasms, T/NK-cell
    2.1.  Mycosis fungoides/Sezary 9700, 9701 X X X 1690 1.2
syndrome (MF/SS)
    2.2. Peripheral T-cell 9675(T), 9702, 9705, 3950 2.9
lymphomas (PTCL) 9708–9709, 9714,
9716–9717, 9724, 9726
     2.2.1. PTCL, NOS 9675(T, NK), 9702 X X X 1660 1.2
     2.2.2. Angioimmunoblastic 9705 X X X 530 0.4
T-cell lymphoma
(AITL)
     2.2.3. Subcutaneous 9708 X X X <50 <0.04
panniculitis-like T-cell
lymphoma (SPTCL)
     2.2.4. Anaplastic large cell 9714 X X 830 0.6
lymphoma (ALCL)
ALK-positive
     2.2.5. Hepatosplenic T-cell 9716 X X X <50 <0.04
lymphoma (HSTL)
     2.2.6. Enteropathy- 9717 X X X 50 0.0
associated T-cell
lymphoma (EATL)
     2.2.7. Primary cutaneous 9726 X X <50 <0.04
gamma-delta T-cell
lymphoma
     2.2.8. Primary cutaneous 9709 X X X 760 0.6
T-cell lymphoma, NOS
     2.2.9. Systemic EBV-positive 9724 X X <50 <0.04
lymphoproliferative
disease
      Anaplastic large cell X
lymphoma ALK-negative
      Breast implant-associated X
anaplastic large-cell
lymphoma
       Primary cutaneous CD8+ X
aggressive epidermotropic
cytotoxic T-cell lymphoma
       Primary cutaneous CD4+ X
small/medium T-cell
lymphoproliferative disorder
       Systemic EBV+ T-cell X
lymphoma of childhood
       Hydroa vacciniforme-like X
lymphoproliferative disorder
1 Epidemiology of Aggressive Lymphomas 7

Table 1.1 (continued)

WHO version New % of
cases, lymphoid
Subtypeb ICD-O-3 codes 2001 2008 2016 2016 neo-plasms
      Follicular T-cell lymphoma X
      Nodal peripheral T-cell X
lymphoma with TFH
phenotype
    2.3.  Adult T-cell leukemia/ 9827 X X X 180 0.1
lymphoma
    2.4.  Extranodal NK/T-cell 9719 X X X 190 0.1
lymphoma, nasal type
    2.5.  T-cell large granular 9831 X X X 670 0.5
lymphocytic leukemia
    2.6.  T-cell prolymphocytic 9832(T, NK), 9834 X X X 160 0.1
leukemia
    2.7.  Aggressive NK-cell 9948 X X X <50 <0.04
leukemia
    2.8.  Primary cutaneous 9718 X X 310 0.2
CD30 + lymphoproliferative
disorders (primary cutaneous
anaplastic large cell
lymphoma)
     Lymphomatoid papulosis X
      Chronic lymphoproliferative X
disorder of NK cells
      Monomorphic epitheliotropic X
intestinal T-cell lymphoma
      Indolent T-cell X
lymphoproliferative disorder
of the GI tract
     Primary cutaneous acral X
CD8+ T-cell lymphoma
   3.  T/NK-cell, lymphoid neoplasms, 9590–9591(T, NK), X X X 120 0.1
NOS 9684(T, NK), 9820
(T, NK), 9970(T, NK)
 3. B-cell lymphoma unclassifiable, with 9596 170 0.1
features intermediate between
DLBCL and classical HL
 4. Lymphoid neoplasm, NOS 9590, 9727,9820, 9835 X X X 2440 1.8
(excluding B, T, NK)
a
Adapted from Teras et al. [2]
b
Subtypes defined using World Health Organization Classification of Tumours of Haematopoietic and Lymphoid
Tissues and organized according to SEER Cancer Statistics Review (CSR), 1975–2012, and the InterLymph hierarchical
classification of lymphoid neoplasms for epidemiologic research (2008)

bolded the specific WHO entities that are the routine pathology practice and concordance with
focus of this chapter, and most of these entities expert review can vary by lymphoma subtype, as
were defined in the first WHO Classification in recently shown in a French study [10]. For major
2001 [6], which gives sufficient time to accrue aggressive subtypes, concordance in the French
cases into cancer registries to provide population- study between referral and expert diagnosis was
level data, as well as time for epidemiologic stud- high for DLBCL not-otherwise-specific (NOS)
ies to be conducted to understand these entities. It (83.8%) and alkaline phosphatase (ALK)-
should be kept in mind that registry data rely on positive anaplastic large cell lymphoma (ALCL)
8 J. R. Cerhan

(82.3%), followed by BL (76.0%), enteropathy- (HSTL, <50 cases/year), EATL (50 cases/year),
associated T-cell lymphoma (EATL) (74.2%), primary cutaneous gamma-delta T-cell lymphoma
angioimmunoblastic T-cell lymphoma (AITL) (PCGD-TCL, <50 cases/year), and systemic
(68.7%), PTCL-NOS (63.8%), and ALK-negative EBV-positive lymphoproliferative disease (<50
ALCL (47.2%). cases/year). The entity “ALCL, T-cell or null-cell
type,” has evolved from the 2001 to the 2008
WHO classification to be classified as ALK-
1.2 Descriptive Epidemiology positive and ALK-negative ALCL, with the latter
initially a provisional entity that is now classified
Descriptive epidemiology evaluates the occur- as a definite entity [1]. Primary cutaneous T-cell
rence of disease and other health-related charac- lymphoma (CTCL, 760 cases/year), included in
teristics in human populations. Descriptive the 2001 and 2008 classification, now has two
patterns are based on aggregate characteristics of new provisional entities. This review does not
disease frequency, person (age, sex, race, etc.), include the less aggressive T-cell lymphomas,
place (generally geographic region), and calen- particularly mycosis fungoides/Sezary syndrome;
dar time. Such data are critical for an initial basic most of the new provisional entities; precursor T/
understanding of a disease in the population and NK-cell lymphoblastic leukemia/lymphoma; or
can also generate hypotheses regarding etiology. other rare NK and T-cell leukemias/lymphomas
listed in Table 1.1.
Aggressive lymphomas, defined as DLBCL,
1.2.1 Frequency BL, and PTCL (see Table 1.1), make up 24% of
lymphoid malignancies overall. If non-Hodgkin
DLBCL is the most common lymphoid malig- lymphoma is defined using the traditional definition
nancy in the USA, with an estimated 27,650 new (i.e., after excluding HL, MM, and lymphoid malig-
cases in 2016, which is 20.2% of all lymphoid nancy NOS), then DLBCL accounts for 27.6% of
malignancies. The vast majority of DLBCL is cases, BL for 1.5%, and PTCL for 3.9% (1.7% for
DLBCL-NOS (25,380 cases/year), with several PTCL-NOS specifically). In the International Non-
rarer entities, including primary DLBCL of the Hodgkin Lymphoma Classification Project of 4539
central nervous system (PCNSL), with an esti- cases from 24 countries on five continents [12],
mated 1100 cases/years; intravascular large B-cell 41% of NHLs from the USA and Europe were clas-
lymphoma (IVBCL), with 60 cases/year; primary sified as aggressive (using the above definition)
effusion lymphoma (PEL), with <50 cases/year; compared with 56.2% for all other world regions
and primary mediastinal (thymic) large B-cell (i.e., non-US and European); a lower percentage
lymphoma (MLBCL), with 240 cases/year. distribution from the USA/Europe versus other
BL, in contrast to DLBCL, is a rare subtype regions was also observed individually for DLBCL
with an estimated 1480 cases/year or ~1% of all (28.9% versus 42.5%), BL (0.8% versus 2.2%), and
lymphoid malignancies in the USA [2]. It is PTCL-NOS (2.6% versus 3.5%). Similar distribu-
commonly classified into the histologically tions from European [13, 14] and Asian [15–19]
indistinguishable subtypes of sporadic, endemic, countries have also been reported, with a comple-
and immunodeficiency-associated BL [11]. mentary decrease in the percentage of more indo-
PTCL is also uncommon, with an estimated lent subtypes, particularly follicular lymphoma, in
3950 cases/year, representing approximately 3% Asian studies.
of all lymphoid malignancies. There is great
heterogeneity in this group, and it includes
PTCL-NOS (1660 case/year), AITL (530 cases/ 1.2.2 Incidence
year), subcutaneous panniculitis-like T-cell
lymphoma (SPTCL, <50 cases/year), ALCL (830 While frequency counts and distributions provide
cases/year), hepatosplenic T-cell lymphoma insight into the scope of cancer burden, these
1 Epidemiology of Aggressive Lymphomas 9

Table 1.2 Incidence rates (age-adjusted per 100,000) and annual percent change (APC) for all lymphomas and selected
aggressive subtypes, overall and by sex, USA, SEER 18, 2000–2014
Sex specific
Overall Males Females
Lymphoma subtypea Rate APC Rate APC Rate APC IRRc (M:F)
All lymphomas 35.8 0.1 44.32 0.1 29.1 −0.1 1.5
DLBCL 6.95 0.5b 8.47 0.6b 5.72 0.2 1.5
 DLBCL-NOS 6.88 0.4b 8.41 0.6b 5.65 0.1 1.5
 IVBCL 0.0097 8.8b 0.01 e
0.0093 e
1.1
 PEL 0.011 e
0.02 e d e e

 MLBCL 0.047 e
0.038 e
0.057 e
0.7
BL 0.40 0.2 0.60 0.3 0.21 −0.1 2.9
PTCL 1.15 0.5 1.48 0.4 0.88 0.7b 1.7
 PTCL-NOS 0.41 1.2b 0.54 1.2 0.31 1.2 1.8
 AITL 0.13 4.6b 0.16 4.9b 0.11 4.4b 1.4
 SPTCL 0.014 3.5 0.0096 e
0.018 1.3 0.5
 ALCL 0.24 −3.2b 0.31 −3.6b 0.17 −2.6b 1.8
HSTL 0.0091 7.1b 0.013 7.5b 0.0055 e
2.3
 EATL 0.012 3.7 0.016 4.4 0.0094 e
1.7
 CTCL 0.23 −0.3 0.30 −0.4 0.18 −0.3 1.6
 PCALCL 0.095 0.5 0.12 0.4 0.075 0.4 1.6
a
Subtypes: DLBCL diffuse large B-cell lymphoma, NOS not otherwise specified, IVBCL intravascular B-cell lym-
phoma, PEL primary effusion lymphoma, MLBCL mediastinal (thymic) large B-cell lymphoma, BL Burkitt lym-
phoma, PTCL peripheral T-cell lymphoma, AITL angioimmunoblastic T-cell lymphoma, SPTCL subcutaneous
panniculitis-like T-cell lymphoma, ALCL anaplastic large cell lymphoma, HSTL hepatosplenic T-cell lymphoma,
EATL enteropathy-associated T-cell lymphoma, CTCL cutaneous T-cell lymphoma, PCALCL primary cutaneous ana-
plastic large cell lymphoma
b
P < 0.05
c
IRR incidence rate ratio, male/female
d
Unable to estimate (less than 25 cases)
e
Statistic could not be calculated

measures do not take into account the size or age coding of new entities in population-based can-
distribution of the underlying population that cer registries, the subtypes are based on the 2001
generates the case counts to provide rates for WHO Classification (Table 1.1) [6]. Incidence
making comparisons. To do this, we use the inci- rates were age-adjusted to the year 2000 US stan-
dence rate, which is defined as the number of dard population. The annual percentage change
newly diagnosed cancer cases in a defined popu- (APC) was calculated using weighted least
lation divided by the number of persons at risk squares method, and the APC was evaluated on
from that population. Incidence rates are used to whether it was different from zero (no change),
make comparisons across cancer types, geo- with statistical significance set at P < 0.05.
graphic regions, calendar time, and in subgroups The age-adjusted incidence (per 100,000) was
(e.g., defined by sex, race, ethnicity, etc.). The 35.8 for all lymphomas, 6.95 for DLBCL, 1.15
incidence rates for selected aggressive lympho- for PTCL, and 0.40 for BL. To put these rates in
mas in the USA are summarized in Tables 1.2 perspective to other lymphoma subtypes, the
and 1.3 and are based on data from the 18 incidence of CLL/SLL is 5.87, MM is 5.86,
Surveillance, Epidemiology, and End Results follicular lymphoma is 3.57, classic HL is 2.57,
(SEER) registries for 2000–2014 [20] using the and marginal zone lymphoma (MZL) is 1.89.
WHO classification system as implemented with Thus, DLBCL has the highest incidence rate,
the InterLymph Classification [21, 22] and with both PTCL and BL being relatively
SEER*Stat [23]. Due to delays in implementing uncommon.
 10

Table 1.3 Incidence rates (age-adjusted per 100,000) and annual percent change (APC) for all lymphomas and selected aggressive subtypes by sex, race, and ethnicity, USA,
SEER 18, 2000–2014
Race specific Hispanic ethnicity
White Black Asian or Pacific Islander No Yes
Lymphoma subtypea Rate APC Rate APC IRRc (B:W) Rate APC IRRc (A:W) Rate APC Rate APC IRRc (no/yes)
All lymphomas 37.1 0 34.9 0.4 0.9 21.5 −0.1 0.6 36.5 0.1 31.1 0 0.9
DLBCL 7.25 0.5b 4.84 0.7 0.7 5.96 0.6b 0.8 6.93 0.5b 7.30 0.5b 1.1
 DLBCL-NOS 7.18 0.4b 4.77 0.6 0.7 5.89 0.4 0.8 6.86 0.3b 7.24 0.4 1.1
d e e d e e d e e
 IVBCL 0.0092 7.3b 0.0096 8.5b
e e d e e e e
 PEL 0.011 0.018 1.7 0.010 0.016 1.6
e e e e e
 MLBCL 0.048 0.038 0.8 0.051 1.1 0.051 0.031 0.6
BL 0.42 0.3 0.32 0.3 0.8 0.34 −1.4 0.8 0.40 0.1 0.43 0.1 1.1
PTCL 1.11 0.3 1.47 0.7 1.3 0.92 0.6 0.8 1.19 0.7b 0.97 −0.2 0.8
 PTCL-NOS 0.38 0.9 0.66 1.7 1.7 0.39 1.1 1.0 0.42 1.5b 0.36 −0.6 0.8
 AITL 0.13 5.1b 0.092 1.8 0.7 0.19 3 1.4 0.13 4.6b 0.15 4.7b 1.1
e e
 SPTCL 0.011 2.9 0.025 −2.3 2.4 0.020 1.9 0.014 3.3 0.013 0.9
 ALCL 0.24 −2.9b 0.28 −3.9b 1.2 0.16 −4.4b 0.7 0.24 −2.8b 0.23 −4.5b 0.9
e e d e e d e e
 HSTL 0.0071 0.021 2.9 0.011 8.3b
d e e d e e d e e
 EATL 0.012 5.4b 0.012 3.1
 CTCL 0.23 −1.1b 0.31 1.8 1.3 0.092 0 0.4 0.25 −0.3 0.14 1.2 0.6
 PCALCL 0.096 0.2 0.0881 1.1 0.9 0.046 −3 0.5 0.10 0.4 0.063 1.6 0.6
a
Subtypes: DLBCL diffuse large B-cell lymphoma, NOS not otherwise specified, IVBCL intravascular B-cell lymphoma, PEL primary effusion lymphoma, MLBCL mediastinal
(thymic) large B-cell lymphoma, BL Burkitt lymphoma, PTCL peripheral T-cell lymphoma, AITL angioimmunoblastic T-cell lymphoma, SPTCL subcutaneous panniculitis-like
T-cell lymphoma, ALCL anaplastic large cell lymphoma, HSTL hepatosplenic T-cell lymphoma, EATL enteropathy-associated T-cell lymphoma, CTCL cutaneous T-cell
lymphoma, PCALCL primary cutaneous anaplastic large cell lymphoma
b
P < 0.05
c
IRR incidence rate ratio
d
Unable to estimate (less than 25 cases)
e
Statistic could not be calculated
J. R. Cerhan