Disease

Morphology

Clinical

Diffuse Large B
Cell Lymphoma
(DLBCL)

20-30% adult NHL

large B cells (>2x in western
normal), diffuse
countries; median
pattern
age 70 years

Follicular
Lymphoma

comprises
centrocytes
(mature) and
centroblasts
(large, immature);
tightly packed
follicles deface
nodal architecture;
grades 1-3 based
on number of
centroblasts/high
power field; backto-back,
monotonous
follicles , no TBMs,
extension into
perinodular
adipose tissue

Burkitt Lymphoma

highly
aggressive ,
monomorphic
small, noncleaved B cells
w/ basophilic
vacuolated
cytoplasm, multiple
nucleoli, high
mitotic rate, tingible
body
macrophages;
starry sky
appearance

Mantle Cell
Lymphoma

cells resemble
centrocytes of
germinal center;
may show more
aggressive
features han other
MBCNs (mature B
cell lymphoplasms)

20% adult NHL in

western countries;
median age 70
years; slow
growing nontender (rubbery)
lymph nodes

EBV present in
subset of cases;
highly aggressive,
GI/airway
obstruction, 30%
childhood NHLs in
US, endemic type
often presents as
mass involving
mandible and
involvement of
abdominal viscera
(kidneys, ovaries,
adrenal glands)

Sites

nodal (65%),
extranodal (35% CNS, cutaneous,
GI, bone, testes,
spleen, kidney,
adrenal)

Etiology

transformation
lower grade
lymphoma or de
noval;
immunocompromise
d is risk factor

nodes, spleen,
bone marrow,
peripheral blood

tumor mass
localized to jaw
and
retroperitoneum
and involvement of
abdominal
viscera (kidneys,
ovaries, adrenal
glands), bone, and
CNS

Cytogenetics

translocations
involving
chromosomes
3q26, 18, 14

t(14:18)

EBV present in
subset of cases

t(8:14); t(2:8) and t

(8:22) can also
occur

t(11:14) cyclin D1IgH translocation

Prognosis

Special Types

CD20 expression
-> sensitivity to
rituximab ;
germinal center
type is better and
non-germinal
center type is
worse

1.
Immunodeficiency/
AIDS related
(strongly
associated w/
EBV) 2. primary
effusion
lymphoma/body
cavity large B cell
lymphomas KSHV/HHSV-8

positive for CD19,

CD20, CD10;
express BCL2
gene, not
considered to be
treatable disease

sensitive to
chemotherapy

3 types: 1.)
African/endemic children/young
adults equatorial
Africa; associated
w/ EBV infection
and malaria
infection 2.) US
(nonendemic) children/adolescent
s, EBV-associated
in minority of cases
3.)
immunodeficiencyassociated
lymphoma - subset
of aggressive
lymphomas in HIV
patients

Staging

Treatment

Ann Arbor, FLIP 1.) age > 60, 2.)

stage III or IV Ann
Arbor, 3.)
increased LDH, 4.)
Hb > 12 g/dl, 5.) > 5
nodal sites of
involvement

radiation for
early stage
disease,
chemotherapy
and immunotherapy
(rituximab ) for
more advanced
disease

chemotherapy

Disease

Morphology

Lymphoplasmacyti
c Lymphoma

small
"plasmacytoid " B
cells; paraprotein > Waldenstrom
macroglobulinemia
(hyperviscosity)

Clinical

Solitary
Plasmacytoma

Etiology

Cytogenetics

Prognosis

Special Types

Staging

Treatment

Hepatitis C
infection

cells have
"monocytoid "
Extranodal Marginal appearance; 50%
Zone (MALT)
of primary gastric
Lymphoma
lymphoma

Multiple Myeloma

Sites

stomach, ocular
glands

multifocal malignant
neoplastic
proliferation of
plasma cells; peak
incidence 65-70
years, higher
incidence in men
and African
descent; diagnosis
- clonal bone
marrow plasma
cells > or = 10%
bone marrow
and presence
infiltration sheets
serum/urinary
of plasma cells ; > monoclonal protein
or = 10% nucleated and CRAB
cellular elements
(hypercalcemia,
(usually >30% of
renal insufficiency,
marrow); mature
anemia, bone lytic
plasma cells with
lesions) in end
perinuclear
organ damage;
clearing (prominent complete clonal
Golgi apparatus =
immunoglobulin
Hof) and
s (M protein) ,
eccentrically
free clonal light
placed clock faced chains ( bence
nucleus;
jones ),
multinucleated
hyperviscosity (M
myeloma cells
protein > 3 mg/dl) and
> rouleaux
plasmablastic
formation, bence
cells (nucleoli,
jones > 6 mg/dl ->
centrally place
precipitates/ amylo
nuclei), Mott cell
id deposits

t(11:18) ->
stomach: H pylori
resistance to
infection, C psitacci eradication of
infection
organism

one of most
serious
complications of
muliple myeloma ->
AL
(amyloidosis );
affects heart,
kidneys, caused by
accumulation
excess light chains
esp lambda form ->
beta pleated
sheets; causes
organ failure;
detected in tissue
bone, bence jones biopsy by congo
deposits in kidney - red stain -> apple
> renal failure
green
(myeloma kidney)
birefringence

isolated mass of
monoclonal plasma
cells in bone/soft
tissue; absence
other plasma cell
proliferative lesions
OR systemic
disease consistent
w/ MM; majority
bone cases
progress to MM
(soft tissue -> 35%
progress to MM)
bone or soft tissue

stem cell
therapy/chemother
apy

Disease

Morphology

Clinical

Smoldering
myeloma

high plasma M
component w/o
symptoms

MGUS (monoclonal
gammopathy of
undetermined
significance)

present in about
3% Caucasian
population > 50; M
protein < 3 gm/dl;
plasma cells <10%
nucleated bone
marrow; no
evidence
CRAB/end organ
damage

Adult T Cell
Leukemia/Lymphom
a (ATLL)
floret cell

widespread
involvement,
leukocytosis w
eosinophilia,
hypercalcemia,
skin
rash/exfoliative

Anaplastic large
cell lymphoma

ALK positive ;
horshoe shaped
nuclei cells
(hallmark cells),
large tumor cells
w/ abundant
cytoplasm ;
difficult to
distinguish from
carcinoma;
embryoid nuclei

malignant T cell
lymphoma
characterized by
presence of large
tumor cells w/
abundant
cytoplasm and
pleomorphic
horseshoe shaped
nuclei (hallmark
cells)

Sezary
syndrome/Mycosis
Fungiodes

indolent tumors w/
median survival 8-9
years; mycosis
fungiodes presents
as cutaneous
cerebriform
lesions that
nuclei; haloed
progress through 3
mature appearing
stages; sezary
lymphocytes in
syndrome =
basal epidermal;
generalized
collections of
exfoliative
atypical cells
erytrhoderma w/
(plaque stage) are associated
referred to as
leukemia of sezary
pautrier
cells (cerebriform
microabscesses
nuclei)

Sites

Etiology

Cytogenetics

Prognosis

Special Types

Staging

Treatment

watch and wait;

approximately 1%
progress to MM

skin, spleen, liver,

lung, GI, CNS

HTLV 1 caused;
occurs frequently
in Japan, West
Africa, Caribbean
basin

very good
prognosis (75-80%
cure rate w/
rearrangement of
chemotherapy),
ALK gene on
ALK negative
chromosome
ALCL in adults 2p23; CD30+ (Ki-1) poorer prognosis

involves soft
tissue, mainly
children/young
adults

late in disease
course
extracutaneous
spread to lymph
nodes and bone
marrow

1. acute, 2.
lymphomatous, 3.
chronic, 4.
smoldering

tumor of CD4+
helper T cells

8-9 years median

survival

chemotherapy

3 stages inflammatory
premycotic phase,
plaque phase,
tumor phase;
many subtypes ichthyotic,
granulomatous;
diagnosis made by
clincial features,
aberrant T cell
antigen expression
and T cell clonanity
studies

Disease

Langerhans cell
histiocytosis
("Histiocytosis X")

Morphology

Langerhans cell abnormal

proliferation of
immature
dendritic cell
(nuclear grooves
and few scattered
eosinophils);
derived from bone
marrow monocytes
and found
predominantly in
skin; monoclonal,
thus neoplastic;
Birbeck granules
("tennis
rackets") seen on
ultrastructural
examination;
sometimes called
eosinophilic
granuloma

Clinical

proliferation of
Langerhans cell;
mainly seen in
children/young
adult

Sites

Etiology

Cytogenetics

CD1a, S-100, HLADR +

immunophenotype
by IHC study

Prognosis

Special Types
1. Letterer-Siwe
disease (acute
disseminated
disease) malignant, presents
in infancy/early
childhood (<2);
diffuse
eczematous skin
rash, cystic
skeletal defects
(skull, pelvis, long
bones); multiple
organ involvement;
rapidly fatal, 2.
Hand-SchullerChristian
disease
(multifocal disease)
- malignant;
classically has
scalp rash, lytic
skull defects,
diabetes insipidus,
exophthalmos,
intermediate
prgonosis, 3.
eosinophilic
granuloma
(unifocal disease)

Staging

Treatment

Disease

Morphology

Clinical

40% adult
lymphomas; men
slightly more
affected (except
for nodular
sclerosis subtype more women);
Caucasians,
bimodal age
distribution,
strong EBV
Reed Sternberg
association ;
(RS) cells (>45 um commonly presents
w/ multiple nuclei
as painless
or single nucleus
lymphadenopathy,
w/ multiple lobes
cutaneous anergy,
each with large
spread of HL is
inclusion like
predictable: nodal
nucleolus 5-7 um), -> splenic ->
peculiar tumor giant hepatic ->
cells w/
marrow and other
exuberant tissue
tissues; B
response
symptoms (reactive
fever, weight loss,
lymphocytes,
night sweats; also
granulocytes,
HIV status, BCL-2
macrophages,
expression, IL-10
plasma cells);
levels important;
tumor cells small
Classical fraction (<1%)
lymphadenopathy,
overall tumor mass; multiple, rubberty to
RS cells can be
firm nontender and
lacunar cell or
matted lymph
mummified RS
nodes; extranodal
Hodgkin Lymphoma cells
disease uncommon

Nodular
lymphocyte
predominant
hodgkin lymphoma
(NLPHL)

monoclonal B cell
neoplasm
characterized by
nodular pattern;
nodular infiltrate of
small lymphocytes
mixed w/
macrophages;
variants of RS cells
(popcorn cells);
eosinophils and
plasma cells
usually
scant/absent;
nodal
architecture
usually
obliterated

5% of cases
young adults and
children, male >
female

Sites

Etiology

often localized to
single axial group
of nodes
(cervical,
mediastinal,
para-aortic );
orderly spread by
contiguity;
mesenteric nodes
and waldeyer ring
rarely involved,
rare extranodal
presentation

RS cells originate
from germinal
center or post
germinal center
B cell; florid
accumulation
reactive cells due
to IL-5, IL-10, IL13, TGF beta and
chemokines
(TARC, MDC, IP-10,
CCL28) secreted
by RC cells; RS cell
also activates
monocyte/macroph
age, suppress TH1
and killer T cell
response, enhance
TH2 response,
promote fibrosis,
cause tissue
eosinophila, and
increase plasma
cell and Ig levels;
RS cells also
upregulate NF
kappa B

solitary enlarged
peripheral lymph
node, most
commonly neck,
groin, axilla ; 80%
present with early
stage I or II, relapse
in another nodal
site is common and
may be delayed

Cytogenetics

CD30 and CD15 +;

EMA and CD45 -,
CD20 -, CD79a
positive,
associated w/ EBV
most of the time

CD30 and CD15

negative, EMA and
CD45 positive,
CD20 and CD79a
positive, not EBV
associated

Prognosis

Special Types

Staging

increased risk for

development of
NHL

gray zone
lymphoma - not firm
distinction b/w HL
and NHL;
CLASSICAL
HODGKIN
LYMPHOMA
TYPES - nodular
sclerosis (70%),
mixed cellularity
(20%), lymphocyte
depleted (4% worst prognosis),
lymphocyte rich
(1%)

IPS - based on
serum albumin (<4
g/dl), Hb
concentration (<10.
5 g/dl), male sex
age >45 years,
stage IV disease,
WBC count >
15,000/mm^3,
lymphopenia <
600/mm^3 or < 8%

Treatment

Disease

Morphology

HL nodular
sclerosis

frequent lacunar
cells and
occasional RS
cells ; background
infiltrate of T cells,
eosinophils,
macrophages,
plasma cells;
fibrous bands divide cellular
areas into nodules

Clinical

Sites

Etiology

Cytogenetics

most common
subtype, usually
stage I or II

frequent
mediastinal
involvement, most
patients young
adults (slight
female
predominance)

usually EBV
negative

RS cells, CD 15+,
CD30+

frequent
mononuclear and
RS cells,
background
infiltrate rich in T
cells, eosinophils,
macrophages,
HL mixed cellularity plasma cells

more than 50%

stage III or IV;
males > females;
bimodal age
distribution

EBV+ in 70% of
cases

RS cells CD15+ or
CD30+

frequent
mononuclear,
diagnostic RS cells;
background
infiltrate rich in T
HL lymphocyte rich lymphocytes

uncommon, affects
males more than
females; older
adults

EBV + in 40% of
cases

RS cells CD15+ or
CD30+

uncommon, more
common in older
males, HIV infected
indivdiuals,
developing
countries; often
presents w/
advanced disease

EBV +

RS cells CD 15 +,
CD 30+

HL lymphocyte
depletion

paucity
background
reactive cells

Prognosis

Special Types

Staging

Treatment