Chapter 8: Hodgkin’s Lymphoma
·
30% of all lymphomas
·
Absolute incidence unchanged
·
Arise in lymph node, cervical
region
·
Young adults
·
Neoplastic tissue usually contain
a small number of tumor cells
·
Bimodal age incidence 15-35,
>55 years
·
Childhood form (0-14) more common
in developing countries
·
M:F=1.5:1; in all subtypes except
NS
·
Rye classification (1966)
o
Nodular sclerosis
o
Lymphocyte predominant
o
Mixed cellularity
o
Lymphocyte depleted
·
W.H.O Classification (2001)
o
Nodular lymphocyte predominant
Hodgkin Lymphoma (NLPHL)
o
Classical Hodgkin lymphoma (CHL)
o
Nodular sclerosis (NSHL)
o
Mixed cellularity
o
Lymphocyte rich
o
Lymphocyte depleted
·
Neoplastic cells and Hodgkin
Lymphoma
o
Classical Hodgkin:
§
Reed-Sternberg cell
§
Mononuclear Hodgkin cell
§
Lacunar cell
o
Nodular LP Hodgkin:
§
L&H (lymphocytic and
histiocytic) cells, also known as “Popcorn” cells
NLPHL (Nodular lymphocyte predominant Hodgkin
lymphoma)
·
5% of Hodgkin lymphoma
·
Male; 30-50 years
·
Bimodal age distribution not seen
·
Most present with localized
peripheral lymphadenopathy, develops slowly and is responsive to therapy
- Usually
involves cervical, axillary or inguinal LNs
·
Tends to spare mediastinum,
spleen or BM
·
Analogous to “low grade” B-cell
lymphomas; but disseminated disease not usually seen and younger age
·
EBV negative
·
Progressively transformed
germinal centers (PTGC) are seen in association with NLPHL. It is uncertain whether these lesions are
preneoplastic
·
Most patients with reactive
hyperplasia and PTGC do not develop HL
·
LN architecture is totally or
partially replaced predominantly consisting of small lymphocytes, histiocytes,
epithelioid histiocytes and intermingled L&H cells
o
Nodular
o
Nodular and diffuse
- Neutrophils
and eosinophils are absent in both nodular and diffuse regions
- Most
of the L&H cells ringed by CD3+ T-cells (to a lesser extent by CD57+
T-cells)
- L&H
cells
- Usually
have one large nucleus and scant cytoplasm
- Often
folded or multilobated
- Chromatin
is mostly vesicular with a thin nuclear membrane
- Nucleoli
usually multiple, basophilic and smaller than classical Hodgkin/R-S cells
(HRS cells)
·
Popcorn cells and the back ground
cells are CD20 positive; CD20 can be used to highlight the nodularity
·
Immunophenotype (popcorn cells)
o
CD45+
o
CD20+
o
EMA+ in 50% of cases
o
CD15 and CD30 are negative; CD30+
occasionally seen; most instances due to reactive CD30+ lymphoid blasts
unrelated to L&H cells
o
CD57 (+) T cells surround popcorn
cells
·
Prognosis is good especially for
earlier stage
·
3% to 5% of cases progress to
large B-cell lymphoma
Classical Hodgkin lymphoma (CHL)
·
95% of Hodgkin lymphomas
·
Bimodal age distribution
·
EBV has been postulated to play a
role
·
Sites of involvement
o
Cervical lymph nodes,
mediastinal, axillary, and para-aortic regions
o
60% have mediastinal involvement
(majority with NSHL)
o
Bone marrow involvement rare (5%)
– stage IV disease
·
Defining characteristics
o
RS cells in the appropriate
cellular background
o
RS cells positive for CD15 and
CD30
o
The neoplastic cells are usually
not CD20 positive
o
The background lymphocytes are T
cells (CD20 negative)
- BSAP
(B-cell specific activator protein) positive in 90% of cases
- Weak
staining of HRS cells
- A
B-cell specific transcription factor and a product of the PAX5 gene
·
The prevalence of EBV in RS cells
varies according to the histological subtype:
o
Highest in mixed cellularity
(75%)
o
Lowest in nodular sclerosis
(10-40%)
·
Prognosis is now based on the
clinical stage rather than the histological subtype.
Nodular Sclerosis (NSHL)
·
A subtype of CHL with collagen
bands that surround at least one nodule and lacunar type HRS cells
·
Most common type
- Accounts
for approximately 70% of CHL
- Median
age 37 years
·
The only type of HL without a
male predominance
- M:F
ratio approximately 1:1
·
Cellular phase and fibrotic phase
·
Syncitial variant: an extreme
form of the cellular phase
- Lacunar
cells may form cellular aggregates which are occasionally associated with
necrotic nodules
- Term
syncitial variant used when aggregates are prominent
·
Grade for NSHL
o
NS1:
§
75% or more of the nodules
contain scattered RS cells in a lymphocyte rich, mixed cellular, or
fibrohistiocytic background.
o
NS2:
§
At least 25% of the nodules
contain increased numbers of RS cells
Mixed cellularity classical Hodgkin lymphoma
·
A subtype of CHL with scattered
classical HRS cells in a diffuse or vaguely nodular mixed inflammatory background
without nodular sclerosing fibrosis
·
More frequent in patients with
HIV infection and in developing countries
·
A bimodal age distribution is not
seen
- Median
age 37 yrs
- Approximately
70% are male
- Mediastinal
involvement uncommon
Lymphocyte rich classical Hodgkin lymphoma
·
A subtype of CHL with scattered
HRS cells and a nodular (most common) or diffuse cellular background
characterized by an abundance of small lymphocytes and with an absence of
neutrophils and eosinophils
- Approximately
70% pts are male
- Peripheral
LNs are typically involved
- HRS
cells
- Generally
found within the expanded mantle zone
- May
resemble L&H cells or mononuclear lacunar cells
- Eosinophils
and neutrophils usually absent but may be present in small numbers
- Two
growth patterns
- Common
nodular
- Encompass
most of the involved tissue so that the T-zone is attenuated or absent
between the nodules
- Composed
of small lymphocytes and may harbor germinal centers that are usually
eccentrically located and relatively small or regressed
- Rare
diffuse
·
Differential diagnosis:
NLPHL (popcorn cells are positive for
CD20, negative for CD15 and CD30)
Lymphocyte depleted HD
- A
diffuse form of CHL rich in HRS cells and/or depleted in non-neoplastic
lymphocytes
- Rarest
subtype of HL
- Median
age 37 yrs, with 75% male
- Often
associated with HIV infection and seen more often in developing countries
- Morphology
- Highly
variable
- Relative
predominance of HRS cells to the background lymphocytes
- Most
HIV+ cases are EBV infected and stain positively for LMP1
·
Subtypes:
o
Diffuse fibrosis
o
Reticular
·
Differential diagnosis
o
Non-Hodgkin lymphoma
o
NS2, reticular variant of
lymphocyte depleted HL
o
ALCL
§
Large cells with abundant
cytoplasm
§
CD20–
§
T-cell markers positive, can be
“null” phenotype
§
CD30+
o
T-cell rich DLBCL