Haematopathology: an introduction to lymphoid neoplasms

Haematopathology
THE LYMPHOID NEOPLASMS
Dr Brian Mitchelson
Qatar Cardiovascular Research Centre

Definition
Lymphoid Neoplasms:
Lymphoid neoplasms are derived from the clonal
expansion and proliferation of B- and T-lymphocytes.
They encompass a heterogeneous group of lymphomas
and leukemias including B-cell, T-cell, and natural killer
(NK)-cell disorders.

Classification
In 2008 the WHO classified 8 separate categories of
lymphoid neoplasms:
1. Chronic lymphocytic leukemia
2. Lymphoplasmacytic lymphoma and Waldenström
macroglobulinemia
3. Plasma cell neoplasms
4. Immunoglobulin deposition diseases.
5. Follicular lymphoma:
6. Diffuse large B-cell lymphomas
7. Enteropathy-associated T-cell lymphoma
8. ALK-positive anaplastic large cell lymphoma

Chronic Lymphocytic Leukemia
CLL
Chronic lymphocytic leukemia (CLL) is a type of cancer that
starts from the B lymphocytes in the bone marrow.
It then invades the blood.
Leukemia cells tend to build up over time, and many people
don't have any symptoms for at least a few years.
In time, it can also invade other parts of the body, including
the lymph nodes, liver, and spleen.
Compared with other types of leukemia, CLL usually grows
slowly.

Chronic Lymphocytic Leukemia
CLL
Chronic lymphocytic leukemia is a monoclonal disorder
characterized by a progressive accumulation of functionally
incompetent lymphocytes.
It is the most common form of leukemia found in adults in
Western countries.
Some patients die rapidly, within 2-3 years of diagnosis,
because of complications from CLL, but most patients live 5-
10 years.

Diagnosis
Patients with CLL have a higher-than-normal white blood
cell count, which is determined by complete blood count
(CBC).
Peripheral blood flow cytometry is the most valuable test to
confirm a diagnosis of CLL.
Other tests that may be helpful for diagnosis include bone
marrow biopsy and ultrasonography of the liver and spleen.
Immunoglobulin testing may be indicated for patients
developing repeated infections.

Peripheral smear from a patient
with chronic lymphocytic
leukemia, small lymphocytic
variety.
The cells of origin in most
patients with CLL are clonal B
cells arrested in the B-cell
differentiation pathway,
intermediate between pre-B cells
and mature B cells.
Morphologically, in the
peripheral blood, these cells
resemble mature lymphocytes.
CLL Images

Circulating CLL cells
may be recognized as
mature lymphocytes
by the high nuclear
cytoplasmic ratio and
the characteristic
"cobblestone" pattern
of the nuclear
chromatin.
CLL Images

Bone marrow smear of CLL
Beginning in the bone marrow,
CLL is typically due to changes to
the DNA of stem cells in the bone
marrow.
This leads to the growth and
development of mutated cells that
are called leukemic cells.
These do not mature into normal
white cells.
The mutations confer a survival
advantage over regular cells that
over time, take over the bone
marrow and crowd out the normal
blood cells.
CLL Images

Rarer forms of Lymphocytic
Leukemia
The common form of CLL starts in B lymphocytes, but there are some rare
types of leukemia that share some features with CLL.
1.Prolymphocytic leukemia (PLL):
In this type of leukemia the cancer cells are similar to normal cells called
prolymphocytes - immature forms of B lymphocytes (B-PLL) or T
lymphocytes (T-PLL).
Both B-PLL and T-PLL tend to be more aggressive than the usual type of
CLL.
Most people will respond to some form of treatment, but over time they
tend to relapse.
PLL may develop in someone who already has CLL (in which case it tends
to be more aggressive), but it can also occur in people who have never
had CLL.

Prolymphocytic leukemia (PLL)
Approximately 20% of
the lymphocytes had the
morphologic features of
prolymphocytes with
finely dispersed
chromatin and central
nucleoli (arrows).

Large granular lymphocyte (LGL)
leukemia
2. Large granular lymphocyte (LGL) leukemia:
This is another rare form of chronic leukemia.
The cancer cells are large and have features of either T
lymphocytes or natural killer (NK) cells.
Most LGL leukemias are slow-growing, but a small
number are more aggressive.
Drugs that suppress the immune system may be helpful,
but aggressive cases are very hard to treat.

Large granular lymphocyte (LGL)
leukemia
Peripheral blood:
medium/large
lymphocytes with
abundant cytoplasm
containing coarse
azurophilic granules

Hairy cell leukemia (HCL):
This is another cancer of lymphocytes that tends to progress slowly.
It accounts for about 2% of all leukemias.
The cancer cells are a type of B lymphocyte but are different from
those seen in CLL.
There are also important differences in symptoms and treatment.
This type of leukemia gets its name from the way the cells look under
the microscope -- they have fine projections on their surface that make
them look "hairy."
Treatment for HCL by splenectomy can be very effective.

Hairy cells are
characterized by their
fine, irregular
pseudopods and
immature nuclear
features. They are
seen only in hairy cell
leukemia.

This is a scanning
electron micrograph
which illustrates the
multiple cytoplasmic
pseudopodia-like
projections which
gives rise to the
descriptive name.

Lymphoplasmacytic lymphoma and
Waldenström macroglobulinemia
Lymphoplasmacytic lymphoma is a rare type of non-Hodgkin
lymphoma.
Nearly all lymphoplasmacytic lymphomas are a type known
as ‘Waldenström’s macroglobulinaemia’ (WM).
This disease has a wide range of clinical presentations with
symptoms attributable either to tissue infiltration by
neoplastic cells or to the quantity and immunological
properties of the monoclonal IgM produced.

Lymphoplasmacytic lymphoma (LPL) is a rare type of non-Hodgkin
lymphoma that develops from B cells.
Biopsy samples show a mixture of cancerous lymphocytes and plasma
cells .
This is why it is described as 'lymphoplasmacytic'.
LPL is a low-grade lymphoma that usually develops slowly over a period
of months or even years.
There are a few different types of LPL but Waldenström’s
macroglobulinaemia or WM is by far the most common kind.
In LPL cancerous B cells build up in the bone marrow, the spleen and
the lymph nodes

The bone marrow
aspirate shows
increased
lymphoplasmacytoid
lymphocytes with
scattered plasma
cells.

Imprint preparation of
lymphoplasmacytic
lymphoma
demonstrating small
lymphocytes and cells
with plasmacytoid
features (eccentric
nuclei and bluish
cytoplasm).

Bone marrow biopsy:
The yellow arrow
shows the presence of
Dutcher bodies,
intranuclear inclusions
in the plasma cells

Bone Marrow aspirate:
The marrow was
infiltrated by
lymphoplasmacytoid
cells on aspiration.

Plasma cell neoplasms
• Plasma cell myeloma
• Asymptomatic (smoldering) myeloma
• Nonsecretory myeloma
• Plasma cell leukemia
• Plasmacytoma
• Solitary plasmacytoma of bone
• Extraosseous (extramedullary) plasmacytoma
• Immunoglobulin deposition diseases
• Primary amyloidosis
• Systemic light- and heavy-chain deposition diseases
• Osteosclerotic myeloma (POEMS syndrome)

Plasma cell myeloma
In plasma cell myeloma, collections of abnormal plasma
cells accumulate in the bone marrow, where they interfere
with the production of normal blood cells.
Most cases of plasma cell myeloma also feature the
production of a paraprotein —an abnormal antibody which
can cause kidney problems.
Bone lesions and hypercalcemia (high blood calcium
levels) are also often encountered.

Diagnosis
Symptomatic myeloma:
Clonal plasma cells >10% on bone marrow biopsy or in a
biopsy from other tissues (plasmacytoma)
A monoclonal paraprotein in either serum or urine (except
in cases of true non-secretory myeloma)
Evidence of end-organ damage related to the plasma cell
disorder.
HyperCalcemia (corrected calcium >2.75 mmol/L)
Renal insufficiency attributable to myeloma
Anaemia (haemoglobin <10 g/dL)
Bone lesions

Diagnosis
Asymptomatic (smoldering) myeloma:
Serum paraprotein >30 g/L AND/OR
Clonal plasma cells >10% on bone marrow biopsy
NO myeloma-related organ or tissue impairment
Plasma Cell Leukaemia
The WHO criterion for diagnosis of PCL is that
plasma cells constitute more than 20% of cells in the
peripheral blood with an absolute plasma cell count of
more than 2 × 109/L.

Plasma cell myeloma
A classical blood film
picture from a case of
“multiple myeloma”.
Multiple Myeloma is
the most common
malignant plasma cell
dyscrasia.
There are many other
malignant and
secondary plasma cell
disorders

Plasma cell myeloma
The plasma cells seen in
the marrow can be
mature - with classic PC
features or immature -
with prominent nucleoli.
Binucleate and
multinucleate PCs can be
seen. Masses of
immunoglobulin may
form intracytoplasmic
globules or Russell
bodies.

Plasma cell myeloma
Cells containing
multiple
immunoglobulin
globules are known as
Mott cells

Plasma cell myeloma
Myeloma cells may also contain
crystalline inclusions of
immunoglobulin

Plasma cell myeloma
The excessive production of an abnormal immunoglobulin is the second major
characteristic of myeloma.
The abnormal Ig is most often IgG (50%) and sometimes IgA (25%), but rarely
(<1%) IgM ,IgD, or IgE.
Production of excess light chain is frequent and is excreted in the urine as
Bence- Jones proteins.
About 20-25% of cases produce only light chains which are often detectable only in
the urine.
Fewer than 5% of myelomas are nonsecretory.
Immunoglobulin filled cytoplasm may invaginate into the nucleus creating the
appearance of an intranuclear inclusion (a Dutcher body).

Plasmacytoma
Plasmacytoma refers to a malignant plasma cell tumor growing
within soft tissue or within the axial skeleton.
There are three distinct groups of plasmacytoma defined by the
International Myeloma Working Group:
Solitary Plasmacytoma of Bone (SPB)
Extramedullary Plasmacytoma (EP)
and multiple plasmacytomas that are either primary or recurrent.
The most common of these is SPB, accounting for 3–5% of all
plasma cell malignancies.
SPBs occur as lytic lesions within the axial skeleton and EPs most
often occur in the upper respiratory tract (85%), but can occur in any
soft tissue.

Plasmacytoma
Approximately half of all cases produce paraproteinaemia.
The skeletal forms frequently progress to multiple myeloma
over the course of 2–4 years.
Due to their cellular similarity, plasmacytomas have to be
differentiated from multiple myeloma.
For SPB and EP the distinction is the presence of only one
lesion (either in bone or soft tissue), normal bone marrow
(<5% plasma cells), normal skeletal survey, absent or low
paraprotein and no end organ damage.

Plasmacytoma - SPB
Low power photomicrograph
shows classic histological
features of a plasmacytoma.
This is an example of an SPB
found in the pelvis.

Plasmacytoma - SPB
Vertebral
plasmacytoma which
caused compression
of the spinal cord.

Plasmacytoma - EP
An example of EP from a biopsy
of the mouth.
Histopathologic features
showed oral mucosa lined by
nonkeratinizing stratified
squamous epithelium.
Areas of ulceration were seen.
The underlying connective
tissue was infiltrated by closely
packed plasma cells arranged
in sheets and islands with
varying degrees of
differentiation, some with
perinuclear halo, occasionally 2
nuclei within a single cell.
Russell bodies were seen.

Plasmacytoma - EP
Low power view of lesion
demonstrating plasma cells
High power view demonstrating
typical plasma cell cytoplasm and
clock face chromatin. Some
pleomorphic atypical forms also
present

Plasma cell leukemia (PCL) is a rare cancer involving the
plasma cells.
Plasma cell leukemia is one of the most aggressive human
neoplasms and constitutes 2% to 4% of all cases of plasma
cell disorders.
The WHO criterion for diagnosis of PCL is that plasma cells
constitute more than 20% of cells in the peripheral blood with
an absolute plasma cell count of more than 2 × 109/L.

Pathologic diagnosis of PCL is based on histologic,
immunophenotypic, and cytogenetic findings in addition to
circulating high plasma cell counts.
Bone marrow biopsy typically reveals aggregates or sheets of
neoplastic plasma cells that displace normal marrow elements.

Peripheral blood plasma cells range from mature forms with
characteristic "clock-face" chromatin and perinuclear halo, to
immature blast forms.
These have loose reticular chromatin, high
nuclear/cytoplasmic ratio, and prominent nucleoli.
Immature neoplastic cells may be indistinguishable from
myeloblasts.
In some instances, plasma cells display lymphoid morphology.

At routine ante-natal
screening a review of
the peripheral blood
film displayed 90%
plasma cells, a bluish
background, rouleaux,
occasional nucleated
red blood, and low
platelets.
A bone marrow
examination showed
replacement by plasma
cells.

Multiple abnormal
cells with clefted
nuclei and basophilic
cytoplasm suggestive
of plasma cells, in
peripheral blood

Bone marrow
aspiration showed
markedly increased
cellularity with
infiltration by atypical
plasma cells
comprising more than
90% of all nucleated
cells

Immunoglobulin
Deposition Diseases
Light and heavy-chain immunoglobulin deposition diseases belong to a
family of diseases that include:
Light-chain (AL)-amyloid.
Nonamyloid fibrillary and immunotactoid glomerulonephritis, and
cryoglobulinemic glomerulonephritis, in which monoclonal Ig or their
subunits become deposited in kidney.
It is a rare disease characterized by deposition of nonamyloid
immunoglobulin light chains, and they do not stain with Congo red and
do not exhibit a fibrillar structure when examined ultrastructurally.

Immunoglobulin
Deposition Diseases
It is categorized as a “monoclonal deposition disease” in the
World Health Organization (WHO) classification of tumors of
haematopoietic and lymphoid tissues.
A single clone of plasma cells is responsible for
overproduction of kappa chains and, very rarely, lambda
chains.
A monoclonal population of plasma cells can be detected in
the bone marrow, and an altered serum-free light chain ratio is
present.
In 25% of patients, an abnormal serum free light chain ratio is
noted, even without an abnormal finding with serum and or
urine electrophoresis with immunofixation.

Immunoglobulin
Deposition Diseases
Amyloid Disease:
Primary amyloidosis arise from a disease with disordered
immune cell function, such as multiple myeloma or other
immunocyte dyscrasias.
Secondary (reactive) amyloidosis occurs as a
complication of some other chronic inflammatory or
tissue-destroying disease.
Examples are reactive systemic amyloidosis and
secondary cutaneous amyloidosis.

Primary Amyloidosis
Here amyloid deposits
in the kidney are seen
as dense amorphous
pink areas in
glomeruli at the left
and in arteries at the
right.

Cardiac Amyloid
A Congo red stain has
been performed on
the myocardium in a
case of amyloidosis.
The amyloid stains
orange-red, but with
polarized light, the
amyloid has an "apple-green"
birefringence
as seen here
Primary Amyloidosis

Primary Amyloidosis
This electron micrograph
shows the typical
ultrastructure of amyloid:
randomly-oriented, non-branching
fibrils, 7.5-10 nm in
diameter, of indeterminate
length.
Electron microscopy is usually
reserved for cases in which
the stains at the light
microscopic level are non-diagnostic
or for cases with
minimal deposits, as in the
kidney.
All amyloids have a similar
ultrastructure.

Secondary Amyloidosis
In this image of
Cardiac amyloid
disease, the dense
amyloid protein is
seen adjacent to a
blood vessel.
This disease was
secondary to chronic
rheumatic heart
disease

This is a section from a
skin biopsy stained with
Congo Red and shows
the amorphous deposits
surrounding the blood
vessels.
The final histologic
diagnosis was AA
(secondary) amyloidosis,
associated to psoriasis.

This is the same
section as the
previous slide but was
viewed under
polarized light and
shows the Amyloid
deposits as an “apple
green” bi-refringence.

Nonamyloid Fibrillary and
Immunotactoid Glomerulonephritis
Nonamyloid fibrillary GN: This rare disorder comprises less
than 1% in renal biopsy series and usually presents with renal
insufficiency, nephrotic range proteinuria, and
microhaematuria.
It is characterized pathologically by the deposition in glomeruli
of fibrillar deposits that generally range from 16 to 24 nm in
diameter.
These fibrils usually stain for immunoglobulin G (IgG) and C3,
with more variable and weaker positivity for other
immunoglobulins2. By definition, the glomerular deposits are
Congo red–negative, allowing their differentiation from
amyloid.

Nonamyloid Fibrillary and
Immunotactoid Glomerulonephritis
There is considerable debate about the relationship of
Fibrillary Glomerular Nephritis (FGN) to immunotactoid
glomerulonephritis (IT).
IT is an entity with larger microtubular deposits, usually>30
nm in diameter, which are often hollow and arranged in
parallel or stacked arrays.

Nonamyloid FGN
An electron microscopy
example of FGN displays
intramembranous,
randomly oriented fibrils
of a mean 20 nm
diameter that infiltrate
and thicken the
glomerular basement
membrane.
The fibrils lack hollow
centers and parallel
stacking.

Immunotactoid GN
B is also an electron
micrograph from a case of
IT and exhibits
subendothelial
accumulations of
microtubules of 35 nm
diameter with hollow
centers arranged in
parallel stacks.
The microtubules do not
infiltrate the glomerular
basement membrane.

Cryoglobulinaemic GN (CGN)
CGN can be differentiated from idiopathic MPGN, especially
in the acute stage,, by the following findings:
(1) the presence of large deposits filling the capillary lumen
that sometimes are shown to have a characteristic fibrillar or
crystalloid structure by electron microscopy;
(2) the extent of the exudative component consequent to the
frequently massive infiltration of monocytes;
(3) a more diffuse and evident thickening of the glomerular
basement membrane, which has a double-contoured
appearance that is mainly due to the peripheral interposition
of monocytes, with less evident mesangial expansion;

The most common
morphological picture is a
membranoproliferative
exudative
glomerulonephritis,
characterized by variable
degrees of mesangial
proliferation and massive
intracapillary leukocyte
(mainly monocyte-macrophage)
accumulation.

Immunocytochemistry
shows a massive
accumulation of
monocyte-macrophages
(CD68
positive cells) is
evident.
This type of
glomerular infiltration
is rather specific of
Cryoglobulinaemic
nephritis,

Electron microscopy
shows that monocyte-macrophages
are likely
involved in the
degradation of immune
deposits.
In fact they are found in
close proximity to the
subendothelial deposits
and their cytoplasm
contains electron dense
material.

Follicular Lymphoma NHL
Follicular lymphoma (FL) is a B-cell lymphoma and is the
most common indolent (slow-growing) form of NHL,
accounting for approximately 20 percent to 30 percent of all
Non- Hodgkins Lymphomas (NHLs).
Common signs of disease include enlargement of the lymph
nodes in the neck, underarm, stomach, or groin, as well as
fatigue, shortness of breath, night sweats, and weight loss.
Often, people with FL have no obvious symptoms of the
disease at diagnosis.

Follicular Lymphoma-NHL
The average age for people with this lymphoma is about
60. It’s rare in very young people.
Most of the time, this lymphoma occurs in many lymph
node sites in the body, as well as in the bone marrow.
Follicular lymphomas are often slow-growing and respond
well to treatment, but they are hard to cure.
These lymphomas may not require treatment when they
are first diagnosed.
Instead, treatment may be delayed until the lymphoma is
causing problems.
Over time, about 1 in 3 follicular lymphomas turns into a
fast-growing diffuse B-cell lymphoma.

Follicular Lymphoma- NHL
FOLLICULAR LYMPHOMA DIAGNOSIS AND STAGING
The diagnosis of follicular lymphoma is confirmed by removing all or part of an enlarged
lymph node to examine its cells under a microscope, a procedure known as a biopsy.
Once the diagnosis is confirmed, additional tests are performed to obtain more
information about the extent to which the disease has spread in the body. This process
is called staging. The results of these tests will help determine the most effective course
of treatment.
History and physical exam — A careful interview and physical examination will help
determine the extent of the disease. The physical exam may reveal swollen lymph
nodes in various locations.
Staging tests — A number of tests are available to help determine which areas of the
body have been affected by follicular lymphoma. Tests that may be done include:
●Blood tests
●Bone marrow biopsy
●Computed tomography (CT) scan
●Positron emission tomography (PET) scan

Follicular lymphoma.
Nodular aggregates, not
effacement as in
CLL/SLL.

Many small lymphoid cells with
condensed chromatin and
irregular nuclear outlines
(centrocytes)
along with larger cells with
multiple nucleoli (centroblasts).

Immunocytochemistry
A.
Normally, B lymphocyte
mantle cells in the lymph node
express the BCL-2 antibody
(blue arrows) and follicular B-cells
don't.
B.
In the malignant follicle on the
right, the follicular B-cells (red
arrow) are overexpressing
BCL-2.

Hodgkins Lymphoma
The cause of Hodgkin lymphoma is not known.
Hodgkin lymphoma is most common among people ages 15 to 35 and 50
to 70.
Past infection with the Epstein-Barr virus (EBV) is thought to contribute to
some cases.
Persons with HIV infection are at increased risk compared to the general
population.
Symptoms may include any of the following:
Fatigue
Fever and chills that come and go
Itching all over the body that cannot be explained
Loss of appetite
Soaking night sweats
Painless swelling of the lymph nodes in the neck, armpits, or groin Weight
loss that cannot be explained

Hodgkins Lymphoma
Hodgkins Lymphoma is divided into 4 classes
A.Nodular Sclerosing HL :
Is the most common subtype and is composed of large tumor nodules showing scattered lacunar
classical RS cells set in a background of reactive lymphocytes, eosinophils and plasma cells with varying
degrees of collagen fibrosis/sclerosis.
B. Mixed-cellularity subtype:
Is a common subtype and is composed of numerous classic RS cells admixed with numerous
inflammatory cells including lymphocytes, histiocytes, eosinophils, and plasma cells without sclerosis.
This type is most often associated with EBV infection and may be confused with the early, so-called ‘
cellular' phase of nodular sclerosing CHL.
C. Lymphocyte-rich or Lymphocytic predominance:
Is a rare subtype, show many features which may cause diagnostic confusion with nodular lymphocyte
predominant B-cell Non-Hodgkin's Lymphoma (B-NHL). This form also has the most favorable
prognosis.
D. Lymphocyte depleted:
Is a rare subtype, composed of large numbers of often pleomorphic RS cells with only few reactive
lymphocytes which may easily be confused with diffuse large cell lymphoma. Many cases previously
classified within this category would now be reclassified under anaplastic large cell lymphoma.

Hodgkins Lymphoma
Hodgkins lymphoma may be treated with radiation therapy, chemotherapy, or
hematopoietic stem cell transplantation, with the choice of treatment depending on
the age and sex of the patient and the stage, bulk, and histological subtype of the
disease.
The five-year survival rate is currently approximately 85%.
Tumour Staging
Stage I: is involvement of a single lymph node region (mostly the cervical region)
or single extralymphatic site.
Stage II: is involvement of two or more lymph node regions on the same side of
the diaphragm or of one lymph node region and a contiguous
extralymphatic site.
Stage III: is involvement of lymph node regions on both sides of the diaphragm,
which may include the spleen and/or limited contiguous extralymphatic
organ or site.
Stage IV: is disseminated involvement of one or more extralymphatic organs.

Hodgkins Lymphoma
Nodular Sclerosing
Lymph node section showing
the characteristic Reed-
Sternberg (RS cell) giant cells
which are frequently
multinuclear and often found in
clumps in the tumour.
RS cell
Two additional features
distinguish the nodular
sclerosing type of Hodgkin
disease.
Fibrosis: dense bands of
collagenous fibrous tissue
separate the cellular areas
producing a lobular appearance.

Hodgkins Lymphoma
Mixed-cellularity subtype
The lymph node architecture is
diffusely replaced by a
polymorphous population of
small lymphocytes, histiocytes,
plasma cells, and eosinophils in
varying proportions.
Among this mixed inflammatory
cell infiltrate are present
scattered mononucleate and
multinucleate large Reed-
Sternberg cells (arrow).

Nodular lymphocyte predominant
Nodular lymphocyte
predominant –
Hodgkins Lymphoma
The popcorn cells that
characterize this form of the
disease invariably express B
lymphocyte markers such as
CD20 (thus making NLPHL an
unusual form of B cell
lymphoma), and that, unlike
classic HL, NLPHL these tumours
may progress to diffuse large B
cell lymphoma.

Hodgkins Lymphoma
Lymphocyte-depleted
Lymphocyte-depleted,
comprises less than 5% of all
Hodgkin lymphomas. In the
diffuse fibrosis subtype, there is
progressive sclerosis over time
and the number of lymphocytes
decreases.

Hodgkins Lymphoma
Lymphocyte Depletion Type
A Reed-Sternberg cell occupies
the centre, surrounded by a few
lymphocytes and fibrosis that
might be described as
disorganized.
When viewed through polarized
light, it is not birefringent,
unlike the fibrous bands of
nodular sclerosis.

Diffuse large B-cell lymphomas
DLBCL
Diffuse large B-cell lymphoma (DLBCL) is the most common
form of Non-Hodgkins Lymphoma (NHL), accounting for up to
30 percent of newly diagnosed cases in the United States.
It can arise in lymph nodes or outside of the lymphatic
system, in the gastrointestinal tract, testes, thyroid, skin,
breast, bone, or brain.
DLBCL is a fast-growing, aggressive form of NHL.
DLBCL is fatal if left untreated, but with timely and
appropriate treatment, approximately 60 percent of all
patients can be cured.

Diffuse Large B-cell Lymphomas
DLBCL
Age, gender, and ethnicity affect a person's likelihood of developing DLBCL.
Although DLBCL has been found in people of all age groups, it is found most
commonly in people who are middle-aged or elderly.
The average age at the time of diagnosis is 64 years. Men are slightly more
likely to develop DLBCL than women.
In the United States, white people are more likely to develop this type of
lymphoma than are Asians or Blacks.
DLBCL is not an inherited disease. Siblings and children of patients with
DLBCL do not have a substantially increased risk of developing DLBCL.

DLBCL
DIFFUSE LARGE B CELL LYMPHOMA SYMPTOMS
The first sign of DLBCL is often a quickly growing, non-painful mass that is
typically an enlarged lymph node in the neck, groin, or abdomen. Patients may
also experience fever, weight loss, drenching night sweats, or other symptoms.
Extranodal disease — In about 40 percent of cases, the cancer does not begin in
the lymph nodes, but instead develops elsewhere. This is called extranodal
disease. The most common site of extranodal involvement is the stomach or
gastrointestinal tract, but the disease can arise in virtually any normal organ.
Advanced versus localized disease — Most patients (about 60 percent) are not
diagnosed with DLBCL until the disease is advanced (stage III or IV). In the
remaining 40 percent of patients, the disease is confined to one side of the
diaphragm (above or below the diaphragm). This is called localized disease

The normal architecture of this
lymph node from the
mediastinum has been
destroyed by the B-Cell infiltrate
DLBCL

Close-up from the previous
tumour.
The neoplastic lymphocytes are
large, with a large irregular
nucleus and coarse chromatin.
Mitotic figures are easily found.
This type of lymphoma may
occur de novo, or as an
advanced phase of a pre-existing
B-cell lymphoma such
as follicular or monocytoid
types.
DLBCL

The malignant lymphocytes here
are very large with a moderately
abundant cytoplasm, and the
nuclei are round to ovoid with
prominent nucleoli and
occasional mitoses.
The diagnosis is diffuse large B
cell lymphoma (also known as
immunoblastic lymphoma).
DLBCL

Enteropathy-associated T-cell
lymphoma (EATL)
Enteropathy-associated T-cell lymphoma is a very rare type of T-cell
lymphoma. It usually occurs in the small intestine, most often the middle
part (jejunum) or lower part closest to the large intestine (ileum). It may
also be called enteropathy-type T-cell lymphoma or intestinal T-cell
lymphoma.
EATL is associated with gluten sensitive enteropathy (GSE). People with
this disease cannot tolerate gluten, a protein found in many grains, such
as wheat, rye and barley (gluten sensitivity). A gluten-free diet helps
prevent EATL from developing, so this type of lymphoma does not
commonly occur in people diagnosed with GSE at a young age. Most
adults are diagnosed with the disease at the same time as their
lymphoma or shortly before their lymphoma is diagnosed.

lymphoma (EATL)
People with EATL often have ulcers in the small intestine,
an obstruction or a perforation in the wall of the intestine.
All of these can cause abdominal pain. EATL may spread to
the liver, spleen, lymph nodes, gallbladder, stomach, colon
or skin.
EATL is usually a fast-growing (aggressive) lymphoma. The
prognosis for people with EATL is often not very good.

lymphoma.
The tumour is seen deeply
infiltrating into adjacent
enteropathic mucosa.
lymphoma

lymphoma.
There is a heavy infiltrate of
eosinophils between the tumour
cells.
lymphoma

This is a common picture of
EATL with large tumour cells
with round or angulated
vesicular nuclei with prominent
nucleoli, and moderate to
abundant, pale-staining
cytoplasm. A heavy eosinophil
infiltrate is evident between the
tumour cells.
lymphoma

ALK-positive anaplastic large cell
lymphoma (ALCL)
Anaplastic large cell lymphoma (ALCL) is a rare type of T-cell
lymphoma. It accounts for about 1–2% of all cases of non-
Hodgkin lymphoma (NHL) in adults. ALCL usually starts in T
cells but, in some cases, it is hard to tell what type of cell the
cancer started in. This is called null-cell type.
ALCL can occur in any age group, but is more common in
children and young adults. It makes up about 14% of
childhood NHL cases. It affects more males than females.

lymphoma
Types of ALCL
There are 2 types of ALCL. ALCL can appear only in the skin (primary
cutaneous ALCL) or in organs throughout the body (primary systemic
ALCL).
A high number of ALCLs are associated with translocations involving the
ALK (anaplastic lymphoma receptor tyrosine kinase) gene.
ALK-positive tumours (sometimes referred to as ALKomas) have a better
outcome than ALK-negative ALCLs.
People whose lymphomas express ALK are usually younger.
ALK-negative ALCL is more common in older adults and often has an
aggressive course.

lymphoma
Characteristics
The lymphoma cells involved in ALCL have a certain marker
on their surface called the CD30 antigen. They also express
the anaplastic lymphoma kinase (ALK).
People with ALK-positive disease respond to chemotherapy
and have a more favourable outcome than people with ALK-negative
lymphoma.
Many people with ALK-negative ALCL will relapse and may
need more aggressive chemotherapy.
Primary cutaneous ALCL is usually ALK negative, whereas
primary systemic ALCL can be ALK positive or negative.

Fatal ALK-negative systemic
anaplastic large cell lymphoma
presenting with disseminated
cutaneous dome-shaped
papules and nodules
lymphoma

Infiltrate is composed of large
transformed lymphocytes,
including hallmark cells with
kidney-shaped nuclei.
The morphology of ALCL,
systemic type, consists of large
lymphoid cells with pleomorphic
or multiple prominent nuclei
and abundant cytoplasm.
Tumor cells grow in a cohesive
pattern, and there is often
sinusoidal spread in the lymph
nodes. Tumor cells express
CD30 and either T cell or no
specific lineage antigens (null
cell).
lymphoma

The End
Thank you for your attention.
I would like to thank the following for the use of several images and data:
Lichtman’s Atlas of Hematology
The American Society of Hematology
Weill Cornel University
Hematopathology for medical education – WebPath
Atlas of Hematopathology | 978-0-12-385183-3 | Elsevier

Haematopathology: an introduction to lymphoid neoplasms

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