Download Mantle cell lymphoma

lymphoid neoplasms
Rasha M. Abd-Rabh
lecturer of pathology
faculty of medicine –Benha university
Histology
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Bean –shaped structure
Cortex
paracortex
Medulla
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Lymph nodes are usually bean-shaped, with an
indented region known as the hilum.
They are covered by a collagenous capsule that
extends into the body of the node as trabeculae.
The body of the lymph node is divided into an
outer cortex and an inner medulla.
The cortex contains a high concentration of
lymphocytes while the inner medulla is less
cellular.
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In the cortex, B-lymphocytes are localized in
lymphoid follicles just beneath the capsule. In
absence of an active immune response, these
follicles are known as primary lymphoid
follicles.
When an immune response is underway, focal
points of intense B-cell proliferation known as
germinal centers can be found in some follicles.
These follicles then become known as
secondary lymphoid follicles.
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The T-lymphocytes are located deeper within
the cortex and are diffusely distributed in the
paracortical area.
In the medulla, parts of the cortical cell mass
extends as the medullary cords. This region
contains macrophages and antibody-secreting
plasma cells.
Definition
include a diverse group of tumors of B-cell,
T-cell, and NK-cell origin.
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In many instances the phenotype of the
neoplastic cell closely resembles that of
a particular stage of normal lymphocyte
differentiation, a feature that is used in the
diagnosis and classification of these disorders.
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The vast majority (85% to 90%) of lymphoid
neoplasms are of B-cell origin, with most of
the remainder being T-cell tumors; only
rarely are tumors of NK cell origin
encountered.
Origin of lymphoid neoplasms
WHO Classifications
The WHO 2008 classifications uses morphologic,
immunophenotypic, genotypic, and clinical features to sort the
lymphoid neoplasms into five broad categories,which are
separated according to the cell of origin:
1. Precursor B-cell neoplasms (neoplasms of immature B cells)
2. Peripheral B-cell neoplasms (neoplasms of mature B cells)
3. Precursor T-cell neoplasms (neoplasms of immature T cells)
4. Peripheral T-cell and NK-cell neoplasms (neoplasms of
mature T cells and NK cells)
5. Hodgkin lymphoma (neoplasms of Reed-Sternberg cells and
variants)
Pathogenesis
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Chromosomal translocations and other acquired
mutations.
Viruses.
Chronic Immune Stimulation.
Iatrogenic Factors.
To diagnose
Clinical data
Gross examination
Microscopic picture
Immunophenotyping
& cytogenetic
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Clinical data: Age , Sex , Site and pattern of
involvement , Blood picture.
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Gross examination: size of lymph node,
homogenous, nodular .
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Microscpoic examination:
-L.N architecture.
-Pattern of growth; diffuse, nodular, sinusal.
-monomorphic or pleomorphic cellular infiltrate.
-Cellular feature
-cell size
-cytoplasm
- Nucleus &chromatin
-Nucleoli
- mitosis
- characteristic feature
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Immunophenotping :
-Monoclonal or polyconal.
Clonal rearrangement of IG gene → B-cell
lymphoma
Clonal rearrangement of T –cell receptors→T –
cell lymphoma
PRIMARILY T-CELL ASSOCIATED
 CD1 :Thymocytes and Langerhans cells
 CD3 :Thymocytes, mature T cells
 CD4 :Helper T cells, subset of thymocytes
 CD5 :T cells and a small subset of B cells
 CD8 :Cytotoxic T cells, subset of thymocytes, and some NK
cells
PRIMARILY B-CELL ASSOCIATED
 CD10: Pre-B cells and germinal-center B cells
 CD19: Pre-B cells and mature B cells but not plasma cells
 CD20 :Pre-B cells after CD19 and mature B cells but not plasma
cells
 CD21:EBV receptor; mature B cells and follicular dendritic cells
 CD23:Activated mature B cells
 CD79aMarrow pre-B cells and mature B cells
1-Acute Lymphoblastic
Leukemia/Lymphoma
(ALLs) are neoplasms composed of immature B
(pre-B) or T (pre-T) cells which are referred to
as lymphoblasts
children and adolescents, but it also occurs in
adults (About 50% of the cases present as a
mediastinal mass).
Morphology
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Diffuse &paracortical region.
Scant basophilic cytoplasm.
nuclei somewhat larger than those of small lymphocytes
The nuclear chromatin is delicate and finely stippled. In
many cases the nuclear membrane is deeply subdivided,
imparting a convoluted appearance.
nucleoli are either absent or inconspicuous.
the mitotic rate is high.
As with other rapidly growing lymphoid tumors,
interspersed macrophages ingesting apoptotic tumor cells
may impart a “starry sky” appearance
Differential diagnosis
1- Burkitt lymphoma
2- blastoid variant of mantle cell lymphoma
Immunophenotyping
All express TDT ( am marker of thymocytes)
80-85% show T –cell markers (CD1, CD2, CD7).
15-20% show B-cell markers (CD19, CD20,).
CD99+ve
CD34 +ve
2-Small lymphocytic lymphoma
Low grade –B cell lymphoma.
Affects middle aged and elderly individuals.
It is the most common of the B –cell neoplasms to
involve the spleen.
-Diffuse
effacement of the nodal architecure.
-monotonous population .
-small round mature –appearing lymphocytes -clumped chromatin.
-inconspicuous nucleoli.
-barely visible cytoplasm.
-Scanty mitotic activity .
as well as scattered
pro-lymphocytes/paraimmunoblasts(large cell with
vesicular nuclei and distinct nucleoli, singly or in small
aggregates that simulate germinal centers. These
formations (known as proliferative centers, growth
centers, or pseudofollicles) have an increased number
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Diffuse
Small sized
Scanty cytoplasm
Clumped chromatin
Inconspicious nucleoli
Low mitosis
Scattered
prolymphocytes
Immunohistochemistry
-Pan –B- cell markers(CD20,CD19, Surface Ig)
-CD23, CD5 +ve.
Differential diagnosis
1- mantle zone lymphoma.
3-Follicular lymphoma
It is a low grade neoplasm composed of
follicle center (germinal center) B cells
(typically both centrocytes and
centroblasts)
The disease occurs with a median age of 60 years
and with a slight female predominance. Pediatric
cases are rare.
Microscopically :
a predominantly nodular or nodular and diffuse growth
pattern.
Two principal cell types are present in varying
proportions:
(1) small cells with irregular or cleaved nuclear contours
and scant cytoplasm, referred to as centrocytes (small
cleaved cells);
and
(2) larger cells with open nuclear chromatin, several
nucleoli, and modest amounts of cytoplasm, referred to
as centroblasts
3) Absent or low mitosis.
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Depending on the relative proportion of small and
large cells, follicular lymphomas are subdivided into
three categories, respectively designated in the WHO
classification as follows :
Grade 1: with 0 – 5 centroblasts (large nucleolated
cells) per high-power field.
Grade 2: with 6–15 centroblasts per high-power
field
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Grade 3 : with more than 15 centroblasts per highpower field. G3a&G3b
Immunohistochemistry:
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expressing CD19, CD20, and, surface Ig.
Germinal center B- cell markers: Cd10&Bcl-6
BCL2 is expressed in more than 90% of cases,
in distinction to normal follicular center B cells,
which are BCL2-negative
Cytogenetic :
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The hallmark of follicular lymphoma is a (14;18)
translocation that juxtaposes the IgH locus on
chromosome 14 and the BCL2 locus on
chromosome 18. leads to overexpression of
BCL2 .
BCL2 antagonizes apoptosis and promotes the
survival of follicular lymphoma cells.
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Nodular
Closely packed follicles
Two populations of cells
Absent mitosis
Differential diagnosis
1- reactive follicular hyperplasia
4- Mantle cell lymphoma
Mantle cell lymphoma is a low-grade B-cell
neoplasm.
Also known as intermediate lymphocytic, mantle
zone, centrocytic, and diffuse small cleaved cell
lymphoma.
it usually occurs in middle-aged and elderly
individuals.
Commonly affects male.
Microscopically
1Diffuse effacement by monomorphic small lymphocytes
2- irregular nuclear contours
3- clumped chromatin
4- inconspicuous nucleoli
5- minimal cytoplasm
6-no residual germinal centers formation
7-hyalinized blood vessels & scattered epithloid cells
Immunophenotyping
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Pan B cell markers
Over expression of cyclin D1
+ve for CD5
_ve for CD23, CD10 and BCL-2.
5- marginal zone lymphoma
An uncommon and indolent B-cell lymphoma.
Affect eldelry patients & slight female
predominance.
Microscopically
the nodules are formed of medium -sized
lymphocytes with irregular nuclear contours,
moderate abundant clear cytoplasm, and
condensed nuclear chromatin.
The pattern of involvement is predominantly
sinusal and interfollicular.
Immunophenotyping
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Pan B-cell markers(CD19, CD20)
_ve for CD5, CD23 and cyclin D1,CD10
No Bcl-2 or Bcl-6 genes rearrangement.
Immuno
Histochemical
markers
Pan-B-cell
markers
1-Mantle
cell
lymphoma
+ve
CD10
2-Follicular
lymphoma
+ve
3-Marginal
zone
lymphoma
4- small
lymphocytic
lymphoma
+ve
+ve
+ve
CD5
+ve
-ve
-ve
+ve
CD23
-ve
-ve
-ve
+ve
Cyclin D1
+ve
-ve
-ve
-ve
+ve
-ve
-ve
Bcl-2
6-Burkitt lymphoma
Is a highly aggressive B-cell neoplasm that
occurs in three major clinical forms:
endemic, sporadic, and immunodeficiency
associated.
All three types present primarily
in extranodal sites, including the GI tract.
There are three variants of BL:
 the endemic form occurs in Africa, is caused by
infection with the Epstein Barr virus (EBV), and
affects children between 4 and 7 years of age.
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the sporadic form occurs throughout the word
in children and young adults.
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immunodeficiency-associated form is related to
HIV infection.
Microscopically
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Nodal architecture is effaced with a diffuse or nodular
infiltrate
The cells are medium sized and uniform.
Large vesicular nuclei.
scant cytoplasm, clumpy chromatin,
multiple small nucleoli.
numerous mitotic figures.
Many apoptotic bodies and tingible body macrophages
with phagocytosed nuclear debris create a starry-sky
pattern.
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Diffuse or nodular
Medium –sized
Clumped chromatin
Vesicular nulcei
Multiple prominent
nucleoli
Increased mitosis
Starry sky appearance
Immunohistochemistry:
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B-cell phenotype (positive for CD10, CD19,
CD20, PAX5, and bcl-6); expresses sIg.
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High Ki67
Negative for CD23, Cd30, TdT
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Cytogenetic :
-all three forms are linked with Myc translocation
(t8,14) in about 90% of cases.
7-Diffuse large B cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL) is the
most common form of NHL
Predominantly affects females; peak incidence
between 20 and 40 years of age
Microscopically
Diffuse growth pattern composed of large
atypical
lymphoid cells with reniform or multilobated
nuclei, vesicular chromatin, and distinct nucleoli
Large amounts of pale or clear cytoplasm
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Diffuse
Large –sized
Vesicular nuclei
Prominent nucleoli
Immunohistochemistry:
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These mature B-cell tumors express CD19 and
CD20 and show variable expression of germinal
center B-cell markers such as CD10 and BCL6.
Most have surface Ig