2. NEOPLASTIC PROLIFERATIONS OF WHITE BLOOD CELLS
Lymphoid Neoplasms
Lymphoid Neoplasms
• Diverse group of entities
•
• In most (not all) instances , phenotype of neoplastic
In most (not all) instances , phenotype of neoplastic
cell closely resemble that of a particular stage of
cell closely resemble that of a particular stage of
cell closely resemble that of a particular stage of
cell closely resemble that of a particular stage of
normal lymphocyte differentiation
normal lymphocyte differentiation
• Neoplastic proliferation of lymphoid cells may present
as
Lymphocytic Leukemia
Lymphocytic Leukemia
Lymphoma
Lymphoma
3. NEOPLASTIC PROLIFERATIONS OF WHITE BLOOD CELLS
Lymphoid Neoplasms
Lymphoid Neoplasms
• Lymphoma- is proliferation of tumor cells arising
as discrete tissue masses in
Lymph Nodes or Extra Nodal Sites
Lymph Nodes or Extra Nodal Sites
• Lymphocytic Leukemia- presenting with
widespread BM involvement , accompanied by
presence of large number of tumor cells in PB.
Lymphocytic Leukemia and Lymphoma
Lymphocytic Leukemia and Lymphoma OVERLAP
OVERLAP
4. LYMPHOMA
LYMPHOMA
• This is a large group of > 100
large group of > 100 lympho
lympho-
-reticular
reticular
neoplasms
neoplasms
• The current WHO classification scheme uses
Morphological
Morphological Immunophenotypical
Immunophenotypical
Genotypical
Genotypical and Clinical Features
Clinical Features
to categorize these neoplasms.
5. Lymphoid Neoplasms : Classification
Present WHO classification: sorts the Lymphoid
Neoplasms into Five Broad Categories
1. Pre- B cell neoplasm (of immature B cell)
2. Peri- B cell neoplasm (of mature B cell)
2. Peri- B cell neoplasm (of mature B cell)
3. Pre T cell neoplasm (of immature T cell)
4. Peri T cell neoplasm (of mature T cell)
5. Hodgkin’s Lymphoma/ Disease ( HD)
Category 1, 2, 3, & 4 are collectively known as
Non Hodgkin’s Lymphoma ( NHL)
7. Lymphoid Neoplasms - Points of General Relevance
Facts & Important Principles
Facts & Important Principles
•
• Histological examination of LN / tissue
Histological examination of LN / tissue –
– Prerequisite
Prerequisite
•
• Neoplastic monoclonality vs. reactive polyclonality of
Neoplastic monoclonality vs. reactive polyclonality of
cells
cells.
cells
cells.
•
• 80
80-
-85% lymphoma are neoplasia of B cell origin
85% lymphoma are neoplasia of B cell origin
( genomic instability)
( genomic instability)
•
• Resemble some recognizable stage of cell
Resemble some recognizable stage of cell
differentiation
differentiation
8. Lymphoid Neoplasms - Points of General Relevance
Important Principle
Important Principle
•
• Often Immune system abnormalities
Often Immune system abnormalities
Loss of vigilance – susceptibility to infection
Breakdown of tolerance - auto immunity
•
• Neoplastic B & T cells tend to recapitulate the
Neoplastic B & T cells tend to recapitulate the
behavior of there normal counterparts
behavior of there normal counterparts
•
• Hodgkin lymphoma spread more orderly than others.
Hodgkin lymphoma spread more orderly than others.
Staging is very significant as HD is sometimes
Staging is very significant as HD is sometimes
restricted to one group of nodes.
restricted to one group of nodes.
9. Lymphoid Neoplasms
Hodgkin’s Lymphoma
Encompasses a group of lymphoid neoplasms,
Encompasses a group of lymphoid neoplasms,
Morphologically
Morphologically characterized by the presence
characterized by the presence
of
of Distinctive Neoplastic Giant Cells
Distinctive Neoplastic Giant Cells called
called -
of
of Distinctive Neoplastic Giant Cells
Distinctive Neoplastic Giant Cells called
called -
Reed Sternberg Cells
Reed Sternberg Cells - that induce the
that induce the
accumulation of reactive lymphocytes ,
accumulation of reactive lymphocytes ,
histiocytes ( macrophages) and granulocytes.
histiocytes ( macrophages) and granulocytes.
11. Hodgkin Lymphoma
•
• Arises
Arises - in single node or in chain of nodes
•
• Spread
Spread - anatomically contiguous nodes
•
• Characterized by
Characterized by -
- presence of
Distinctive Neoplastic Giant Cells
Distinctive Neoplastic Giant Cells R
R-
-S Cells
S Cells or Variants
Variants
•
• Neoplastic cells
Neoplastic cells are derived from GC
GC or Post GC B
Post GC B cells.
Neoplastic cells
Neoplastic cells are derived from GC
GC or Post GC B
Post GC B cells.
•
• Neoplastic cells constitute minor fraction
Neoplastic cells constitute minor fraction
1
1-
-5% of total tumor cell mass.
5% of total tumor cell mass.
•
• Accumulation of Reactive Infiltrate
Accumulation of Reactive Infiltrate
lymphocyte, granulocytes and macrophages
induced by R-S cells ( cytokine induced)
Occurs in young Pts and is almost curable now
12. Hodgkin Lymphoma
Hodgkin Lymphoma
Morphology
Identification of Reed Sternberg cells and their variants is
essential for the histological diagnosis of 5 subtypes
Classical HL subtypes :
RS & variant
RS & variant have similar immunopheno type
(CD 15 +, CD 30+)
(CD 15 +, CD 30+)
:Nodular sclerosis : Mixed
:Nodular sclerosis : Mixed cellularity
cellularity
:Lymphocyte depletion : Lymphocyte
:Lymphocyte depletion : Lymphocyte-
-rich
rich
(Non-classical form)
:Lymphocyte predominance, nodular
:Lymphocyte predominance, nodular :
RS have characteristic B cell immunopheno type
(CD 20 +)
(CD 20 +)
13. Hodgkin Lymphoma
R-S cell & variants
Diagnostic R-S cell
•Large 15-45µ in diam.
•
•Multiple nuclei or single
Multiple nuclei or single
multi lobated nuclei
multi lobated nuclei
•
•Each with large inclusion
Each with large inclusion
like nucleolus
like nucleolus
•Abundant cytoplasm
14. Hodgkin Lymphoma
R-S cell & variants
Mononuclear
Variant
•Similar to diagnostic RS
with only
only single ,
single ,
with only
only single ,
single ,
round or oblong
round or oblong
nucleus
nucleus
•
•Large inclusion like
Large inclusion like
nucleoli
nucleoli
15. Hodgkin Lymphoma
R-S cell & variants
Lacunar cells
•Delicate folded or
multi lobated nuclei
•
•Abundant pale
Abundant pale
•
•Abundant pale
Abundant pale
cytoplasm
cytoplasm
often disrupted,
often disrupted,
leaving nucleus sitting
in empty hole
(Lacunae)
(Lacunae)
17. Hodgkin Lymphoma
R-S cell & variants
• R-S cells are requisite for the diagnosis
but must be present in
An appropriate
An appropriate background
background of
of non
non-
-neoplastic
neoplastic
inflammatory cells
inflammatory cells
•
• R
R-
-S like cells
S like cells ( not variants) may be seen in some
NHLs; solid tissue tumors and infectious
mononucleosis
IHC markers & genetic studies are important for
IHC markers & genetic studies are important for
establishing the diagnosis
establishing the diagnosis
18. Hodgkin Lymphoma
Classical sub types
Nodular Sclerosis
•Most common form of HL
(65-70%)
• Equal in M:F, young adults
• Lower cervical, supra
clavicular & mediastinal
clavicular & mediastinal
Morphology –
NS-HL characterized by
1. Collagen bands
dividing the lymphoid
tissue into
circumscribed nodule
19. Hodgkin Lymphoma Classical sub types
Nodular Sclerosis
2. A particular variant of
R-S cell - Lacunar cell
Polymorphus small T cell
background CD - +3
background CD - +3
R-S cells CD 15 +, CD 30 +,
EBV : – ve
Prognosis : excellent with
therapy
20. Hodgkin Lymphoma Classical sub types
Mixed Cellularity – 20-25%
Age - older than NS HD,
male predominance
Morphology:
• Diffuse effacement of nodal
parenchyma by heterogeneous
heterogeneous
cellular infiltrate
cellular infiltrate
cellular infiltrate
cellular infiltrate
• Diagnostic RS cells &
mononuclear variant are
plentiful
•Immunophenotype
•
•CD 15+, CD30+
CD 15+, CD30+ : EBV + in 70%
EBV + in 70%
•B symptoms +
but prognosis is very good
21. Hodgkin Lymphoma Classical sub types
HL-Lymphocyte Rich Type
• Uncommon form of
classical HL
•Diffuse effacement by reactive
reactive
lymphocytic cellular infiltrate
lymphocytic cellular infiltrate
•
•Diagnostic RS cells &
Diagnostic RS cells &
mononuclear variant are
mononuclear variant are
frequent
frequent
mononuclear variant are
mononuclear variant are
frequent
frequent
• Immunophenotype
Immunophenotype
CD 15 +
CD 15 + ve
ve, CD30 +
, CD30 + ve
ve
with
with EBV +
EBV + ve
ve -
- 40%
40%
( D/d –HL, Lymphocyte
predominant)
Prognosis : Very good to
excellent
22. Hodgkin Lymphoma Classical sub types
HL Lymphocyte Depletion
type
•Least common less than 5%
•Older pts, HIV + pts, EBV +
Morphology:
Characterized by
• Paucity of lymphocytes
Paucity of lymphocytes
• Paucity of lymphocytes
Paucity of lymphocytes
•Relative abundance of
abundance of
R
R-
-S cells
S cells & pleomorphic cells.
•Phenotyping is critical to
diagnosis and identical to
HL-NS and HL-MC (CD15;30 +
ve) HBV – 90%
(Major D/d Large cell NHL)
Prognosis: Less favourable
23. Hodgkin Lymphoma Non Classical form
HL Lymphocyte Predominant
Uncommon variant
Uncommon variant -
- <5%,
Male predominance, < 35 yrs,
Cervical, Axillary LN common
Morphology
Morphology: characterized by
nodal effacement by
nodal effacement by
Nodular infiltrate
Nodular infiltrate of
small lymphocytes
small lymphocytes and
benign histiocytes.
benign histiocytes.
•
• L&H variant
L&H variant -
- frequent
frequent and
show B cell
B cell pheno
pheno type
type (CD 20 +)
(CD 20 +)
Diagnostic R-S cells -
- rare
rare
• Prognosis: excellent
27. Burkitt’s Lymphoma
Is a Nonhodgkin Lymphoma of Peripheral B-cell type
Presents clinically in 3 ways
1. African ( endemic
endemic ) Burkitt’s lymphoma
1. African ( endemic
endemic ) Burkitt’s lymphoma
2. Sporadic ( non endemic
non endemic ) Burkitt’s lymphoma
3. A subset of aggressive lymphomas
occurring in HIV infected individuals
in HIV infected individuals
28. Burkitt’s Lymphoma
•
• Both
Both endemic and sporadic forms are found in
children and young adults
children and young adults
30% of childhood NHLs in USA
•
• Most
Most manifest in extra nodal sites
manifest in extra nodal sites
- Endemic type
Endemic type involves
- Endemic type
Endemic type involves
Mandible and
Abdominal viscera
– ovaries, kidneys and adrenal glands
- Sporadic type
Sporadic type presents as an
abdominal mass in ileo-caecum and peritoneum
30. Burkitt’s Lymphoma
Immunophenotype:
Immunophenotype:-
-
• Tumors of mature B-cells -
express surface IgM, CD19, CD20 and CD10
and BCL 6
and BCL 6
Phenotype that closely resembles that of
rapidly dividing B cells within the dark zone of
normal germinal centre ( centroblasts
centroblasts )
31. Burkitt’s Lymphoma
• Diffuse infiltrate of
intermediate sized
lymphoid cells (10- 25μm
dia.)
• Moderate amount of faintly
basophilic or amphophilic
cytoplasm
• Round to oval nuclei with
• Round to oval nuclei with
coarse chromatin and
several nucleoli
•
• High mitotic index
High mitotic index
•
• Apoptotic
Apoptotic tumor cell death
and numerous macrophages
with ingested cell debri
diffusely distributed among
the tumor cells
•
• Starry sky
Starry sky appearence
appearence
32. Burkitt’s Lymphoma
Cytogenetics
Cytogenetics and Molecular genetics
and Molecular genetics
•
• Burkitt’s lymphoma are associated with
translocation c- MYC gene on chromosome 8
Molecular analysis shows that
Molecular analysis shows that
- All endemic tumors are latently infected with EBV
- All endemic tumors are latently infected with EBV
- All tumor cells in an individual case have identical
configuration of episomal
episomal EBV DNA
EBV DNA Indicating
Infection precedes cellular transformation and
supports role of EBV in lymphoma
lymphoma-
-genesis
genesis
33. Burkitt’s Lymphoma
• Involvement of BM and PB is uncommon
• Burkitt’s Lymphoma is very aggressive but
responds very well to high dose , short term
chemotherapy .
chemotherapy .
• Children and young adults are almost cured
• Outcome is more guarded in older adults
