1. 1

2. 2

3. STAGE CRITERIA
I In one lymph node only
II In 2 or more LN on same side of the diaphragm
III In the Lymph nodes, Spleen, or Both AND on Both
sides of the diaphragm
1 Above the renal vessels (eg. Spleen, splenic, hilar,
celiac, portal nodes
2 In the lower abdomen ( periaortic, pelvic, or
imguinal nodes )
IV Extranodal involvement ( eg. Bone marrow, Lung,
Liver )
A – absence of Systemic manifestation
B – presence of Systemic manifestation
NIGHT SWEATS, FEVER, WEIGHT LOSS

4.  LYMPHOID NEOPLASM
 MYELOID NEOPLASM - Hematopoietic stem
cells
◦ MYELOID LINEAGE
 1. ERYTHROID
 2. GRANULOCYTIC
 AML
 MYELODYSPLASTIC
 CHRONIC MYELOPROLIFERATIVE D/O
 3. THROMBOCYTIC
 HISTIOCYTOSES
4

5.  Acute Myelogenous
◦ Immature progenitor cells accumulate in BM
 Myelodysplastic Syndromes
◦ Ineffective Hematopoiesis
◦ Peripheral Cytopenias
 Chronic Myeloproliferative D/O
◦ Increased production
◦ 1 or more terminally differentiated myeloid
elements
 GRANULOCYTES
◦ Leads to elevated peripheral blood counts
5

6. •Lymphoid Neoplasms
•Oncogenic rearrangement
•Mutation in oncogenes r/t inherent
genomic instability of germinal B cells
•Myeloid Neoplasms
•Chromosmal translocation
•Unknown mechanism
CHROMOSOMAL
TRANSLOCATION AND
ONCOGENES
6

7.  Mutated genes  Produce Negative protein
◦ Interfere with its normal function/ or Inapropriate
increase in some normal activity ( MALTomas )
 Translocation of either MALT1 or BCL10 protein 
Upregulation of NF-kB
 Normally Bind to form complex  regulate NF-kB
 NF-kB has important pro-survival function in normal
lymphocytes
 Oncoprotein created by genomic abberations
◦ Often Block normal maturation  Affect rapidly
proliferating cells
◦ Acute Leukemias
 Proto-Oncogenes
◦ Often activated in lymphocytes by errors that occur
during attempted antibody diversification
7

8. •Promote genomic instability
•Down syndrome
•Fanconi anemia
Inherent Genetic Factors
8

9. Viruses
•HTLV-1
•Adult T cell Leukemia/ Lymphoma
• EBV
•Burkitts, Hodgkins
•Diminsihed T cell dependent Immune surveillance
• KSHV/HHV-
• Kaposi sarcoma herpes virus/
• Human herpes Virus 8
9

10. Chronic Immune Stimulation
•H. pylori- Gastric
lymphoma
•Gluten enteropathy –
Intestinal lymphoma
T cell dysregulation 
Systemic hyperplasia of
germinal center B cells
•HIV B cell Lymphoma
•Arise w/in virtually any
organ
Diminsihed T
cell dependent
Immune
surveillance
• EBV
10

11. Iatrogenic Factors
Mutagenic effects on
Progenitor cells
•Radiotherapy
•Chemotherapy
11

12. Incidence of AML increased 1.3 to 2 fold
in smokers
Exposure to carcinogens
like benzene in tobacco
smoke
12

13. STAGE CRITERIA
I In one lymph node only
II In 2 or more LN on same side of the diaphragm
III In the Lymph nodes, Spleen, or Both AND on Both
sides of the diaphragm
1 Above the renal vessels (eg. Spleen, splenic, hilar,
celiac, portal nodes
2 In the lower abdomen ( periaortic, pelvic, or
imguinal nodes )
IV Extranodal involvement ( eg. Bone marrow, Lung,
Liver )
A – absence of Systemic manifestation
B – presence of Systemic manifestation
NIGHT SWEATS, FEVER, WEIGHT LOSS

14. 14

15. 1. Lymphocytic Leukemia
2. Lymphoma
3. Plasma cell Neoplasm
15

16.  Lymphoid neoplasm
 Widespread Bone Marrow
Involvement
 Usually (+) Large Numbers of
Tumor cells in Peripheral smear
16

17.  Proliferations arising as Discrete
tissue masses
 2 Types
◦ 1. Non-Hodgkins Lmphoma
◦ 2. Hodgkins Lymhoma
 Many types present with Leukemia
◦ Term used – Tissue distribution of the
disease at time of clinical presentation
17

18.  Most commonly arise in Bone
Marrow
 Rarely present as Leukemia
 R/T Secretion of Antibodies by
tumor cells
18

19.  Vast majority are B cell in origin
 Markers recognized by Antibodies
help in characterization into 5
categories
 Often disrupt normal architecture &
function of Immune system
◦ Susceptibility to infection
◦ Autoimmune
19

20.  Inherited or acquired
Immunedeficiency  High risk
certain lymphoid neoplasm
◦ Particularly caused by oncogenic
virus eg. EBV
20

21.  Tend to home to a particular tissue
sites
◦ Follicular Lymphoma – Germinal center
◦ T-cell Lymphomas – Skin
 Some recirculate through the
lymphatics & peripheral blood 
Distant sites
◦ Except Hodgkins, Marginal zone
lymphoma ( MALToma )
21

22.  Determined by Anatomic distribuation
of disease
◦ 2/3 NHL and 100% of Hodgkin
Lymphomas
 Enlarged Nontender LN
 Often > 2 cm
◦ Remaining 1/3 NHL
 Symptoms r/t to involvement of Extranodal
sites
 Skin, Stomach, Brain
22

23.  Abrupt stormy onset
◦ Present w/in days to few weeks
 S/S related to Suppression of
normal Hematopoiesis by tumor
cells in BM
 Characteristic is Infiltrate in
Spleen & Liver
23

24.  Involve the skeleton
◦Local bone destruction
◦Pain
◦Pathologic Fractures
 Addendum
◦Secretion of whole Ab or Ig
fragments
24

25.  Precursor B cell Neoplasm
◦ Immature B cells
 Peripheral B cell Neoplasms
◦ Mature B cells
 Percursor T-cell Neoplasm
◦ Immature T cells
 Peripheral T-cell & NK cell
Neoplasm
◦ Mature T cell & NK cells
 Hodgkin Lymphoma
25

26. Precursor B and T –Cell Neoplasms
-Neoplasm of Immature B & T cells
-lymphoblast
26

27.  Group of Neoplasm composed of
Immature pre-B or Pre-T
LYMPHOBLASTS
 Most common cancer of Children
 Slightly higher in boys
 2 Types:
◦ 1. Pre-B cell
◦ 2. Pre-T cell
◦ Both tumors types are
morphologically indistinguishable
27

28.  85% Childhood Acute Leukemia
◦ Are pre B cells
◦ Affect children
◦ Peak age is 3 y/o
◦ Extensive BM involvement
◦ Variable Peripheral involvement
◦ Uncommonly present as Lymphoma
 Less common As Thymic Lymphoma
◦ Are pre-T cells
◦ Adolescent males
◦ Many evolve to Leukemia
28

29.  B-ALL
◦ Leukemic Presentation
◦ Marrow Hyperplasia and packed with
Lymphoblast
 T-ALL
◦ Mediastinal thymic mass
◦ Often with LNadenopathy & Splenomegaly
29

30.  Lymphoblast in PBS
◦ Definitve Dx based on Lymphocyte –
specific markers with Antibodies
◦ Histochemical stain
 Negative for myeloperoxidase
 Often (+) PAS in cytoplasmic aggregates
◦ Immunophenotype
 (+) TdT in > 95% of cases
 DNA polymerase
 Expressed only in pre-B and pre-T
lymphoblast
30

31. 31

32.  B-ALL lymphoblast (+)
◦ CD19, CD10, CD19, CD20
 T-ALL lymphoblast (+)
◦ CD1, CD2, CD5, CD7
 Arrest in normal Maturation of
Lymphoblast
◦ Dysregulation in epxression and function
of transcription factors
32

33.  About 90% ALL have numerical or structural
chromosomal changes
◦ Most commonly – Hyperploidy
 > 50 chromosomes
◦ Hypoploidy
◦ Translocation
 Hyperploidy & Hypoploidy are seen only in
B-ALL
 B & T ALL are associated wuth completely
different sets of translocation
33

34.  70% of T-ALL
◦ Have gain-of-function mutations in NOTCH1
◦ NOTCH1 is essential for T-cell development
 High Fraction of B-ALL
◦ Have loss-of-function mutations in genes for B cell
development
NET EFFECT:
1. Disturb differentiation of Lymphoid precursor
2. Promote Maturation arrest
Single mutations are not sufficient to produce ALL 
Must Acquire additional mutation before ALL
develop
34

35.  Abrupt stormy onset
 Present w/in days to few weeks
 Symptoms r/t bone marrow
suppression
◦ Anemia , Infection, Bleeding episodes
35

36.  Mass Effects
◦ Bone pain & tenderness
◦ Generalized Lymphadenopathy, Splenomegaly,
Hepatomegaly
◦ T-ALL
 Complications R/T complression of large vessels and
Airways in mediastinum
 Both may have CNS manifestation
◦ Due to meningeal spread
◦ Headache, Vomiting, Nerve palsies
36

37. 37

38.  Aggressive ChemoTx often w/
prophylactic CNS treatment
◦> 95% of children achieve
complete remission
◦75-85% of choldren are Cured
 Still the leading cause of
cancer death in children
38

39.  < 2y/o
 Presentation in adolescence or
childhood
 Peripheral blast count > 100,000
 Presence of Ph’ chromosome
◦ T(9;22)
◦ Commonly seen in adult patients
 ALLOGENIC BM TRANSPLANT – POOR
PROGNOSTIC CATEGORIES
39

40.  Age 2-10 y/o
 Low WBC count
 Early pre-B phenotype
 Hyperploidy or t(12;21)
40

41. 41
1. Chronic Lymphocytic Leukemia & Small
Lymphocytic Lymphoma
2. Follicular Lymphoma
3. Diffuse Large Cell Lymphoma
4. Extranodal marginal zone Lymphoma
5. Burkitts Lymphoma

42. 42

43. •Similar - Morphological,
Phenotype, Genotype
•Differ only in degree of peripheral
blood Lymphocytosis
43

44. • CLL – Chronic Lymphocytic Leukemia
▫ Most common leukemia of Adults in Western
countries
 Median age 60 y/o
 2:1 male preponderance
▫ Diagnostic Criteria
 Absolute Lymphocytosis > 4000 per mm3
▫ PERIPHERAL BLOOD
 WBC counts is High
 Increased numbers of Small Lymphocytes
 Smudge cell
44

45. Chronic Lymphocytic Leukemia
45

46. • SLL – Small Lymphocytic Lymphoma.
▫ Represent 4% of Non-Hodgkin Lymphoma
▫ Total WBC count is Variable
▫ If w/ Bone Marrow Involvement can present as
Leukopenia
▫ LYMPH NODE
 Diffusely Effaced , Predominant Small Lymphocytes
 Variable large Prolymphocytes
 CREATE PROLIFERATION CENTERS
▫ PATHOGNOMONIC FOR CLL/SLL
46

47. 47

48. Immunophenotype/ Molecular
Genetics
• CD5 – present in tumor cells
▫ T-cell marker
▫ Expressed by small subset of normal B
lymphos
• Chromosomal translocation is rare
• Most are Deletions
▫ 13q14
▫ 11q
▫ 17p
48

49. Clinical Features
• Mostly over 50 y/o
• Male > Female 2:1
• Often Asymptomatic
• Nonspecific symptoms when manifest
• BONE MARROW INVOLVEMENT
▫ All cases of CLL
▫ Most cases of SLL
49

50. Clinical Features
• 50-60% show
▫ Generalized Lymphadenopathy
▫ Hepatosplenomegaly
• VARIABLE INVOLVEMENT OF SPLEEN
& HEPATIC PORTAL TRATS
50

51. Clinical Features
•Disrupts Immune function
▫ Hypogammaglobulinemia – Susceptible
to INFXN
▫ Autoimmune
 Auto-Antibodies produced by non-
neoplastic B cells
▫ 10-15% develop Hemolytic anemia
/Thrombocytopenia
51

52. •Extremely Variable
▫ Depend mostly on Stage
•Overall Median is 4-6 years
•Minimal Tumor burden  10
years
52

53. • Presence of Deletions 11q & 17p
▫ Usually higher stage
• Transformation to higher grades
▫ Prolymphocytic 15%-30%
 Worsening cytopenias
 Increasing Splenomegaly
▫ Diffuse Large cell 5%-10%
 Rapidly enlarging mass w/in LN or spleen
 Richter syndrome
▫ Survival < 1 year
53