Lymphomas are cancers that begin in the lymphatic system. They start in the lymph nodes or other lymphatic tissues such as the spleen. There are two main types of non-Hodgkin's lymphoma: B-cell and T-cell lymphomas. B-cell lymphomas account for about 80% of cases and start in B-cells. T-cell lymphomas account for 15% of cases and start in T-cells. Common types of B-cell lymphomas include diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Burkitt's lymphoma and lymphoblastic lymphoma are more common in children.

1. Lymphoma’sLymphoma’s
Where They BeginWhere They Begin
• Lymphomas are aLymphomas are a
cancer of thecancer of the
lymphatic systemlymphatic system
– Lymphatic vesselsLymphatic vessels
– Lymph nodesLymph nodes
(underarms, groin,(underarms, groin,
neck, spleen, tonsilsneck, spleen, tonsils
and bone marrow)and bone marrow)

2. Lymphoma’sLymphoma’s
Where They BeginWhere They Begin
• The Lymphatic system is our bodies mainThe Lymphatic system is our bodies main
fight against infectionfight against infection
• Lymphocytes (B-cell and T-cell)Lymphocytes (B-cell and T-cell)
– Carried through our lymphatic system andCarried through our lymphatic system and
help our bodies fight infectionhelp our bodies fight infection
– Lymphocytes are carried through the lymphLymphocytes are carried through the lymph
vessels as well as the blood stream, sovessels as well as the blood stream, so
cancer can start in nodes and spreadcancer can start in nodes and spread
anywhere throughout the body.anywhere throughout the body.
• The Lymphatic system is our bodies mainThe Lymphatic system is our bodies main
fight against infectionfight against infection
• Lymphocytes (B-cell and T-cell)Lymphocytes (B-cell and T-cell)
– Carried through our lymphatic system andCarried through our lymphatic system and
help our bodies fight infectionhelp our bodies fight infection
– Lymphocytes are carried through the lymphLymphocytes are carried through the lymph
vessels as well as the blood stream, sovessels as well as the blood stream, so
cancer can start in nodes and spreadcancer can start in nodes and spread
anywhere throughout the body.anywhere throughout the body.

3. Lymphatic TissueLymphatic Tissue
• Lymph nodes, spleen, liver, skin andLymph nodes, spleen, liver, skin and
the respiratory, GI and GTU tractthe respiratory, GI and GTU tract
• Lymphocytes undergo furtherLymphocytes undergo further
proliferation and differentiation inproliferation and differentiation in
lymphoid tissuelymphoid tissue
– B-lymphocytesB-lymphocytes
• tend to reside in lymph nodes & spleentend to reside in lymph nodes & spleen
– T-lymphocytesT-lymphocytes
• tend to circulate throughout the lymphatic systemtend to circulate throughout the lymphatic system

5. Lymph Node - normalLymph Node - normal
histologyhistology
afferent lymphatic vessel capsule
follicle (mainly B-
cells)
- germinal centre
- mantle zone
C
cortex
medulla
paracortex
efferent lymphatic vessel
artery
vein

6. Thomas Hodgkin
English pathologist, described the disease that bears his name in 1832.

8. • A heterogeneous group of B- and T-cellA heterogeneous group of B- and T-cell
malignancies that are diverse in cellularmalignancies that are diverse in cellular
origin, morphology, cytogeneticorigin, morphology, cytogenetic
abnormalities, response to treatment,abnormalities, response to treatment,
and prognosisand prognosis
• Any of a large group of cancers ofAny of a large group of cancers of
lymphocytes (white blood cells).lymphocytes (white blood cells).
NON-HODGKIN’SNON-HODGKIN’S
LYMPHOMA (NHL):LYMPHOMA (NHL):

9. Former First Lady
Jacqueline Kennedy Onassis

10. • Incidence of 13.3/100,000 per yearIncidence of 13.3/100,000 per year
• Predominates in the 40-70 yearsPredominates in the 40-70 years
age groupage group
– most common neoplasm in themost common neoplasm in the
20-40 age group20-40 age group
• Incidence is risingIncidence is rising
– 150% growth over the past 30150% growth over the past 30
yearsyears
– increasing by 4% annually sinceincreasing by 4% annually since
1970’s1970’s
• Mortality rate is also risingMortality rate is also rising
– 2% rise per year2% rise per year
– third highest rise, exceeded onlythird highest rise, exceeded only
by lung cancer in women andby lung cancer in women and
malignant melanomamalignant melanoma
NHL INCIDENCENHL INCIDENCE

11. Estimated Incidence of NHLEstimated Incidence of NHL
in the Year 2000 (Worldwide)in the Year 2000 (Worldwide)
Micronesia
Melanesia
Caribbean
Australia/New Zealand
Northern Africa
Western Africa
Northern Europe
Southeast Asia
Eastern Europe
South Central Asia
North America
0 10,000 20,000 30,000 40,000 50,000 60,000
Micronesia
Melanesia
Caribbean
Australia/New Zealand
Northern Africa
Western Africa
Northern Europe
Southeast Asia
Eastern Europe
South Central Asia
North America

12. B-Cell CancersB-Cell Cancers

13. EtiologyEtiology
• Not known.Not known.
• It is a late manifestation in HIV infection.It is a late manifestation in HIV infection.
• Specific lymphoma types are associated with EBV,HHV8Specific lymphoma types are associated with EBV,HHV8
• Gastric lymphoma can be associated with H.pyloriGastric lymphoma can be associated with H.pylori
infection.infection.
• Some lymphomas are associated with specificSome lymphomas are associated with specific
chromosomal lesion.chromosomal lesion.
• Lymphomas occur in congenital immunodeficiencyLymphomas occur in congenital immunodeficiency
states, immune suppressed individuals and after organstates, immune suppressed individuals and after organ
transplantaion.transplantaion.

14. PathogenesisPathogenesis

15. Malignant transformation of
either the T or B cells
Differentiation in the peripheral
lymphoid tissues
Predisposing
•Gender
•Race
•Family History
•Infections
•Immune System Deficiency
Disorders
•Autoimmune Disorders
•Chemical Exposure
•Radiation Exposure
•Lifestyle Factors
Precipitating
•Unknown
(idiopathic)

16. T lumphocytes proliferate on antigenic
stimulation and migrate into follicles,
where they intact in B lymphocytes
These activated follicles becme
germinal centers, containing
macrophages, follicular dendrite
cells and maturing T and B cells
Develops in any
lymphoid tissues (lymph
nodes

17. Spreads to various lymphoid
tissues throughout the body,
especially the liver, spleen and
bone marrow
Non-hodgkin’s
lymphoma
Group of tumors will
develop

18. Most common:
•painless
enlargement of one
or more lymph
node, usually in the
neck, armpits, or
groin. (painless,
superficial
lymphadenopathy)
•Usually
asymptomatic
Systemic B Sx:
•Drenching night
sweats
•Unexplained
weight loss
•Fever
•Severe itching

19. Types of LymphomaTypes of Lymphoma
• Indolent (low grade)Indolent (low grade)
– Life expectancy in years,Life expectancy in years,
untreateduntreated
– 85-90% present in Stage III or IV85-90% present in Stage III or IV
– IncurableIncurable
• IntermediateIntermediate
• Aggressive (high grade)Aggressive (high grade)
– Life expectancy in weeks,Life expectancy in weeks,
untreateduntreated
– Potentially curablePotentially curable

21. STAGING OF NHLSTAGING OF NHL

22. • Stage is the term used to describe theStage is the term used to describe the
extent of tumor that has spread throughextent of tumor that has spread through
the body( I and II are localized where as IIIthe body( I and II are localized where as III
and IV are advanced.and IV are advanced.
• Each stage is then divided into categoriesEach stage is then divided into categories
A, B, and EA, B, and E
– A: No systemic symptomsA: No systemic symptoms
– B: Systemic Symptoms such as fever,B: Systemic Symptoms such as fever,
night sweats and weight lossnight sweats and weight loss
– E: Spreading of disease from lymphE: Spreading of disease from lymph

23. The Non-Hodgkin’s Lymphoma Pathologic Classification Project. Cancer. 1982;49:2112.
MODIFIED ANN ARBORMODIFIED ANN ARBOR
STAGING OF NHLSTAGING OF NHL
• Stage IStage I Involvement of a single lymph node regionInvolvement of a single lymph node region
• Stage IIStage II Involvement ofInvolvement of ≥≥2 lymph node regions on2 lymph node regions on
the samethe same side of the diaphragmside of the diaphragm
• Stage IIIStage III Involvement of lymph node regions on bothInvolvement of lymph node regions on both
sides of the diaphragmsides of the diaphragm
• Stage IVStage IV Multifocal involvement ofMultifocal involvement of ≥≥1 extralymphatic1 extralymphatic
sites ± associated lymph nodes or isolatedsites ± associated lymph nodes or isolated
extralymphatic organ involvement with distant nodalextralymphatic organ involvement with distant nodal
involvement.involvement.

25. CATEGORIECATEGORIE
SS OF NON-OF NON-
HODGKIN’SHODGKIN’S
LYMPHOMALYMPHOMA

26. • Two main types of Non-Hodgkin’sTwo main types of Non-Hodgkin’s
Lymphoma:Lymphoma:
B-Cell and T-Cell LymphomasB-Cell and T-Cell Lymphomas
– B-Cell lymphomas (80%)B-Cell lymphomas (80%)
– T-Cell lymphomas (15%)T-Cell lymphomas (15%)

27. • B-Cells help make antibodies, which are proteinsB-Cells help make antibodies, which are proteins
that attach to and help destroy antigensthat attach to and help destroy antigens
• Lymphomas are caused when a mutation arisesLymphomas are caused when a mutation arises
during the B-cell life cycleduring the B-cell life cycle
• Various different lymphomas can occur duringVarious different lymphomas can occur during
several different stages of the cycleseveral different stages of the cycle
– Follicular lymphoma, which is a type of B-cellFollicular lymphoma, which is a type of B-cell
lymphoma is caused by a gene translocationlymphoma is caused by a gene translocation
which results in an over expressed gene calledwhich results in an over expressed gene called
BCL-2, which blocks apoptosis.BCL-2, which blocks apoptosis.

28. • The T-cells are born from stem cells,The T-cells are born from stem cells,
similar to that of B-cells, but mature in thesimilar to that of B-cells, but mature in the
thymus.thymus.
• They help the immune system work in aThey help the immune system work in a
coordinated fashion.coordinated fashion.
– These types of lymphomas are categorized byThese types of lymphomas are categorized by
how the cell is affectedhow the cell is affected
• Anaplastic Large cell Lymphoma, t-cell lymphomaAnaplastic Large cell Lymphoma, t-cell lymphoma
caused by a gene translocation in chromosome 5caused by a gene translocation in chromosome 5

29. •Diffuse Large B-Cell LymphomaDiffuse Large B-Cell Lymphoma
(DLBLC).(DLBLC). DLBCL is the most commonDLBCL is the most common
type of non-Hodgkins lymphoma,type of non-Hodgkins lymphoma,
accounting for about 30% of all NHLaccounting for about 30% of all NHL
cases. It is an aggressive, fast-growingcases. It is an aggressive, fast-growing
lymphoma that usually affects adults butlymphoma that usually affects adults but
can also occur in children. DLBCL cancan also occur in children. DLBCL can
occur in lymph nodes or in organsoccur in lymph nodes or in organs
outside of the lymphatic system. DLBCLoutside of the lymphatic system. DLBCL
includes several subtypes such asincludes several subtypes such as
mediastinal large B-cell lymphoma,mediastinal large B-cell lymphoma,
intravascular large B-cell lymphoma,intravascular large B-cell lymphoma,
and primary effusion lymphoma.and primary effusion lymphoma.

30. • Follicular LymphomaFollicular Lymphoma
(FLs).(FLs). FollicularFollicular
lymphoma is the secondlymphoma is the second
most common typemost common type
lymphoma, accountinglymphoma, accounting
for about 20% of all NHLfor about 20% of all NHL
cases. It is usuallycases. It is usually
indolent (slow growing)indolent (slow growing)
but about half ofbut about half of
follicular lymphomasfollicular lymphomas
transform over time intotransform over time into
the aggressive diffusethe aggressive diffuse
large B-cell lymphoma.large B-cell lymphoma.

31. • Mantle Cell LymphomaMantle Cell Lymphoma ..
Mantle cell lymphoma is anMantle cell lymphoma is an
aggressive type of lymphoma thataggressive type of lymphoma that
represent about 7% of NHL cases.represent about 7% of NHL cases.
It is a difficult type of lymphoma toIt is a difficult type of lymphoma to
treat and often does not respond totreat and often does not respond to
chemotherapy. It is found in lymphchemotherapy. It is found in lymph
nodes, the spleen, bone marrow,nodes, the spleen, bone marrow,
and gastrointestinal system. Mantleand gastrointestinal system. Mantle
cell lymphoma usually develops incell lymphoma usually develops in
men over agemen over age 60.60.

32. • SmallSmall
LymphocyticLymphocytic
LymphomaLymphoma
(SLL).(SLL). SLL is anSLL is an
indolent type ofindolent type of
lymphoma that islymphoma that is
closely related toclosely related to
B-cell chronicB-cell chronic
lymphocyticlymphocytic
leukemia (CLL).leukemia (CLL).
It accounts forIt accounts for
about 5% of NHLabout 5% of NHL
cases.cases.

33. • Marginal ZoneMarginal Zone
LymphomasLymphomas (MZL).(MZL).
MZLs are categorizedMZLs are categorized
depending on where thedepending on where the
lymphoma is located.lymphoma is located.
Mucosa-associatedMucosa-associated
lymphoid tissuelymphoid tissue
lymphomas (MALT)lymphomas (MALT)
usually involve theusually involve the
gastrointestinal tract,gastrointestinal tract,
thyroid, lungs, salivathyroid, lungs, saliva
glands, or skin. MALT isglands, or skin. MALT is
often associated with aoften associated with a
history of anhistory of an
autoimmune disorderautoimmune disorder
(such as Sjogren(such as Sjogren
syndrome in thesyndrome in the
salivary glands orsalivary glands or
Hashimoto's thyroiditisHashimoto's thyroiditis
in the thyroid gland).in the thyroid gland).

34. • Burkitt's LymphomaBurkitt's Lymphoma.. ThisThis
is one of the mostis one of the most
common types ofcommon types of
childhood NHL,childhood NHL,
accounting for about 40%accounting for about 40%
of NHL pediatric cases inof NHL pediatric cases in
the United States. Itthe United States. It
usually starts in theusually starts in the
abdomen and spreads toabdomen and spreads to
other organs, includingother organs, including
the brain. In Africanthe brain. In African
children, it often involveschildren, it often involves
facial bones and isfacial bones and is
associated with Epstein-associated with Epstein-
Barr infection.Barr infection.

35. • LymphoblasticLymphoblastic
LymphomaLymphoma. This. This
lymphoma is alsolymphoma is also
common in children,common in children,
accounting for aboutaccounting for about
25% of NHL pediatric25% of NHL pediatric
cases, most often boys.cases, most often boys.
It is associated with aIt is associated with a
large mediastinal masslarge mediastinal mass
(occurring in chest(occurring in chest
cavity between thecavity between the
lungs) and carries alungs) and carries a
high risk for spreadinghigh risk for spreading
to bone marrow, theto bone marrow, the
brain, and other lymphbrain, and other lymph
nodes.nodes.

36. Clinical featuresClinical features
• Peak incidence at 60 years. Can occur at any age.Peak incidence at 60 years. Can occur at any age.
• Usually widespread at the time of diagnosis.Usually widespread at the time of diagnosis.
• Discrete, painless, firm lymph nodal enlargement is theDiscrete, painless, firm lymph nodal enlargement is the
most common presentation. Waldeyer’s ring andmost common presentation. Waldeyer’s ring and
epitrochlear lymph nodes are frequently involved.epitrochlear lymph nodes are frequently involved.
• B symptoms: night sweats, weight loss, fever are lessB symptoms: night sweats, weight loss, fever are less
prominent.prominent.
• Early involvement of extra lymphatic organ is a feature ofEarly involvement of extra lymphatic organ is a feature of
NHL.NHL.
• GIT, CNS, skin, thyroid are frequently involved.GIT, CNS, skin, thyroid are frequently involved.
• Bone marrow involvement is common and early.Bone marrow involvement is common and early.
• Involvement of liver and spleen results inInvolvement of liver and spleen results in
hepatosplenomegaly.hepatosplenomegaly.
• Bone involvement can manifest as pathological fractureBone involvement can manifest as pathological fracture
with pain.with pain.

37. ManagementManagement

38. InvestigationsInvestigations
• Lymph node biopsy.Lymph node biopsy.
• Hemogram: Anemia, lymphocytosis in some patients,Hemogram: Anemia, lymphocytosis in some patients,
leukemic phase develops in 20-40% of lymphocyticleukemic phase develops in 20-40% of lymphocytic
patients.patients.
• Bone marrow aspiration.Bone marrow aspiration.
• Immunotyping of blood, lymph node, marrow lymphoidImmunotyping of blood, lymph node, marrow lymphoid
cells.cells.
• S.Uric acid.S.Uric acid.
• X-Rays.X-Rays.
• CT scans.CT scans.
• Magnetic Resonance Imaging (MRI).Magnetic Resonance Imaging (MRI).

40. T
R
E
A
T
M
E
N
T

41. • Non-Hodgkin’s Lymphoma is usually treated byNon-Hodgkin’s Lymphoma is usually treated by
a team of physicians including hematologists,a team of physicians including hematologists,
medical oncologists and a radiation oncologist.medical oncologists and a radiation oncologist.
• In some cases such as for Indolent lymphomas,In some cases such as for Indolent lymphomas,
the Doctor may wait to start treatment until thethe Doctor may wait to start treatment until the
patient starts showing symptoms, known aspatient starts showing symptoms, known as
“watchful waiting”“watchful waiting”

42. •Radiation therapy
-uses high doses of X-
rays, gamma rays, or
other types of ionizing
(damaging) radiation
to kill cancer cells. It
may be applied to the
whole body or to a
specific zone.

43. •Chemotherapy is the
use of cytotoxic (cell
damaging) medicines
to target and kill
tumors. The drugs
work by interrupting
the DNA of fast-
growing cells,
preventing them from
growing or
reproducing.

44. Chemotherapy regimenChemotherapy regimen
• CHOP regimen- Cyclophophamide,CHOP regimen- Cyclophophamide,
Hydroxunorubicin(adriamycin), OncovinHydroxunorubicin(adriamycin), Oncovin
(vincristine), Prednisolone.(vincristine), Prednisolone.

45. •Immunotherapy uses the
body’s own immune system
to attack and remove cancer
cells. Doctors inject a
patient with a special type of
antibody, or cell marker, that
binds to antigens on a cell’s
surface. Antibody against
CD20: Rituxan, Bexxar,
Zevalin.

46. •Bone marrow
transplantation
•For patients with very
advanced disease,
extremely high does of
chemotherapy may be
needed. This type of
chemotherapy wipes out
the body’s entire immune
system, including the bone
marrow that produces blood
cells. So, patients need a
bone marrow transplant in
order to recover.

47. • Survival Rates vary widely by cell type andSurvival Rates vary widely by cell type and
staging.staging.
– 1 Year Survival Rate: 77%1 Year Survival Rate: 77%
– 5 Year Survival Rate: 56%5 Year Survival Rate: 56%
– 10 Year Survival Rate: 42%10 Year Survival Rate: 42%