Lymphoma’sLymphoma’sWhere They BeginWhere They Begin

• Lymphomas are a Lymphomas are a cancer of the cancer of the lymphatic systemlymphatic system– Lymphatic vesselsLymphatic vessels– Lymph nodes Lymph nodes

(underarms, groin, (underarms, groin, neck, spleen, tonsils neck, spleen, tonsils and bone marrow)and bone marrow)

Lymphoma’sLymphoma’sWhere They BeginWhere They Begin

• The Lymphatic system is our bodies The Lymphatic system is our bodies main fight against infectionmain fight against infection

• Lymphocytes (B-cell and T-cell)Lymphocytes (B-cell and T-cell)– Carried through our lymphatic system Carried through our lymphatic system

and help our bodies fight infectionand help our bodies fight infection– Lymphocytes are carried through the Lymphocytes are carried through the

lymph vessels as well as the blood lymph vessels as well as the blood stream, so cancer can start in nodes and stream, so cancer can start in nodes and spread anywhere throughout the body.spread anywhere throughout the body.

• The Lymphatic system is our bodies The Lymphatic system is our bodies main fight against infectionmain fight against infection

• Lymphocytes (B-cell and T-cell)Lymphocytes (B-cell and T-cell)– Carried through our lymphatic system Carried through our lymphatic system

and help our bodies fight infectionand help our bodies fight infection– Lymphocytes are carried through the Lymphocytes are carried through the

lymph vessels as well as the blood lymph vessels as well as the blood stream, so cancer can start in nodes and stream, so cancer can start in nodes and spread anywhere throughout the body.spread anywhere throughout the body.

Lymphatic TissueLymphatic Tissue

• Lymph nodes, spleen, liver, skin and Lymph nodes, spleen, liver, skin and the respiratory, GI and GTU tractthe respiratory, GI and GTU tract

• Lymphocytes undergo further Lymphocytes undergo further proliferation and differentiation in proliferation 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

Lymph Node - normal Lymph Node - normal histologyhistology

afferent lymphatic vessel capsule

follicle (mainly B-cells)- germinal centre- mantle zone

C

cortex

medullaparacortex

efferent lymphatic vessel

artery

vein

Thomas Hodgkin

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

•A heterogeneous group of B- and T-A heterogeneous group of B- and T-cell malignancies that are diverse in cell malignancies that are diverse in cellular origin, morphology, cellular origin, morphology, cytogenetic abnormalities, response cytogenetic abnormalities, response to treatment, and prognosisto treatment, and prognosis

•Any of a large group of cancers of Any of a large group of cancers of lymphocytes (white blood cells). lymphocytes (white blood cells).

NON-HODGKIN’S NON-HODGKIN’S LYMPHOMA (NHL):LYMPHOMA (NHL):

Former First Lady

Jacqueline Kennedy Onassis

• Incidence of 13.3/100,000 per Incidence of 13.3/100,000 per year year

• Predominates in the 40-70 years Predominates in the 40-70 years age groupage group

– most common neoplasm in most common neoplasm in the 20-40 age groupthe 20-40 age group

• Incidence is risingIncidence is rising– 150% growth over the past 30 150% growth over the past 30

yearsyears– increasing by 4% annually increasing by 4% annually

since 1970’ssince 1970’s

• Mortality rate is also risingMortality rate is also rising– 2% rise per year2% rise per year– third highest rise, exceeded third highest rise, exceeded

only by lung cancer in women only by lung cancer in women and malignant melanomaand malignant melanoma

NHL INCIDENCENHL INCIDENCE

Estimated Incidence of NHL Estimated Incidence of NHL in the Year 2000 in the Year 2000 (Worldwide)(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

B-Cell CancersB-Cell Cancers

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 Specific lymphoma types are associated with

EBV,HHV8EBV,HHV8• Gastric lymphoma can be associated with H.pylori Gastric lymphoma can be associated with H.pylori

infection.infection.• Some lymphomas are associated with specific Some lymphomas are associated with specific

chromosomal lesion.chromosomal lesion.• Lymphomas occur in congenital Lymphomas occur in congenital

immunodeficiency states, immune suppressed immunodeficiency states, immune suppressed individuals and after organ transplantaion.individuals and after organ transplantaion.

PathogenesisPathogenesis

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)

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

Spreads to various lymphoid tissues throughout the body, especially the liver, spleen

and bone marrow

Non-hodgkin’s lymphoma

Group of tumors will develop

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

Types of LymphomaTypes of Lymphoma• Indolent (low grade)Indolent (low grade)

– Life expectancy in years, untreatedLife expectancy in years, untreated– 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

STAGING OF NHLSTAGING OF NHL

•Stage is the term used to describe the Stage is the term used to describe the extent of tumor that has spread through extent of tumor that has spread through the body( I and II are localized where as III the body( I and II are localized where as III and IV are advanced.and IV are advanced.

•Each stage is then divided into categories Each 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 lymph node E: Spreading of disease from lymph node

to another organto another organ

The Non-Hodgkin’s Lymphoma Pathologic Classification Project. Cancer. 1982;49:2112.

MODIFIED ANN ARBOR MODIFIED ANN ARBOR STAGING OF NHLSTAGING OF NHL• Stage I Stage I Involvement of a single lymph node region Involvement of a single lymph node region

• Stage II Stage II Involvement of Involvement of 2 lymph node regions on 2 lymph node regions on the same the same side of the diaphragm side of the diaphragm

• Stage IIIStage III Involvement of lymph node regions on Involvement of lymph node regions on both sides of the diaphragm both sides of the diaphragm

• Stage IVStage IV Multifocal involvement of Multifocal involvement of 1 1 extralymphatic sites ± associated lymph nodes or extralymphatic sites ± associated lymph nodes or isolated extralymphatic organ involvement with isolated extralymphatic organ involvement with distant nodal involvement.distant nodal involvement.

CATEGORIESCATEGORIES OF NON-OF NON-HODGKIN’S HODGKIN’S LYMPHOMALYMPHOMA

• Two main types of Non-Hodgkin’s Two 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%)

•B-Cells help make antibodies, which are B-Cells help make antibodies, which are proteins that attach to and help destroy proteins that attach to and help destroy antigensantigens

•Lymphomas are caused when a mutation Lymphomas are caused when a mutation arises during the B-cell life cyclearises during the B-cell life cycle

•Various different lymphomas can occur during Various different lymphomas can occur during several different stages of the cycleseveral different stages of the cycle– Follicular lymphoma, which is a type of B-Follicular lymphoma, which is a type of B-

cell lymphoma is caused by a gene cell lymphoma is caused by a gene translocation which results in an over translocation which results in an over expressed gene called BCL-2, which blocks expressed gene called BCL-2, which blocks apoptosis.apoptosis.

•The T-cells are born from stem cells, The T-cells are born from stem cells, similar to that of B-cells, but mature similar to that of B-cells, but mature in the thymus.in the thymus.

•They help the immune system work They help the immune system work in a coordinated fashion.in a coordinated fashion.– These types of lymphomas are These types of lymphomas are

categorized by how the cell is affectedcategorized by how the cell is affected•Anaplastic Large cell Lymphoma, t-cell Anaplastic Large cell Lymphoma, t-cell

lymphoma caused by a gene translocation in lymphoma caused by a gene translocation in chromosome 5chromosome 5

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

•Follicular Lymphoma Follicular Lymphoma (FLs).(FLs). Follicular Follicular lymphoma is the lymphoma is the second most common second most common type lymphoma, type lymphoma, accounting for about accounting for about 20% of all NHL cases. 20% of all NHL cases. It is usually indolent It is usually indolent (slow growing) but (slow growing) but about half of follicular about half of follicular lymphomas transform lymphomas transform over time into the over time into the aggressive diffuse aggressive diffuse large B-cell lymphoma.large B-cell lymphoma.

•Mantle Cell LymphomaMantle Cell Lymphoma..

Mantle cell lymphoma is an Mantle cell lymphoma is an aggressive type of lymphoma that aggressive type of lymphoma that represent about 7% of NHL cases. represent about 7% of NHL cases. It is a difficult type of lymphoma It is a difficult type of lymphoma to treat and often does not to treat and often does not respond to chemotherapy. It is respond to chemotherapy. It is found in lymph nodes, the spleen, found in lymph nodes, the spleen, bone marrow, and bone marrow, and gastrointestinal system. Mantle gastrointestinal system. Mantle cell lymphoma usually develops cell lymphoma usually develops in men over agein men over age 60. 60.

•Small Lymphocytic Small Lymphocytic LymphomaLymphoma (SLL).(SLL). SLL is an indolent SLL is an indolent type of lymphoma type of lymphoma that is closely that is closely related to B-cell related to B-cell chronic chronic lymphocytic lymphocytic leukemia (CLL). It leukemia (CLL). It accounts for about accounts for about 5% of NHL cases.5% of NHL cases.

•Marginal Zone Marginal Zone LymphomasLymphomas (MZL).(MZL). MZLs are categorized MZLs are categorized depending on where depending on where the lymphoma is the lymphoma is located. Mucosa-located. Mucosa-associated lymphoid associated lymphoid tissue lymphomas tissue lymphomas (MALT) usually involve (MALT) usually involve the gastrointestinal the gastrointestinal tract, thyroid, lungs, tract, thyroid, lungs, saliva glands, or skin. saliva glands, or skin. MALT is often MALT is often associated with a associated with a history of an history of an autoimmune disorder autoimmune disorder (such as Sjogren (such as Sjogren syndrome in the syndrome in the salivary glands or salivary glands or Hashimoto's thyroiditis Hashimoto's thyroiditis in the thyroid gland). in the thyroid gland).

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

•Lymphoblastic Lymphoblastic LymphomaLymphoma. This . This lymphoma is also lymphoma is also common in children, common in children, accounting for about accounting for about 25% of NHL pediatric 25% of NHL pediatric cases, most often boys. cases, most often boys. It is associated with a It is associated with a large mediastinal mass large mediastinal mass (occurring in chest (occurring in chest cavity between the cavity between the lungs) and carries a lungs) and carries a high risk for spreading high risk for spreading to bone marrow, the to bone marrow, the brain, and other lymph brain, and other lymph nodes.nodes.

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 Discrete, painless, firm lymph nodal enlargement is

the most common presentation. Waldeyer’s ring and the most 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 less B symptoms: night sweats, weight loss, fever are less prominent.prominent.

• Early involvement of extra lymphatic organ is a Early involvement of extra lymphatic organ is a feature of NHL.feature of 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 in Involvement of liver and spleen results in

hepatosplenomegaly.hepatosplenomegaly.• Bone involvement can manifest as pathological Bone involvement can manifest as pathological

fracture with pain.fracture with pain.

ManagementManagement

InvestigationsInvestigations

• Lymph node biopsy.Lymph node biopsy.• Hemogram: Anemia, lymphocytosis in some Hemogram: Anemia, lymphocytosis in some

patients, leukemic phase develops in 20-40% of patients, leukemic phase develops in 20-40% of lymphocytic patients.lymphocytic patients.

• Bone marrow aspiration.Bone marrow aspiration.• Immunotyping of blood, lymph node, marrow Immunotyping of blood, lymph node, marrow

lymphoid cells.lymphoid cells.• S.Uric acid.S.Uric acid.• X-Rays.X-Rays.• CT scans.CT scans.• Magnetic Resonance Imaging (MRI).Magnetic Resonance Imaging (MRI).

TREATMENT

•Non-Hodgkin’s Lymphoma is usually Non-Hodgkin’s Lymphoma is usually treated by a team of physicians including treated by a team of physicians including hematologists, medical oncologists and a hematologists, medical oncologists and a radiation oncologist.radiation oncologist.

•In some cases such as for Indolent In some cases such as for Indolent lymphomas, the Doctor may wait to start lymphomas, the Doctor may wait to start treatment until the patient starts showing treatment until the patient starts showing symptoms, known as “watchful waiting”symptoms, known as “watchful waiting”

•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.

•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.

Chemotherapy regimenChemotherapy regimen

• CHOP regimen- Cyclophophamide, CHOP regimen- Cyclophophamide, Hydroxunorubicin(adriamycin), Hydroxunorubicin(adriamycin), Oncovin (vincristine), Prednisolone.Oncovin (vincristine), Prednisolone.

•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.

•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.

•Survival Rates vary widely by cell Survival Rates vary widely by cell type and staging.type and 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%