LYMPHOMALYMPHOMAHodgkin`s Disease Hodgkin`s Disease

Non-Hodgkin`s DiseaseNon-Hodgkin`s Disease

Acibadem UniversityAcibadem UniversityAcibadem Medical FacultyAcibadem Medical FacultyPaediatrics DepartmentPaediatrics Department

Ertugrul Eryilmaz MDErtugrul Eryilmaz MDAssistant Professor PaediatricsAssistant Professor Paediatrics

LLymph ymph SSystemystem

Lymphoma may affect any of the parts of the Lymphoma may affect any of the parts of the lymph system. Most commonly, patients first lymph system. Most commonly, patients first notice an enlargement of lymph nodes - usually notice an enlargement of lymph nodes - usually in the neck, groin or armpits. in the neck, groin or armpits.

LLymphomas can occur in other organs as well. ymphomas can occur in other organs as well. This is because small amounts of lymph and This is because small amounts of lymph and lymph tissue pass through practically all organs lymph tissue pass through practically all organs in the body in order that white blood cells can in the body in order that white blood cells can reach them to control infections. reach them to control infections.

RESRES

++Timus

LLymphoid tissueymphoid tissue

Two types of lymphoid tissueTwo types of lymphoid tissue exist: exist: – CCentral (bone marrow and thymus) and entral (bone marrow and thymus) and – PeripheralPeripheral (blood, spleen,(blood, spleen,liver,liver, lymph node, lymph node,

and mucosa-associated).and mucosa-associated).

Within central lymphoid tissue, cells arise Within central lymphoid tissue, cells arise and differentiateand differentiate into mature lymphocytes; into mature lymphocytes; they then migrate into peripheralthey then migrate into peripheral lymphoid lymphoid tissues and recirculate throughout the tissues and recirculate throughout the bodbodyy

DLBCL=diffuse large B-cell lymphoma; FL=follicular lymphoma; HL Hodgkin Lymphoma, MM Multiple Myeloma ALL Acutel lymphocytic lymphoma; CLL Chronic Lymphoblastic Lymphoma

stemcell

lymphoidprogenitor

progenitor-B

pre-B

immatureB-cell

memoryB-cell

plasma cellplasma cell

DLBCL,FL, HL

ALL

CLL

MM

germinalgerminalcentercenterB-cellB-cell

maturenaiveB-cell

ALLALL MM MM CLLCLL LymphomasLymphomas

Hematopoieticstem cell

Neutrophils

Eosinophils

Basophils

Monocytes

Platelets

Red cells

Myeloidprogenitor

Myeloproliferative disordersMyeloproliferative disordersAMLAML

Lymphoidprogenitor T-lymphocytes

Plasmacells

B-lymphocytes

nanaïïveve

PProto-roto-OOncogenes ncogenes / S/ Suppressoruppressor GGenesenes

Similar to most human cancers, the Similar to most human cancers, the genetic lesionsgenetic lesions involved in non-Hodgkin involved in non-Hodgkin lymphoma include activation oflymphoma include activation of proto-proto-oncogenes and disruption of tumour oncogenes and disruption of tumour suppressorsuppressor genesgenes

LymphomaLymphoma

Lymphoma is the third most common Lymphoma is the third most common cancer in children, with an annual cancer in children, with an annual incidence of 13-14 per million children. incidence of 13-14 per million children.

The two broad categories of lymphoma, The two broad categories of lymphoma, Hodgkin disease and non-Hodgkin Hodgkin disease and non-Hodgkin lymphoma (NHL), have such different lymphoma (NHL), have such different clinical manifestations and treatments that clinical manifestations and treatments that they are considered separately. they are considered separately.

Incidence of lymphomas in comparison Incidence of lymphomas in comparison with other cancers in Canadawith other cancers in Canada

Year

1985 1990 1995 2000

age

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20

30

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70

Hodgkinlymphoma

NHL

breastcolorectallung

Hodgkin lymphomaHodgkin lymphoma

Thomas Hodgkin(1798-1866)

Hodgkin Disease Hodgkin Disease EpidemiologyEpidemiology

Three forms of Hodgkin disease have been identified in Three forms of Hodgkin disease have been identified in epidemiologic studies: a childhood form (≤ 14 yr of age), epidemiologic studies: a childhood form (≤ 14 yr of age), a young adult form (15-34 yr of age), and an older adult a young adult form (15-34 yr of age), and an older adult form (55-74 yr of age). form (55-74 yr of age). Hodgkin disease accounts for about 5% of cancers in Hodgkin disease accounts for about 5% of cancers in persons younger than 15 yr of age and for about 15% in persons younger than 15 yr of age and for about 15% in persons 15-19 yr of age, persons 15-19 yr of age, In industrialized countries the highest rate is in In industrialized countries the highest rate is in adolescents and young adults, in contrast to developing adolescents and young adults, in contrast to developing countries, where the highest rate is in younger children. countries, where the highest rate is in younger children.

Hodgkin Disease Hodgkin Disease EpidemiologyEpidemiology

The role of Epstein-Barr virus (EBV) is supported by The role of Epstein-Barr virus (EBV) is supported by serologic studies and the frequent presence of EBV serologic studies and the frequent presence of EBV genome in biopsy material. genome in biopsy material. Males predominate in patients younger than 10 yr of age Males predominate in patients younger than 10 yr of age at diagnosis, with roughly equal gender incidence in at diagnosis, with roughly equal gender incidence in adolescence. adolescence. Pre-existing immunodeficiency, either congenital or Pre-existing immunodeficiency, either congenital or acquired, increases the risk of developing Hodgkin acquired, increases the risk of developing Hodgkin disease. disease. A genetic predisposition or a common exposure to the A genetic predisposition or a common exposure to the same etiologic agent could account for an apparent same etiologic agent could account for an apparent increased risk in twins and first-degree relatives ranging increased risk in twins and first-degree relatives ranging from 3- to 7-fold. from 3- to 7-fold.

Age distribution of new Hodgkin Age distribution of new Hodgkin lymphoma cases in Canadalymphoma cases in Canada

Age (years)

0-1

1-4

5-9

10-1

415

-19

20-2

425

-29

30-3

435

-39

40-4

445

-49

50-5

455

-59

60-6

465

-69

70-7

475

-79

80-8

485

+

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1

2

3

4

5

6

PathogenesisPathogenesis

The The Reed-Sternberg cell,Reed-Sternberg cell, a large cell (15- a large cell (15-45 μm in diameter) with multiple or 45 μm in diameter) with multiple or multilobulated nuclei, is considered the multilobulated nuclei, is considered the hallmark of Hodgkin diseasehallmark of Hodgkin disease

There is now general agreement that the There is now general agreement that the Reed-Sternberg cell arises from germinal Reed-Sternberg cell arises from germinal center B-cells in most cases.center B-cells in most cases.

HHistologic subtypesistologic subtypes

lymphocyte predominant, lymphocyte predominant,

nodular sclerosing nodular sclerosing

mixed cellularitymixed cellularity

lymphocyte depleted.lymphocyte depleted.

Most cases previously classified as lymphocyte Most cases previously classified as lymphocyte depleted are now considered to represent high-depleted are now considered to represent high-grade non-Hodgkin lymphoma. grade non-Hodgkin lymphoma.

PathognomonicPathognomonic

Lymphocyte PredominantLymphocyte Predominant

Reed Sternberg & CD20 (+)Reed Sternberg & CD20 (+)

Mixed CellularityMixed Cellularity

Clinical ManifestationsClinical Manifestations

Painless, firm, cervical, or supraclavicular lymphadenopathy is the Painless, firm, cervical, or supraclavicular lymphadenopathy is the most common presenting sign. most common presenting sign. Inguinal or axillary lymphadenopathy sites are uncommon areas of Inguinal or axillary lymphadenopathy sites are uncommon areas of presentation. presentation. An anterior mediastinal mass is often present and can rapidly An anterior mediastinal mass is often present and can rapidly disappear with therapydisappear with therapyClinically detectable hepatosplenomegaly is rarely encountered. Clinically detectable hepatosplenomegaly is rarely encountered. Depending on the extent and location of nodal and extranodal Depending on the extent and location of nodal and extranodal disease, patients might present with symptoms and signs of airway disease, patients might present with symptoms and signs of airway obstruction, pleural or pericardial effusion, hepatocellular obstruction, pleural or pericardial effusion, hepatocellular dysfunction, or bone marrow infiltration (anemia, neutropenia, or dysfunction, or bone marrow infiltration (anemia, neutropenia, or thrombocytopenia). thrombocytopenia). Nephrotic syndrome is a rare but recognized presenting Nephrotic syndrome is a rare but recognized presenting manifestation of Hodgkin diseasemanifestation of Hodgkin disease

                  

Some causes of mediastinal Some causes of mediastinal MMasses in adults. asses in adults.

Some Causes of Mediastinal Some Causes of Mediastinal Masses in ChildrenMasses in Children

AnteriorAnteriorEctopic thyroidEctopic thyroidLymphomaLymphomaSarcomaSarcomaTeratomaTeratomaIn thymus:CystIn thymus:Cyst HistiocytosisHistiocytosis HistoplasmosisHistoplasmosis Normal thymusNormal thymus ThymomaThymoma

MiddleMiddleBronchogenic cystBronchogenic cystCardiac tumorCardiac tumorCystic hygromaCystic hygromaLymphadenopathyLymphadenopathyLymphomaLymphomaPericardial cystPericardial cystVascular abnormalitiesVascular abnormalities

PosteriorPosteriorEsophageal duplicationEsophageal duplicationMeningomyeloceleMeningomyeloceleNeuroenteric abnormalitiesNeuroenteric abnormalitiesNeurogenic tumorsNeurogenic tumors

SYMPTOMSSYMPTOMSSystemic symptoms considered important in staging Systemic symptoms considered important in staging – UUnexplained fever nexplained fever – WWeight losseight loss– DDrenching night sweats. renching night sweats.

Less common Less common non-non-prognostic significance are prognostic significance are – pruritus, pruritus, – lethargy, lethargy, – anorexia, anorexia, – pain that worsens after ingestion of alcohol. pain that worsens after ingestion of alcohol.

Because of the impaired cellular immunity, concomitant tuberculous or Because of the impaired cellular immunity, concomitant tuberculous or fungal infections may complicate Hodgkin disease and predispose to fungal infections may complicate Hodgkin disease and predispose to complications during immunosuppressive therapy. complications during immunosuppressive therapy.

In the pre-vaccine era varicella-zoster infections occurred at some time In the pre-vaccine era varicella-zoster infections occurred at some time during the course of the disease in about 30% of cases. during the course of the disease in about 30% of cases.

DiagnosisDiagnosis

Any patient with persistent, unexplained Any patient with persistent, unexplained lymphadenopathy unassociated with an obvious lymphadenopathy unassociated with an obvious underlying inflammatory or infectious process should underlying inflammatory or infectious process should have a chest radiograph to identify the presence of a have a chest radiograph to identify the presence of a mediastinal mass before undergoing node biopsy. mediastinal mass before undergoing node biopsy. Formal excisional biopsy is preferred over needle biopsy Formal excisional biopsy is preferred over needle biopsy to ensure that adequate tissue is obtained, to ensure that adequate tissue is obtained, Hodgkin disease is rarely diagnosed with certainty on Hodgkin disease is rarely diagnosed with certainty on frozen section. Ideally, a portion of the biopsy specimen frozen section. Ideally, a portion of the biopsy specimen should be frozen and stored to allow for additional should be frozen and stored to allow for additional studies. studies.

Modified Ann Arbor Staging System Modified Ann Arbor Staging System for Hodgkin Diseasefor Hodgkin Disease**

STAGESTAGE II Involvement of a single lymph node region or of a single Involvement of a single lymph node region or of a single extralymphatic organ or site extralymphatic organ or site STAGE IISTAGE II Involvement of two or more lymphoid regions on the same side of Involvement of two or more lymphoid regions on the same side of the diaphragm; or localized involvement of an extralymphatic organ or site the diaphragm; or localized involvement of an extralymphatic organ or site and of one or more lymph node regions on the same side of the diaphragm and of one or more lymph node regions on the same side of the diaphragm STAGE IIISTAGE III Involvement of lymph node regions on both sides of the Involvement of lymph node regions on both sides of the diaphragm, which may be accompanied by localized involvement of an diaphragm, which may be accompanied by localized involvement of an extralymphatic organ or site or by splenic involvement extralymphatic organ or site or by splenic involvement STAGE IVSTAGE IV Diffuse or disseminated involvement of one or more Diffuse or disseminated involvement of one or more extralymphatic organs or tissues, with or without associated lymph node extralymphatic organs or tissues, with or without associated lymph node enlargement enlargement *Stages are further categorized as: *Stages are further categorized as: A or BA or B, based on the absence or , based on the absence or presence, respectively, of systemic symptoms of fever and/or weight loss presence, respectively, of systemic symptoms of fever and/or weight loss Bulky diseaseBulky disease, based on mediastinal mass larger than one third thoracic , based on mediastinal mass larger than one third thoracic diameter; lymph node masses ≥10 cm in diameter and/or four or more nodal diameter; lymph node masses ≥10 cm in diameter and/or four or more nodal regions involved.regions involved.

Stage I Stage II Stage III Stage IV

Staging of lymphomaStaging of lymphoma

A: absence of B symptomsB: fever, night sweats, weight loss

Studies Necessary for Clinical Studies Necessary for Clinical Staging of Hodgkin DiseaseStaging of Hodgkin Disease

Measurement of palpable lymph nodes, liver, and spleen Measurement of palpable lymph nodes, liver, and spleen Complete blood cell count Complete blood cell count Erythrocyte sedimentation rate, Erythrocyte sedimentation rate, SSerum ferritin, erum ferritin, SSerum copper erum copper Liver function tests Liver function tests Chest radiograph with measurement of mediastinal ratio Chest radiograph with measurement of mediastinal ratio Chest CT with contrast medium enhancement Chest CT with contrast medium enhancement Neck CT if high cervical nodes palpable Neck CT if high cervical nodes palpable Abdominal CT or MRI Gallium scan Abdominal CT or MRI Gallium scan Bone marrow biopsy with advanced disease or "B" symptoms Bone marrow biopsy with advanced disease or "B" symptoms Bone scan with elevated serum alkaline phosphatase level and/or Bone scan with elevated serum alkaline phosphatase level and/or bone pain bone pain

TreatmentTreatment

Because of concern about late effects, treatment of children in North Because of concern about late effects, treatment of children in North America and Europe has evolved from primary treatment with America and Europe has evolved from primary treatment with extended-field radiation therapy to use of multiagent chemotherapy extended-field radiation therapy to use of multiagent chemotherapy as the cornerstone of treatment, supplemented in selected cases by as the cornerstone of treatment, supplemented in selected cases by relatively low-dose involved-field irradiation (2,000-2,500 cGy). relatively low-dose involved-field irradiation (2,000-2,500 cGy). Treatment is largely determined by disease stage, patient's age at Treatment is largely determined by disease stage, patient's age at diagnosis, the presence or absence of "B" symptoms, and the diagnosis, the presence or absence of "B" symptoms, and the presence of hilar lymphadenopathy and/or bulky nodal disease. presence of hilar lymphadenopathy and/or bulky nodal disease. Although there is not yet general agreement on their definitions, Although there is not yet general agreement on their definitions, three risk groups have been identified. three risk groups have been identified. Favorable presentations include stages I and IIA. Favorable presentations include stages I and IIA. Intermediate presentations include stages I, IIB (with symptoms, Intermediate presentations include stages I, IIB (with symptoms, bulky disease, or hilar lymphadenopathy), and stage IIIA. bulky disease, or hilar lymphadenopathy), and stage IIIA. Unfavorable presentations include stages IIIB and IV. Unfavorable presentations include stages IIIB and IV.

CChemotherapyhemotherapy

The chemotherapy regimens in current use are based on The chemotherapy regimens in current use are based on – MOPPMOPP (nitrogen mustard [Mustargen], vincristine [Oncovin], (nitrogen mustard [Mustargen], vincristine [Oncovin],

procarbazine, and prednisone), or procarbazine, and prednisone), or – ABVDABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and (doxorubicin [Adriamycin], bleomycin, vinblastine, and

dacarbazine), dacarbazine), – or variations and/or combinations of the two together with or variations and/or combinations of the two together with

additional active agents such as etoposide and methotrexate. additional active agents such as etoposide and methotrexate. – As originally conceived, a minimum of six cycles of As originally conceived, a minimum of six cycles of

chemotherapy was given with significant cumulative chemotherapy was given with significant cumulative toxicity, including toxicity, including

second malignancies, second malignancies, sterility, sterility, and cardiac and cardiac and pulmonary dysfunction. and pulmonary dysfunction.

– The long-term toxicity is determined by the total dose of the The long-term toxicity is determined by the total dose of the agents. agents.

EORTC risk factors in localised EORTC risk factors in localised diseasedisease

FavourableFavourablePatients must have all features:Patients must have all features: Clinical stage 1 and 2Clinical stage 1 and 2 Maximum of three nodal areas involvedMaximum of three nodal areas involved Age younger than 50 yearsAge younger than 50 years Erythrocyte sedimentation rate (ESR) less than 50 mm/hErythrocyte sedimentation rate (ESR) less than 50 mm/h without B without B symptoms or symptoms or

ESR less than 30 mm/h with BESR less than 30 mm/h with B symptomssymptoms Mediastinal/thoracic ratio less than 0·35Mediastinal/thoracic ratio less than 0·35

UnfavourableUnfavourablePatients have any features:Patients have any features:Clinical stage 2 with involvement of at least four nodal areasClinical stage 2 with involvement of at least four nodal areasAge older than 50 yearsAge older than 50 yearsESR greater than 50 mm/h if asymptomatic or ESRESR greater than 50 mm/h if asymptomatic or ESR greater than 30 mm/h if greater than 30 mm/h if B B

symptomssymptomsMediastinal/thoracic ratio greater than 0·35Mediastinal/thoracic ratio greater than 0·35

UNFAVORABLE UNFAVORABLE PRESENTATIONSPRESENTATIONS

Chemotherapy, based on the same regimens Chemotherapy, based on the same regimens used in early stage disease, is considered the used in early stage disease, is considered the primary treatment for patients with advanced primary treatment for patients with advanced disease, but the role of radiation is still under disease, but the role of radiation is still under study. study.

Because the cure rate with conventional drug Because the cure rate with conventional drug combinations, with or without radiation therapy, combinations, with or without radiation therapy, is only 60-70%, newer and more aggressive is only 60-70%, newer and more aggressive regimens have been developed and are now in regimens have been developed and are now in clinical trials. clinical trials.

RELAPSERELAPSE

Patients who suffer relapse after initial treatment Patients who suffer relapse after initial treatment with radiation alone or after an initial remission with radiation alone or after an initial remission of more than 12 mo after chemotherapy alone or of more than 12 mo after chemotherapy alone or combined modality therapy usually respond to combined modality therapy usually respond to additional chemotherapy or radiation or both. additional chemotherapy or radiation or both. Those who never achieve remission or who Those who never achieve remission or who suffer relapse after an initial remission of less suffer relapse after an initial remission of less than 12 mo after chemotherapy or combined than 12 mo after chemotherapy or combined modality therapy have a poorer prognosis and modality therapy have a poorer prognosis and are candidates for myeloablative chemotherapy are candidates for myeloablative chemotherapy and autologous stem cell or bone marrow and autologous stem cell or bone marrow rescue.rescue.

PrognosisPrognosis

Most treatment programs result in disease-free survival Most treatment programs result in disease-free survival rates of more than 60%, with overall cure rates greater rates of more than 60%, with overall cure rates greater than 90% in those with early stage disease and more than 90% in those with early stage disease and more than 70% in more advanced cases. than 70% in more advanced cases. All newly diagnosed cases in children and adolescents All newly diagnosed cases in children and adolescents should be treated with curative intent; this is consistently should be treated with curative intent; this is consistently and effectively achieved with combined modality therapy. and effectively achieved with combined modality therapy. The choice of regimen is then selected on the basis of The choice of regimen is then selected on the basis of risk category and observed or anticipated long-term risk category and observed or anticipated long-term complications. Elimination of routine staging laparotomy complications. Elimination of routine staging laparotomy and splenectomy avoids concerns about surgical and splenectomy avoids concerns about surgical morbidity and postsplenectomy infections. morbidity and postsplenectomy infections.

Classical Hodgkin Lymphoma

Non-Hodgkin LymphomaNon-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) results from malignant clonal Non-Hodgkin lymphoma (NHL) results from malignant clonal proliferation of lymphocytes of T-, B-, or indeterminate cell origin. proliferation of lymphocytes of T-, B-, or indeterminate cell origin. In the United States, NHL occurs with an annual incidence of 10.5 In the United States, NHL occurs with an annual incidence of 10.5 per million white and 7.3 per million black children younger than 20 per million white and 7.3 per million black children younger than 20 yr of age. yr of age. In equatorial Africa, 50% of childhood cancers are lymphomas, a In equatorial Africa, 50% of childhood cancers are lymphomas, a result of the very high incidence of Burkitt lymphoma and possibly result of the very high incidence of Burkitt lymphoma and possibly related to the immunosuppressive effects of malaria. Unlike that of related to the immunosuppressive effects of malaria. Unlike that of Hodgkin disease, the incidence of NHL increases steadily Hodgkin disease, the incidence of NHL increases steadily throughout life. throughout life. In some situations there is overlap with acute lymphoblastic or B-cell In some situations there is overlap with acute lymphoblastic or B-cell leukemia. Patients with lymphoblastic NHL and more than 25% leukemia. Patients with lymphoblastic NHL and more than 25% lymphoblasts in the bone marrow are arbitrarily classified and lymphoblasts in the bone marrow are arbitrarily classified and treated as if they had acute lymphoblastic leukemia, whereas treated as if they had acute lymphoblastic leukemia, whereas patients with B-cell ALL are treated similarly to patients with Burkitt patients with B-cell ALL are treated similarly to patients with Burkitt lymphoma even if no extramedullary disease is present. lymphoma even if no extramedullary disease is present.

Age distribution of new NHL cases in Age distribution of new NHL cases in CanadaCanada

Age (years)

0-1

1-4

5-9

10-1

415

-19

20-2

425

-29

30-3

435

-39

40-4

445

-49

50-5

455

-59

60-6

465

-69

70-7

475

-79

80-8

485

+

Inci

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0/an

num

0

20

40

60

80

100

PathogenesisPathogenesis

EBV infection has a major role in the EBV infection has a major role in the pathogenesis of Burkitt lymphoma. The EBV pathogenesis of Burkitt lymphoma. The EBV genome is present in tumor cells in 95% of genome is present in tumor cells in 95% of "endemic" cases in equatorial Africa compared "endemic" cases in equatorial Africa compared with 15% in "sporadic" cases in the United with 15% in "sporadic" cases in the United States. States. How EBV contributes to the pathogenesis of How EBV contributes to the pathogenesis of Burkitt lymphoma remains unclear. Burkitt lymphoma remains unclear. Congenital or acquired immunodeficiency also Congenital or acquired immunodeficiency also predisposes to the development of NHL. predisposes to the development of NHL. Epidemiologic studies have also implicated Epidemiologic studies have also implicated pesticide exposure as a possible risk factor. pesticide exposure as a possible risk factor.

CClassificationlassification

Most cases of NHL in children are high-grade, Most cases of NHL in children are high-grade, diffuse neoplasms. diffuse neoplasms. Three histologic subtypes are recognized:Three histologic subtypes are recognized:– lymphoblastic,lymphoblastic, usually of T-cell origin; usually of T-cell origin; – small nonsmall non--cleaved cell lymphoma (SNCCL),cleaved cell lymphoma (SNCCL), with with

Burkitt and non-Burkitt subtypes and of B-cell originBurkitt and non-Burkitt subtypes and of B-cell origin– large cell lymphoma (LCL),large cell lymphoma (LCL), with diffuse and with diffuse and

anaplastic subtypes and of T-, B-, or indeterminate anaplastic subtypes and of T-, B-, or indeterminate cell origin.cell origin.

The diagnosis and classification of childhood NHL requires The diagnosis and classification of childhood NHL requires considerable hematopathologic expertise and adequate considerable hematopathologic expertise and adequate diagnostic tissue, both fresh and frozen. diagnostic tissue, both fresh and frozen.

CChromosomal hromosomal TTranslocationsranslocations

Different chromosomal translocations are specific for Different chromosomal translocations are specific for some histologic subtypes and involve various proto-some histologic subtypes and involve various proto-oncogenes, resulting in malignant transformation through oncogenes, resulting in malignant transformation through a variety of mechanisms. a variety of mechanisms. In SNCCL (Burkitt type), one of three chromosomal In SNCCL (Burkitt type), one of three chromosomal translocations [t(8;14), t(8;22), t(2;8)] results in translocations [t(8;14), t(8;22), t(2;8)] results in approximation of the approximation of the MYCMYC proto-oncogene on proto-oncogene on chromosome 8 to a regulatory region of one of the chromosome 8 to a regulatory region of one of the immunoglobulin chain genes, resulting in dysregulation immunoglobulin chain genes, resulting in dysregulation of of MYCMYC; ; IIn anaplastic LCL, fusion of the n anaplastic LCL, fusion of the NPMNPM gene on gene on chromosome 5 with the chromosome 5 with the ALKALK gene on chromosome 2 gene on chromosome 2 leads to formation of a chimeric protein that can leads to formation of a chimeric protein that can influence cell growth and proliferation. influence cell growth and proliferation.

Clinical ManifestationsClinical Manifestations

Presenting signs and symptoms vary with disease site and extent, Presenting signs and symptoms vary with disease site and extent, and these in turn differ with histologic subtype. and these in turn differ with histologic subtype. Lymphoblastic NHL often presents as an intrathoracic tumor, usually Lymphoblastic NHL often presents as an intrathoracic tumor, usually a mediastinal mass, and is associated with dyspnea, chest pain, a mediastinal mass, and is associated with dyspnea, chest pain, dysphagia, pleural effusion, and superior vena cava syndrome. dysphagia, pleural effusion, and superior vena cava syndrome. Cervical or axillary lymphadenopathy is present in up to 80% of Cervical or axillary lymphadenopathy is present in up to 80% of patients at diagnosis. Primary involvement of bone, bone marrow, patients at diagnosis. Primary involvement of bone, bone marrow, testis, or skin is not uncommon. The central nervous system (CNS) testis, or skin is not uncommon. The central nervous system (CNS) may also be involved. may also be involved. SNCCL presents as an abdominal tumor in 80% of U.S. cases in SNCCL presents as an abdominal tumor in 80% of U.S. cases in patients with abdominal pain or distention, bowel obstruction, patients with abdominal pain or distention, bowel obstruction, change in bowel habits, intestinal bleeding, or, rarely, intestinal change in bowel habits, intestinal bleeding, or, rarely, intestinal perforation. Other sites include CNS, bone marrow, and peripheral perforation. Other sites include CNS, bone marrow, and peripheral lymph nodes. Jaw involvement occurs in less than 20% of U.S. lymph nodes. Jaw involvement occurs in less than 20% of U.S. cases, compared with 70% of younger patients in equatorial Africa. cases, compared with 70% of younger patients in equatorial Africa. LCL occurs in many sites, including the abdomen and mediastinum. LCL occurs in many sites, including the abdomen and mediastinum. Extramedullary sites include skin, bone, and soft tissues. CNS Extramedullary sites include skin, bone, and soft tissues. CNS involvement is rare, in contrast to SNCCL and lymphoblastic NHLinvolvement is rare, in contrast to SNCCL and lymphoblastic NHL. .

LABORATORY FINDINGSLABORATORY FINDINGS

Pretreatment Studies for Staging Pediatric Non-Pretreatment Studies for Staging Pediatric Non-Hodgkin LymphomaHodgkin Lymphoma– Complete blood cell count Complete blood cell count – Serum electrolytes, Serum electrolytes, – UUric acid, lactate dehydrogenase, creatinine, calcium, ric acid, lactate dehydrogenase, creatinine, calcium,

phosphorus phosphorus – Liver function tests Liver function tests – Chest radiograph and chest CT if abnormal Chest radiograph and chest CT if abnormal – Abdominal and pelvic ultrasonography and/or CT Abdominal and pelvic ultrasonography and/or CT – Gallium scan and/or bone scan Gallium scan and/or bone scan – Bilateral bone marrow aspirate and biopsy Bilateral bone marrow aspirate and biopsy – Cerebrospinal fluid cytologyCerebrospinal fluid cytology

Investigations done before initiation ofInvestigations done before initiation oftreatmenttreatment

Essential proceduresEssential procedures

A full history, recording growth rate, symptoms A full history, recording growth rate, symptoms present,present, performance statusperformance status

A detailed physical examination, with special A detailed physical examination, with special attention toattention to all node-bearing areas including all node-bearing areas including Waldeyer’s ringWaldeyer’s ring

Adequate surgical biopsy specimen, allowingAdequate surgical biopsy specimen, allowing

immunophenotyping and examined by a skilled immunophenotyping and examined by a skilled pathologistpathologist

Investigations done before initiation ofInvestigations done before initiation oftreatmenttreatment

Laboratory procedures:Laboratory procedures: Full blood count, including erythrocyte sedimentationFull blood count, including erythrocyte sedimentation

raterate Serum lactate dehydrogenase, calcium, uric acid,Serum lactate dehydrogenase, calcium, uric acid,

proteins and electrophoresis, alkaline phosphataseproteins and electrophoresis, alkaline phosphatase Assessment of renal and liver functionAssessment of renal and liver function

Radiological studies:Radiological studies:Chest radiographChest radiographThoracic and abdominal-pelvic CT scanThoracic and abdominal-pelvic CT scanBone-marrow aspirate and trephine, to includeBone-marrow aspirate and trephine, to include molecular molecular genetic analysis if availablegenetic analysis if available

Optional procedures, depending on Optional procedures, depending on clinical pictureclinical picture

2 microglobulin2 microglobulin

Endoscopy, eg, for gastric MALT lymphomaEndoscopy, eg, for gastric MALT lymphoma

Plain radiographs, bone scan, or MRIPlain radiographs, bone scan, or MRI

Positron electron tomography (PET)Positron electron tomography (PET)

Head or spinal MRI for neurological symptomsHead or spinal MRI for neurological symptoms

Cerebrospinal fluid analysis in patients at riskCerebrospinal fluid analysis in patients at risk

Laboratory findingsLaboratory findings

Laboratory findings vary, depending on sites or Laboratory findings vary, depending on sites or organs involved. organs involved. – Elevated serum uric acid levels and other features of Elevated serum uric acid levels and other features of

tumor lysis syndrome often complicate the tumor lysis syndrome often complicate the presentation of SNCCL. presentation of SNCCL.

– Elevated serum level of lactate dehydrogenase is a Elevated serum level of lactate dehydrogenase is a measure of tumor burden and may occur with any measure of tumor burden and may occur with any NHL subtype. NHL subtype.

– A normal CBC does not preclude marrow A normal CBC does not preclude marrow involvement. involvement.

– CT or MRI of the chest or abdomen or both provides CT or MRI of the chest or abdomen or both provides key information on disease extent. key information on disease extent.

– Surgical staging is not necessary. Surgical staging is not necessary.

Symptoms of non-Hodgkin lymphomaSymptoms of non-Hodgkin lymphomaneeding urgent referralneeding urgent referral

Lymphadenopathy (>1 cm persisting for 6 weeks)Lymphadenopathy (>1 cm persisting for 6 weeks) HepatosplenomegalyHepatosplenomegaly Three or more of the following symptoms:Three or more of the following symptoms: FatigueFatigue Night sweatsNight sweats Weight lossWeight loss ItchingItching BreathlessnessBreathlessness BruisingBruising Recurrent infectionRecurrent infection Bone painBone pain

DiagnosisDiagnosis

Prompt tissue diagnosis and staging is important Prompt tissue diagnosis and staging is important because of the rapid growth rate of lymphomas, because of the rapid growth rate of lymphomas, especially SNCCL. especially SNCCL. To ensure adequate tissue for accurate diagnosis and To ensure adequate tissue for accurate diagnosis and subtyping, multiple needle biopsy specimens or a large subtyping, multiple needle biopsy specimens or a large wedge of tumor should be obtained. wedge of tumor should be obtained. Several studies are necessary to accurately stage the Several studies are necessary to accurately stage the disease and provide baseline measurements of organ disease and provide baseline measurements of organ function before treatment is instituted function before treatment is instituted In cases with airway compromise, potential for In cases with airway compromise, potential for anesthetic complications, and no easily accessible tissue anesthetic complications, and no easily accessible tissue to sample, empirical therapy may be started using to sample, empirical therapy may be started using corticosteroids. corticosteroids.

An algorithm for evaluation and treatment of children with an anterior mediastinal mass.

Hammer G B Anesth Analg 2001;92:1449-1464

©2001 by Lippincott Williams & Wilkins

DiagnosisDiagnosis

The St. Jude staging system defines tumor The St. Jude staging system defines tumor extent, which is important for designing extent, which is important for designing treatment. treatment. Stage I applies to localized disease, stage II to Stage I applies to localized disease, stage II to regional disease (except for mediastinal tumors, regional disease (except for mediastinal tumors, which are designated stage III), stage III to which are designated stage III), stage III to extensive disease, and stage IV to disseminated extensive disease, and stage IV to disseminated (CNS and/or bone marrow) disease. Elevated (CNS and/or bone marrow) disease. Elevated levels of serum lactic dehydrogenase (>500 U/L) levels of serum lactic dehydrogenase (>500 U/L) correlate with tumor mass and have proved correlate with tumor mass and have proved useful for stratifying therapy intensity. useful for stratifying therapy intensity.

St. Jude Staging System for St. Jude Staging System for Childhood Non-Hodgkin LymphomaChildhood Non-Hodgkin Lymphoma

STAGE ISTAGE I A single tumor (extranodal) or single anatomic area A single tumor (extranodal) or single anatomic area (nodal), with the exclusion of mediastinum or abdomen. (nodal), with the exclusion of mediastinum or abdomen. STAGE IISTAGE II A single tumor (extranodal) with regional node A single tumor (extranodal) with regional node involvement. Two or more nodal areas on the same side of the involvement. Two or more nodal areas on the same side of the diaphragm. Two single (extranodal) tumors with or without regional diaphragm. Two single (extranodal) tumors with or without regional node involvement on the same side of the diaphragm. A primary node involvement on the same side of the diaphragm. A primary gastrointestinal tract tumor, usually in the ileocecal area, with or gastrointestinal tract tumor, usually in the ileocecal area, with or without involvement of associated mesenteric nodes only, which without involvement of associated mesenteric nodes only, which must be grossly (>90%) resected. must be grossly (>90%) resected. STAGE IIISTAGE III Two single tumors (extranodal) on opposite sides of the Two single tumors (extranodal) on opposite sides of the diaphragm. Two or more nodal areas above and below the diaphragm. Two or more nodal areas above and below the diaphragm. Any primary intrathoracic tumor (mediastinal, pleural, or diaphragm. Any primary intrathoracic tumor (mediastinal, pleural, or thymic). Any extensive primary intra-abdominal disease. thymic). Any extensive primary intra-abdominal disease. STAGE IVSTAGE IV Any of the above, with initial involvement of central Any of the above, with initial involvement of central nervous system and/or bone marrow at time of diagnosis.nervous system and/or bone marrow at time of diagnosis.

Stage I Stage II Stage III Stage IV

Staging of lymphomaStaging of lymphoma

A: absence of B symptomsB: fever, night sweats, weight loss

Treatment and PrognosisTreatment and Prognosis

Surgical excision of localized intra-abdominal tumors often Surgical excision of localized intra-abdominal tumors often precedes the diagnosis of NHL and should always be precedes the diagnosis of NHL and should always be attempted, if feasible. attempted, if feasible. In this and other situations, multiagent chemotherapy is the In this and other situations, multiagent chemotherapy is the primary treatment. primary treatment. Tumor lysis syndrome (i.e., high serum potassium, uric acid, Tumor lysis syndrome (i.e., high serum potassium, uric acid, and high phosphorus with low calcium levels) frequently and high phosphorus with low calcium levels) frequently complicates initial treatment of disseminated disease. complicates initial treatment of disseminated disease. Appropriate hydration with addition of sodium bicarbonate Appropriate hydration with addition of sodium bicarbonate to produce dilute alkaline urine, administration of allopurinol, to produce dilute alkaline urine, administration of allopurinol, and correction of electrolyte abnormalities are essential to and correction of electrolyte abnormalities are essential to minimize this life-threatening complication. minimize this life-threatening complication. In contrast to HD, second malignancies and infertility have In contrast to HD, second malignancies and infertility have not been major problems in long-term survivors of NHLnot been major problems in long-term survivors of NHL

EARLY-STAGE NHLEARLY-STAGE NHL

Unlike HD, NHL is considered a disseminated disease Unlike HD, NHL is considered a disseminated disease from the time of diagnosis. Even patients with apparently from the time of diagnosis. Even patients with apparently localized and resected disease require chemotherapy. localized and resected disease require chemotherapy. Patients with stage I/II NHL, irrespective of histologic Patients with stage I/II NHL, irrespective of histologic subgroup, are effectively treated with six cycles of subgroup, are effectively treated with six cycles of COMPCOMP (cyclophosphamide, vincristine [Oncovin], (cyclophosphamide, vincristine [Oncovin], methotrexate, and prednisone) or three cycles of methotrexate, and prednisone) or three cycles of COPACOPA (substituting doxorubicin for methotrexate) followed by 6 (substituting doxorubicin for methotrexate) followed by 6 mo of mercaptopurine and methotrexate or, mo of mercaptopurine and methotrexate or, IIn the case of T-cell lymphoblastic NHL, an acute n the case of T-cell lymphoblastic NHL, an acute lymphoblastic leukemia-like regimen. About 90% of lymphoblastic leukemia-like regimen. About 90% of cases are cured with these regimens. The emphasis now cases are cured with these regimens. The emphasis now is on decreasing morbidity of therapy for these children is on decreasing morbidity of therapy for these children while maintaining the high cure rate. while maintaining the high cure rate.

ADVANCED-STAGE NHLADVANCED-STAGE NHL

Patients with stage III/IV NHL are best treated Patients with stage III/IV NHL are best treated with therapy based on the histologic subtype. with therapy based on the histologic subtype. Lymphoblastic lymphoma is treated with intensive Lymphoblastic lymphoma is treated with intensive chemotherapy regimens, generally of 2 yr duration chemotherapy regimens, generally of 2 yr duration and consisting of multiple chemotherapeutic and consisting of multiple chemotherapeutic agents given in cycles or a regimen based on agents given in cycles or a regimen based on those used for high-risk acute lymphoblastic those used for high-risk acute lymphoblastic leukemia. leukemia. Cranial radiation, intrathecal chemotherapy, Cranial radiation, intrathecal chemotherapy, and/or high-dose methotrexate are important for and/or high-dose methotrexate are important for prevention of CNS disease. prevention of CNS disease. Early relapse require cytoablativeEarly relapse require cytoablativecchemotherapy, hemotherapy, and and allogenic bone marrowallogenic bone marrow t transplantationransplantation..

ADVANCED-STAGE NHLADVANCED-STAGE NHL

SNCCL is treated with relatively short-duration (3-6 mo) intensive SNCCL is treated with relatively short-duration (3-6 mo) intensive chemotherapy regimens, including an alkylating agent (usually chemotherapy regimens, including an alkylating agent (usually cyclophosphamide) coupled with other active systemic agents cyclophosphamide) coupled with other active systemic agents (vincristine, prednisone, methotrexate, cytarabine, etoposide, and/or (vincristine, prednisone, methotrexate, cytarabine, etoposide, and/or doxorubicin) and intrathecal therapy, which produces survival rates doxorubicin) and intrathecal therapy, which produces survival rates of more than 90% in localized and 70-80% in those with of more than 90% in localized and 70-80% in those with disseminated disease. disseminated disease. If relapse occurs, it becomes evident in the 1st yr after diagnosis If relapse occurs, it becomes evident in the 1st yr after diagnosis and is often rapidly progressive and relatively resistant to additional and is often rapidly progressive and relatively resistant to additional therapy, especially in patients with stage IV disease. therapy, especially in patients with stage IV disease. LCL is treated with intensive multiagent chemotherapy regimens LCL is treated with intensive multiagent chemotherapy regimens similar to those used for lymphoblastic lymphoma, which have similar to those used for lymphoblastic lymphoma, which have produced long-term survival rates of 50-70% in those of T-cell produced long-term survival rates of 50-70% in those of T-cell origin. For B cell-derived LCL, short, intensive regimens as outlined origin. For B cell-derived LCL, short, intensive regimens as outlined earlier for SNCLL have produced 6-yr event-free survival as high as earlier for SNCLL have produced 6-yr event-free survival as high as 95%. 95%.

Extranodal lymphomasExtranodal lymphomas

Extranodal lymphomas in general should be Extranodal lymphomas in general should be treated as fortreated as for nodal disease. nodal disease.

Aggressive lymphomas are usually treatedAggressive lymphomas are usually treated with with combined chemoradiotherapy, producing an combined chemoradiotherapy, producing an 80%80% 5-year survival, a 20–30% improvement on 5-year survival, a 20–30% improvement on treatment withtreatment with radiotherapy alone.radiotherapy alone.

Certain extranodal lymphomasCertain extranodal lymphomas present special present special clinical management problems.clinical management problems.

Gastric lymphoma of MALT typeGastric lymphoma of MALT type

MMucosa-associated lymphatic tissue, or "MALT" ucosa-associated lymphatic tissue, or "MALT" lymphomalymphoma Although MALT-type marginal-zone lymphomas arise atAlthough MALT-type marginal-zone lymphomas arise at other sites (such as salivary gland, lung, and thyroid), other sites (such as salivary gland, lung, and thyroid), gastricgastric MALT lymphomas are uniquely related to MALT lymphomas are uniquely related to previousprevious infection with infection with Helicobacter pyloriHelicobacter pylori. . Eradication withEradication with appropriate antibiotics results in appropriate antibiotics results in regression of theregression of the lymphoma in three-quarters of patients,lymphoma in three-quarters of patients,AAlthough fewerlthough fewer than half achieve sustained molecular than half achieve sustained molecular remission.Theremission.The 10-year survival is about 90%, although 10-year survival is about 90%, although transformation totransformation to diffuse large B-cell lymphoma can diffuse large B-cell lymphoma can happen.happen.

Lymphoma of the central nervous Lymphoma of the central nervous systemsystem

Primary lymphoma of the central nervous system is anPrimary lymphoma of the central nervous system is an aggressive tumour (usually of diffuse large B-cell type)aggressive tumour (usually of diffuse large B-cell type) arising in brain, leptomeninges, or eye. arising in brain, leptomeninges, or eye. Its prevalence hasIts prevalence has risen strikingly in the risen strikingly in the iimmunocompetent population.mmunocompetent population.Traditionally, radiotherapy was the treatment of choice,Traditionally, radiotherapy was the treatment of choice, but tumour recurrence was common, and chemotherapybut tumour recurrence was common, and chemotherapy (with high-dose methotrexate-based regimens), (with high-dose methotrexate-based regimens), combinedcombined with irradiation, has strikingly enhanced with irradiation, has strikingly enhanced average survival toaverage survival to up to 5 years.up to 5 years.However, late neurotoxic effects are a typicalHowever, late neurotoxic effects are a typical complication of this approach, and chemotherapy alone complication of this approach, and chemotherapy alone isis being tested.being tested.

Testicular lymphomaTesticular lymphoma

Although rare, primary testicular lymphoma is Although rare, primary testicular lymphoma is the mostthe most frequent testicular malignancy in men frequent testicular malignancy in men older than ageolder than age 60 years. 60 years. Pathology is usually of diffuse large B-cell type,Pathology is usually of diffuse large B-cell type, and despite apparently localised presentation, and despite apparently localised presentation, prognosis isprognosis is worse than with most other sites worse than with most other sites with the same histologicalwith the same histological findings. findings. A high frequency of central nervous system A high frequency of central nervous system relapserelapse has been noted, so much so that has been noted, so much so that prophylactic intrathecalprophylactic intrathecal chemotherapy has been chemotherapy has been advocated in addition to CHOPadvocated in addition to CHOP and adjuvant and adjuvant radiotherapy. radiotherapy.

New approachesNew approaches

High-dose chemotherapy High-dose chemotherapy For aggressive lymphoma in first remissionFor aggressive lymphoma in first remissionFor refractory or relapsed aggressive high-grade For refractory or relapsed aggressive high-grade lymphomalymphomaFor indolent lymphomaFor indolent lymphomaAllogeneic stem-cell transplantationAllogeneic stem-cell transplantationRadiolabelled monoclonal antibody treatmentsRadiolabelled monoclonal antibody treatmentsVaccine treatmentsVaccine treatments

Radiolabelled monoclonal Radiolabelled monoclonal antibody treatmentsantibody treatments

Rituximab is a chimeric human-murine IgG1 monoclonalRituximab is a chimeric human-murine IgG1 monoclonal antibody that binds antibody that binds specifically to the B-cell surface antigenspecifically to the B-cell surface antigen CD20 CD20 The glycosylated protein consists of theThe glycosylated protein consists of the constant regions of human IgGs constant regions of human IgGs combined with the variablecombined with the variable region from murine IgGs, and is produced by region from murine IgGs, and is produced by ChineseChinese hamster ovary cells in suspension culture.hamster ovary cells in suspension culture.The antibodyThe antibody induces both complement-mediated and antibodydependentinduces both complement-mediated and antibodydependent cytotoxic effects on CD20-positive cells. cytotoxic effects on CD20-positive cells. It hasIt has also been reported to induce apoptosis and sensitisealso been reported to induce apoptosis and sensitise chemoresistant chemoresistant human lymphoma cell lines to cytotoxichuman lymphoma cell lines to cytotoxic chemotherapy.23–25 The antibody chemotherapy.23–25 The antibody is well tolerated and itsis well tolerated and its main toxic effect is either haematological main toxic effect is either haematological (thrombocytopenia(thrombocytopenia and neutropenia) or infusion-related. and neutropenia) or infusion-related. PrevalencePrevalence of human antichimeric antibody is less than 10%.26–28 It hasof human antichimeric antibody is less than 10%.26–28 It hasimportant single-agent efficacy, giving remission rates ofimportant single-agent efficacy, giving remission rates of 40–50% in the 40–50% in the treatment of relapsed indolenttreatment of relapsed indolent lymphoma,lymphoma, NNow received UK National Instituteow received UK National Institute for Clinical Excellence approval for for Clinical Excellence approval for patients who have failedpatients who have failed standard chemotherapy.standard chemotherapy.

Unusual Non-Hodgkin Lymphomas Unusual Non-Hodgkin Lymphomas Mycosis fungoidesMycosis fungoides

Mycosis fungoidesMycosis fungoides is a rare, persistent, very slow-growing non-Hodgkin is a rare, persistent, very slow-growing non-Hodgkin lymphoma. lymphoma. Most people who develop it are older than 50.Most people who develop it are older than 50.It originates from mature T lymphocytes and first affects the skin. It originates from mature T lymphocytes and first affects the skin. Mycosis fungoides starts so subtly and grows so slowly that it may not be Mycosis fungoides starts so subtly and grows so slowly that it may not be noticed initially. It causes a long-lasting, itchy rash—sometimes a small area noticed initially. It causes a long-lasting, itchy rash—sometimes a small area of thickened, itchy skin that later develops nodules and slowly spreads. of thickened, itchy skin that later develops nodules and slowly spreads. In some people, it develops into a form of leukemia (Sézary syndrome). In In some people, it develops into a form of leukemia (Sézary syndrome). In other people, it progresses to the lymph nodes and internal organs. Even other people, it progresses to the lymph nodes and internal organs. Even with a biopsy, doctors have trouble diagnosing this disease in its early with a biopsy, doctors have trouble diagnosing this disease in its early stages. However, later in the course of the disease, a biopsy shows stages. However, later in the course of the disease, a biopsy shows lymphoma cells in the skin.lymphoma cells in the skin.The thickened areas of skin are treated with a form of radiation called The thickened areas of skin are treated with a form of radiation called electron beam or with sunlight and corticosteroids applied to the skin..electron beam or with sunlight and corticosteroids applied to the skin.. On average, people live 7 to 10 years after the diagnosis is made, but On average, people live 7 to 10 years after the diagnosis is made, but survival varies widely depending on how far the cancer has spread. survival varies widely depending on how far the cancer has spread. Treatment does not cure the disease, but it slows it down even further.Treatment does not cure the disease, but it slows it down even further.

SEZARY SYNDROME/Erythema

Unusual Non-Hodgkin Lymphomas Unusual Non-Hodgkin Lymphomas Burkitt's lymphomaBurkitt's lymphoma

Burkitt's lymphomaBurkitt's lymphoma is a very fast-growing non-Hodgkin lymphoma that is a very fast-growing non-Hodgkin lymphoma that originates from B lymphocytes. originates from B lymphocytes. Burkitt's lymphoma can develop at any age, but it is most common in Burkitt's lymphoma can develop at any age, but it is most common in children and young adults, particularly males. children and young adults, particularly males. Unlike other lymphomas, Burkitt's lymphoma has a specific geographic Unlike other lymphomas, Burkitt's lymphoma has a specific geographic distribution: It is most common in central Africa and rare in the United distribution: It is most common in central Africa and rare in the United States. States. Infection with Epstein-Barr virus is associated with Burkitt's lymphoma. Infection with Epstein-Barr virus is associated with Burkitt's lymphoma. It is more common in people who have AIDS.Burkitt's lymphoma grows and It is more common in people who have AIDS.Burkitt's lymphoma grows and spreads quickly, often to the bone marrow, blood, and central nervous spreads quickly, often to the bone marrow, blood, and central nervous system. system. When it spreads, weakness and fatigue often develop. When it spreads, weakness and fatigue often develop. Large numbers of lymphoma cells may accumulate in the lymph nodes and Large numbers of lymphoma cells may accumulate in the lymph nodes and organs of the abdomen, causing swelling. Lymphoma cells may invade the organs of the abdomen, causing swelling. Lymphoma cells may invade the small intestine, resulting in blockage or bleeding. small intestine, resulting in blockage or bleeding. The neck and jaw may swell, sometimes painfully. The neck and jaw may swell, sometimes painfully. To make the diagnosis, doctors do a biopsy of the abnormal tissue and To make the diagnosis, doctors do a biopsy of the abnormal tissue and order procedures to stage the disease.order procedures to stage the disease.

Indolent (Slow-Growing, Low Indolent (Slow-Growing, Low Grade) LymphomasGrade) Lymphomas

Slow-growing lymphomas are subdivided into numerous B-cell and Slow-growing lymphomas are subdivided into numerous B-cell and T-cell subtypes, for example:T-cell subtypes, for example:

B-cellB-cell Small lymphocytic / pro-lymphocytic lymphoma (SLL)Small lymphocytic / pro-lymphocytic lymphoma (SLL)

Follicular lymphoma (few large cells)Follicular lymphoma (few large cells)

Lymphoplasmacytoid lymphomaLymphoplasmacytoid lymphoma

Marginal zone lymphomaMarginal zone lymphoma

T-cellT-cell Large granular lymphocyte leukemiaLarge granular lymphocyte leukemia

Adult T-cell leukemia/lymphoma (ATL/L )Adult T-cell leukemia/lymphoma (ATL/L )

Mycosis fungoides/Sézary Syndrome Mycosis fungoides/Sézary Syndrome

INDOLENT LYMPHOMAINDOLENT LYMPHOMA

A type of lymphoma that tends to grow and spread slowly, and has few symptoms. Also called low-grade lymphoma. lymphoma, usually takes several years to develop.Follicular lymphoma is typically a slow-growing, or indolent, form of non-Hodgkin lymphoma. This cancer, which accounts for roughly 20 to 30 percent of all non- Hodgkin It usually appears in a lumpy, or nodular pattern, within lymph nodes throughout the body. Often, the first sign of follicular lymphoma is a painless swelling in the neck, armpit or groin caused by enlarged lymph nodes. Some people also report loss of appetite and fatigue.Doctors sometimes suggest watchful waiting for people with indolent lymphoma. People with indolent lymphoma may not have problems that require cancer treatment for a long time.

Waldenstrom’s Macroglobulinemia

Waldenstrom’s macroglobulinemia (also known as lympho-plasmacytic lymphoma or immunocytoma) is a rare, slow-growing B-cell lymphoma that occurs in less than 2 percent of people with NHL.

Waldenstrom’s is characterized by a high level of a protein called immunoglobulin M (IgM) in the blood. These high levels of IgM can cause a thickening of the blood (hyperviscosity), resulting in symptoms such as nosebleeds, headaches, dizziness and blurring or loss of vision

Angioimmunoblastic T-cell lymphoma

Angioimmunoblastic T-cell lymphoma is a rare, aggressive (fast-growing) T-cell lymphoma that accounts for between 1 percent and 2 percent of all NHL cases. Symptoms include high fever, night sweats, skin rash and some types of autoimmune disorders, such as autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP), in which the body does not recognize its own cells. As a result of these autoimmune disorders, the body makes antibodies against and destroys its own cells and tissues, such as platelets (in the case of ITP) and red blood cells (in the case of AIHA).

Further Listening Further Listening

http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300123

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