Lymphomas

Ismail M. Siala

Objectives:

The types of lymphoma.

Clinical Presentation of lymphomas

Diagnosis of lymphomas

Investigations of lymphomas.

Staging of lymphomas

Treatment options of Lymphomas.

Lymphomas

Definition

Neoplasms of lymphoid tissuesTypically causes lymphadenopathy.

Epidemiology of lymphomas

A common cancer5th most frequently diagnosed cancer

Males > Females

CLASSIFICATION OF LYMPHOMAS

• Routine microscopic examination

• Immunological examination

• Routine microscopic examination

• Immunological examination

Lymph NodeBone Marrow Bx

Other Tissue

Reed-Sternberg Cell

Large malignant lymphoid cell

Bi-nucleated

B-cell origin

Present in small numbers

Surrounded by reactive T-cells, plasma cells and eosinophils.

The pathology reportThe pathology report

Hodgkin Lymphoma

Hodgkin Lymphoma

Non-Hodgkin Lymphoma

Non-Hodgkin Lymphoma

Reed Sternberg Cell

Based on the pathological findings:

Hodgkin lymphoma

Non Hodgkin lymphoma

Hodgkin’s LymphomaHodgkin’s Lymphoma

Thomas Hodgkin(1798-1866)

Hodgkin Lymphoma

All are B-Cells

Hodgkin Lymphoma=

Reed-Sternberg cell

EpidemiologySex

>1.5 1:

EpidemiologyAge

A bimodal peaks: the 3rd and the 6th decades.

Age (years)

0-1

1-4

5-9

10

-14

15

-19

20

-24

25

-29

30

-34

35

-39

40

-44

45

-49

50

-54

55

-59

60

-64

65

-69

70

-74

75

-79

80

-84

85

+

incid

en

ce

/10

0,0

00

/an

nu

m

0

1

2

3

4

5

6

20s

>50s

a bimodal age-incidence curve

EpidemiologyAetiology

Unknown Well-educated background Small families. Past history of infectious mononucleosis, no

proven link to EB virus yet.

Clinical Features

Symptoms

Clinical Features of Hodgkin LymphomaSymptoms

Painless Neck Swelling

Large Mediastinal MassNodular Sclerosing disease

Dry Cough

Breathlessness

Weight lossSweating ItchingFever

Clinical Features of Hodgkin LymphomaSystemic Symptoms

Clinical Features

Physical Signs

Painless, Rubbery Usually at neck and supraclavicular areas 10% sub-diaphragmatic

Lymphadenopathy

Sites of LN involvment in HL

Peripheral LN Cervical, supraclavicular and axillary LN (70%) Generalized lymphadenopathy is not typical in HL

Thorax Anterior mediastinum in NS HL Others, Rare:

Lung Pleural effusion Pericardial effusion SVC obstruction

Abdomen Hepatosplenomegaly. Retroperitoneal LN.

Differential Diagnosis

of Lymph-

adenopathy

Infections

Autoimmune disorders

HaematologicalLymphomas

Leukemias

Metastases

AIDS

Benign

Hepatosplenomegaly

Could be because of:

Disease infiltration.

Reactive ( no infiltration).

Spread to other LN groups

CONTIGUOUS SPREAD

From one LN to the next.

Extranodal Disease

Rare

Extranodal Disease: Bone Brain Skin

Investigations of HL

Hodgkin lymphoma

Treatment depends on:1. Histological Subtype2. Clinical Stage

Investigations of HL

Confirm the DiagnosisHistological Subtype

Lymph Node Biopsy Biopsy from other tissues

Staging Hodgkin Lymphoma

Blood Tests Radiology Other biopsies

Lymph Node BiopsyTaking the biopsy?

Surgical excision

Percutaneous needle biopsy under radiological guidance

Hodgkin lymphoma - Histological subtypesThe WHO classification

Nodular lymphocyte predominant HL (5%) Slow growing Localized Rarely Fatal

Classical Hodgkin lymphoma (95%) nodular sclerosing

young, F>M mixed cellularity Elderly lymphocyte-rich Men lymphocyte depleted ?NHL

Investigations of HL

Confirm the DiagnosisHistological Subtype

Lymph Node Biopsy Biopsy from other tissues

Staging Hodgkin Lymphoma

Blood Tests Radiology Other biopsies

Blood Investigations

Complete blood count May be Normal Normochromic, normocytic anaemia Lymphopenia ( A bad sign) Eosinophilia Neutrophilia

ESR, may be raised

Liver function tests May be Normal Abnormal

With infiltraion or without infiltraion Obstructive pattern enlarged LN at porta hepatis.

Renal function tests, need to be normal before Rx.

Serum LDH Reflect level of tumor bulk and turnover Not of great significance in HL

Blood Investigations

Radiological Investigations

Chest X-Ray

Abdominal UltrasoundEvaluation of the abdomen and retroperitoneum

Lymph NodesLiver, Spleen, Kidneys

CT-Scan of Chest, Abdomen and Pelvis

Blood Investigations

Radiological Investigations

Bone Marrow Biopsy

Bone Marrow biopsy

Indications

1- Hodgkin Lymphoma when bone marrow involvement is suspected

• abnormal full blood count• advanced stage of the disease.

2-ALL cases of Non Hodgkin Lymphoma.

Stage I Stage II Stage III Stage IV

Staging of lymphomaAnn Arbor classification

Bulky Disease

1. Mediastinal mass >⅓ of the maximum transverse diameter of the chest

2. Presence of nodal mass with a maximal dimension > 10cm

“B” symptoms Unexplained Fever > 38oC Unexplained Weight loss > 10% body

weight within the preceding 6 months. Drenching night sweets

Stage A No B symptoms Stage B any one of the B symptoms

LYMPHOMASTAGING

Stages of Lymphoma

I A I B

II A II B

III A III A

IV A IV B

Management of Hodgkin Lymphoma

INTENTION OF TREATMENT

IS

CUREWith appropriate treatment: 90% of Stage IA are cured 70% of other stages are cured

HODGKIN`S LYMPHOMAMANAGEMENT

Hodgkin lymphoma

Treatment depends on:1. Histological Subtype2. Clinical Stage

• Stage IA-IIA Nodular Lymphocyte Predominant HL

• Stage IA-IIA Nodular Lymphocyte Predominant HL

Chemotherapy (ABVD) 2-6 courses

+ Involved Field Radiotherapy (IFRT)

Chemotherapy (ABVD) 2-6 courses

+ Involved Field Radiotherapy (IFRT)

Treatment of HLTreatment of HL

Stage I-IIStage I-II

1- Bulky disease2- Residual disease

1- Bulky disease2- Residual disease

Stage III-IVStage III-IV

Chemotherapy (ABVD) 8 courses

Chemotherapy (ABVD) 8 courses

Radiotherapy ONLY FOR:Radiotherapy ONLY FOR:

Radiotherapy ONLYRadiotherapy ONLY

ABVD

A ADRIAMYCIN(DOXORUBICIN)

B BLEOMYCIN

V VINBLASTINE

D DACARBAZINE

Give day 1 & 15 every 4 weeks

Long term complications of treatment

Infertility sperm banking should be discussed premature menopause

secondary malignancy skin, AML, lung, MDS, NHL, thyroid, breast...

cardiac disease

Non-Hodgkin LymphomaNon-Hodgkin Lymphoma

EpidemiologySex

>

Age distribution of new NHL cases

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

denc

e/10

0,00

0/an

num

0

20

40

60

80

100

Median Age: 65-70 yrs

Etiology of NHL

Infection: Viral Infections:

EBV Burkitt Human Herpes virus 8 HTLV

Chronic H.pylori infection gastric lymphoma

Immunodeficiency: AIDS Organ transplant

Previous treatment for HL chemo or radiotherapy

Chromosomal, T(14:18) in follicular lymphoma

NHLNHL

Low grade NHLLow grade NHL Intermediate/High grade NHL

Intermediate/High grade NHL

• Small cell size• Round or cleaved nuclei• Low mitotic rate

• Small cell size• Round or cleaved nuclei• Low mitotic rate

• Larger cell size• Prominent nucleoli• Higher mitotic rate

• Larger cell size• Prominent nucleoli• Higher mitotic rate

• Indolent/ non aggressive NHL

• Low proliferation rate

• Late symptoms

• Indolent course – uncurable with conventional therapy

• Indolent/ non aggressive NHL

• Low proliferation rate

• Late symptoms

• Indolent course – uncurable with conventional therapy

• Aggressive NHL

• High proliferation rate

• Rapidly produce symptoms

• Fatal if untreated

• Aggressive NHL

• High proliferation rate

• Rapidly produce symptoms

• Fatal if untreated

Non-Hodgkin lymphomaIncidence

Diffuse large B-cell lymphoma

(High Grade)

Follicular Lymphoma(Low Grade)

Other NHL

85% of NHL

Clinical Features

Symptoms

Clinical Features of NHLSymptoms

Painless Swelling Neck Axilla Groins

Weight lossSweating ItchingFever

Clinical Features of NHLSystemic Symptoms

Clinical Features

Physical Signs

Lymphadenopathy

Hepatosplenomegaly

If present indicates;

Disease infiltration.

Spread to other LN groups

SKIPPY SPREAD

Extranodal Disease

Extranodal Disease:

Bone Marrow: Low Grade> High Grade Gut Thyroid Lung Testis Brain Skin Bone , rare

MORE COMMON IN NHL

SPECIALLY IN T-CELL LYMPHOMA

Compression Syndromes

Intestinal Obstrucion Ascites SVC obstrucion Spinal Cord Compression

More Common in NHL

NHL vs. HL Clinical Features

HL NHL

Extent at presentation Localized Disseminated

Spread to LN Contingous Skippy

Extra-nodal Disease Rare More common

Obstruction Syndromes Less Common

More common

Stage I Stage II Stage III Stage IV

Staging of lymphomaCotswolds Staging classification

“B” symptoms Unexplained Fever > 38oC Unexplained Weight loss > 10% body

weight within the preceding 6 months. Drenching night sweets

Stage A No B symptoms Stage B any one of the B symptoms

LYMPHOMASTAGING

INVESTIGATIONS OF NHL

As in Hodgkin Lymphoma

1. Hematological examinatons:

Complete blood count Liver function tests Renal function tests Serum LDH

Reflect level of tumor bulk and turnover Particularly of relevance in aggressive NHL

2. Radiological examinatons

3-Bone Marrow biopsy

Indications of bone marrow biopsy:

1- Hodgkin Lymphoma when bone marrow involvement is suspected

• abnormal full blood count• advanced stage of the disease.

2-ALL cases of Non Hodgkin Lymphoma.

As in Hodgkin Lymphoma

PLUS Immunophenotyping of surface

antigens: B-Cell or T-Cell

Immunoglobulin Levels, some NHL cause raised IgG or IgM levels.

Serum Uric Acid Raised in high grade NHL renal failure if not

treated.

HIV testing, If relevant to clinical condition..

Non Hodgkin lymphoma

Treatment depends on:1. Grade ( Low or High)2. Clinical Stage

Indications for treatment• Systemic Symptoms• Rapid nodal growth• Bone Marrow involvment.• Compression Syndromes

Indications for treatment• Systemic Symptoms• Rapid nodal growth• Bone Marrow involvment.• Compression Syndromes

Treatment of Low Grade NHLTreatment of Low Grade NHL

Stage I-IIStage I-II

Radiotherapy Radiotherapy

Stage III-IVStage III-IV

Chemotherapy • Single agent (Chlarambucil, Fludarabine)

• Or; Combination chemotherapy (CVP)• Rituximab (Monoclonal Antibody) for CD-

20 positive follicular lymphoma

Chemotherapy • Single agent (Chlarambucil, Fludarabine)

• Or; Combination chemotherapy (CVP)• Rituximab (Monoclonal Antibody) for CD-

20 positive follicular lymphoma

Observation and Follow upObservation and Follow up

Palliative Radiotherapy for:

• SVC obstruction• Spinal Cord

Compression• Pain

Palliative Radiotherapy for:

• SVC obstruction• Spinal Cord

Compression• Pain

Active TreatmentActive Treatment

Treatment of high Grade NHLTreatment of high Grade NHL

Stage I-II – Non BulkyStage I-II – Non Bulky

Chemotherapy (CHOP) 3 cycles Chemotherapy (CHOP) 3 cycles

Stage III-IVStage III-IV

Chemotherapy (CHOP) 6-8 cycles Chemotherapy (CHOP) 6-8 cycles

Chemotherapy (CHOP) + Rituximab For CD20 + Diffuse large B Cell lymphoma

Chemotherapy (CHOP) + Rituximab For CD20 + Diffuse large B Cell lymphoma

AND Radiotherapy AND Radiotherapy

Stage I-II – BulkyStage I-II – Bulky

Radiotherapy to area of bulky disease Radiotherapy to area of bulky disease

Relapsed DiseaseRelapsed Disease Autologus Stem Cell TransplantationAutologus Stem Cell Transplantation

CHOPC CYCLOPHOSPHAMIDE

H DOXORUBICIN

O VINCRISTINE (Oncovin)

P PREDNISOLONE

Repeat cycle every 3 weeks

Rituximab

Monoclonal Antibody Against CD20 antigen. Can be combined with other chemotherapy Used for

Diffuse Large B cell Lymphoma Follicular Lymphoma that is CD20 positive

Gastric MALToma

Low grade histology Related to H.pylori infection Surgery is not routinely performed.

Treatment:Treat H.pylori infectionChemotherapy if;

Large cell component Deeply penetrating Metastatic Relapsing

Thank you all for your attention

Classification of NHL

The working formulation (1982) Clinical behaviour + histopathological features Not incorporated the origin of the cell ( B or T) Missing a large variaty of new clinicopathological

entities.

The WHO/REAL classification (1993) Incorporates immunophenotypes Differentiate between cells of T or B origin Recognizes seversal less common entities

The International Prognostic Index (IPI) for NHL

Five independent prognostic factors

1- age older than 60 years

2- higher stage (III or IV)

3- More than one extranodal site involvement

4- lower performance status ( ECOG>1)

5- elevated serum LDH

0-1 5 yr survival is 73% 4-5 5 yr survival is 26%

A practical way to think of lymphoma

HL NHL

Incidence 4:100 000/yr 12: 100 000/yr

Reed-Sternberg cells Present Absent

Cell Type B-cell B-cell(70%), T-cell(30%)

Sex Males>Females Males>Females

Medial Age 31 yrs 65-70 yrs

LN enlragement Usually supradiaphragmatic Any where

Spread pattern Contiguous Skipped

Extranodal involvement Less common More common

Determinants of treatment

Stage (I,II,III,IV)B symptoms

Grade (Low/High)Stage(I,II,III,IV)

A practical way to think of lymphoma

Category Survival of untreated patients

Curability To treat or not to treat

Non-Hodgkin

lymphoma

IndolentLow Grade

Years Generally not curable

Generally defer Rx if

asymptomatic

AggressiveHigh Grade

Weeks Months

Curable in some

Treat

Hodgkin lymphoma

All types Variable – months to

years

Curable in most

Treat

Modes of Spread of Lymphoma

Hodgkin Lymphoma

Almost always originate in a LN

Contiguous spread

Extranodal disease to bone, brain or skin is rare.

Non Hodgkin Lymphoma

Usually widespread at presentation

Skippy spread

Extranodal involvement is more common than in HL

Bone marrow, GIT, Thyroid, Lung, Skin , testis, Brain and Bone.