Lymphoma

Ismail M. Siala

Lymphomas

Neoplasms of lymphoid tissues that typically causes lymphadenopathy.

Classified pathologically into 2 types: Hodgkin lymphoma Non Hodgkin lymphoma

Epidemiology of lymphomas

A common cancer; 5th most frequently diagnosed cancer overall for both males and females

males > females

Epidemiology of Hodgkin Lymphoma

less frequent than non-Hodgkin lymphoma

A bimodal peaks at the 3rd and from the 6th decades.

Age (years)0-

11-

45-

910

-14

15-1

920

-24

25-2

930

-34

35-3

940

-44

45-4

950

-54

55-5

960

-64

65-6

970

-74

75-7

980

-84

85+

inci

denc

e/10

0,00

0/an

num

0

1

2

3

4

5

6

20s

>50s

a bimodal age-incidence curve

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

Etiology of HL

Etiology of NHL

Infection: Viral Infections:

EBV Burkitt Chronic H.pylori infection gastric lymphoma

Immunodeficiency: AIDS Organ transplant

Previous treatment for HL with chemo or radiotherapy

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.

Sites of involvment in HL Peripheral LN

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

Thorax Anterior mediastinum in NS HL Lung Pleural effusion Pericardial effusion SVC obstruction

Abdomen Spleenomegaly Hepatomegaly Retroperitoneal LN

How a patient with lymphoma presents?Symptoms:

Painless swelling

Systemic symptoms; Weight loss Sweating Itching Fever

Pain; Abdominal, bone, neurogenic or pain

Physical sings:

Enlarged Lymph nodes

Physical signs:

Splenomegaly

Hepatomegaly

Physical signs:Other physical findings Effusions

Neurological deficits

Compression syndromes SVC obstruction Intestinal obstruction Spinal cord compression

Skin infiltration

Differential Diagnosis of Lymphadenopathy

Infections Autoimmune disorders Malignant haematological diseases

Leukemias Lymphoma

Metastasis from other primary. AIDS Benign

occiptial Posterior auricular Shotty inguinal nodes Cervical nodes

Differential diagnosis of

Splenomegaly: Portal hypertension

Haematological Malignancies. Leukemia Lymphoma Myeloma

Myeloproliferative disorders Chronic Myeloid Leukemia. Myelofibrosis. Polycythemia Rubra Vera Essential thrombocytosis

Autoimmune disorders Systemic Lupus Erythematosus Rheumatoid arthritis

Infections

Others• Normal• Splenic systs• Thyrotoxicosis• Sarcoidosis• Amyloidosis

What is next?

Get a tissue diagnosis

A biopsy could be obtained from:

Lymph node

Bone marrow biopsy

Imaging guided biposy for retroperitoneal and mesentric masses

Endocopic gastric biopsy

Send for pathological examination

• Routine microscopic examination

• Immunological examination• Hodgkin vs Non Hodgkin

• CD20 positive or negative for some types of NHL

• Routine microscopic examination

• Immunological examination• Hodgkin vs Non Hodgkin

• CD20 positive or negative for some types of NHL

Reed-Sternberg Cells

Large malignant lympoid cells Bi-nucleated B-cell origin Present in small numbers Surrounded by reactive Tcells,

plasma cells and eosinophils.

The pathology reportThe pathology report

Hodgkin Lymphoma

Hodgkin Lymphoma

Non-Hodgkin Lymphoma

Non-Hodgkin Lymphoma

Reed Sternberg Cell

Which lymph node groups and

organs are affected?

THE EXTENT OF DISEASE

Staging investigationsEvaluation of the chest 1-Chest X-Ray

Staging investigationsEvaluation of the abdomen and retroperitoneum

2-Abdominal ultrasonography Lymphnodes Liver, spleen, kidneys

Staging investigations

3-CT scan of the chest, abdomen and pelvis

Staging investigations

4 -Bone Marrow biopsy

Indications of bone marrow biopsy:

1- ALL cases of Non Hodgkin Lymphoma.

2- Hodgkin Lymphoma when bone marrow involvement is suspected

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

Staging InvestigationsHematological examination

Complete blood count

ESR

Liver function tests

Renal function tests

Serum LDH Reflect level of tumour bulk and turnover Particularly of relevance in aggressive NHL

Other staging investigations

Endoscopy for GIT lymophomas Lumbar puncture

In some cases of Non Hodgkin Lymphoma Burkitt lymphoma Lymphoblastic lymphoma Intermediate or high grade lymphoma involving; Testes, paranasal sinuses, extensive bone marrow involvment.

MRI brain for AIDS related lymphoma PET scan:

differentiate involved from non involved LN

Stage I Stage II Stage III Stage IV

Staging of lymphomaCotswolds Staging 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

Lymphoma Stages

I A I BII A II BIII A III AIV A IV B

Hodgkin’s LymphomaHodgkin’s Lymphoma

Thomas Hodgkin(1798-1866)

Reed-Sternberg cell

Hodgkin lymphoma - Histological subtypesThe WHO classification

Nodular lymphocyte predominant HL (5%) Slow growing localized

Classical Hodgkin lymphoma (95%) nodular sclerosing mixed cellularity lymphocyte-rich lymphocyte depleted

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

Note:

For Stage IA-IIA of Nodular Lyphocyte Predominant HL Radiotherapy alone is enough

Note:

For Stage IA-IIA of Nodular Lyphocyte Predominant HL Radiotherapy alone is enough

Chemotherapy (ABVD) 2-6 coursesChemotherapy (ABVD) 2-6 courses

Treatment of HLTreatment of HL

Stage I-IIStage I-II

1- Bulky disease2- Residual disease

1- Bulky disease2- Residual disease

AND Radiotherapy AND Radiotherapy

Stage III-IVStage III-IV

Chemotherapy (ABVD) 8 coursesChemotherapy (ABVD) 8 courses

Radiotherapy ONLY FOR:Radiotherapy ONLY FOR:

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

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

Treatment of NHL

1- Grade of NHL ( Low or High)

2-STAGE OF NHL

1- Grade of NHL ( Low or High)

2-STAGE OF NHL

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)

Chemotherapy • Single agent (Chlarambucil, Fludarabine)

• Or; Combination chemotherapy (CVP)

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

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

regimens for Diffuse Large B cell 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