Objectives: The types of lymphoma. Clinical Presentation of lymphomas Diagnosis of lymphomas...
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Transcript of Objectives: The types of lymphoma. Clinical Presentation of lymphomas Diagnosis of lymphomas...
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.