Transcript Lymphoma

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 tissues
 Typically causes lymphadenopathy.
Epidemiology of lymphomas
A common cancer
5th most frequently diagnosed cancer
Males > Females
•Routine microscopic examination
•Immunological examination
 Large malignant lymphoid cell
 Bi-nucleated
 B-cell origin
 Present in small numbers
 Surrounded by reactive T-cells, plasma cells and
eosinophils.
Reed Sternberg Cell
The pathology report
 Based on the pathological findings:

Hodgkin lymphoma
Non Hodgkin lymphoma
Hodgkin
Lymphoma

Non-Hodgkin
Lymphoma
Hodgkin’s Lymphoma
Hodgkin Lymphoma
All are B-Cells
Epidemiology
Sex
1.5
:
1
Epidemiology
Age
 A bimodal peaks: the 3rd and the 6th decades.
5
20s
>50s
4
3
2
1
0
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+
incidence/100,000/annum
6
Age (years)
a bimodal age-incidence curve
Epidemiology
Aetiology
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 Lymphoma
Symptoms
Painless Neck Swelling
Large Mediastinal Mass
Nodular Sclerosing disease
Clinical Features of Hodgkin Lymphoma
Systemic Symptoms
 Weight loss
 Sweating
 Itching
 Fever
Clinical Features
Physical Signs
 Painless, Rubbery
 Usually at neck and supraclavicular areas
 10% sub-diaphragmatic
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.
Infections
Autoimmune disorders
Haematological
Lymphomas
Leukemias
AIDS
Metastases
Benign
Could be because of:
 Disease infiltration.
 Reactive ( no infiltration).
CONTIGUOUS SPREAD
From one LN to the next.
Rare
Extranodal Disease:
 Bone
 Brain
 Skin
Investigations of HL
Confirm the Diagnosis
Histological Subtype
 Lymph Node Biopsy
 Biopsy from other tissues
Staging
Hodgkin Lymphoma
 Blood Tests
 Radiology
 Other biopsies
Lymph Node Biopsy
Taking the biopsy?
 Surgical excision
 Percutaneous needle biopsy under
radiological guidance
Hodgkin lymphoma - Histological subtypes
The WHO classification
 Nodular lymphocyte predominant HL (5%)



Slow growing
Localized
Rarely Fatal
 Classical Hodgkin lymphoma (95%)




nodular sclerosing
mixed cellularity
lymphocyte-rich
lymphocyte depleted
young, F>M
Elderly
Men
?NHL
Investigations of HL
Confirm the Diagnosis
Histological Subtype
 Lymph Node Biopsy
 Biopsy from other tissues
Staging
Hodgkin Lymphoma
 Blood Tests
 Radiology
 Other biopsies
 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
Evaluation of the abdomen and retroperitoneum
Lymph Nodes
Liver, Spleen, Kidneys
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
Bulky Disease
1. Mediastinal mass
>⅓ of
the maximum transverse
diameter of the chest
2. Presence of nodal mass
with a maximal
dimension > 10cm
LYMPHOMA
STAGING
“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
IA
IB
II A
II B
III A
III A
IV A
IV B
INTENTION OF TREATMENT
IS
CURE
With appropriate treatment:
 90% of Stage IA are cured
 70% of other stages are cured
Radiotherapy ONLY
Chemotherapy
•Stage IA-IIA Nodular
Lymphocyte Predominant HL
(ABVD) 8 courses
Radiotherapy
Chemotherapy
(ABVD) 2-6 courses
+ Involved Field
Radiotherapy (IFRT)
1- Bulky disease
2- Residual disease
:
A
B
V
D
ADRIAMYCIN(DOXORUBICIN)
BLEOMYCIN
VINBLASTINE
DACARBAZINE
Give day 1 & 15 every 4 weeks
Long term complications of treatment


sperm banking should be discussed
premature menopause

skin, AML, lung, MDS, NHL, thyroid, breast...



Non-Hodgkin Lymphoma
Epidemiology
Sex
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+
Incidence/100,000/annum
Age distribution of new NHL cases
Median Age: 65-70 yrs
100
80
60
40
20
0
Age (years)
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
NHL
Low grade NHL
•Small cell size
•Round or cleaved nuclei
•Low mitotic rate
Intermediate/High
grade NHL
•Larger cell size
•Prominent nucleoli
•Higher mitotic rate
•Indolent/ non aggressive NHL
•Aggressive NHL
•Low proliferation rate
•High proliferation rate
•Late symptoms
•Rapidly produce symptoms
•Indolent course – uncurable
with conventional therapy
•Fatal if untreated
Non-Hodgkin lymphoma
Incidence
Diffuse large B-cell
lymphoma
(High Grade)
Follicular Lymphoma
(Low Grade)
Other NHL
Clinical Features
Symptoms
Clinical Features of NHL
Symptoms
Painless Swelling
 Neck
 Axilla
 Groins
Clinical Features of NHL
Systemic Symptoms
 Weight loss
 Sweating
 Itching
 Fever
Clinical Features
Physical Signs
 If present indicates;
 Disease infiltration.
SKIPPY SPREAD
Extranodal Disease:
 Bone Marrow: Low Grade> High Grade
 Gut
 Thyroid
 Lung
 Testis
 Brain
 Skin
 Bone , rare
 Intestinal Obstrucion
 Ascites
 SVC obstrucion
 Spinal Cord Compression
More Common in NHL
NHL vs. HL Clinical Features
HL
NHL
Localized
Disseminated
Contingous
Skippy
Extra-nodal Disease
Rare
More
common
Obstruction Syndromes
Less
Common
More
common
Extent at presentation
Spread to LN
Staging of lymphoma
Cotswolds Staging classification
Stage I
Stage II
Stage III
Stage IV
LYMPHOMA
STAGING
“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
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.
 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..
Observation and Follow up
Indications for treatment
•Systemic Symptoms
Active Treatment
•Rapid nodal growth
•Bone Marrow involvment.
•Compression Syndromes
Radiotherapy
Chemotherapy
•Single agent (Chlarambucil, Fludarabine)
•Or; Combination chemotherapy (CVP)
•Rituximab (Monoclonal Antibody) for CD-20
positive follicular lymphoma
Palliative
Radiotherapy for:
•SVC obstruction
•Spinal Cord
Compression
•Pain
Chemotherapy (CHOP) 3 cycles
AND Radiotherapy
Chemotherapy (CHOP) 6-8 cycles
Chemotherapy (CHOP) + Rituximab
For CD20 + Diffuse large B Cell lymphoma
Radiotherapy to area of bulky disease
Autologus Stem Cell Transplantation
C
H
O
P
CYCLOPHOSPHAMIDE
DOXORUBICIN
VINCRISTINE (Oncovin)
PREDNISOLONE
Repeat cycle every 3 weeks
 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 infection
 Chemotherapy if;
 Large cell component
 Deeply penetrating
 Metastatic
 Relapsing
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%
HL
NHL
4:100 000/yr
12: 100 000/yr
Present
Absent
B-cell
B-cell(70%), T-cell(30%)
Males>Females
Males>Females
31 yrs
65-70 yrs
LN enlragement
Usually
supradiaphragmatic
Any where
Spread pattern
Contiguous
Skipped
Less common
More common
Stage (I,II,III,IV)
B symptoms
Grade (Low/High)
Stage(I,II,III,IV)
Incidence
Reed-Sternberg cells
Cell Type
Sex
Medial Age
Extranodal involvement
Determinants of
treatment
Category
NonHodgkin
lymphoma
Hodgkin
lymphoma
Survival of
untreated
patients
Curability
To treat or
not to treat
Indolent
Low Grade
Years
Generally
not curable
Generally
defer Rx if
asymptomatic
Aggressive
High Grade
Weeks
Months
Curable in
some
Treat
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  Extranodal involvement
bone, brain or skin is
rare.
is more common than in
HL
Bone marrow, GIT, Thyroid, Lung,
Skin , testis, Brain and Bone.