Upload
stanley-hulen
View
215
Download
0
Tags:
Embed Size (px)
Citation preview
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