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LYMPHOMA

dr Putra Hendra SpPD


UNIBA

ALL

CLL

Lymphomas

MM

nave
B-lymphocytes

Lymphoid
progenitor

AML
Hematopoietic
stem cell

Myeloid
progenitor

Plasma
cells
T-lymphocytes

Myeloproliferative disorders
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells

Bone Marrow Aspiration/Biopsy

B-cell development
CLL

stem
cell
lymphoid
progenitor

mature
naive
B-cell

germinal
center
B-cell

MM

progenitor-B

ALL

memory
B-cell

pre-B
immature
B-cell

DLBCL,
FL, HL

plasma cell

Disease states correlate with stages in normal B-cell development

Diseases:

AML

Pro-B-ALL

Pre-B-ALL

B-ALL

-MGUS
-B-CLL
-Multiple Myeloma
-DLBCL
-Plasmacytoma
-FLL
-BL
-Mantle Cell lymphoma
-Marginal Zone lymphoma
-MALT
-GALT
-Hodgkins (?)

Mantle zone
lymphoma

Chronic lymphocytic
leukemia
Small lymphocytic lymphoma
Waldenstrms macroglobulinemia

Follicular lymphoma
Burkitts lymphoma

Szary syndrome
Mycosis fungoides
Peripheral T cell
lymphoma

Lymphocytic Leukemia &


Lymphoma
Leukemia: widespread involvement of BM and
presence of large number of tumor cells in
peripheral blood
Lymphoma: lymphoid proliferations as discrete
tissue masses

Lymphoma classification
(2001 WHO)

B-cell

neoplasms

precursor
mature

T-cell

& NK-cell neoplasms

precursor
mature

Hodgkin

lymphoma

NonHodgkin
Lymphomas

Lymphomas

15%

85%

Hodgkins
Non Hodgkins
B Cells Nodular sclerosing 50%
Mixed cellularity 30-40%

T Cells

Hodgkin Disease

Hodgkin Disease
Definition:

neoplastic disorder with development of


specific infiltrate containing pathologic
Reed-Sternberg cells. It usually arises in
lymph nodes and spreads to contiguous
groups. Extranodal presentation are rare.
Disease is associated with defective
cellular immunity.

REED-STERNBERG ( RS) Cell

Hodgkin Disease
Incidence:

- 2-4 cases per 100000 population / year


- bimodal age distribution :
15-35 years and above 50 years
- male predominance M:F = 1,7:1

Epidemiology Hodgkins
Bimodal
Postulated

to have
infectious
association

Classical Hodgkin Lymphoma

Clinical Presentation

Nontender lymph nodes enlargement ( localised )

systemic symptoms (B symptoms) 30%

neck and supraclavicular area


60-80%
mediastinal adenopathy 50%
other ( abdominal, extranodal disease )
fever
night sweats
unexplained weight loss (10% per 6 months)

Pel-Ebstein fever.
relapsing, high-grade fever that can reach 105-106F,
periodicity of 7-10 days. Fever spikes abrupt in onset
and resolution
other symptoms

fatigue, weakness, pruritus


cough , chest pain, shortness of breath, vena cava syndrome
abdominal pain, bowel disturbances, ascites
bone pain

Pel-Ebstein Fever

Investigations
CBP

:
Anemia ( normochromic / normocytic), eosinophilia,
neutrophilia, lymphopenia
ESR
LFT- (liver infil / obs at porta hepatis)
RFT- prior to treatment
Urate , Ca,
LDH - adverse prognosis
CXR- mediastinal mass
CT thorax / abdomen / pelvis-for staging
Other: Gallium scan, PET, Lymphangiography ,
Laporotomy
Excisional biopsy of a lymph node

Staging of lymphoma
Stage I

Stage II

Stage III

A: absence of B symptoms
B: fever, night sweats, weight loss

Stage IV

A practical way to think of lymphoma


Category

Non-Hodgkin
lymphoma

Hodgkin
lymphoma

Survival of
untreated
patients

Curability

To treat or
not to treat

Indolent

Years

Generally not
curable

Generally defer
Rx if
asymptomatic

Aggressive

Months

Curable in
some

Treat

Very
aggressive

Weeks

Curable in
some

Treat

All types

Variable
months to
years

Curable in
most

Treat

Non Hodgkin Lymphoma

Jacqueline Kennedy Onassis

Former First Lady

King Hussein of Jordan

Types of Non-Hodgkins Lymphoma

Small lymphocytic

Immunoblastic

Mantle cell

Large Cell

Etiology of NHL
Immune

suppression

congenital

(Wiskott-Aldrich)
organ transplant (cyclosporine)
AIDS
increasing age
DNA

repair defects

ataxia

telangiectasia
xeroderma pigmentosum

Etiology of NHL
Chronic

inflammation and antigenic stimulation

Helicobacter

pylori inflammation, stomach


Chlamydia psittaci inflammation, ocular adnexal
tissues
Sjgrens syndrome
Viral

causes

EBV

and Burkitts lymphoma


HTLV-I and T cell leukemia-lymphoma
HTLV-V and cutaneous T cell lymphoma
Hepatitis C

Current up-front treatment regimens for aggressive lymphomas

Regimen

Drugs

CHOP

Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

BACOP

Bleomycin, Doxorubicin, Cyclophosphamide, Vincristine.


Prednisone

M-BACOD

Methotrexate, Leucovorin, Bleomycin, Cyclophosphamide,


Vincristine, Dexamethasone

ProMACE/MOPP

Prednisone, Methotrexate, Leucovin, Doxorubicin,


Cyclophosphamide, Etoposide

MACOP-B

Methotrexate, Leucovorin, Doxorubicin, Cyclophosphamide,


Vincristine, Bleomycin, Prednisone, Trimethoprimsulfamethoxazole

(Used at various doses, with, or without radiation)

Treatment Options in
Advanced Indolent Lymphomas
Observation

only.
Radiotherapy to site of problem.
Systemic chemotherapy
oral

agents: chlorambucil and prednisone


IV agents: CHOP, COP, fludarabine, 2-CDA.

Antibody

against CD20: Rituxan, Bexxar,

Zevalin.
Stem cell or bone marrow transplant.

Hodgkin's Lymphoma

VS

Non-Hodgkin's Lymphomas

Average age is 27.7 with two age peaks, the


major one between 15 and 24 with a lesser peak
after age 55.

Average age is about 67.

Men 0.23%
Women 0.20%

Men 2.12%
Women 1.79%

About 15% of all lymphomas

About 85% of all lymphomas

Location

The disease occurs most often in lymph nodes


above the collar bone. In Hodgkin's it is also
more likely to appear in the chest cavity between
the lungs (the mediastinum), particularly in
younger patients.
Only about 15% to 20% of cases are found in
areas below the diaphragm.

In NHL it is more likely to appear in the


nodes in the abdomen (called the
mesenteric nodes).
The disease occurs in the chest cavity in
less than 40% of patients. (An exception,
lymphoblastic lymphoma, which is seen
most often in young people, is likely to first
appear in the chest.)

Affected Lymph
Cells

B limfosit
Disease occurs outside the nodes in about 4% of
cases.
characterized
by the Reed-Sternberg Cell

B-Lymphocytes, T-Lymphocytes or Natural Killer

Age
Chance of getting
in all people over
an entire lifetime
Occurrence

Symptoms

Progression

More likely than NHL (40%) to have systemic


("B") symptoms (such as fever and night sweats)
at the time of diagnosis.
Less likely than NHL to be diagnosed in stage IV (10%).
Hodgkin's disease usually progresses in an orderly way
from one lymph node region to the next. This process
may be slow, particularly in younger people, or very
aggressive. The disease typically spreads downward from
the initial site. If it spreads below the diaphragm, it usually
reaches the spleen first; the disease then may spread to

(NK) Cells depending on the subtype


Disease occurs outside the nodes in about
23% of patients. Slow-growing lymphomas
are common in the liver and bone marrow.
Less likely than HL to have systemic ("B")
symptoms (27%) at the time of diagnosis.
More likely than HD to be diagnosed in stage IV
(36%) but this will vary by NHL subtype.
The Non-Hodgkin's lymphomas are less predictable
in their course than Hodgkin's and they are more
apt to spread.

Multiple Myeloma

Multiple Myeloma
More

than 15% plasma cells in the bone


marrow.
Monoclonal immunoglobulin peak on SPEP
more

Bence

than 3 gm/dL.

Jones protein in urine (+).


normal immunoglobulins .

Clinical Features
Bone

marrow failure
- Anemia, thrombocytopenia,
neutropenia
Renal failure
Bone disease with skeletal destruction
lytic lesions
generalized decrease in bone density
Hypercalcemia

Diagnosis and Staging


Workup
Bone

marrow biopsy and aspirate


Serum protein electrophoresis and
immunofixation
Skeletal survey
Plain

x-rays are better than bone scan.


Lytic lesions do not show up well on bone scan.
Quantitative

immunoglobulins

Serum Protein Electrophoresis

Alb. 1 2

Total protein 7.2


2 globulin 0.5
albumin 4.5
globulins 0.7
1 globulin 0.15 globulin 1.4
Normal

Alb. 1 2

Total protein 7.9 2 globulin 0.6


albumin 3.9
globulins 0.7
1 globulin 0.19 globulin 2.4
Monoclonal Spike

Monoclonal Immunoglobulin Spike


on Serum Protein Electrophoresis
(SPEP)
Multiple myeloma
Non-Hodgkins

lymphoma
Monoclonal gammopathy of
undetermined significance (MGUS).
Not clinically significant unless present
in high quantity (over 3 gm/dL).

Lytic Bone Lesions in Multiple Myeloma

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