Lymphoma is a collection of lymphoid malignancies in which malignant lymphocytes accumulate at lymph nodes and lymphoid tissues, leading to lymphadenopathy, extranodal disease, and constitutional symptoms. There are two main types: Hodgkin's lymphoma and non-Hodgkin's lymphoma. Hodgkin's lymphoma is characterized by the presence of Reed-Sternberg cells and causes inflammation and fibrosis. Non-Hodgkin's lymphoma encompasses a variety of subtypes of B-cell and T-cell lymphomas that present with widespread disease. Staging guides treatment for Hodgkin's lymphoma while it is less important for non-Hodgkin's lymphoma.
2. Collection of lymphoid
malignancies in which
malignant lymphocytes
accumulate at lymph nodes
and lymphoid
tissuesleading to
lymphadenopathy, extranodal
disease, and constitutional
symptoms,
“B” symptoms .
Lymphoma
Lymphoma
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SUB-TYPES
A = absence of B-
symptoms
B = presence of
B-symptoms
“B” symptoms: fever, weight
loss, drenching night sweats
CHROMOSOMAL
TRANSLOCATIONS
TRANSLOCATION GENE ACTIVATION ASSOCIATED NEOPLASM
t(8;14) c-myc activation Burkitt’s lymphoma
t(14;18) bcl-2 activation Follicular lymphoma
t(9;22) Philadelphia chromosome
(bcr-abl hybrid)
CML, ALL in adults (25% of
the time)
t(11;14) Overexpression of cyclin D1
protein
Mantle Cell Lymphoma
5. Hodgkin’s
Lymphoma
Hodgkin’s Lymphoma
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Malignant proliferation of lymphoid cells
with Reed-Sternberg cells (thought to
arise from germinal centre B-cells)
Epidemiology
• bimodal distribution with peaks at 20 yr
and >50 yr
• association with Epstein-Barr virus in up
to 50% of cases, causal role not
determined
Band of fibrosis (left), lacunar cells (a variant of Reed sternberg cells –
right)
6. Pathology
Large B cells (CD 15 and CD 30 +ve)
with multilobed nuclei and prominent
nucleoli that looks like “Owl eye”
They produce cytokines which attract
inflammatory cells and cause fibrosis
Due to cytokine release:
1. B symptoms – fever, chills, wt loss,
night cells
2. Presence of reactive inflammatory
cells that make bulk of tumor
3. Fibrosis
HODGKIN’S LYMPHOMA
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Reed-
Sternberg Cells
Cytokines
release
7. Types of Hodgkin’s Lymphoma
Hodgkin Lymphoma
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Type Characteristics
Nodular sclerosis Most common type of HL
- Classic pt is young adult female
- Presents as enlarged cervical or mediastinal
lymph nodes
Lymph node is divided by band of fibrosis
Reed sternberg cells are present in lake like
spaces (lacunar cells)
Mixed cellularity Associated with abundant eosinophils (reed
sternberg cells produce IL-5)
Lymphocyte rich Best prognosis of all types
Lymphocyte depleted - Most aggressive of all types
-Usually seen in HIV pt or old pt
8. HODGKIN’S LYMPHOMA
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CLINICAL FEATURES
Asymptomatic lymphadenopathy (70%)
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non-tender, rubbery consistency
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cervical/supraclavicular (60-80%), axillary (10-20%), inguinal (6-12%)
Splenomegaly (50%) ± hepatomegaly
Mediastinal mass
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found on routine CXR, may be symptomatic (cough)
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rarely may present with SVC syndrome, pleural efusion
Systemic symptoms
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B symptoms (especially in widespread disease; fever in 30%), pruritus
Non-specifc/paraneoplastic
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alcohol-induced pain in nodes, nephrotic syndrome
Starts at a single site in lymphatic system (node), spreads frst to adjacent
nodes
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disease progresses in contiguity with lymphatic system
9. Lymphoma
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SVC syndrome
Slow healing
of wounds
Easy bruising
Pale skin
Pleural effusion
Shortness of
breath
Fever
Joint Pain
Swollen
lymph nodes
in neck,
armpit and
groin
11. INVESTIGATIONS
HODGKIN’S LYMPHOMA
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CBC
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Anemia (chronic disease, rarely hemolytic), eosinophilia, leukocytosis, platelets normal or increased early,
decreased in advanced disease
Biochemistry
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HIV serologyƒ
LFTs (liver involvement)
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renal function tests (prior to initiating chemotherapy)
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ALP, Ca2+ (bone involvement) ƒ
ESR, LDH (monitor disease progression)
Imaging
ƒ
CXR, CT chest (lymph nodes, mediastinal mass), CT abdomen/pelvis (liver or spleen involvement), gallium
scan (assess treatment response), PET scans
ƒ
Cardiac function assessment (MUGA scan or echocardiography): for patients at high risk of pre-treatment
cardiac disease (age >60, history of HTN, CHF, PUD, CAD, MI, CVA), treatment can be cardiotoxic
PFTs: if history of lung disease (COPD, smoking, previous radiation to lung)
• excisional lymph node biopsy confrms diagnosis
Bone marrow biopsy to assess marrow infltration (only necessary if B-symptoms, stage III or IV, bulky
disease or cytopenia)
12. TREATMENT
Stage Ia and IIa: local radiation with a small course of
chemotherapy
Stage III and IV or anyone with “B” symptoms: ABVD
A = adriamycin (doxorubicin)
B = bleomycin
V = vinblastine
D = dacarbazine
Lymphoma Disease
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Radiation increases the risk of solid tumors such as breast, thyroid, or lung
cancer. Screening for breast cancer is recommended 8 years or more after
treatment. Radiation also increases the chance of premature coronary artery
disease. The risk of acute leukemia, MDS, and NHL as a complication of
chemotherapy is about 1% per year.
COMPLICATIONS OF CHEMOTHERAPY
AND RADIATION
14. NON-HODGKIN LYMPHOMA
Non-Hodgkin lymphoma (NHL) is a
proliferation of lymphocytes in the
lymph nodes and spleen. NHL is
most often widespread at
presentation and can affect
any lymph node or organ that has
lymphoid tissue.
Malignant proliferation of lymphoid
cells of progenitor or mature B- or
T-cells.
Non-Hodgkin Lymphoma
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15. Small B-cells
Follicular lymphoma - enlarged and
too many follicles-Can progress to
diffuse large B cell lymphoma
Mantle cell lymphoma - cancer of
mantle (area around follicle)-Often
present in late adulthood with painless
lymphadenopathy
Marginal zone lymphoma - cancer
of marginal zone (area around
mantle)-Marginal zone made of
postgerminal B cells
Small lymphocytic lymphoma (CLL
that involve tissue)
CLASSIFICATION Intermediate B cell
lymphoma
Burkitt lymphoma
Often present in child or young adult
as extranodal mass
•African form – in jaws
•Sporadic form – in
abdomen
Large B cells
Diffuse large B-cell lymphoma
Most common NHL
-High grade (aggressive)
Present in late adulthood as extranodal mass or
enlarging lymph nodes
NON-HODGKIN LYMPHOMA
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16. NON-HODGKIN LYMPHOMA
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CLINICAL FEATURES
Painless superfcial lymphadenopathy, usually >1 lymph node region
Usually presents as widespread disease (exception is aggressive lymphoma)
Constitutional symptoms not as common as in Hodgkin lymphoma
Cytopenia: anemia ± neutropenia ± thrombocytopenia can occur when bone marrow is
involved
Abdominal signs
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hepatosplenomegaly
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retroperitoneal and mesenteric involvement (second most common site of involvement)
Oropharyngeal involvement in 5-10% with sore throat and obstructive apnea
Extranodal involvement: most commonly GI tract; also testes, bone, kidney
CNS involvement in 1% (ofen with HIV)
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INVESTIGATIONS
CBC
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normocytic normochromic anemia
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autoimmune hemolytic anemia
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advanced disease: thrombocytopenia,
neutropenia, and leukoerythroblastic anemia
Peripheral blood flm may show lymphoma
cells
Flow cytometry of peripheral blood is valuable
for low-grade NHL
BIOCHEMISTRY
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increase in uric acid
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abnormal LFTs in liver metastases
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increased LDH (rapidly progressing disease,
poor prognostic factor)
CXR, CT neck, abdomen, pelvis for staging
PET is useful for
monitoring response
to treatment and
evaluation of
residual tumour
following therapy in
aggressive
histological disease
DIAGNOSIS
Lymph node
biopsy: excisional
biopsy preferred,
FNA unreliable
Bone marrow
biopsy: not optimal
for diagnosis as BM
may not be involved
18. NON-HODGKIN LYMPHOMA
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Treatment
Local disease (stage Ia and
IIa)
Advanced disease (stage III
and IV, any “B” symptoms)
Local radiation and small dose/course of
chemotherapy
Combination chemotherapy with CHOP
and rituximab, an antibody against
CD20
C = cyclophosphamide
H = adriamycin (doxorubicin or “hydroxydaunorubicin”)
O = vincristine (Oncovin)
P = prednisone
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Hodgkin Lymphoma Non-Hodgkin Lymphoma
Frequency 40% 60%
Malignant Cells Reed-Sternberg cells (owl eye
cells) – B cells –induce
inflammation and fibrosis
Lymphoid cells – many
subtypes – most are B cell than
T cells
Mass Composition Inflammatory cells and fibrosis
(reactive cells)
Lymphoid cells
Clinical Painless lymphadenopathy
- B symptoms
Bimodal: classically seen in
young adult and >55 yrs
- Painless lymphadenopathy
- Classically seen in late adults
Spread Contiguous (touching); rarely
extranodal
Diffuse; often extranodal
Staging Guides therapy
Radiation mainstray treatment
Limited importance
Leukemic Phase Doesn’t occur Occurs
Prognosis Much better prognosis than non-
Hodgkins
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Lymphoma
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