Lymphoma: Pro - Dr.Ahmed Eisa

Lymphoma
Pro.Dr.Ahmed Eisa
Overview
• Concepts, classification, biology
• Epidemiology
• Clinical presentation
• Diagnosis
• Staging
• Three important types of lymphoma
How Cancer Develops
• Normal cells are programmed to multiply, die
when they’re old
• Signals to multiply and die are controlled by
specific genes
• Mutations can occur in these genes
• If enough mutations occur in genes controlling
growth or cell death a cell begins to multiply
uncontrollably
• The cell has then become cancerous or
“malignant”
Features common to cancer cells
• Growth in the absence of “go” signals

• Growth despite “stop” signals
• Locally invasive growth and metastases
to distant sites
Hematopoietic Malignancies
􀂄 Lymphoma is a general term for

hematopoietic solid malignancies of
the lymphoid series.
􀂄 Leukemia is a general term for liquid

malignancies of either the lymphoid
or the myeloid series.
What is Lymphoma
• Lymphomas are cancers that begin by
the “malignant transformation” of a
lymphocyte in the lymphatic system
• Many lymphomas are known to be due
to specific genetic mutations
• Follicular lymphoma due to
overexpression of BCL-2 (gene that
blocks programmed cell death)
What is the Lymphatic System?
• Made up of organs, such as the tonsils,
spleen, liver, bone marrow and a network of
lymphatic vessels that connect glands, called
lymph nodes
• Lymph nodes located throughout the body
• Lymph nodes filter foreign particles out of the
lymphatic fluid
• Contain B and T lymphocytes
Lymphatic System
• Lymph nodes act as a filter to
remove bacteria, viruses, and
foreign particles
• Most people will have had “swollen
glands” at some time as a response
to infection
Blood Cell and Lymphocyte
Development
STEM CELLS
Multipotential Multipotential
myeloid cells lymphocytic cells
Differentiate & mature into 6 Differentiate & mature into 3
Types of blood cells Types of lymphocytes
red cells basophils T lymphocytes

neutrophils monocytes B lymphocytes
eosinophils platelets Natural Killer Cells
Lymphocytes
• Most lymphocytes are in lymph nodes,
spleen, bone marrow and lymphatic vessels
• 20% of white blood cells in blood are
lymphocytes
• T cells, B cells, natural killer cells
• B cells produce antibodies that help fight
infectious agents
• T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
􀂄 Immature lymphocytes that travel to the

thymus differentiate into T-Cells
– “T” is for thymus
􀂄 Immature lymphocytes that travel to the
spleen or lymph nodes differentiate into B
cells
Classification
• Usually classified by how the cells look
under a microscope and how quickly
they grow and spread
– Aggressive lymphomas (high-grade
lymphomas)
– Indolent Lymphomas (low-grade

lymphomas)
Lymphoma classification
(2001 WHO)
• B-cell neoplasms
– precursor
– mature Non-
Hodgkin
• T-cell & NK-cell neoplasms Lymphomas
– precursor
– mature
• Hodgkin lymphoma
Three common lymphomas
• Follicular lymphoma
• Diffuse large B-cell lymphoma
• Hodgkin lymphoma
Relative frequencies of
different lymphomas
Non-Hodgkin Lymphomas
Diffuse large B-cell

Hodgkin NHL Follicular
lymphoma
Other NHL
~85% of NHL are B-lineage

Follicular lymphoma
• most common type of “indolent”
lymphoma
• usually widespread at presentation
• often asymptomatic
• not curable (some exceptions)
• associated with BCL-2 gene
rearrangement [t(14;18)]
• cell of origin: germinal center B-cell
• defer treatment if asymptomatic
(“watch-and-wait”)
• several chemotherapy options if
symptomatic
• median survival: years
• despite “indolent” label, morbidity and
mortality can be considerable
• transformation to aggressive lymphoma
can occur
Diffuse large B-cell lymphoma
• most common type of “aggressive”

lymphoma
• usually symptomatic
• extranodal involvement is common
• cell of origin: germinal center B-cell
• treatment should be offered
• curable in ~ 40%
B-Cell Lymphoma (80%)
• B-Cells help make antibodies, which are
proteins that attach to and help destroy antigens
• Lymphomas are caused when a mutation arises
during the B-cell life cycle
• Various different lymphomas can occur during
several different stages of the cycle
– Follicular lymphoma, which is a type of B-cell
lymphoma is caused by a gene translocation which
results in an over expressed gene called BCL-2,
which blocks apoptosis.
T-Cell Lymphoma (15%)
• The T-cells are born from stem cells,
similar to that of B-cells, but mature in the
thymus.
• They help the immune system work in a
coordinated fashion.
– These types of lymphomas are categorized
by how the cell is affected
• Anaplastic Large cell Lymphoma, t-cell lymphoma
caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
• Genetic alterations
• Infection
• Antigen stimulation
• Immunosuppression
Epidemiology of lymphomas
• males > females
• incidence
– NHL increasing
– Hodgkin lymphoma stable
• in NHL: 3rd most frequently diagnosed
cancer in males and 4th in females
• in HL: 5th most frequently diagnosed
cancer in males and 10th in females
Risk factors for NHL
• immunosuppression or immunodeficiency
• connective tissue disease
• family history of lymphoma
• infectious agents
• ionizing radiation
Clinical manifestations
• Variable
• severity: asymptomatic to extremely ill
• time course: evolution over weeks, months, or
years
• Systemic manifestations
• fever, night sweats, weight loss, anorexia, pruritis
• Local manifestations
• lymphadenopathy, splenomegaly most common
• any tissue potentially can be infiltrated
Other complications of lymphoma
• bone marrow failure (infiltration)

• CNS infiltration
• immune hemolysis or thrombocytopenia
• compression of structures (eg spinal
cord, ureters)
• pleural/pericardial effusions, ascites
Non-Hodgkin’s Lymphoma
Staging
• Stage is the term used to describe the extent
of tumor that has spread through the body ( I
and II are localized where as III and IV are
advanced.
• Each stage is then divided into categories A,
B, and E
– A: No systemic symptoms
– B: Systemic Symptoms such as fever, night sweats
and weight loss
– E: Spreading of disease from lymph node to
another organ
Staging of lymphoma
Stage I Stage II Stage III Stage IV
A: absence of B symptoms
B: fever, night sweats, weight loss
Staging
Symptoms
• Painful Swelling of lymph nodes located
in the neck, underarm and groin.
• Unexplained Fever
• Night Sweats
• Constant Fatigue
• Unexplained Weight loss
• Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
• The Exact causes are still unknown
– Higher risk for individuals who:
• Exposed to chemicals such as pesticides or
solvents
• Infected w/ Epstein-Barr Virus
• Family history of NHL (although no hereditary
pattern has been established)
• Infected w/ Human Immunodeficiency Virus
(HIV)
Lymphoma.org
Diagnosis
Staging Studies
• Bone marrow aspiration and biopsy
• Radionuclide scans:
• GI x-rays
• Spinal fluid analysis
• CT scans
• Magnetic Resonance Imaging (MRI)
• Biopsy
Diagnosis requires an
adequate biopsy
• Diagnosis should be biopsy-proven

before treatment is initiated
• Need enough tissue to assess cells and
architecture
– open bx vs core needle bx vs FNA
Treatment
• Non-Hodgkin’s Lymphoma is usually treated
by a team of physicians including
hematologists, medical oncologists and a
radiation oncologist.
• In some cases such as for Indolent

lymphomas, the Doctor may wait to start
treatment until the patient starts showing
symptoms, known as “watchful waiting”
Treatment Options
•Chemotherapy
•Radiation
•Bone Marrow Transplantation
•Surgery
•Immunotherapy
•Using the bodies own immune system combined with
material made in a lab.
Hodgkin lymphoma
• cell of origin: germinal centre B-cell
• Reed-Sternberg cells (or RS variants)
in the affected tissues
• most cells in affected lymph node are
polyclonal reactive lymphoid cells, not
neoplastic cells
Reed-Sternberg cell
Hodgkin lymphoma
Histologic subtypes
• Classical Hodgkin lymphoma
– nodular sclerosis (most common subtype)
– mixed cellularity
– lymphocyte-rich
– lymphocyte depleted
Histology Lab
RS cell and variants
classic RS cell lacunar cell popcorn cell

(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
Epidemiology
• less frequent than non-Hodgkin
lymphoma
• overall M>F
• peak incidence in 3rd decade
Clinical manifestations
• lymphadenopathy
• contiguous spread
• extranodal sites relatively uncommon
except in advanced disease
• “B” symptoms
Hodgkin’s Disease/Lymphoma
Treatment
With appropriate treatment about 85% of patie

nts with Hodgkin’s disease are curable
I A,B Radiation Therapy

II A Combination Chemo +
Radiotherapy
IIB; IIIA,B; IVA,B Combination Chemo
(+/- radiotherapy)
Hodgkin’s Disease/Lymphoma
Treatment
Radiation therapy (35-40 Gy) 80-90% RC

Mantle field
Paraaortic field
Pelvic field
Combination chemotherapy
ABVD 80% RC
BEACOPP 90% RC
Long term complications
of treatment
• infertility
– MOPP > ABVD; males > females
– sperm banking should be discussed
– premature menopause
• secondary malignancy
– skin, AML, lung, MDS, NHL, thyroid,
breast...
• cardiac disease
MCQ
most common subtype of Classical Hodgkin

lymphoma?
1-nodular sclerosis
2-mixed cellularity
3-lymphocyte-rich
4-lymphocyte depleted
THANK YOU

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Lymphoma

• Growth in the absence of “go” signals

􀂄 Lymphoma is a general term for

􀂄 Leukemia is a general term for liquid

red cells basophils T lymphocytes

􀂄 Immature lymphocytes that travel to the

– Indolent Lymphomas (low-grade

Diffuse large B-cell

~85% of NHL are B-lineage

• most common type of “aggressive”

• bone marrow failure (infiltration)

• Diagnosis should be biopsy-proven

• In some cases such as for Indolent

classic RS cell lacunar cell popcorn cell

With appropriate treatment about 85% of patie

I A,B Radiation Therapy

Radiation therapy (35-40 Gy) 80-90% RC

most common subtype of Classical Hodgkin

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