About Lymphoma >
What is Lymphoma?
Last update:
02/18/2012
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TOPICS
Lymphoma
- general
| Where Lymphoma develops | B-cells
& T-cells |
Characteristics of b-cell Lymphomas -
Stage &
Grade |
WHO &
REAL Classification
Systems | Host/Tumor Interactions
Also see
Lymphoma simplified
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What is Cancer?
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Cancer cells are also
called malignant cells
Malignant "behavior" refers to cells that have lost the ability to contribute to the
well-being of the host.
Cancer cells begin as normal cells.
Damage to DNA causes the cells to lose growth or survival controls. The cancer
cells live too long and/or divide
too rapidly.
Cancer cells are frozen at a stage of
development - they are unable to differentiate or have a normal life
span.
Understanding the basic concepts of DNA
and genes is not difficult and it can help you to appreciate current
directions in clinical research. Click here
for a summary explanation.
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Lymphoma
is a type of cancer.
Cancer
cells are the descendants of a single normal cell in which genetic
errors, or mutations, have occurred. These errors cause the
cancer cells to over- or under-produce proteins that abnormally affect
the cell's behavior - causing these cells divide too fast or fail to
die when they should.
Cancer cells are typically clonal
meaning that the descendent cells share the defects of the
parent cell, but they can acquire additional mutations.
The
malignant behavior, such as how aggressive or slow growing it might
be, is determined by the cell type, the kinds of mutations, and
sometimes the host environment.
There are
as many kinds of cancers as there are cell types: skin, lung
cancer, and blood cell cancers, etc.
In cells, genetic errors occur in the
basic building blocks of DNA
called
genes. These errors might
occur randomly when the cell divides, or they may result from exposure
to environmental toxins called carcinogens - meaning able to cause
cancer.
 Normally the
damage that can lead to cancer is detected and addressed:
When a cell detects errors within
itself it can sometimes make repairs.
If the cell cannot repair the
errors,
a secondary safeguard can be executed by the cell called apoptosis.
The damaged cell sacrifices itself for the good of the body by
committing suicide.
The
immune system can also recognize damage cells - cells that express
abnormal proteins - and kill them before
tumors can form and cause problems.
So cancers are not thought
to be the result of a single event. A combination of negative
events and missed opportunities are probably required.
When a malignant cell does form, it
eventually reproduces to create a collection of cancer cells called a tumor.
This mass can
interfere with the proper functioning of the body.
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Lymphoma is
a group of related cancers
Download our
What's Lymphoma brochure
PDF
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Lymphoma
is not one cancer, but a name for a group of related cancers that arise when a Lymphocyte
(a blood cell) becomes malignant.
The normal function of
lymphocytes is to defend the body against pathogens and infected
cells: germs, viruses,
fungi, even cancer. There are many subtypes and maturation
stages of lymphocytes and therefore
there are many kinds of lymphomas. When a lymphocyte becomes
malignant (goes bad), it's biologic behavior is arrested at that
stage.
"Malignant
lymphomas represent clonal malignancies in which the majority of
cells are frozen at a single stage of normal lymphocyte
differentiation" Source: Norman
Levy, MD - Lecture
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Where Lymphoma
develops
Extranodal means 'beyond nodal' -
sites are identified by the following notation:
| N |
= lymph nodes |
| H |
= liver (hepatic) |
| L |
= lung |
| M |
= bone marrow |
| S |
= spleen |
| P |
= pleura (lung) |
| O |
= bone |
| D |
= skin (dermis) |
Also see Musshoff -
classification of gastrointestinal lymphomas
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Like normal cells, malignant lymphocytes
can move to many parts of the
body. Typically, lymphoma cells form tumors in the lymphatic
system: bone marrow, lymph nodes, spleen, and blood.
However, these cells can migrate to other organs.
Lymphoma Sites of Presentation.
Click image to enlarge it.
Certain types of lymphoma
will tend to grow in locations in which the normal version of the cell
resides. For example, it's common for follicular NHL tumors to develop
in the lymph nodes. MALT lymphomas will manifest in other areas as
described here:
"Lymphoid tissue in the
human body is associated with the mucosal system. This tissue,
mucosa-associated
lymphoid tissue (MALT), is scattered along mucosal linings and
protects the body from antigens entering along mucosal surfaces."
- emedicine
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The
maturation stage of the cell of origin determines the type of lymphoma
Click image to enlarge
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Normal
lymphocytes are part of a group of cells called
white blood cells. There are two main kinds of lymphocytes.
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B-cells
originate and mature (differentiate) in the
bone marrow.
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T-cells also start out in the bone marrow, but they
differentiate and mature in the thymus gland.
Natural Killer cells are a third
kind of lymphocyte. They specialize in killing foreign cells and
possibly signaling to alert other immune cells of invaders.
Two broad types of lymphoma are T-cell
and b-cell lymphoma. We will focus mainly on the b-cell lymphomas in
this text.
Hodgkin's
disease describes a cancer of
a unique
malignant cells known as Reed-Sternberg cells. It is not as common as Non-Hodgkin’s
Lymphoma. Fortunately, Hodgkin's
disease is considered curable in many cases.
B-cells originate
from stem cells in the bone marrow. They then mature and migrate
to different parts of the body and perform unique functions at each
stage. The developmental
stage of the b-cell when it becomes malignant determines
the specific kind of lymphoma.
For example, follicular, large cell and
immunoblastic Lymphomas result when a malignancy develops after
a b-cell has been exposed to antigens (bacteria, virus etc.), while
CLL and SLL malignancy develop when a mutation occurs prior to antigen exposure.
See the illustration on the left.
What makes one
lymphoma aggressive
and the other indolent? The cell type, the type of damage within the cell, and level
of maturation (stage of development) of the cell when it became
malignant are few reasons. For example, just as
children grow faster than adults, cells at various stages of
development grow faster than at other stages.
When a cell becomes malignant its
maturation stage is arrested (stopped) at that stage, and it's
behavior (fast growing, refusing to die) is therefore determined in
part by the level of maturation of
the cell of origin.
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Characteristics of Lymphomas
Extranodal
(beyond nodal) sites are identified by the following notation:
N = lymph nodes
H = liver (hepatic)
L = lung
M = bone marrow
S = spleen
P = pleura (lung)
O = bone
D = skin (dermis)
Disease Staging may also be accompanied by local
involvement of an extranodal organ or site, such as the spleen (IIIS).
ANN ARBOR STAGING
further classifies patients with NHL into A or B categories:
A = without symptoms
B = with symptoms including unexplained weight loss (10% in 6 months prior
to diagnosis, unexplained fever, and drenching night sweats.
STAGE IV: It is common for
b-cell lymphomas to be diagnosed at stage IV, which includes bone marrow involvement.
Please note that successful treatment is often
possible for stage IV disease and bone marrow involvement is reversible.
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Characteristics of B-Cell
Lymphomas
.gif) |
Cell
type are primarily determined by Histology
- The size; nuclear and cellular features of lymphoma cells allow
for the identification of the lymphoma by its appearance and
its markers. (See WHO and REAL classification systems below)
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Pattern
(follicular or diffuse) - The pattern by which a lymphoma
infiltrates and replaces a previously normal lymph node is
predictive of its biological behavior. The architectural
pattern of the proliferating process, that of either a diffuse or
a follicular appearance, is of prognostic value -
in general follicular
pattern has a better prognosis than diffuse pattern.
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Grading
defines how aggressive or slow growing the malignant cells are
likely to be. This is sometimes called histologic
grade, which is determined by the appearance of cells under the
microscope:
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low
grade or indolent
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Grade 1
= small cell
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Grade 2 =
mixed small and large cell
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Note: both grade 1 & 2 can behave
similarly.
The
determination of these grades can depend on the sample
evaluated under the microscope.
Sometimes
grades of indolent lymphoma are subdivided in this way:
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A. Small
lymphocytic
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B.
Follicular, predominantly small cleaved cell
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C.
Follicular mixed, small and large cell |
Also see Grade
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intermediate-
or high-grade
(today these
are both often referred to as aggressive).
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Staging
defines how widespread the disease is and the locations of the
disease in the body. * See Extranodal
and Ann Arbor Staging codes in left column, which may be added to the staging
designations.
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Click the image to enlarge it.
Anne Arbor staging for Hodgkin's disease - Virginia.edu
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Stage
I disease in single lymph node or lymph node region.
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Stage
II disease in two or more lymph node regions
on same
side of diaphragm.
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Stage III disease
in lymph node regions on both sides of the
diaphragm are
affected.
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Stage
IV disease is wide spread, including multiple
involvement at
one or more extranodal (sites such as the bone marrow). |
Also see Staging - Oncologychannel.com
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"The
prognosis and treatment of lymphomas is based on
- The dominant cell type (and it's inherent
biologic behavior)
- The extent of spread (Stage) and
- The underlying health of the patient
Source:
Norman
Levy, MD - Lecture
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B-Cell Non-Hodgkin's Lymphoma in the
WHO Classification System
WHO utilizes morphologic differences in cells.
Morphologic - appearance
or structure
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WHO CLASSIFICATION SYSTEM FOR B-CELL LYMPHOMAS
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Small lymphocytic lymphoma (SLL/CLL)
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Mantle cell lymphoma (MCL)
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Follicular lymphoma (FL)
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Marginal zone lymphoma (MZL)
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Extranodal (MALT lymphoma)
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Nodal (Monocytoid B-cell
lymphoma)
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Splenic
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Diffuse large cell lymphoma
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Burkitt's lymphoma
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Lymphoblastic lymphoma
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B-Cell Non-Hodgkin's Lymphoma in the
REAL Classification System
The REAL system utilizes morphologic, immunophenotypic,
and genotypic differences in cells.
Morphologic - appearance or structure
Immuno - pertaining to immune cells.
Phenotype - observed properties or outward appearance of a trait or
expression of proteins. CDs are expressed on immune cells
depending on their maturation. Identifying these CDs (clusters of
differentiation) that appear in immune cells helps to identify
immunophenotypic differences.
Genotype - a cell's genetic composition.
Phenotype - results from the interaction of the genotype with the
environment.
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REAL CLASSIFICATION SYSTEM FOR B-CELL LYMPHOMAS
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Small lymphocytic lymphoma (SLL/CLL)
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Mantle cell lymphoma (MCL)
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Follicular lymphoma (FL)
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Marginal zone lymphoma (MZL)
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Extranodal (MALT lymphoma)
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Nodal (Monocytoid B-cell lymphoma)
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Splenic
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Diffuse large cell lymphoma
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Burkitt's lymphoma
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High grade Burkitt-like lymphoma
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Lymphoblastic lymphoma
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Host/tumor
interactions: the microenvironment
angiogenesis
immune system
cytokines
growth factors
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Scientists
are working to understand how the body interacts with malignant cells
to restrain and/or promote the growth of tumors. Malignant cells
don't exist in a vacuum. They may interact with the body in
normal, near-normal, or dysfunctional ways.
Angiogenesis:
As b-cell tumors grow, they form microvessels, presumably to obtain oxygen and nutrition from
the blood
supply. Hypoxic (low oxygen) conditions can induce malignant cells to
over express genes that promote angiogenesis-the process in which
cells recruit the formation of a blood supply by secreting vascular
(blood) growth factors.
Immune system:
There is evidence that the immune system can fight lymphoma and
inhibit it's progression in some cases. Immune cells use
cytokines and cytokine receptors to send and receive messages. These
complex interactions can be positive or negative in respect to
progression of the disease.
Self-stimulation:
Malignant cells can acquire additional mutations that can
cause them to become self-stimulating. For example, a malignant cell
could express a growth factor that causes itself to grow faster.
Cytokine
stimulation: Inflammatory and growth stimulation may
develop from dysfunctional interactions with other immune cells that
may express (give off) protein messages called cytokines (such
as IL-6), that may promote the growth of malignant lymphocytes.
Antigen
stimulation: Some b-cell cancers, such as follicular NHL,
are antigen driven. That is they are activated like normal b-cells to
divide by the presence of antigens (allergens, bacteria, etc.) in the
body. Malignant cells may act normally in this regard, but one or more
genetic defects prevents them from dying when their work is done. Thus, malignant b-cells are often said to be
immortal.
RELATED ABSTRACTS
-
Chronic B cell malignancies and bone marrow
microenvironment.
Semin Cancer Biol. 2002 Apr;12(2):149-55. Review. PMID: 12027587-
PubMed
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The indispensable role of microenvironment in the
natural history of low-grade B-cell neoplasms.
Adv Cancer Res.
2000;79:157-73. Review. PMID: 10818680 PubMed
| Related
Abstracts
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CXCL13 (BCA-1) is produced by follicular lymphoma
cells: role in the accumulation of malignant B cells.
Br J Haematol. 2002 Nov;119(2):492-5. PMID: 12406091 PubMed
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Scientists Unlocking Lymphoma's Secrets - The
microenvironment healthscout.com
2004
"Genetic differences -- not in lymphoma cells, but in immune
cells surrounding the tumor -- may determine how aggressive a
particular case of follicular lymphoma turns out to be"
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How do follicular dendritic cells interact
intimately with B cells in the germinal centre?
Microenvironment
connection to lymphoma: "Follicular Dendritic cells (FDCs)
prevent apoptosis of germinal centre B cells and stimulate
cellular interaction and proliferation." ochsner.org
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