Lymphoma
Simplified
Our body is made of countless cells
of many types. Cells have specialized jobs and names, such as skin,
nerve, heart, lung, blood, immune cells, and so on. For the human body to function normally, each organ must have a certain number of cells.
By design, the cells in most organs have a short
lifespan. Therefore, to continue functioning the body needs to replace these lost cells by the process of cell division.
Cell division and cell death are controlled by genes that are located in the cell nucleus.
Genes function like
an instruction manual telling the cell what proteins to make. These
proteins in turn control the behavior of the cell.
Some proteins direct the cell to divide; others how long it will live;
and others begin cell death - a normal process by which the body rids
itself of old, unneeded, or damaged cells.
Under normal conditions there is a balance
in which new cells replace old, and each cell carries out tasks
specific to its kind: Heart cells pump, stomach cells produce
acids, immune cells recognize invaders and kill them, and so on.
The balance ensures that the organs and systems function properly and
serve the needs of the body.
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The beginning of cancer
In any cell the genetic code can get damaged so
that the instructions in the "manual" are altered in ways that
produce abnormal types and amounts of proteins that can lead to abnormal behavior of the
cell. Instead of resting, the cell may continue
dividing; instead of dying the cell stays alive.
The type of cancer has a lot to do with identifying the more plausible
reasons for the cancer. Lymphocytes are highly active cells, which undergo
many normal transformations in their life cycle and many more cell divisions
than most other cell types.
Cell division, being a highly complex process, is prone to mistakes. Mistakes may not be "picked up" or may often be inconsequential ... a
defective heart versus a sixth toe.
But sometimes a mistake occurs in a cell that impairs a gene that's "in
charge" of detecting mistakes (a so-called tumor suppressor
gene) ... probably this kind of mistake is a rare occurrence, but likely
it's a necessary beginning step in a cancer.
The defective, atypical cell will not necessarily lead to a cancer, however ... additional errors
must occur. Before it's a cancer the cell divides, and passes on the defects
that have malignant potential. Additional "hits" on the atypical cell may result from chemical
exposures, viral infections, oxidation, random errors ...
For
example: An atypical (slightly defective) lymphocyte may be kept active longer
because of chronic stimulation by a bug or virus (chronic infection being associated with higher risk of lymphoma)
- making additional random copy errors more likely to occur.
... The first cell to lose normal growth
control is called the cell
of origin. When the cell of origin divides,
the new cells inherit the genetic defects of the parent cell. Thus,
in cancer, the
descendants of the cell of origin are clones
of this cell.
A hallmark of cancer cells is that they have growth
and survival advantages over normal cells. Their cell division is not
balanced by cell death. The abnormal cells may eventually form lumps called tumors.
The word tumor simply means a mass of cells. Tumors can be either
benign or malignant. Benign
tumors are not a threat to life or long-term health, while malignant
tumors are. The word malignant means 'showing great malevolence and being disposed to do evil.'
One way that pathologists identify a tumor as being malignant is if
the cells within it are clonal -
all identical to the cell of origin. In contrast, benign tumors are
made up of related but different cells.
The hallmarks of cancer
cells include:
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Lymphoma is a kind of blood cancer
Blood is a fluid made up of plasma and many types of
blood cells, such as red blood cells (erythrocytes), white blood cells
(leukocytes) and platelets.
Blood circulates through the heart, arteries and veins. It carries
"nourishment, hormones, vitamins, antibodies, heat and oxygen to the body's tissues."
labtestsonline.org
B-cell Cancers by Cell Maturation Stage -
Click to enlarge
Lymphoma is a cancer that affects a type of white blood cells called lymphocytes – immune cells that normally protect you from illness. About
85% of lymphomas are of b-cell origin, and 15% of t-cell
origin.
B-cells
originate and mature (differentiate) in the bone marrow.
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.
Leukocytes -
Click to enlarge
The different types of lymphoma are determined according to what type of lymphocyte has become
cancerous, and the stage of development. Click b-cell cancers by cell development
to enlarge the illustration shown above.
As with other cancers, the root cause of lymphomas is
damage to genes that leads to abnormal growth controls in the cell.
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Lymph node |
Lymphatic system |
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Lymphomas are a Family of Related Cancers.
The cell of origin determines the subtype of
lymphoma, and influences its clinical behavior - growth
rate and sensitivity to treatments.
The cell of origin,
such as T-cell, B-cell, and NK cell, and the stage of maturation
of that cell determines the type of lymphoma. This is often referred to as the cell
type or diagnosis,
such as follicular small cleaved lymphoma.
When a lymphocyte becomes malignant, its
biologic behavior is arrested at that stage. This stage of development
influencing its location tendencies
and growth rate and other cellular
behaviors.
Analogy: Consider that just as
children grow faster than adults, cells at earlier stages of
development tend to grow faster than they do at mature stages.
The malignant cells then may accumulate to form tumors that enlarge the
lymph nodes or spread to other areas of the lymphatic system, such as the spleen or bone marrow, or outside the
lymphatic system to the skin, or mucosal linings of the stomach.
How widespread the lymphoma is, is summarized by
the stage.
Staging is the process of determining where the lymphoma is located by imaging
and other methods.
NOTE: It's common for the lymphoma to be at stage IV at diagnosis. But, advanced stage of disease
does not mean the treatments will not be effective.
About growth rate. The
cell of origin will also influence
how fast or slow the lymphoma cells will
tend to grow. The growth tendency of the lymphoma is also called
the grade.
Aggressive grade lymphomas
divide
and grow rapidly, and therefore prompt and aggressive treatment is
indicated.
Indolent grade lymphomas
may not divide faster than normal lymphocytes. Here the malignant
behavior can be resistance to cell death - a
failure to "erase" itself after it's normal functions have
been completed. This results in a slow buildup of excess
cancer cells causing tumors to form, but more
slowly.
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Mutations also influence the clinical behavior
The specific damage to DNA - and the gene expression
- is likely to be variable
for patients who have the same diagnosis.
These differences may explain,
in part, why
patients with the same diagnosis can have lymphomas that develop at
different rates, and respond differently to the same treatments.
Recall that genes expression determine what proteins the cells express
and this determines behavior. Response to treatment
is also cell behavior. For example, cells detecting damage to
DNA - induced by treatment - will initiate cell death, but only if the
genes that can activate the cell-death program are functioning or
activated by the treatment.
"Ultimately, it may well
be that the optimal treatment will be determined by patient clinical and biological characteristics." ~ Dr. Bruce Cheson - Advances in the Treatment of
Non-Hodgkin's Lymphoma - Medscape
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Your Lymphoma is Unique
Factors that may account for clinical differences in
lymphomas:
