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Lymphoma, A Detailed Update

Lymphoma is a cancer that starts in cells that are part of the body's immune system. Knowing the type of lymphoma is important because this determines the treatment options and outlook (prognosis). This is an in depth article on lymphoma. If you wish to look at an overview of this diesease go to the article, "Lymphoma Overview".

The lymph system (also known as the lymphatic system) is part of the immune system, which helps fight infections. It also helps fluids move in the body. The lymph system is composed mainly of::

Lymphoid tissue: includes the lymph nodes and related organs that are part of the immune and blood-forming systems
Lymph: a clear fluid that travels through the lymph system, carrying waste products and excess fluid from tissues, as well as lymphocytes and other immune system cells
Lymphatic vessels: small tubes, similar to blood vessels, through which lymph travels to different parts of the lymph system

The major sites of lymphoid tissue are:

Lymph nodes: Lymph nodes are bean-sized collections of lymphocytes and other immune system cells throughout the body, including inside the chest, abdomen, and pelvis. They can sometimes be felt as small lumps under the skin in the neck, under the arms, and in the groin. Lymph nodes are connected to each other by a system of lymphatic vessels. Lymph nodes get bigger when they fight an infection. Lymph nodes that grow because of infection are called reactive or hyperplastic nodes. These often hurt when they are touched. People with sore throats or colds might have enlarged neck lymph nodes. An enlarged lymph node is not always a sign of a serious problem, but it can be a sign of lymphoma.

Spleen: The spleen is an organ under the lower part of the rib cage on the left side of the body. The spleen makes lymphocytes and other immune system cells to help fight infection. It also stores healthy blood cells and filters out damaged blood cells, bacteria, and cell waste.

Bone marrow: The bone marrow is the spongy tissue inside certain bones, which is where new white blood cells (including some lymphocytes), red blood cells, and platelets are made

Thymus: The thymus is a small organ behind the upper part of the breastbone and in front of the heart. It is important in the development of T lymphocytes.

Adenoids and tonsils: These are collections of lymphoid tissue in the back of the throat. They help make antibodies against germs that are breathed in or swallowed.

Digestive tract: The stomach, intestines, and many other organs also have lymphoid tissue.

Types of Lymphocytes

Lymphoid tissue is made up mainly of cells called lymphocytes, a type of white blood cell. The 2 major types of lymphocytes are B lymphocytes (B cells) and T lymphocytes (T cells). Normal B cells and T cells have different jobs.

B lymphocytes: B cells help protect the body from germs (bacteria and viruses) by making proteins called antibodies. The antibodies attach to the germs, marking them for destruction by other parts of the immune system. Almost all cases of Hodgkin disease start in B lymphocytes.

T lymphocytes: There are several types of T cells, and each has a special job. Some T cells directly destroy certain kinds of bacteria or cells infected with viruses or fungi. Other types of T cells play a role in either boosting or slowing the activity of other immune system cells.

Types of Lymphoma

There are 2 kinds of lymphomas:

Hodgkin disease (named after Dr. Thomas Hodgkin, who first recognized it). This type of lymphoma contains a specific type of abnormal cell called a Reed-Sternberg cell.
Non-Hodgkin lymphoma - (also known as non-Hodgkin's lymphoma, NHL, or sometimes just lymphoma) is a cancer that starts in cells called lymphocytes, which are part of the body's immune system. Lymphocytes are in the lymph nodes and other lymphoid tissues (such as the spleen and bone marrow).

Signs & Symptoms of Lymphoma

swelling [Abdominal pain or swelling]
Lumps - Enlarged lymph nodes [Painless, swollen lymph nodes in your neck, armpits or groin].
Pain [Chest pain, coughing or trouble breathing, such as breathlessness].
Weight Loss [Unexplained weight loss - as much as 10 percent or more of your body weight
Lingering Fever [intermittent or repalsing]; chills
Lack of appetite [Feeling full after only a small amount of food]
Night sweats; [Sweating heavily, especially at night, leaving bed sheets very wet]
Fatigue; lack of energy
Low red blood cell counts (anemia)
Itching (up to 25% of patients develop this itch, most commonly in the lower extremity but it can occur anywhere, be local, or spreading over the whole body); [Itching, which may be worse after drinking alcohol].
Increased sensitivity to the effects of alcohol or pain in your lymph nodes after drinking alcohol; Abdominal pain or vomiting after drinking alcohol
Shortness of breath or cough

PROGNOSIS for Hodgkin disease

The rates below are based on the stage of the cancer when it is first diagnosed. When looking at survival rates, it's important to understand that the stage of a cancer does not change over time, even if the cancer progresses. If a cancer comes back or spreads, the survival rates may be different from those shown below.

The 5-year survival rate is the percentage of patients who live at least 5 years after their cancer is diagnosed. Of course, many of these people live much longer than 5 years, and many are cured.

The numbers below are among the most current available. But to get 5-year survival rates, doctors have to look at people who were treated at least 5 years ago. Improvements in treatment since then might result in a better outlook for people now being diagnosed with these cancers.The numbers below come from the National Cancer Institute's SEER database, looking at more than 8,000 people diagnosed with Hodgkin disease between 1988 and 2001.

Stage

Criteria

5-year Survival Rate

I

Single lymph node group

About 90%

II

Multiple lymph node groups on same side of diaphragm

About 90%

III

Multiple lymph node groups on both sides of diaphragm

About 80%

IV

Multiple extranodal sites or lymph nodes and extranodal disease

About 65%

Now the percentages above come from studies over fourteen years ago. Treatments have changed and the rates are likely to be better now.

Other prognostic factors

Along with the stage of the Hodgkin disease, other factors can affect a person's prognosis (outlook). For example, some factors mean the disease is likely to be more serious and might prompt the doctor to give more intensive treatment:

Having B symptoms [weight loss > 10%; fever; drenching night sweats]
Having bulky disease [Exists when the mediastinal mass is greater than a third of the mediastinum or if the nodal mass is greater than 10 cm in diameter].
Being older than 45
Being male
Having a high white blood cell count (above 15,000)
Having a low red blood cell count (hemoglobin level below 10.5)
Having a low blood lymphocyte count (below 600)
Having a low blood albumin level (below 4)
Having a high erythrocyte sedimentation rate, or ESR (over 30 in someone with B symptoms, or over 50 for someone without B symptoms)

PROGNOSIS for NON-Hodgkin disease

How is non-Hodgkin lymphoma staged?

Once non-Hodgkin lymphoma is diagnosed, tests are done to determine the stage (extent of spread) of the disease. The treatment and prognosis (outlook) for a patient with non-Hodgkin lymphoma depend in part on the stage of the lymphoma.

Tests used to gather information for staging include:

Physical exam
Biopsies of enlarged lymph nodes or other abnormal areas
Blood tests
Imaging tests, such as CT scans
Bone marrow aspiration and biopsy (often but not always done)
Lumbar puncture (spinal tap – this may not need to be done)

Ann Arbor staging system

A staging system is a way for members of a cancer care team to summarize the extent of a cancer's spread. The Ann Arbor staging system is most often used to describe the extent of non-Hodgkin lymphoma in adults.The stages are described by Roman numerals I through IV (1-4). Lymphomas that affect an organ outside the lymph system (an extranodal organ) have E added to their stage (for example, stage IIE), while those affecting the spleen have an S added.

Stage I Either of the following means the disease is stage I:

The lymphoma is in only 1 lymph node area or lymphoid organ such as the thymus (I).
The cancer is found only in 1 area of a single organ outside of the lymph system (IE).

Stage II Either of the following means the disease is stage II:

The lymphoma is in 2 or more groups of lymph nodes on the same side of (above or below) the diaphragm (the thin band of muscle that separates the chest and abdomen). For example, this might include nodes in the underarm and neck area but not the combination of underarm and groin nodes (II).
The lymphoma extends from a single group of lymph node(s) into a nearby organ (IIE). It may also affect other groups of lymph nodes on the same side of the diaphragm.

Stage III Either of the following means the disease is stage III:

The lymphoma is found in lymph node areas on both sides of (above and below) the diaphragm.
The cancer may also have spread into an area or organ next to the lymph nodes (IIIE), into the spleen (IIIS), or both (IIISE).

Stage IV Either of the following means the disease is stage IV:

The lymphoma has spread outside the lymph system into an organ that is not right next to an involved node.
The lymphoma has spread to the bone marrow, liver, brain or spinal cord, or the pleura (thin lining of the lungs)

Other modifiers may also be used to describe the lymphoma stage:

Bulky disease - This term is used to describe tumors in the chest that are at least one-third as wide as the chest, or tumors in other areas that are at least 10 centimeters (about 4 inches) across. It is usually designated by adding the letter X to the stage. Bulky disease might need more intensive treatment.

A vs. B - Each stage may also be assigned an A or B. The letter B is added (stage IIIB, for example) if a person has any of the B symptoms listed below:

Loss of more than 10% of body weight over the previous 6 months (without dieting)
Unexplained fever of at least 101.5 degrees fahrenheit
Drenching night sweats

These symptoms usually mean the disease is more advanced. If a person has any of these, then more intensive treatment is usually recommended. If no B symptoms are present, the letter A is added to the stage.

Survival rates and factors that affect prognosis (outlook) for non-Hodgkin lymphoma

The overall 5-year relative survival rate for people with NHL is 69%, and the 10-year relative survival rate is 59%. The type and stage of the lymphoma provide useful information about a person's prognosis (outlook), but for some types of lymphomas the stage isn’t too helpful on its own. In these cases, other factors can give doctors a better idea about a person's prognosis.

International Prognostic Index

The International Prognostic Index (IPI) was first developed to help doctors determine the outlook for people with fast-growing lymphomas. However, it has proven useful for most other lymphomas as well. The index depends on 5 factors:

The patient's age
The stage of the lymphoma
Whether or not the lymphoma is in organs outside the lymph system
Performance status (PS) - how well a person can complete normal daily activities
The blood (serum) level of lactate dehydrogenase (LDH), which goes up with the amount of lymphoma in the body

Good prognostic factors are:

Age 60 or below
Stage I or II
No lymphoma outside of lymph nodes, or lymphoma in only 1 area outside of lymph nodes Lymphoma is in more than 1 organ of the body outside of lymph nodes
PS: Able to function normally
Serum LDH is normal

Poor prognostic factors are:

Age above 60
Stage III or IV
PS: Needs a lot of help with daily activities
Serum LDH is high

Each poor prognostic factor is assigned 1 point. People with no poor prognostic factors would have a score of 0, while those with all of the poor prognostic factors would have a score of 5. The index divides people with lymphomas into 4 risk groups:

Low (0 or 1 poor prognostic factors)
Low intermediate (2 poor prognostic factors)
High intermediate (3 poor prognostic factors)
High (4 or 5 poor prognostic factors)

In the studies used to develop the index, about 75% of people in the lowest risk group lived at least 5 years, whereas only about 30% of people in the highest risk group lived at least 5 years. These numbers show the difference the index scores can make, but the IPI was devised in the early 1990s. Newer treatments have been developed since then, so current survival rates are likely to be higher.

Revised International Prognostic Index

A more recent version of the IPI is based on people with fast-growing lymphomas who have received more modern treatment, including a newer drug called rituximab (Rituxan). The revised IPI uses the same factors but divides patients into only 3 risk groups:

Very good (no poor prognostic factors)
Good (1 or 2 poor prognostic factors)
Poor (3 or more poor prognostic factors)

In t In the study used to develop this index, about 95% of people in the very good risk group lived at least 4 years, whereas only about 55% of people in the poor risk group lived at least 4 years.

The IPI allows doctors to plan treatment better than they could just based on the type and stage of the lymphoma. This has become more important as new, more effective treatments have been developed that sometimes have more side effects. The index helps doctors figure out whether these treatments are needed.

Follicular Lymphoma International Prognostic Index

The IPI is useful for most lymphomas, but it's not as helpful for follicular lymphomas, which tend to be slower growing. Doctors have developed the Follicular Lymphoma International Prognostic Index (FLIPI) specifically for this type of lymphoma. It uses slightly different prognostic factors than the IPI.

Good prognostic factors

Age 60 or below
Stage I or II
Blood hemoglobin level below 12 g/dL
Serum LDH is normal

Poor prognostic factors

4 or fewer lymph node areas affected
Age above 60
Stage III or IV
Blood hemoglobin 12 g/dL or above
More than 4 lymph node areas affected
Serum LDH is high

Patients are assigned a point for each poor prognostic factor. People without any poor prognostic factors would have a score of 0, while those with all poor prognostic factors would have a score of 5. The index then divides people with follicular lymphoma into 3 groups:

Low risk: no or 1 poor prognostic factor(s)
Intermediate risk: 2 poor prognostic factors
High risk: 3 or more poor prognostic factors

The study used to develop the FLIPI produced the following survival rates:

Risk group for 5-year survival rate for

Low-risk is 91%
Intermediate-risk is 78%
High-risk is 53%

Risk group for 10-year survival rate

Low-risk is 71%
Intermediate-risk is 51%
High-risk High-risk is 36%

These rates reflect the number of people who lived for at least 5 or 10 years after being diagnosed - many people lived longer than this. The rates were based on people diagnosed with follicular lymphoma in the 1980s and 1990s. Newer treatments have been developed since then, so current survival rates are likely to be higher.

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