Lymphoma

There are different types of Hodgkin lymphoma (also called HL or Hodgkin’s disease) that grow and spread differently. The two main types of Hodgkin lymphoma in adults are classic (cHL) and nodular lymphocyte predominant.

• About 95% of cases of Hodgkin lymphoma are the classic type. Classic Hodgkin lymphoma is marked by the presence of large, cancerous cells called Reed-Sternberg cells. These cells are usually an abnormal type of B lymphocyte. Classic Hodgkin lymphoma is grouped into 4 subtypes based on the location of affected lymph nodes and how those nodes look under a microscope.
• The nodular lymphocyte predominant type makes up about 5% of Hodgkin lymphomas. The cancerous lymphoma cells are often very big and have a “popcorn”-shaped nucleus (so called “popcorn cells”). This type is most common in younger people. It tends to grow more slowly and is treated differently than the classic type.

Hodgkin lymphoma can affect people of any age, but it is most common in young adults in their 20’s and people over age 55. It is slightly more common in males than females. According to the American Cancer Society, about 8,500 people in the United States are diagnosed with Hodgkin lymphoma each year and about 970 people die of it.

Hodgkin lymphoma is caused by a change (mutation) in the DNA of a lymphocyte. Experts don’t yet know what causes the DNA changes in lymphocytes that make them turn into Reed-Sternberg cells. Some scientists think that a reaction to an infection with Epstein-Barr virus (the virus that causes “mono”) can cause a mutation in B lymphocytes and this sometimes leads to the development of Reed-Sternberg cells. Other infections may be the trigger that lead to Reed-Sternberg cells in some cases. More research is needed to determine the cause of Hodgkin lymphoma.

According to the American Cancer Society, non-Hodgkin lymphoma (NHL) accounts for about 4% of all cancers. About 74,000 people are diagnosed with non-Hodgkin lymphoma per year and about 20,000 people die from it. The cellular composition seen under microscope and clinical behavior of NHL are very different from that of Hodgkin lymphoma.

• NHL can occur at any age, but the risk grows greater as you get older. More than half of people diagnosed with NHL are age 65 or older.
• The overall risk for NHL is slightly greater in men than women, but there are some types of NHL that are more common in women.
• In the U.S., whites (Caucasians) are more likely than African Americans or Asian Americans to develop NHL.

Experts believe the DNA (gene and/or chromosome) changes in lymphocytes that lead to NHL usually happen during a person’s lifetime, although in some cases, they are inherited. Exposure to radiation, certain chemicals or drugs, and certain infections can increase risk of developing NHL. People with weakened immune systems and autoimmune disorders (such as rheumatoid arthritis or lupus) may also be at increased risk for NHL.

In general, non-Hodgkin lymphomas are classified by cell type and characteristics, and how fast or slow they grow and spread (metastasize). The World Health Organization has classified over 80 different types of NHL. In the United States, B-cell non-Hodgkin lymphomas are much more common than T-cell and NK-cell lymphomas.

About 85 to 90% of non-Hodgkin lymphomas involve mature B-lymphocytes. Examples of some of these include:

• Diffuse large B-cell lymphoma (DLBCL): this is the most common type in the U.S., accounting for about one in three cases of all non-Hodgkin lymphomas. It is a fast-growing lymphoma and can affect anyone of any age but occurs mostly in older people.
• Follicular lymphomas: these make up about one in five of all lymphomas in the U.S. This is generally a very slow-growing lymphoma, but over time some transform into fast-growing DLBCL.
• Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL / SLL): These are two closely related diseases. The difference between them is that CLL mainly affects the bone marrow and blood, while SLL is found mainly in the lymph nodes. These are usually slow-growing diseases, and the treatment for both is the same.
• Waldenstrom macroglobulinemia (WM): in this condition, cancerous B cells grow mainly in the bone marrow, but they can also grow in the liver, spleen, and lymph nodes. The cancer cells make excess amounts of big protein (immunoglobulin of IgM type) that builds up in the blood, causing it to thicken. WM is a slow-growing lymphoma that typically affects people in their 60s.

Some other examples include:

• Marginal zone lymphoma (MZL)
• Mantle cell lymphoma (MCL)
• Gastric mucosa-associated lymphoid tissue (MALT) lymphoma
• Lymphoblastic lymphoma (LPL) (LPL can progress to WM)
• Burkitt lymphoma (BL)
• Primary mediastinal (thymic) large B-cell lymphoma (PMBCL)
• Hairy cell leukemia

About 10 to 15% of non-Hodgkin lymphomas affect mature T-lymphocytes and NK-cells. Examples of some of these include:

• T-lymphoblastic lymphoma (leukemia): this type can be considered either a lymphoma or a type of acute lymphoblastic leukemia depending on how much of the bone marrow is affected. About 1% of all lymphomas are this type. It is most common in teens and young adults and affects males more than females.
• Peripheral T-cell lymphomas (PTCL) not otherwise specified: there are many kinds of mature T-cell lymphomas that don’t fit into any of the defined categories. All together, they make up about 4% to 5% of all lymphomas.
• Cutaneous T-cell lymphomas (mycosis fungoides, Sezary syndrome, and others): these are less common forms of lymphoma. While most lymphomas begin in lymphoid tissue or internal organs, these types start in the skin. Skin lymphomas make up about 4% of all lymphomas.

A few other examples include:

• Systemic anaplastic large-cell lymphoma (ALCL)
• Adult T-cell leukemia/lymphoma
• Angioimmunoblastic T-cell lymphoma (AITL)

Lymphoma can sometimes be difficult to diagnose because the signs and symptoms are often mild. You may not have any signs or symptoms, especially at first, but may develop some symptoms if the lymphoma grows larger. Usually there are swollen lymph nodes, but the node may not be visible or felt by you or your healthcare provider.

Some of the main signs and symptoms of lymphoma include:

• Painless swelling of one or more lymph nodes in the armpits, neck, or groin; other conditions can cause swollen lymph nodes, including infections, but these are usually painful when touched.
• Enlarged spleen
• An increase in abnormal lymphocytes in the blood

Other common signs and symptoms may include:

• Fever without an infection (it may come and go over several weeks)
• Night sweats
• Unexplained weight loss (as much as 10% of body weight or more)
• Frequent and/or serious infections
• Easy bruising, bleeding

There may be various other general signs and symptoms present, but many of these can also be caused by other conditions. Some examples include:

• Fatigue (extreme tiredness)
• Loss of appetite
• Itchiness
• Neck or flank pain

Depending on where the lymphoma is in your body, it can cause other serious signs and symptoms:

• If the lymphoma is in a lymph node in your chest, it may cause chest pain or pressure. It may affect your breathing, causing shortness of breath or cough.
• If it is in your abdomen, it can cause a swollen abdomen and /or abdominal pain.

Your healthcare practitioner will perform a physical exam and find out about your medical history. Additionally, a number of laboratory tests may be used to help diagnose lymphoma, determine the exact type, and monitor the effectiveness of treatment. After successful treatment (remission), testing may be used to check whether lymphoma has returned.

Laboratory tests

A biopsy of affected lymph nodes or lymphoid tissue is the gold standard diagnostic test for both Hodgkin lymphoma and non-Hodgkin lymphoma. A pathologist uses a microscope to examine samples of lymph tissue to determine whether cancer is present. The sample is usually collected during surgery or by a fine needle aspiration or biopsy procedure. Immunohistochemistry can be performed on tissue biopsy to help diagnose and classify lymphoma. (To learn more about biopsies, read the article on Anatomic Pathology.)

Several other laboratory tests that may be used to help diagnose and monitor lymphoma as well as any complications.

General laboratory tests may include:

• Complete blood count (CBC) – this panel of tests evaluates white blood cells, red blood cells, and platelets. It may be used to rule out non-lymphoma conditions (such as leukemia) and/or to see if anemia is present. A CBC can determine if the platelet count and/or white blood cell count are low, which may indicate that lymphoma is present in the bone marrow and/or blood.
• Bone marrow biopsy and examination – used to evaluate the cells present in the bone marrow. Abnormal lymphocytes can be seen in the bone marrow involved by lymphoma.
• Blood smear – a microscope is used to evaluate red blood cells, white blood cells, and platelets as well as any abnormal cells (e.g., lymphoma cells) that may be present.

Selective laboratory tests may include:

• Immunophenotyping by flow cytometry – this testing can identify specific cells involved by testing for the presence or absence of certain markers on the surface of the cells or inside the cells. It is used to help diagnose lymphoma and determine the type.
• Molecular genetic analysis – evaluating the cancer cell’s DNA for genetic changes, particularly to determine whether all of the cells belong to a single clone. (See B-cell Immunoglobulin Gene Rearrangement and T-cell Receptor Gene Rearrangement.)
• If it is thought that lymphoma has spread (metastasized) to other areas of the body, cerebrospinal fluid or other body fluids may be tested.
• Beta-2 microglobulin – this test is used to help determine disease burden and predict the outlook (prognosis) of lymphoma.
• Lactate dehydrogenase (LDH) – to help determine the prognosis of lymphoma
• Hepatitis B – this testing is done for patients who will undergo rituximab therapy because there are negative side effects associated with that treatment (reactivation of hepatitis B).

Non-laboratory tests
Examples of some imaging tests that may be performed include:

• Computed tomography (CT) scans
• Positron emission tomography (PET) scan
• Chest X-ray
• Magnetic resonance imaging (MRI)

For more on these imaging studies, visit RadiologyInfo.org.

Because more than one lymph node can be involved, it is important to find out which ones are affected and where they are in the body. This process is called staging. The following table contains an example of a classification system that describes how widespread the disease is. The Ann Arbor staging system is most used for non-Hodgkin lymphoma in adults.

Stages Found in Lymphomas

Staging can help guide therapy. For example, if you have Stage I lymphoma with only one node involved, then surgically removing that node may result in a cure. On the other hand, if you have Stage IV lymphoma, then surgical removal is not generally possible.

The most commonly used staging tests performed in the clinical laboratory are the complete blood count (CBC), liver and kidney function studies, and bone marrow biopsy. Non-laboratory tests include CT scans, MRI evaluations, and X-ray procedures.

Each lymphoma is unique. Some are more likely to grow and spread (aggressive) than others. The healthcare professional will “grade” the cancer based on its apparent aggressiveness. This information, along with the type and location(s) of the lymphoma, are used to guide treatment. Some people without troublesome or serious symptoms may be monitored closely and only treated when symptoms worsen.

The ultimate goal of treatment is a cure. When a cure is not possible, the goals are to put the lymphoma into remission (no signs of disease) for as long as possible, slow or prevent the disease from getting worse (progressing), relieve any symptoms, and prevent and treat any complications.

Lymphoma treatment often uses a combination of approaches. This may include:

• Chemotherapy
• Radiation therapy
• High-dose chemotherapy followed by stem cell transplantation
• Targeted therapy—these are drugs that target the specific changes in lymphoma cells that make them grow out of control.
• Immunotherapy—this is treatment that may help boost your immune system to fight the cancer or is man-made immune system parts that can help kill or slow the cancer.
• Surgery—this is rarely used to remove organs affected by lymphoma.

The choice of treatments and the outlook for your disease (prognosis) depends on the type, stage, and grade of the disease and your general health. Hodgkin lymphoma is mainly treated with chemotherapy and radiation therapy. One or more of the other options might be used as well.

All people diagnosed with lymphoma, even those whose lymphoma has been “cured” or put into remission, must be monitored for the rest of their lives. Many never experience lymphoma again but in others, it may come back years later.

For more details on specific treatments, see the links in the Related Content section.