Lymphoma

People who have lymphoma may experience painless swelling of the lymph nodes in the armpits, neck, or groin and/or enlargement of the spleen. They may also be found to have an increase in abnormal lymphocytes in the blood. Those with lymphoma may experience other signs and symptoms such as:

• Fatigue
• Fever and chills
• Night sweats
• Unexplained weight loss (as much as 10% of body weight or more)
• Loss of appetite
• Itchiness
• Neck or flank pain

If the affected lymph node is in the chest, it may affect the person's breathing; if it is in the abdomen, it can cause abdominal discomfort. Lymphoma can sometimes be difficult to diagnose because these signs and symptoms are often mild. Some people may have no noticeable signs while others might have a low-grade fever. Usually there are swollen lymph nodes, but the node may not be visible or felt by the person or a healthcare provider.

Hodgkin lymphoma (HL, also called Hodgkin's disease), which is characterized by the presence of large distinctive cells called Reed-Sternberg cells. 

Hodgkin lymphoma is most prevalent in two age groups: in those between about 20 and 40 years of age and in those over 55. According to the American Cancer Society (ACS), about 9,000 people in the United States are diagnosed with Hodgkin lymphoma each year and about 1,300 people die of it.

There are many different theories concerning the cause of HL. Some think that a type of infectious agent, such as a virus, might be involved. Others think that a mutation in a cell is the cause. While this is an area of active research, specific causes have not yet been identified. Likewise, there is no clear understanding of why males seem to be slightly more susceptible to the disease.

HL can be subdivided based on the structure of the abnormal lymph node and the types of cells that are present. Lymph nodes may have a predominance of small lymphocytes, the presence of bands of scarring (fibrosis), a mixture of different cell types, or lymphocyte depletion. In HL, tumor cells (so-called Reed-Sternberg cells) are the minority, while the majority is a benign, often mixed, reactive cell population.

Non-Hodgkin lymphoma represents just over 4% of all new cancer cases in the United States. It is slightly more common in men than women and more common in Caucasians. The incidence of NHL increases with age and is higher in those with HIV/AIDS and in people whose immune system is suppressed.

According to the ACS, non-Hodgkin lymphoma accounts for about 4% of all cancers. About 72,000 people are diagnosed with non-Hodgkin lymphoma per year and about 20,000 people die from it. Incidence rates of NHL have almost doubled since the 1970s. The reasons for this are not yet known, but the greatest increase has been in women. However, death rates from non-Hodgkin lymphoma have been decreasing since the late 1990s.

There are many types of non-Hodgkin lymphoma and as knowledge about them grows, the systems used to classify them has evolved. New methods of evaluating the cells involved in non-Hodgkin lymphoma have led to changes in classification systems.

In the 1990s, the Revised European American Lymphoma (REAL) classification was proposed by the International Lymphoma Study Group and adopted by many physicians. It looked at the function that the cell should be providing. B-lymphocytes are responsible for producing antibodies, for instance, while T-lymphocytes are responsible for cell-to-cell interactions. The newest method, the World Health Organization or WHO Classification, combines these characteristics with phenotypic and genetic studies of the cells. The WHO classification expanded on REAL and has been accepted by many as the current standard.

Some Types of Non-Hodgkin Lymphomas
Classification of non-Hodgkin lymphomas can be confusing because there are so many different types and because of the various classification systems that have been developed and amended over the years. In the United States, B-cell non-Hodgkin lymphomas are much more common than T-cell and NK-cell lymphomas. About 85% of non-Hodgkin lymphomas involve mature B-lymphocytes with about 15% affecting T-lymphocytes.

Some of the more common forms of B-cell lymphomas include:

• Diffuse large B-cell lymphoma (DLBCL): this form constitutes about one in three cases of all non-Hodgkin lymphomas in the United States. 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 about one in three turns into a fast-growing DLBCL.
• B cell chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL): this is a slow-progressing disease in which the lymphoma cells are predominantly small in size. CLL / SLL is the same disease; however, CLL mainly involves the bone marrow and the blood while SLL is found mainly in the lymph nodes. These two together make up approximately 24% of all lymphomas.

Some of the more common forms of T-cell lymphomas include:

• Precursor T-lymphoblastic lymphoma (leukemia): a disease that can be considered either a lymphoma or leukemia depending on whether affected cells are found in the blood and/or in the bone marrow. About 1% of all lymphomas are this type.
• Mature or peripheral T-cell lymphomas: there are many different kinds of mature T-cell lymphomas that all together 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 but are unusual because, while most lymphomas begin in lymphoid tissue or internal organs, these types start in the skin. This group of skin cancers makes up less than 1% of nonmelanoma skin cancers. Skin lymphomas make up 5% of all lymphomas.

The goals with testing are to diagnose and stage lymphoma, to distinguish it from other conditions, and to identify and monitor any associated complications. There are few blood tests that clearly indicate lymphoma.

Laboratory tests

The gold standard diagnostic test for both Hodgkin lymphoma and non-Hodgkin lymphoma is the examination of involved lymph nodes or lymphoid tissue by a pathologist. The sample is usually collected from an affected lymph node or tissue using a biopsy or fine needle aspiration procedure and is examined under the microscope. (To learn more about biopsies, read the article on Anatomic Pathology.)

Other laboratory tests that may be useful include:

• Complete blood count (CBC) – may be ordered 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. The presence of abnormal lymphoid cells and/or lymphoid aggregates may be seen with lymphoma.
• Blood smear – used to evaluate the quality of red and white blood cells and platelets as well as abnormal cells (lymphoma cells, for example), if present.
• Immunophenotyping can identify the cells involved by testing for the presence or absence of certain markers on the membrane of the cells or inside the cells. These commonly used markers are called clusters of differentiation (CD) and are listed numerically. By developing a list of the CDs present on the cells, it is possible to classify the cells. This test can be done by several different methods, including flow cytometry and immunohistochemistry.
• Chromosome analysis – an evaluation of the chromosomes in the nucleus of cancer cells to determine if pieces of the chromosomes have moved (translocation). This is rarely used for lymphomas. 
• 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, analysis of cerebrospinal fluid or other body fluids may be performed. 
• Beta-2 microglobulin – this test may be used to help predict the prognosis.
• Serum creatinine – levels may be elevated if a kidney disease called nephrotic syndrome is associated with Hodgkin lymphoma
• Serum chemistry studies, including lactate dehydrogenase (LDH) – to help determine the prognosis
• Hepatitis B – this testing is done for patients who will undergo rituximab therapy because there are negative side effects associated with that treatment and hepatitis B
• Human immunodeficiency virus (HIV) testing – this is recommended because treating people with antiretroviral can improve their lymphoma outcome if they have HIV

Non-laboratory tests
Primarily used to help stage and monitor lymphoma, non-laboratory tests include:

• Physical examination
• Computed tomography (CT) scans
• Positron emission tomography (PET) scan
• Chest X-ray
• Exploratory surgery (occasionally necessary)
• 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 located 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 commonly used for non-Hodgkin lymphoma in adults.

Stages Found in Lymphomas

Staging allows the health practitioner to determine what choices of therapy are available. For example, if a person has Stage I with only one node involved, then surgically removing that node may result in a cure. On the other hand, if the person is at Stage IV, 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.