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It should be noted that non-Hodgkin's lymphoma (NHL) is not a single disease but includes a heterogeneous (diverse) group of diseases, each of which carries a different prognosis (outlook). Over the years, several different classification systems have been developed to classify non-Hodgkin's lymphomas including:

• International Working Formulation (IWF) Classification System
• Revised European-American Classification of Lymphoid Neoplasms (REAL)
• Ann Arbor Staging System

International Working Formulation Classification System

The International Working Formulation (IWF) classification system loosely groups non-Hodgkin's lymphomas into the following 3 grades:

• Low-grade lymphomas - these are slow-growing lymphomas that are also referred to as indolent lymphomas.

• Intermediate-grade lymphomas - these are considered to be moderately aggressive lymphomas.

• High-grade lymphomas - these lymphomas are considered to be more aggressive than the intermediate-grade lymphomas.

Revised European-American Classification of Lymphoid Neoplasms

The Revised European-American Classification of Lymphoid Neoplasms (REAL) classification system is based upon the cellular type of the lymphocytes that are affected by the lymphoma. In general, the REAL classification system groups non-Hodgkin's lymphomas as follows:

• B-cell lymphomas - if B-lymphocytes are affected
• T-cell lymphomas - if T-lymphocytes are affected.

Ann Arbor Staging System

"Staging" is a system used by doctors to evaluate the extent of spread of a cancer and is an important factor in determining both the type of treatment as well as predicting the prognosis. Patients with non-Hodgkin's lymphoma are usually staged by the Ann Arbor staging system which evaluates two major factors:

• Site (location) of the lymphoma
• Presence or absence of clinical symptoms.

The Ann Arbor staging system classifies patients with non-Hodgkin's lymphoma into one of the following four stages (categories):

• Stage I - The lymphoma is only present in a single region of the body and involves either a single lymph node region (e.g., groin, neck, armpit) or a single organ outside the lymphatic system (extralymphatic involvement).

• Stage II - The lymphoma affects two or more lymph node regions on the same side of the diaphragm (the large muscle attached to the rib cage that is involved in breathing) or the lymphoma has spread from the lymph node into the surrounding tissue.

• Stage III - The lymphoma affects lymph node areas on both sides of the diaphragm and may have also spread to the surrounding tissue or the spleen.

• Stage IV - Patients in this category have lymphoma that affects one or more organs outside of the lymphatic system (extralymphatic lymphoma). Lymphoma cells may or may not be present in nearby lymph nodes. Stage IV disease represents a disseminated (widespread) form of non-Hodgkin's lymphoma.

The Ann Arbor classification system also takes into consideration whether symptoms of non-Hodgkin's lymphoma are present or absent. Patients without symptoms are designated with the letter "A" while those with symptoms are designated with the letter "B". The letters "A" or "B" are added to the stage designation (stage I through stage IV) as a means of further classifying the extent of the non-Hodgkin's lymphoma. An international group of lymphoma experts has incorporated the Ann Arbor staging classification along with other clinical attributes to predict overall prognosis and survival (see Prognosis for Non-Hodgkin's Lymphoma section). This staging system is useful for both aggressive and indolent non-Hodgkin's lymphoma.