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How many stages are there in non-Hodgkin's lymphoma?
Every weekday, a CNNHealth expert doctor answers a viewer question. On Wednesdays, it's Dr. Otis Brawley, chief medical officer at theAmerican Cancer Society.
Question asked by Paula Holman-Yorba of San Bernardino, California

How many stages are there in non-Hodgkin's lymphoma?

Expert answer
Two weeks ago, Paula asked about staging of non-Hodgkin's lymphoma. We discussed cancer staging in general. This week, we discuss lymphoma and its staging and prognosis.
Lymphoma is cancer of the lymphatic system, which is an important part of the immune system. The lymphatic system consists of conduits or tubes throughout the body with filters called lymph nodes along the path. The system carries a clear fluid with immune fighting cells such as lymphocytes.
Lymphoma is a disease that is increasing in incidence in the Western world. Common risk factors include exposure to:
• ionizing radiation;
• certain chemicals such as benzene, insecticides, or herbicides; and
• some viruses such as HIV, HTLV 1 and 2.

There is also evidence that people with immune diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE, or lupus), or celiac sprue are at higher risk of developing lymphoma. Patients with immune hyperstimulation from H. pylori infection of the stomach or hepatitis C are also at increased risk of certain types of lymphoma.

The appropriate treatment and the prognosis for a lymphoma patient are related to a combination of the type of lymphoma and stage of disease. The type of tumor is determined by a pathologist's microscopic examination of a biopsy of the tumor.

There are two major types of lymphoma: the Hodgkin's lymphomas and the non-Hodgkins lymphomas. HL spreads primarily through the ducts of the lymph system. NHL spreads more through blood vessels. There are five subtypes of HD and more than two dozen types of NHL. These NHL are categorized into three groups: the indolent, intermediate and aggressive.
The stage or degree of spread of the disease is determined by the physical examination and radiologic imaging.

A TNM stage, discussed last week, is determined and usually translated into what is known as the Ann Arbor staging system with Cotswolds modifications. This is the overall or summary stage, in brief:
• Stage I - Lymphoma involving a single lymph node region (I) or a single node and the organ next to it.
• Stage II - Involvement of two or more lymph node regions in the chest or two or more in the abdomen or the area of the retroperitoneum (low back). There can be direct extension of lymphoma from the lymph node chain into an adjacent organ.
• Stage III - Involvement of lymph node in the abdomen and the chest or the retroperitoneum and the chest. Involvement of the spleen, which is located in the left upper abdomen, is stage III disease.
• Stage IV - Diffuse or disseminated lymphoma involving one or more organs or tissues without associated lymphatic involvement.

Patients with stage I or stage II disease are then further stratified for treatment purposes into favorable and unfavorable prognosis disease, based upon the presence or absence of certain clinical features, such as age and B symptoms (weight loss, fevers, night sweats, and large volume of disease in the chest).

Laboratory studies are done to determine the type of cancerous cells. There are drugs specific to the treatment of what are known as B cell lymphomas. B cell positive versus T cell positive or other laboratory markers can also be used to predict patterns of spread and patterns of invasion of a lymphoma.
The appropriate treatment of a lymphoma varies by the type of tumor and by the stage. Stage I and II lymphomas can often be treated with radiation alone. They are of limited size and spread, such that they can be illuminated by one radiation beam. Stage III and IV lymphomas generally must be treated with a series of chemotherapy drugs active in lymphoma. Type of tumor is very important, as indolent lymphoma usually presents as widely spread or stage IV disease, but can often be appropriately watched, and treatment can sometimes be deferred for a decade or more. On the other hand, the aggressive lymphomas can be a medical emergency requiring immediate treatment.

The international prognostic index (IPI) is used to determine prognosis for patients with lymphoma. The index takes into account the the type of lymphoma, stage of disease, and what markers or genes are expressed in the tumor. As a whole, lymphoma is one of the most treatable of malignancies. While the prognosis for many of the lymphomas can be very good, there are some lymphomas that are very difficult to treat.
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