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Stages of Non-Hodgkin Lymphoma

Posted on June 10, 2021
Medically reviewed by
Mark Levin, M.D.
Article written by
Maureen McNulty

If you are diagnosed with non-Hodgkin lymphoma (NHL) — a type of blood cancer — your doctor will also determine the stage of your disease. The stage describes how advanced the lymphoma is and where in your body the cancer cells have spread. Your doctor will use your lymphoma stage as one factor to estimate your prognosis (outlook) and recommend the best treatment plan for your particular diagnosis.

Staging for Non-Hodgkin Lymphoma

Most types of non-Hodgkin lymphoma are staged using the same systems, which allow doctors to classify all cases of lymphoma in the same way. NHL is staged with Lugano classification, adapted from an older system called the Ann Arbor system.

Lugano classification has four stages, divided into stages 1-4. (Staging numbers may sometimes appear as Roman numerals, e.g., stage I, stage II, and so on). The stages report how far cancer cells have spread. They also describe whether cancer is found inside or outside of the lymphatic or lymph system — the collection of tissues, tubes, and organs that help the body get rid of foreign substances or fight infections. The lymphatic system contains lymph nodes and lymph organs. Lymph nodes are small glands that tend to be grouped together in specific regions within the body. There are several lymph organs, including the:

  • Spleen
  • Thymus
  • Tonsils
  • Bone marrow (soft tissue inside certain bones that makes new blood cells)

An “E” is sometimes added to the stage (e.g., stage 1E) if lymphoma cells are found in organs that are extranodal — outside the lymphatic system.

Stage 1

People with stage 1 NHL have cancer in just one area of the body. Lymphoma cells are usually located in a single lymph node region or lymph organ in stage 1. If the cells are in a small part of a single organ outside of the lymphatic system, it’s called stage 1E.

Stage 2

In stage 2 NHL, cancer cells are located in two or more nearby locations. This often includes two different lymph node regions on the same side of the diaphragm. The diaphragm is a thin muscle that sits under the lungs and helps them expand and contract during breathing. It divides the abdomen into two sections. For the condition to be classified as stage 2, affected lymph node regions all need to be located in the top half or the bottom half of the abdomen.

Sometimes, lymphoma cells will exist within one or more lymph node regions on the same side of the diaphragm and also within a nearby organ outside the lymphatic system. In this instance, the person has stage 2E lymphoma.

Stage 3

There are two different cases in which someone is diagnosed with stage 3 NHL:

  • There are lymphoma cells in lymph node regions on both sides of the diaphragm.
  • There are lymphoma cells in lymph node regions above the diaphragm and within the spleen.

Stage 4

In stage 4 NHL, cancer cells are spread more widely in the body, located throughout one or more organs outside of the lymphatic system. Multiple lymph node regions in different parts of the body may also be affected.

Other Ways of Staging Non-Hodgkin Lymphoma

Doctors sometimes use other letters or words to describe non-Hodgkin lymphoma, in addition to the aforementioned “E” for cases of extranodal lymphoma. A person with a lymphoma tumor that is more than 10 centimeters large, for example, will have an “X” added to their stage. Doctors may call it “bulky disease.”

Other letters may also be added to the stage to describe which exact locations contain lymphoma cells. They include:

  • D — Skin
  • H — Liver
  • L — Lung
  • M — Bone marrow
  • N — Lymph nodes
  • O — Bone
  • P — Pleura (lining of the lungs)
  • S — Spleen

Chronic Lymphocytic Leukemia/Small-Cell Lymphocytic Lymphoma

Different staging systems are used for one subtype of NHL: chronic lymphocytic leukemia/small-cell lymphocytic lymphoma (CLL/SLL). CLL and SLL are the same condition involving the same type of cancerous white blood cells. When these cancer cells appear in the blood and bone marrow, doctors call it CLL. When they are located in the lymph nodes, the condition is called SLL.

CLL/SLL that only affects the lymph nodes is generally staged using the Lugano system. However, when the cancer cells are in the bone marrow or blood, the staging is different. Doctors in the United States usually stage CLL/SLL using the Rai system, while doctors in Europe stage it with the Binet system.

The Rai system includes five stages. People with stage 0 CLL/SLL are low risk — they are likely to have a good outlook. Stages 1 and 2 are intermediate risk, while stages 3 and 4 are high risk. These stages are based on certain clinical signs:

  • Stage 0 — High levels of lymphocytes
  • Stage 1 — High levels of lymphocytes and enlarged lymph nodes
  • Stage 2 — High levels of lymphocytes and enlarged spleen or liver
  • Stage 3 — High levels of lymphocytes and anemia (low red blood cell counts)
  • Stage 4 — High levels of lymphocytes, with anemia; thrombocytopenia (low platelet counts); and enlarged spleen, liver, or lymph nodes

The Binet system divides people with CLL/SLL into three groups based on how many areas of lymphoid tissue are affected. Lymphoid tissue includes lymph organs or groups of lymph nodes. The Binet system stages are:

  • Stage A — Fewer than three lymphoid tissue areas are enlarged.
  • Stage B — At least three lymphoid tissue areas are enlarged.
  • Stage C — Any number of lymphoid tissue areas are enlarged, and the person has anemia or thrombocytopenia.

Non-Hodgkin Lymphoma Grading

Doctors classify different types of lymphoma as “low grade” or “high grade.” Low-grade lymphomas — also called indolent lymphomas — grow slowly. Treatments help control low-grade lymphomas. However, the disease may go through phases of remission (when it disappears) and relapse (when it returns). People with low-grade lymphoma may only need treatment during periods of relapse and can then go without treatment during times when they feel fine. Types of low-grade lymphoma include:

  • CLL/SLL
  • Follicular lymphoma
  • Marginal zone lymphoma

High-grade lymphomas grow and get worse quickly. However, treatment usually works well to control these lymphomas and put them into remission. Types of high-grade lymphoma include diffuse large B-cell lymphoma and Burkitt’s lymphoma.

Lymphoma Staging and Prognosis

The lymphoma stages help predict prognosis, though stage alone does not determine your outlook. Factors such as your age and type of NHL also matter.

In general, people with early stage lymphoma have a higher chance of a better outcome and may not need many treatments. However, they may need to undergo treatment for many years. Advanced stage lymphoma is likely to lead to a worse outcome and may require more aggressive treatment options.

The general prognosis for each stage is as follows:

  • Stage 1 — More than 83 percent of people diagnosed at stage 1 live for five years or more after being diagnosed.
  • Stage 2 — Close to 76 percent of people live at least five years.
  • Stage 3 — More than 70 percent of people live at least five years.
  • Stage 4 — Around 63 percent of people live for five years or more after diagnosis.

Doctors may also use other systems, such as the International Prognostic Index (IPI), to determine a person’s outlook and come up with a treatment plan. The IPI provides a score based on:

  • Age
  • Lymphoma stage
  • Whether lymphoma cells are located outside of the lymphatic system
  • Blood levels of lactate dehydrogenase (LDH), which helps in the process of converting sugar into energy
  • Overall well-being (how well a person can perform daily activities)

Lower scores indicate a good prognosis and suggest that treatment is not needed. Higher scores indicate that more aggressive treatments will be helpful.

Measuring CLL/SLL Prognosis

CLL/SLL prognosis is measured using a related system called the CLL-International Prognostic Index (CLL-IPI). The CLL-IPI takes into account the Rai or Binet stage, as well as age and whether a person has certain mutations in their genes.

Measuring Follicular Lymphoma Prognosis

Doctors also use a separate prognostic system for follicular lymphoma, called the Follicular Lymphoma International Prognostic Index (FLIPI). The FLIPI considers slightly different factors:

  • Age
  • Lymphoma stage
  • Levels of hemoglobin in the blood
  • Number of lymph-node regions that contain cancer cells
  • LDH levels

How Are Non-Hodgkin Lymphoma Stages Measured?

When staging non-Hodgkin lymphoma, doctors use many of the same tests that were used to initially diagnose the disease. Tests may include:

  • A physical exam
  • Blood tests
  • A biopsy (removal of a small piece of tissue) of the lymph nodes or other affected tissues
  • Imaging tests, like CT scans or positron emission tomography scans
  • Bone marrow tests, including a biopsy (removal of cells) and aspiration (removal of fluid)
  • Lumbar puncture (removal of a sample of the fluid that surrounds the brain and spinal cord)

Your doctor may use some or all of these tests when staging non-Hodgkin lymphoma. Ask your health care team if you have any questions about why a certain test is needed or if you want to better understand what your test results mean.

Talk With Others Who Understand

MyLymphomaTeam is the social network for people with lymphoma and their loved ones. On MyLymphomaTeam, more than 8,100 members come together to ask questions, give advice, and share their stories with others who understand life with lymphoma.

Are you living with non-Hodgkin lymphoma? Share your experiences in the comments below, or start a conversation by posting on MyLymphomaTeam.

All updates must be accompanied by text or a picture.
Mark Levin, M.D. is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

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