The diagnosis and prognosis of non-Hodgkin's lymphoma includes the following:

Diagnosis begins with a visit to the doctor. He or she will complete a history and physical. A biopsy will be necessary to confirm the presence of cancer cells.


Review of Medical History

The doctor will ask you about your symptoms and medical history. He or she will inquire about past infections and whether or not you have had an organ transplant. This is because people with decreased immune function are at greater risk of developing non-Hodgkin’s lymphoma, and the drugs ordered after an organ transplant to reduce the chance of rejection decrease immune function.

Non-Hodgkin’s lymphoma also seems to occur in people who have had been infected with the human immunodeficiency virus (HIV) and Epstein-Barr virus, which causes infectious mononucleosis.

The doctor also will ask you about any nonspecific symptoms you may be having. For instance, whether or not you are experiencing fatigue, changes in appetite, or night sweats.

Physical Exam

The doctor will perform a physical exam, including checking your temperature. He or she will carefully palpate (feel while applying pressure to) the areas where lymph nodes are found. Most enlarged or swollen lymph nodes are caused by an infection, not lymphomas. If infection is suspected, you may be given an antibiotic and instructed to return for re-examination. If swelling persists, your doctor may order a lymph node biopsy.

Diagnostic Testing

If your doctor suspects non-Hodgkin's lymphoma, you will have a lymph node biopsy.

Lymph node biopsy – your doctor will remove all or part of one of your lymph nodes, and a pathologist will examine this tissue sample under a microscope. The biopsy may show whether or not there is cancer and the type of cancer cells present. Completely removing the lymph node is optimal. Accurate diagnosis and classification of the type of cancer depend on removal of an adequate amount of tissue, which may or may not be possible, depending on the location.


Cytology is the study of cells. The cytology of cancer cells differs significantly from normal cells, and physicians use the unique cellular features seen on biopsy samples to determine the diagnosis and assess the prognosis of a cancer.

After the biopsy, a pathologist in the laboratory will look at the type of cells within the sample under a microscope to identify its cell type. Because non-Hodgkin’s lymphoma is classified by cell type, precise classification also requires immunophenotyping. This test is used to identify the characteristics or patterns of antigens produced by the cancer cells.


In non-Hodgkin’s lymphoma, the type of cell, which is determined by the pathologist, is considered more important than the stage of the cancer in determining prognosis and expected response to treatment.

Several classification systems exist for non-Hodgkin’s lymphoma. In the United States, the two most commonly used are the Working Formulation and the REAL classification systems.

Working Formulation System

Pathologists using the Working Formulation system assess the size and shape of the cells and their growth pattern. The Working Formulation system divides non-Hodgkin’s lymphoma into three categories:

  • High grade: grows very quickly and causes serious symptoms
  • Intermediate: grows more rapidly than low grade and causes serious symptoms
  • Low grade: grows more slowly and produces few symptoms

REAL Classification System

The REAL classification system stands for Revised European American Lymphoma. It is newer a system of classification. REAL classifies the types of lymphoma by how the disease behaves. Pathologists using this system assess the cells’ appearance, genetic features, and chemistry. The system also takes into account what normally happens to patients with the disease. The REAL classification system divides non-Hodgkin’s lymphoma into four categories:

  • Excellent prognosis: average five-year survival rate of 70%
  • Good prognosis: average five-year survival rate of 50% to 70%
  • Fair prognosis: average five-year survival rate of 30% to 49%
  • Poor prognosis: average five-year survival rate of less than 30%


Staging is the process by which physicians determine the prognosis of a cancer that has already been diagnosed. Staging is essential for making treatment decisions (e.g., surgery vs. chemotherapy). Several features of the cancer are used to arrive at a staging classification, the most common being the size of the original tumor, extent of local invasion, and spread to distant sites (metastasis). Low staging classifications (0 – 1) imply a favorable prognosis, whereas high staging classifications (4 – 5) imply an unfavorable prognosis. If cancer is found, your prognosis and treatment depend on the location, size, and stage of the cancer as well as your general health.

Your doctor will consider the following factors to determine the stage of your disease:

  • The number and location of lymph nodes affected
  • If you have systemic symptoms, such as nigh sweats, fever, fatigue or decreased appetite
  • The type of cell involved
  • Whether the affected lymph nodes are on one or both sides of the diaphragm (the thin muscular sheet that separates the chest from the abdomen)
  • Whether the disease has spread to other lymphatic tissues such as the spleen
  • Whether the disease has spread to the bone marrow, liver, or other places outside the lymphatic system

Additional tests to determine staging may include:

  • Urine and blood tests
  • Additional physical exam – to check for any swollen nodes
  • X-rays of various parts of the body, including lungs, bladder, kidney, and lymph nodes to check for signs of lymphoma.
  • CT scan – a type of x-ray that uses a computer to produce cross-sectional images of the inside of the body
  • Ultrasound – the use of sound waves and the characteristic patterns they make bouncing off of various structures in the body to identify tumors and other conditions.
  • MRI scan – a test that uses magnetic waves to produce images of the inside of the body. Using a large magnet, radio waves, and a computer, an MRI produces two-dimensional and three-dimensional pictures.
  • Bone marrow biopsy – a sample of bone marrow and a small piece of bone are removed and tested for cancer cells. The samples are obtained by inserting a needle into the pelvic bone. This may be done in the hospital or outpatient setting.
  • Positron emission tomography (PET) scan – a test that assesses metabolic activity in the tissue. Cancer cells typically generate more activity than non-cancerous cells. A PET scan can be performed on a variety of body tissues. A nurse or technologist administers a radioactive substance. This may be done through an injection, or in some cases, you will be asked to breathe in a gas with the substance. The compound travels through the blood to the area of the body under study. It takes between 30 and 90 minutes for the substance to be absorbed by the tissue under study. You lie on a table and are moved into a machine that looks like a large, square-shaped doughnut. This machine detects and records the energy levels emitted from the substance that was injected earlier. The images are viewed on a nearby computer monitor.
  • Bone scan – an injection of a radioactive compound called technetium is given. Three hours later, you lie on a table. Special cameras move slowly above and below the table taking pictures; these cameras detect small amounts of radioactivity in the injected technetium. This allows the doctor to see areas of the bone that may contain cancer cells.
  • Endoscopy – the insertion of a fiberoptic tube with a lighted tip (an endoscope) through the mouth and down through the gastrointestinal (GI) tract to examine the entire passageway from mouth to stomach. This allows your doctor to look for abnormalities, and perhaps to obtain a biopsy specimen of the cancer.
  • Lumbar puncture (spinal tap) – removal of a small amount of fluid that surrounds the brain and spinal cord to test for cancer cells. A needle is inserted between the third and fourth lumbar vertebrae in the back to extract a sample of fluid.
  • Laparoscopy – tiny incisions are made in the abdomen, and a small fiberoptic tube with a lighted tip (a laparoscope) is inserted. This allows for a visual examination of the abdomen. Miniature surgical tools can also be inserted into the abdomen to remove tissue samples (biopsies). The tissue samples will be checked for cancer cells.

The following stages are used to classify non-Hodgkin’s lymphoma:

Stage I – Cancer involves a single lymph node region. Or if the cancer started in an organ, it is limited to that organ.

Stage II – Cancer has spread to two or more lymph node regions on the same side of the diaphragm. Or if the cancer started in an organ, it has spread to one or more lymph node groups on the same side of the diaphragm.

Stage III – Cancer has spread to both sides of the diaphragm.

Stage IV – Cancer has spread to organs other than lymph nodes with or without diseased lymph nodes.

Stages have an “A” and a “B” level. In Stage B, a person with non-Hodgkin's lymphoma experiences general symptoms from the disease—fever, night sweats, or significant weight loss. If these specific symptoms are not present the classification is "A."

The third stage has an “S” or “SE” level. The S refers to involvement of one organ or the spleen. SE refers to both one organ and the spleen.


Prognosis is a forecast of the probable course and/or outcome of a disease or condition. Prognosis is most often expressed as the percentage of patients who are expected to survive over five or ten years. Cancer prognosis is a notoriously inexact process. This is because the predictions are based on the experience of large groups of patients suffering from cancers at various stages. Using this information to predict the future of an individual patient is always imperfect and often flawed, but it is the only method available. Prognoses provided in this monograph and elsewhere should always be interpreted with this limitation in mind. They may or may not reflect your unique situation.

Doctors use an international prognosis index to predict how the cancer will respond to treatment. The index helps doctors plan treatments. The index includes the following factors:

Age – whether you are younger or older than 60; one point is assigned for over 60

Stage – one point is assigned for stage III or IV

Whether the lymphoma is evident outside the lymph nodes – one point is assigned for disease outside the lymph nodes

Patient’s ability to function normally, despite the tumor – one point is assigned if you need help with activities of daily living

Blood test for LDH, which is elevated with fast-growing tumors – one point is assigned if the LDH level is elevated

With this system, the lower the score the better the prognosis. More than 75% of the people in the lowest group will survive for five or more years. Of the people with the poorest (highest) scores, only 30% live for five years or more.