Non-Hodgkin Lymphoma Diagnosis and Staging

July 13, 2024

This page was reviewed under our medical and editorial policy by Alex Herrera, M.D., professor, division of lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope^® Cancer Center Duarte

In diagnosing non-Hodgkin lymphoma (NHL), doctors generally begin by asking patients questions about symptoms and medical history, and performing a physical exam. However, a biopsy is necessary to confirm the diagnosis. From there, additional tests may be performed to pinpoint the NHL subtype, determine the extent of the cancer’s spread and develop a treatment plan.

How Is Non-Hodgkin Lymphoma Diagnosed?

Several tests may be performed to confirm that a patient has non-Hodgkin lymphoma and determine how far it has advanced.

Biopsy for Non-Hodgkin Lymphoma

A biopsy is the only way to make a definite diagnosis of NHL. This usually means removing a lymph node (or part of one) to be examined in a laboratory. Most often, the tissue is surgically removed to ensure there is enough of a sample to thoroughly evaluate. In some cases, doctors may recommend a needle biopsy first if they suspect a different cause of an enlarged lymph node, for instance. During this procedure, the doctor uses a hollow needle attached to a syringe to draw a small sample from a lymph node or other tissue.

Biopsied tissue is typically analyzed in multiple ways. A pathologist examines the samples under a microscope to look for certain signs of cancer, such as abnormalities in the size and shape of cells. In addition, one or more of the lab tests listed below may be performed.

Cytogenetic testing: This detects cancer-specific changes in the number and/or structure of chromosomes within the cells.

Fluorescent in situ hybridization (FISH): This test also looks for cancer-specific chromosomal abnormalities. Through the use of a specialized microscope, it may find chromosome changes that cytogenetic testing may miss.

Flow cytometry and immunohistochemistry: These tests examine proteins on the surface of or inside cancer cells. The results may be used to help diagnose the disease or determine the non-Hodgkin lymphoma type.

Molecular profiling/gene sequencing: This may be performed to find cancer-specific changes in cells’ DNA. Most of these tests use a technique known as polymerase chain reaction, or PCR. Because PCR is so sensitive, it may detect DNA changes too small to be seen with a microscope, even if the tissue sample contains only a small number of lymphoma cells.

Once a lymphoma diagnosis is made, a number of additional tests may be performed to help determine the type and stage (extent) of the cancer, or to zero in on the cause of particular symptoms. These may include those listed below.

Bone Marrow Aspiration and Biopsy

A bone marrow aspiration and biopsy may be performed to see whether the lymphoma has reached the bone marrow, and they may be important for determining the cancer’s stage. During aspiration, the doctor inserts a thin hollow needle into an area of bone (usually the hip) and uses a syringe to draw out a small amount of liquid bone marrow. It is performed with local anesthesia, so the area is numbed but the patient remains awake. Usually, aspiration is immediately followed by a bone marrow biopsy in which the doctor uses a slightly larger needle to remove more marrow and a small piece of bone. As with other tissue biopsies, the bone marrow is analyzed and tested for various markers of cancer.

Computed Tomography (CT) Scan

A CT scan uses X-rays to create detailed, 3D images of tissues. This may be helpful in gauging a tumor’s size or in spotting lymphoma that has spread to organs such as the lungs, spleen or liver.

Magnetic Resonance Imaging (MRI)

MRI scans also produce detailed images of the body’s soft tissues, but they are not used as often as CT in diagnosing lymphoma. Doctors may want to perform MRI in some cases, such as when they suspect the cancer might have spread to the brain or spinal cord.

Positron Emission Tomography (PET) or PET/CT Scan

PET is another technology that creates images of body tissue. Most often, it is combined with a CT scan, though doctors commonly refer to the procedure simply as a PET scan. With this test, patients first receive an injection of a radioactive sugar substance. Because cancer typically uses more energy than normal body tissue does, the sugar substance mainly collects in cancer cells. That allows the scanner to create images that may help doctors learn more about the structure of the tumor, for example, or how much energy it is using in comparison to healthy tissue.

Non-Hodgkin Lymphoma Stages

Staging is a way of describing the extent of a cancer, and it is critical in forming a treatment plan. In general, doctors stage NHL by considering the number of lymph nodes affected; where the cancerous nodes are located in the body (whether they are in one or both sides of the diaphragm, which is the muscle that separates the chest and abdomen); and whether the lymphoma has spread to the bone marrow, spleen or organs that are not part of the lymphatic system.

Stage 1 Non-Hodgkin Lymphoma

These lymphomas are either confined to one lymph node region or one lymphatic organ, or found in only one area of a single organ outside the lymphatic system.

Stage 2 Non-Hodgkin Lymphoma

The cancer is in two or more lymph node regions on the same side of the diaphragm; or confined to one organ and its regional lymph nodes, with or without cancer in other lymph node regions on the same side of the diaphragm.

Stage 3 to 4 Non-Hodgkin Lymphoma

The cancer is in lymph nodes on both sides of the diaphragm (Stage 3), or it has spread beyond the lymph nodes (Stage 4) — most often to the bone marrow, liver or lungs. These two stages are often paired together, because the non-Hodgkin lymphoma treatment and survival rates are similar for both. Importantly, NHL is often highly treatable even at these more advanced stages.

Recurrent or Relapsed Non-Hodgkin Lymphoma

Both terms refer to lymphoma that has come back after treatment. For some people, the disease recurs in the same area of the body where it started; for others, it returns in a different location. A recurrence may happen soon after treatment or years later.

When it comes to prognosis, or a patient’s outlook, it is not only the non-Hodgkin lymphoma stage that matters. So does functional status, or how well a person is able to perform everyday tasks and keep up usual activities. Doctors often assess this using a standard scale that considers whether patients are able to be as active as they were before their diagnosis.