Lymphoma - Non-Hodgkin: Diagnosis

Approved by the Cancer.Net Editorial Board, 03/2021

ON THIS PAGE: You will find a list of common tests, procedures, and scans that doctors use to find the cause of a medical problem. Use the menu to see other pages.

Doctors use many tests to find, or diagnose, cancer. They also do tests to learn what parts of the body are affected by the cancer. Because the lymph system is throughout the body, any lymph organ may be involved with NHL. Imaging tests can show pictures of the inside of the body and help doctors find which areas of the body may be involved with the cancer. Doctors may also do tests to learn which treatments could work best.

For most types of cancer, a biopsy is the only sure way for the doctor to know if an area of the body has cancer. In a biopsy, the doctor takes a small sample of tissue for testing in a laboratory. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis.

How NHL is diagnosed

There are many tests used for diagnosing NHL. Not all tests described here will be used for every person. Your doctor may consider these factors when choosing a diagnostic test:

  • The type of lymphoma suspected

  • Your signs and symptoms

  • Your age and general health

  • The results of earlier medical tests

To determine if a person has NHL, the doctor will first take a complete medical history. They will also do a physical examination, paying special attention to the lymph nodes, liver, and spleen. The doctor will also look for signs of infection that may cause the lymph nodes to swell and may prescribe an antibiotic. If the swelling in the lymph nodes still does not go down after antibiotic treatment, the swelling may be caused by something other than an infection. If the doctor suspects lymphoma, they will recommend a biopsy, as well as laboratory and imaging tests.

In addition to a physical examination, the following tests may be used to diagnose and manage NHL:

  • Biopsy. A biopsy is the removal of a small amount of tissue for examination under a microscope. Other tests can suggest that cancer is present, but only a biopsy can make a definitive diagnosis and find out the subtype. This tissue may be removed using a core biopsy needle or surgery. To diagnose lymphoma, tissue is usually taken from the lymph nodes in the neck, under an arm, or in the groin. A biopsy may also be taken from the chest or abdomen using a fine needle during a computed tomography scan (CT scan, see below) or an ultrasound (see below) or from the stomach or intestine during an endoscopy. An endoscopy is a test that allows the doctor to see inside the body with a thin, lighted, flexible tube. A biopsy of the skin may also be needed depending on which subtype of lymphoma is suspected.

    Having enough tissue in the biopsy sample is very important in making a diagnosis. Biopsies may be done by needle, such as a core biopsy or fine needle aspiration, or by surgical biopsy. A pathologist or a hematopathologist experienced in diagnosing lymphoma then analyzes the samples. A pathologist is a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease. A hematopathologist is a pathologist who has additional training in the diagnosis of blood cancers. Because there are so many subtypes of lymphoma and because some of these subtypes are uncommon or rare, getting a second opinion that includes a formal hematopathology review of previous tissue biopsies may be helpful.

  • Computed tomography (CT or CAT) scan. A CT scan takes pictures of the inside of the body using x-rays taken from different angles. A computer combines these pictures into a detailed, 3-dimensional image that shows any abnormalities or tumors. A CT scan can be used to measure the tumor’s size. Sometimes, a special dye called a contrast medium is given before the scan to provide better detail on the image. This dye can be injected into a patient’s vein, given as a pill or liquid to swallow, or both. A doctor who specializes in performing imaging tests to diagnose disease, called a radiologist, interprets CT scans. CT scans of the chest, abdomen, and pelvis can help find cancer that has spread to the lungs, lymph nodes, spleen, and liver.

  • Magnetic resonance imaging (MRI). An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. MRI can be used to measure the tumor’s size. A special dye called contrast medium is given before the scan to create a clearer picture. This dye can be injected into a patient’s vein. A radiologist interprets the scan.

  • Positron emission tomography (PET) or PET-CT scan. A PET scan is usually combined with a CT scan (see above), called a PET-CT scan. However, you may hear your doctor refer to this procedure just as a PET scan. A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive sugar substance is injected into the patient’s body. This sugar substance is taken up by cells that use the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. However, the amount of radiation in the substance is too low to be harmful. A scanner then detects this substance to produce images of the inside of the body. A nuclear medicine physician interprets the scan. A doctor can use this technique to look at both the structure of the tumor and how much energy the tumor and healthy tissues use. If, after 1 or more imaging tests, the doctor decides the lymphoma might be affecting the bone marrow, they may recommend a bone marrow biopsy.

  • Bone marrow aspiration and biopsy. These 2 procedures are similar and typically done at the same time to examine the bone marrow. Bone marrow has both a solid and a liquid part. A bone marrow aspiration removes a sample of the fluid with a needle. A bone marrow biopsy is the removal of a small core of solid tissue using a needle.

    A pathologist or hematopathologist then analyzes the sample(s). A common site for a bone marrow aspiration and biopsy is the pelvic bone, which is located in the lower back by the hip. Doctors generally give a type of medication called local anesthesia beforehand to numb the area. Anesthesia is medication that blocks the awareness of pain. Stronger types of anesthesia can also be used to lessen the pain.

    Lymphoma often involves the bone marrow, so looking at a sample of the bone marrow can be important for diagnosing lymphoma and determining the stage. The doctor can also use the sample removed during the aspiration to find any genetic changes. With certain types of lymphoma, these procedures may not be required if a PET scan has been done.

  • Biomarker testing. Your doctor may recommend running laboratory tests on a tumor and/or bone marrow sample to identify specific genes, proteins, and other factors unique to the disease. This may also be called molecular testing. Results of these tests can help determine your treatment options. There are several types of molecular and genetic testing:

    • Cytogenetics detects cancer-specific changes in the number and/or structure of chromosomes.

    • Fluorescent in situ hybridization (FISH) uses fluorescent probes under a special microscope to find cancer-specific chromosome changes that may not be seen by cytogenetics.

    • Flow cytometry looks at proteins that are on the surface of or inside a cancer cell.

    • Immunohistochemistry (IHC) is a special staining process to look at proteins on the surface of or inside the cancer cell.

    • Polymerase chain reaction (PCR)-based tests find cancer-specific DNA changes.

    • Molecular profiling/gene sequencing finds cancer-specific changes in the DNA sequence of genes in the cancer cells. Recent advances in sequencing technology, often called next-generation sequencing or NGS, allow testing of many genes from a single sample.

After diagnostic tests are done, your doctor will review the results with you. If the diagnosis is NHL, these results also help the doctor describe the subtype and stage of the NHL.

The next section helps explain the different subtypes of NHL that may be diagnosed. Use the menu to choose a different section to read in this guide.