To diagnose non-Hodgkin‘s lymphoma, doctors may use blood tests, biopsies, and imaging scans such as CT scans or MRIs. These tests help doctors confirm the presence of the disease and plan the right treatment.

The lymphatic system is a major part of your body’s immune system. It includes your lymph nodes, bone marrow, spleen, and thymus.

Lymphoma occurs when cancer forms in the lymphatic system. There are two main types:

  • Hodgkin’s lymphoma: Hodgkin’s lymphoma involves large cancer cells called Reed-Sternberg (RS) cells.
  • Non-Hodgkin’s lymphoma: RS cells are not present in non-Hodgkin’s lymphoma. This type is more common.

There are more than 70 subtypes within these two categories. They range from slow-growing cancers to aggressive, fast-growing forms.

Most cases of lymphoma are usually considered treatable. But it’s still a serious disease that requires medical attention. Your overall outlook will depend on the timing of your diagnosis. The sooner you get checked, the better your outcome will be.

If you have lymphoma symptoms, visit a doctor as soon as possible. They can provide a diagnosis using tests such as blood panels and biopsies.

We’ll explain how your doctor would diagnose non-Hodgkin’s lymphoma, including a breakdown of tests they might use.

A doctor will use multiple procedures to diagnose non-Hodgkin’s lymphoma. The exact combination of tests will depend on your symptoms and your overall health.

Physical exam

When you first see the doctor, they’ll perform a physical exam. This helps them analyze your symptoms to determine a baseline for your diagnosis.

During a physical exam, a doctor will:

  • look for swollen lymph nodes in your neck, groin, and underarms
  • check for swelling in your spleen and liver
  • ask about your medical history
  • examine any other physical symptoms you have

A doctor will carry out several tests to confirm a non-Hodgkin’s lymphoma diagnosis.

Lymph node biopsy

A lymph node biopsy is the gold standard for diagnosing lymphoma. Often, it’s the only test that can provide an official diagnosis.

During the procedure, a healthcare professional takes a sample of a lymph node. They then send the sample to be examined under a microscope for signs of lymphoma.

The sample may also help your doctor determine the type of lymphoma and how fast it’s growing.

There are several types of lymph node biopsy:

  • Excisional biopsy: A healthcare professional removes an entire lymph node.
  • Incisional biopsy: They remove part of a lymph node.
  • Core needle biopsy: They remove only a small lymph node sample.
  • Laparoscopic biopsy: They use small instruments to remove a sample from deep within your body.

The best option will depend on your overall health and the location of the affected lymph nodes. Multiple biopsies may be necessary to accurately diagnose non-Hodgkin’s lymphoma.

Blood panel

After the physical exam, the doctor will likely order a blood test to check for specific markers in your blood that might indicate lymphoma. Blood tests can also help your doctor rule out other possible causes of your symptoms.

A typical blood panel includes the following tests:

Complete blood count (CBC)

A CBC measures certain components of your blood, including:

  • Red blood cells: These cells transport oxygen throughout your body. If lymphoma disrupts red blood cell production in your bone marrow, you may have a low red blood cell count, or anemia.
  • White blood cells: These cells fight infections in your body. A low white blood cell count can result from lymphoma or other conditions, such as autoimmune disorders. Lymphoma sometimes shows as an abnormally high white blood cell count in blood test results.
  • Platelets: These cells help your blood form clots. Lymphoma in your bone marrow may result in a low platelet count.

Liver and kidney function

Your doctor may also want to check how well your liver and kidneys are working.

A liver function test for albumin (a protein produced by your liver) might help them diagnose advanced lymphoma. The disease can decrease albumin levels.

Lactic dehydrogenase (LDH)

Your blood panel might also measure your level of LDH, an enzyme found in most of your tissues. Some forms of lymphoma increase LDH production.

However, because high LDH levels can be caused by other diseases, you’ll need other tests to help your doctor reach a diagnosis.

C-reactive protein

During the inflammatory response, your body produces C-reactive protein. High levels of this protein in your blood may be a sign of cancer, including lymphoma, but could also be due to other sources of inflammation.

Imaging tests

A lymphoma diagnosis often includes imaging tests, which allow your doctor to:

  • locate enlarged lymph nodes
  • check whether lymphoma has affected other organs
  • look for tumors
  • determine the stage of lymphoma

A doctor might order the following tests:

  • Ultrasound: During an ultrasound, sound waves bounce off your tissues and organs to create an image. Your doctor might use an ultrasound to examine swollen areas or to find the best location for a biopsy.
  • X-ray: An X-ray uses radiation to take detailed images of the inside of your body.
  • CT scan: During a CT scan, a radiographer uses narrow X-rays to create detailed 3D pictures. CT scans take clearer images of swollen lymph nodes than X-rays do.
  • PET scan: Before a PET scan, a doctor will inject you with a radioactive form of sugar, which cancer cells absorb. These cells will appear on the scan.
  • MRI scan: If your doctor thinks you have lymphoma of the central nervous system, they will order an MRI.

Bone marrow biopsy

Bone marrow is the soft, spongy tissue inside most of your bones. It produces important blood cells, including red blood cells and platelets.

Lymphoma can start in your bone marrow. If your doctor thinks this is the case, you might need a bone marrow biopsy. During this test, a healthcare professional removes a small sample of bone marrow to check for lymphoma cells.

A bone marrow biopsy isn’t necessary for everyone with a lymphoma diagnosis. Your doctor will decide whether you need one.

Immunophenotyping

Immunophenotyping is a lab test that checks the affected cells for specific markers called clusters of differentiation. There are multiple possible ways to do this.

Immunohistochemistry

For this test, the doctor uses antibodies to check a tissue sample for specific proteins. The antibodies stick to the proteins and activate an enzyme or a fluorescent dye. The enzyme or dye shows up under a microscope, allowing a specialist to determine the type of lymphoma cells.

Flow cytometry

Flow cytometry uses fluorescent antibodies to stain blood cells. A healthcare professional will place the blood or tissue in a flow cytometer, which evaluates:

  • the number and percentage of cells
  • the cell size and shape
  • specific markers on the cell surface

Your doctor can use the results to diagnose lymphoma.

Chromosome tests

Chromosomes consist of DNA strands. In some people, lymphoma cells may have altered chromosomes.

To find these altered cells, a doctor might request chromosome tests, such as:

  • Cytogenetic analysis: a test that involves using a microscope to check for chromosome abnormalities
  • Fluorescence in situ hybridization (FISH): a test that uses fluorescent dyes to identify chromosome changes not visible under a microscope
  • Polymerase chain reaction (PCR): a test that identifies specific DNA changes

The process of diagnosing lymphoma is typically different for each person. The tests you’ll need depend on the type of lymphoma the doctor is testing for.

A lymph node biopsy is the main method of diagnosing both non-Hodgkin’s and Hodgkin’s lymphoma, including diffuse large B-cell lymphoma, which is the most common form of non-Hodgkin’s lymphoma.

Some subtypes of lymphoma require specialized tests:

  • Central nervous system lymphoma: Diagnosis usually involves a lumbar puncture (also known as a spinal tap), which checks for lymphoma cells in the cerebrospinal fluid.
  • Primary gastric lymphoma (PGL): To diagnose PGL, doctors use an upper endoscopy to collect biopsy samples from your upper digestive tract. This procedure is often combined with an endoscopic ultrasound, which takes pictures of organs and lymph nodes deep inside your body.
  • Skin lymphoma: Diagnosing skin lymphoma (also called cutaneous lymphoma) requires a skin biopsy.
  • Bone marrow lymphoma: If lymphoma starts in or spreads to your bone marrow, you’ll need a bone marrow biopsy.

You might need additional tests to determine the stage of the lymphoma.

After diagnosis, your doctor can create an appropriate treatment plan. The right treatment for you will depend on many factors, including:

Options include:

  • Active monitoring: Also known as “watch and wait,” this approach includes regular checkups without medical treatment. A doctor may recommend this for slow-growing forms of non-Hodgkin’s lymphoma.
  • Chemotherapy: Chemotherapy drugs destroy cancer cells. You might take them orally (by mouth) or receive them as injections into a vein.
  • Radiation therapy: Radiation therapy uses powerful beams of energy to reduce the size and spread of cancer cells.
  • Biologic drug therapy: This treatment helps your immune system target and kill cancer cells.
  • Bone marrow transplant: If non-Hodgkin’s lymphoma is affecting your bone marrow, you might need a bone marrow transplant. This is an infusion of healthy bone marrow stem cells from your body or a donor. A doctor will usually recommend this only for people who are experiencing a relapse of lymphoma.
  • Chimeric antigen receptor T cells (CAR-T cells): Doctors treat some cases of relapsed or refractory lymphoma with CAR-T cells. This is a special treatment that trains your immune system to attack lymphoma cells.

The earlier you consult a doctor and receive a non-Hodgkin’s lymphoma diagnosis, the more effective treatment is likely to be.

Generally, a lymphoma diagnosis requires a lymph node biopsy. During this test, a doctor removes a sample of your lymph node and checks it for cancer cells. You might also need blood tests and imaging tests.

Though diagnosing lymphoma takes time, it’s an important process. The official diagnosis will allow your doctor to create the best treatment plan for your needs.