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 if cancer forms in the lymphatic system. The two main types include:
- Hodgkin’s lymphoma. People with Hodgkin’s lymphoma have large cancer cells called Reed-Sternberg (RS) cells.
- Non-Hodgkin’s lymphoma. In non-Hodgkin’s lymphoma, RS cells aren’t present. This type is more common.
Between these two categories, there are more than 70 subtypes. 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 condition that requires medical attention. Your overall outlook depends on early 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 like blood panels, biopsies, and more.
We explain how your doctor would diagnose non-Hodgkin’s lymphoma, including a breakdown of tests.
A doctor will use multiple procedures to diagnose non-Hodgkin’s lymphoma. The exact combination of tests will depend on your symptoms and overall health.
When you first see the doctor, they’ll perform a physical exam. This helps them analyze your symptoms, which provides a baseline for your diagnosis.
During a physical exam, a doctor will:
- look for swollen lymph nodes in the neck, groin, and underarms
- check for swelling in the spleen and liver
- ask about your medical history
- examine any other physical symptoms
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 specialist takes a sample of a lymph node. The sample is 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.
Types of lymph node biopsies include:
- excisional biopsy, which removes an entire lymph node
- incisional biopsy, which removes part of a lymph node
- core needle biopsy, which only removes a small lymph node sample
- laparoscopic biopsy, which uses small instruments to remove a sample from deep within your body
The best option depends on your overall health and where the affected lymph nodes are located. It may take multiple biopsies to accurately diagnose non-Hodgkin’s lymphoma.
After the physical exam, the doctor will likely order a blood test. This looks for specific markers in your blood that might indicate lymphoma. It also helps your doctor rule out other possible causes of your symptoms.
A typical blood panel includes the following tests:
Complete blood count (CBC)
CBC measures certain parts of your blood, including:
- Red blood cells, which transport oxygen throughout the body. If lymphoma disrupts red blood cell production in the bone marrow, you may have a low red blood cell count, or anemia.
- White blood cells, which fight infection. A low white blood cell count can occur due to lymphoma or other conditions, like an autoimmune disorder. Lymphoma sometimes shows in the blood as an abnormally high white blood cell count.
- Platelets, which are cells that clot the blood. Lymphoma in the 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 might help them diagnose advanced lymphoma. The condition can decrease levels of albumin, a protein produced by the liver.
Lactic dehydrogenase (LDH)
Your blood panel might include LDH, an enzyme in most of your tissues. Some forms of lymphoma increase LDH production.
However, since high levels can occur due to other diseases, you’ll need other tests to help with the diagnosis.
C-reactive protein (CRP)
During the inflammatory response, the body produces C-reactive protein. High levels in the blood may be a sign of cancer, including lymphoma, but could also be due to other sources of inflammation.
A lymphoma diagnosis often includes imaging tests. These tests allow your doctor to:
- locate enlarged lymph nodes
- check if lymphoma has affected other organs
- look for tumors
- staging lymphoma
A doctor might use the following tests:
- Ultrasound. During an ultrasound, sound waves bounce off tissues and organs to create an image. Your doctor may use an ultrasound to examine swollen areas or find the best location for a biopsy.
- X-ray. An X-ray uses radiation to take detailed images of the inside of your body.
- Computed tomography (CT) scan. In a CT scan, a radiographer uses narrow X-rays to create detailed 3D pictures. Compared to X-rays, CT scans take clearer images of swollen lymph nodes.
- Positron emission tomography (PET). Before a PET scan, a doctor will inject you with a radioactive form of sugar, which cancer cells absorb. These cells appear on the scan.
- Magnetic resonance imaging (MRI). If your doctor thinks you have lymphoma of the central nervous system, they’ll order an MRI.
Bone marrow biopsy
Bone marrow is the soft, spongy tissue inside most of our bones. It makes important blood cells, including red blood cells and platelets.
Lymphoma can start in your bone marrow. If your doctor thinks this is the source of your lymphoma, you might need a bone marrow biopsy. In this test, a healthcare professional removes a small sample of bone marrow for lymphoma cells.
A bone marrow biopsy isn’t necessary for all people with a lymphoma diagnosis. Your doctor will decide if you need one.
Immunophenotyping is a lab test that checks the affected cells for specific markers, called clusters of differentiation (CD). There are different methods for achieving this.
In this test, the doctor uses antibodies to check a tissue sample for specific proteins. The antibodies stick to the proteins, which activates an enzyme or fluorescent dye. This shows up under a microscope, which allows a specialist to determine the type of lymphoma cells.
Flow cytometry uses fluorescent antibodies to stain blood cells. A healthcare professional will place the blood or tissue in a flow cytometer, which evaluates:
- number and percentage of cells
- cell size and shape
- specific markers on the cell surface
Your doctor can use the results to diagnose lymphoma.
Chromosomes consist of DNA strands. In some people, the lymphoma cells may have altered chromosomes.
To find these anomalies, a doctor might request chromosome tests, including:
- cytogenetic analysis, which looks for chromosome abnormalities using a microscope
- fluorescence in situ hybridization (FISH), which uses fluorescent dyes to identify chromosome changes not visible under a microscope
- polymerase chain reaction (PCR), which identifies specific DNA alterations
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 you for.
The main way to diagnose both non-Hodgkin’s and Hodgkin’s lymphoma involves a lymph node biopsy. This includes diffuse large B-cell lymphoma, 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 or “spinal tap.” This test checks for lymphoma calls in the cerebrospinal fluid.
- Primary gastric lymphoma (PGL). To diagnose PGL, an upper endoscopy is used to collect biopsy samples from your upper digestive tract. It’s often combined with an endoscopic ultrasound, which takes pictures of organs and lymph nodes deep inside the body.
- Skin lymphoma. Also called cutaneous lymphoma, skin lymphoma diagnosis requires a skin biopsy.
- Bone marrow lymphoma. If lymphoma starts or spreads in the bone marrow, you’ll need a bone marrow biopsy.
You might also need additional tests to determine the stage of your lymphoma.
After diagnosis, your doctor can create an appropriate treatment plan. This depends on many factors, including:
- type and stage of lymphoma
- your symptoms
- your overall health
- your preferences
- Active monitoring. Also known as “watch and wait,” this approach includes regular check-ups without medical treatment. A doctor may recommend this for slow-growing forms of non-Hodgkin’s lymphoma.
- Chemotherapy. Chemotherapy drugs destroy cancer cells. They are taken orally or injected into a vein.
- Radiation therapy. In radiation therapy, powerful beams of energy 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 only recommend this for people whose lymphoma has relapsed.
- Chimeric antigen receptor T cells (CAR-T). Doctors treat some relapsed or refractory cases of lymphoma with CAR-T cells. This is a special treatment that trains your immune system to attack lymphoma cells.
The earlier you see a doctor about 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 may 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.