Non-Hodgkin lymphoma (NHL) diagnosis

An accurate diagnosis is one of the most important aspects of a person’s care. A precise diagnosis will help the doctor to estimate the rate of disease progression and determine the appropriate treatment. 

The information on this page covers how Hodgkin lymphoma is diagnosed in adults. Visit Childhood Non-Hodgkin Lymphoma to learn about signs and symptoms, diagnosis, and treatment information for children with Hodgkin lymphoma. 

Tests your doctor may use to diagnose NHL 

The following are some of the tests a doctor may use to diagnose NHL:

Physical evaluation 

The doctor will take a comprehensive medical history and ask questions regarding either the absence or the presence of B symptoms (fever, drenching night sweats, and loss of more than 10 percent of body weight over 6 months). B symptoms are important to the prognosis and staging of the disease. Your physical examination will include measuring all accessible lymph node groups and the size of organs such as the spleen and liver. 

Lymph node biopsy 

Doctors do a test called a lymph node biopsy to confirm an NHL diagnosis and the subtype.  

A surgeon will remove either a part (an incisional biopsy) or all (an excisional biopsy) of an enlarged lymph node using a special needle. The patient is usually given a local anesthetic to numb the area for the procedure. 

The lymph node is examined by a doctor (hematopathologist) who identifies diseases of the blood and marrow by studying cells and tissues under a microscope.  

The doctor may look at the cells from the biopsy to see if there are changes in the chromosomes of the NHL cells. (Each cell in the body has chromosomes that carry genes. Genes give instructions that tell each cell what to do.) This information is important so that the doctor can identify the specific subtype and the most effective treatment.  

NHL can develop in parts of the body that do not involve lymph nodes, such as the lung or bone. When lymphoma is detected exclusively outside of the lymph nodes, it is called “primary extranodal lymphoma,” and the biopsy sample is taken from that involved tissue. 

Biomarker tests 

A biomarker test uses a sample of tissue, blood or other body fluid to check for certain genes, proteins or other molecules that may be a sign of disease. These tests include the following: 

• Immunophenotyping
• Flow cytometry
• Flourescence in situ hybridization (FISH) 

Learn more about these diagnostic tests.

Getting a second opinion 

NHL is a difficult disease to diagnose; therefore, you may want to get a second opinion by an experienced hematopathologist before you begin treatment. Some types of NHL can be confused with one another. The appropriate treatment will be determined by a correct diagnosis. 

NHL staging  

Once your doctor confirms an NHL diagnosis, they will determine the extent of your disease's progression by staging. Staging helps your doctor predict the disease's progression and develop a treatment plan. 

Staging tests 

Imaging tests  

Your doctor will use imaging tests, a physical exam, and labs to check the following: 

• The number of lymph nodes that are affected
• Where the affected lymph nodes are located (for example, the abdomen or chest or both places)
• Whether organs other than the lymph nodes are involved
• Imaging tests include the following:
• Chest X-rays
• CT (computed tomography) scan
• Magnetic resonance imaging (MRI)
• Positron emission tomography-computed tomography (PET-CT) scans, two tests done at the same time 

 Learn more about lab and imaging tests.

Blood tests 

Blood tests are used to determine whether lymphoma cells are present in the blood; check red blood cell, white blood cell and platelet counts; check kidney and liver functions; and measure important biological markers for certain NHL subtypes.  

Learn more about blood tests and urinalysis. 

Bone marrow biopsy 

Bone marrow aspiration and bone marrow biopsy look for NHL cells in the bone marrow. Bone marrow aspiration and bone marrow biopsy are two tests that may be done in the doctor’s office or in a hospital. These tests are often done at the same time. 

A bone marrow aspiration removes a certain amount of fluid from the bone marrow.  

A bone marrow biopsy is done with a slightly larger needle and removes a portion of solid bone that has marrow inside it. 

Some patients are awake for this procedure. Medication may be used to numb the body area where the procedure will take place. This is usually the area in the back of the pelvic bone. Some patients are given a drug and are sedated (asleep) for the procedure.   

Learn more about bone marrow tests. 

View the interactive 3D model to help you visualize and better understand the procedure. Click the "Interact in 3D" button to begin. 

View all 3D models.

Heart tests 

Some cancer treatments can damage the heart, so members of the treatment team may want to determine how well a patient’s heart functions before starting a specific treatment. Heart tests include the following: 

• An echocardiogram: This is an imaging test that uses ultrasound technology to create a picture of the heart
• A multigated acquisition (MUGA) scan: This scan measures how well the heart pumps blood. A radiotracer substance is injected into a vein. Pictures of the heart are taken with a special camera that detects the radiation released by the tracer.   

NHL stages 

Keep in mind that NHL the staging classification does not have the same implications as it does for many other types of cancer. NHL does not necessarily start at Stage I and then progress to Stage II, and so forth. It also does not reflect how well or poorly someone will respond to treatment. In lymphoma, the stage identifies the specific location of the disease. A disease diagnosed as Stage IV NHL may be highly treatable, depending on the specific subtype.

NHL subtypes 

There are many NHL subtypes. Remember that there are three types of lymphocytes: B cells, T cells and NK cells. Most people with NHL have a B-cell NHL (85% to 90%). It's important to know your subtype, as it plays a large part in determining the type of treatment you'll receive. A hematopathologist should review your biopsy samples. 

NHL is classified by how fast it grows: 

• Slow-growing NHL is called indolent or low-grade NHL
• Fast-growing NHL is called aggressive or high-grade NHL 

The treatments for aggressive and indolent lymphomas are different. Some cases of indolent NHL can transform into aggressive NHL.

Non-Hodgkin lymphoma (NHL) subtypes  

This list provides some of the diagnostic designations for NHL subtypes based on the World Health Organization (WHO) classification, categorized by cell type (B cell, T cell, or NK cell) and rate of progression (aggressive or indolent). The percentages listed reflect the frequency of diagnosed cases of the most common NHL subtypes. To read more about these subtypes, access our Non-Hodgkin Lymphoma booklet. 

Mature B-cell lymphomas (about 85%–90% of NHL cases) 

Aggressive 

• Diffuse large B-cell lymphoma (DLBCL) (30%)
• Mantle cell lymphoma (MCL) (3%)—has features of both indolent and aggressive NHL
• Lymphoblastic lymphoma (2%)
• Burkitt lymphoma (BL) (2%)
• Primary mediastinal (thymic) large B-cell lymphoma (PMBCL)
• Transformed follicular and transformed mucosa-associated lymphoid tissue (MALT) lymphomas
• High-grade B-cell lymphoma with double or triple hits (HBL)
• Primary cutaneous DLBCL, leg type
• Primary DLBCL of the central nervous system
• Primary central nervous system (CNS) lymphoma
• Acquired immunodeficiency syndrome (AIDS)-associated lymphoma 

Indolent 

• Follicular lymphoma (FL) (22%)
• Marginal zone lymphoma (MZL) (7%)
• Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (7%)
• Gastric mucosa-associated lymphoid tissue (MALT) lymphoma (8%)
• Lymphoplasmacytic lymphoma (1%)
• Waldenström macroglobulinemia (WM)
• Nodal marginal zone lymphoma (NMZL) (1%)
• Splenic marginal zone lymphoma (SMZL) 

Mature T-cell and natural killer (NK)-cell lymphomas (about 10%–15% of NHL cases) 

Systemic 

• Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) (6%)
• Systemic anaplastic large-cell lymphoma (ALCL) (2%)
• Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL)
• Lymphoblastic lymphoma (2%)
• Hepatosplenic T-cell lymphoma
• Enteropathy-associated intestinal T-cell lymphoma
• Monomorphic epitheliotropic intestinal T-cell lymphoma
• Angioimmunoblastic T-cell lymphoma (AITL)
• Adult T-cell leukemia/lymphoma
• Extranodal natural killer (NK)/T-cell lymphoma (ENK/TCL), nasal type 

Primary cutaneous 

• Cutaneous T-cell lymphoma (CTCL) (4%)
• Mycosis fungoides (MF)
• Sézary syndrome (SS)
• Primary cutaneous anaplastic large-cell lymphoma (pcALCL)
• Subcutaneous panniculitis-like T-cell lymphoma (SPTCL)
• Primary cutaneous gamma delta T-cell lymphoma