Diagnosis of non-Hodgkin lymphoma

Diagnosing non-Hodgkin lymphoma (NHL) usually begins with a visit to your family doctor. Your doctor will ask you about any symptoms you have and may do a physical exam. Based on this information, your doctor may refer you to a specialist or order tests to check for NHL or other health problems.

The process of diagnosis may seem long and frustrating. It’s normal to worry, but try to remember that other health conditions can cause similar symptoms to NHL. It’s important for the healthcare team to rule out other reasons for a health problem before making a diagnosis of NHL.

The following tests are commonly used to rule out or diagnose NHL. Many of the same tests used to diagnose cancer are used to find out the stage, which is how far the cancer has progressed. Your doctor may also order other tests to check your general health and to help plan your treatment.

Health history and physical exam

Your health history is a record of your symptoms, risk factors and all the medical events and problems you have had in the past. In taking a health history, your doctor will ask questions about a personal history of:

  • symptoms that suggest NHL
  • medicines or conditions that may weaken your immune system
  • immunosuppressant drugs after an organ transplant
  • immunodeficiency disorders
  • autoimmune disorders
  • recent infections
  • previous cancer treatment
  • exposure to pesticides

Your doctor may also ask about a family history of NHL.

A physical exam allows your doctor to look for any signs of NHL. During a physical exam, your doctor may:

  • feel for any lymph nodes in the neck, armpit and groin that are larger than normal, or enlarged
  • feel the abdomen to check for a larger than normal liver or spleen
  • listen to the lungs
  • check for signs of infection

Find out more about a physical exam.


During a biopsy, the doctor removes tissues or cells from the body so they can be tested in a pathology lab. The report from the lab will confirm the diagnosis and the type of NHL.

The type of biopsy that doctors do depends on where they find enlarged lymph nodes. They may remove all or part of a lymph node in the neck, armpit or groin. They may also take a sample from a lymph node in the chest or abdomen. They may use a CT scan to guide them during a lymph node biopsy in these areas.

NHL can develop in organs or tissues outside the lymph nodes (called extranodal sites), including the brain, breast, skin, stomach, liver and intestine. Doctors may do biopsies to find out if NHL or another type of cancer is in these organs or tissues. Sometimes doctors may biopsy these organs and tissues to stage the NHL.

Surgical biopsy

There are 2 types of surgical biopsy:

Excisional biopsy removes all of a lymph node or lump, along with an area of tissue around it.

Incisional biopsy removes a sample of tissue from a lymph node or other part of the body.

Find out more about a surgical biopsy.

Core biopsy

A core biopsy uses a hollow needle to remove a sample from a lymph node or another part of the body.

Find out more about a core biopsy.

Bone marrow aspiration and biopsy

During a bone marrow aspiration and biopsy, the doctor removes cells from the bone marrow so they can be tested in a lab.

Doctors may use bone marrow aspiration and biopsy to diagnose NHL. But it is most useful in staging NHL because it can spread to the bone marrow. The report from the lab will confirm whether or not there are lymphoma cells in the sample.

Find out more about a bone marrow aspiration and biopsy.

Lumbar puncture

A lumbar puncture (also called a spinal tap) removes a small amount of cerebrospinal fluid (CSF) from the space around the spine for examination under a microscope. The sample of CSF will show if NHL is in the brain and spinal cord (called the central nervous system, or CNS). It is used to:

  • help diagnose primary CNS lymphoma
  • find out if NHL that started somewhere else in the body has spread to the CSF or brain

Find out more about a lumbar puncture.

Cell and tissue studies

Cytogenetics is the analysis of a cell’s chromosomes, including the number, size, shape and arrangement of the chromosomes. Cytogenetic techniques show chromosomal abnormalities, which help doctors confirm the diagnosis and identify the type of NHL. The results of cytogenetic studies also help doctors plan treatment and predict how well the treatment will work.

Some major chromosomal abnormalities can be found by looking at cells under a microscope. But most changes in DNA need a closer analysis through other molecular techniques.

Fluorescence in situ hybridization (FISH)

Fluorescence in situ hybridization (FISH) is a molecular genetic test used to identify chromosomal abnormalities and other genetic changes in the lymphoma cells. It uses special DNA probes labelled with fluorescent dyes. FISH is used to diagnose genetic abnormalities in the different types of NHL, which can help doctors plan treatments.

Polymerase chain reaction (PCR)

Polymerase chain reaction (PCR) is used to make many copies of a particular gene segment so that it can be tested in the lab. Doctors use PCR to find gene changes and some chromosome changes that are too small to be seen with a microscope. It can help them diagnose and determine a prognosis for a specific type of NHL.


Immunophenotyping is the study of proteins expressed by cells. It is used to determine the type of NHL.

Immunophenotyping uses a very specific antigen-antibody reaction to identify proteins in tissues or cells. It uses monoclonal antibodies marked with a fluorescent label or specific enzyme label that binds only to specific antigens (proteins). The fluorescent or enzyme label allows doctors to see the lymphoma cells.

The following are the 2 most common methods used in immunophenotyping.

Immunohistochemistry uses a microscope to view the fluorescent labels. It also allows doctors to examine cells and what is around them.

Flow cytometry allows doctors to sort and classify cells using fluorescent labels on their surface. Doctors can view many antibodies at the same time. The cells are exposed to a laser, which makes them give off a light that is measured and analyzed by a computer. It allows data to be collected rapidly from thousands of cells in a single sample.

Flow cytometry helps doctors identify unique features of lymphoma cells. These features can help doctors form a prognosis and measure response to treatment by looking at minimal residual disease (MRD). MRD means that there are lymphoma cells in the bone marrow that can’t be found using standard lab tests.

Find out more about cell and tissue studies.

Complete blood count (CBC)

A CBC measures the number and quality of white blood cells, red blood cells and platelets. A CBC is done to:

  • help rule out infection
  • assess how well the blood-forming organs (such as the bone marrow or spleen) are working
  • see if lymphoma cells have spread to the blood
  • provide a baseline for future blood counts taken during and after treatment

Find out more about complete blood count (CBC).

Blood chemistry tests

Blood chemistry tests measure certain chemicals in the blood. They show how well certain organs are functioning and can help find abnormalities. Blood chemistry tests help stage NHL and includes the following:

Lactate dehydrogenase (LDH) that is higher than normal may mean that NHL has spread to the liver. LDH will often be higher in people who have an aggressive, or fast-growing, type of NHL.

Alanine aminotransferase (ALT) and aspartate transaminase (AST) that are higher than normal may mean that NHL has spread to the liver.

Alkaline phosphatase that is higher than normal may mean that NHL has spread to the bones or the liver.

Find out more about blood chemistry tests.

Other blood tests

You may be tested for HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) if you are diagnosed with a certain type of NHL or if certain treatments may be given. Infection with these viruses may affect your treatment.

Chest x-ray

An x-ray uses small doses of radiation to make an image of the body’s structures on film. A chest x-ray is used to check for enlarged lymph nodes in the chest and to see if NHL has spread to the lungs.

Find out more about x-ray.

CT scan

A computed tomography (CT) scan uses special x-ray equipment to make 3-D and cross-sectional images of organs, tissues, bones and blood vessels inside the body. A computer turns the images into detailed pictures.

A CT scan is used:

  • to assess enlarged lymph nodes
  • to examine organs in the chest, abdomen, pelvis and other areas of the body
  • to monitor response to treatment as part of follow-up care

Find out more about CT scan.


Magnetic resonance imaging (MRI) uses powerful magnetic forces and radio-frequency waves to make cross-sectional images of organs, tissues, bones and blood vessels. A computer turns the images into 3-D pictures.

MRI is used to check if NHL has spread to the brain and spinal cord. Doctors also use MRI to rule out or diagnose primary CNS lymphoma.

Find out more about MRI.


Ultrasound uses high-frequency sound waves to make images of structures in the body. It is used to:

  • check if the liver or spleen is swollen or for signs of NHL in these organs
  • check the testicles for NHL
  • help doctors collect tissue during a biopsy

Find out more about ultrasound.

Bone scan

A bone scan uses bone-seeking radioactive materials (called radiopharmaceuticals) and a computer to create a picture of the bones. It is used to see if the NHL has spread to the bones when someone has bone pain or when the level of alkaline phosphatase in the blood is higher than normal.

Find out more about bone scan.

PET scan

A positron emission tomography (PET) scan uses radioactive materials (called radiopharmaceuticals) to look for changes in the metabolic activity of body tissues. A computer analyzes the radioactive patterns and makes 3-D colour images of the area being scanned.

Doctors are still trying to find out how a PET scan can best be used to help diagnose and stage NHL. It may be used to:

  • identify areas affected by NHL
  • help monitor response to treatment and find recurrences

PET scans are not available in all treatment centres. Find out more about PET scan.

Questions to ask your healthcare team

To make the decisions that are right for you, ask your healthcare team questions about diagnosis.

Expert review and references

  • American Cancer Society. Non-Hodgkin Lymphoma. 2014: http://www.cancer.org/acs/groups/cid/documents/webcontent/003126-pdf.pdf.
  • American Society of Clinical Oncology . Lymphoma Non-Hodgkin Overview . 2014 : https://www.cancer.net/.
  • BC Cancer Agency (BCCA). Non-Hodgkin Lymphoma. 2014: http://www.bccancer.bc.ca/.
  • Faber EA, Vose JM, Armitage JO, Bierman PJ . Diagnosis and treatment of non-Hodgkin's lymphoma of adults. Wiernik PH, Goldman JM, Dutcher JP, Kyle RA (eds.). Neoplastic Diseases of the Blood. 5th ed. Springer; 2013: 47: 1027-1047.
  • Freedman AS, Jacobson CA, Mauch P, Aster JC . Non-Hodgkin lymphoma. DeVita VT Jr, Lawrence TS, & Rosenberg SA. Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2015: 103:1552-1583.
  • Manson SD & Porter C . Lymphomas. Yarbro, CH, Wujcki D, & Holmes Gobel B (eds.). Cancer Nursing: Principles and Practice. 7th ed. Sudbury, MA: Jones and Bartlett; 2011: 60: pp. 1458-1512.