Diagnosis of non-Hodgkin lymphoma

Diagnosis is the process of finding out the cause of a health problem. Diagnosing cancer often means first ruling out other health conditions that share similar symptoms with cancer. It can be a very worrying time for you and your loved ones. Sometimes this process is quick. Sometimes it can feel long and frustrating. But it's important for doctors to get all the information they need before making a diagnosis of cancer.

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 following tests are usually used to rule out or diagnose NHL. Many of the tests that are used to diagnose cancer are also used to find out the stage (how far the cancer has spread). Your doctor may also order other tests to check your general health and to help plan your treatment.

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

• symptoms that suggest NHL
• medicines that may weaken your immune system, such as immunosuppressant drugs taken after an organ transplant
• HIV/AIDS
• 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 (enlarged)
• feel the abdomen to check for a larger than normal liver or spleen
• listen to the lungs
• check for signs of infection
• check the skin for abnormal areas

Find out more about physical exams.

A complete blood count (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
• provide a baseline for future blood counts taken during and after treatment
• see if lymphoma cells are in the blood

Find out more about a complete blood count (CBC).

Blood chemistry tests measure certain chemicals in the blood. They show how well certain organs are working and can help find problems. Blood chemistry tests used to diagnose and stage NHL include the following.

Lactate dehydrogenase (LDH) can be used to measure how well the liver is working, but also shows cell damage. LDH levels can be higher than normal when NHL has spread to the liver or if you have an aggressive, or fast-growing, type of NHL.

Alanine aminotransferase (ALT) and aspartate transaminase (AST) may be measured to check how well the liver is working. Higher than normal levels of ALT or AST may mean that NHL has spread to the liver.

Alkaline phosphatase may be measured to check how well the liver is working and to check the bones. A higher than normal level of this enzyme may mean that NHL has spread to the bones or the liver.

Find out more about blood chemistry tests.

Blood tests for hepatitis B and hepatitis C may be done because having either virus can affect how treatments work. Certain chemotherapy drugs could cause problems if you have these infections. If you have hepatitis B or hepatitis C, your healthcare team can make changes to your treatment plan to make it safer.

An HIV test may be done if doctors think that NHL is related to an HIV (human immunodeficiency virus) infection. An HIV test is a blood test that measures the level of HIV antibodies in the blood. A high level of these antibodies means the body is infected with HIV.

A human T-cell leukemia/lymphoma virus type 1 (HTLV-1) test may be done if doctors think that NHL is related to an HTLV-1 infection. An HTLV test is a blood test that measures the level of HTLV-1 antibodies in the blood. A high level of these antibodies means the body is infected with HTLV-1.

An x-ray uses small doses of radiation to make an image of parts of the body on film. A chest x-ray is used to check for larger than normal lymph nodes in the chest. It is also used to see if NHL has spread to the lungs.

Find out more about x-rays.

An ultrasound uses high-frequency sound waves to make images of parts of the body. It may be used to examine the abdomen and organs that may be affected by NHL, such as the liver, spleen or testicles. It may also be used to help doctors collect tissue during a biopsy.

Find out more about ultrasound.

A computed tomography (CT) scan uses special x-ray equipment to make 3D 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 may be used to check for enlarged lymph nodes or a mass in the neck, chest, abdomen or pelvis. It also allows doctors to see if a tumour is pressing on any organs or large blood vessels, or if there is any disease in the brain or near the spinal cord. A CT scan may also be used to see if the cancer has spread to any organs, such as the lungs, liver or spleen.

Usually a CT scan is combined with a PET scan (called a PET-CT scan) to find more information about the cancer.

Find out more about CT scans.

During a biopsy, the doctor removes tissues or cells from the body so they can be tested in a lab. A report from a pathologist will show whether or not cancer cells are found in the sample.

A biopsy may be done on an enlarged lymph node in the neck, under the arm or in the groin. A biopsy sample may also be taken from a tumour in the chest or abdomen. Doctors 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 NHL.

The type of biopsy done depends on where doctors need to collect the samples.

A surgical lymph node biopsy is usually done to collect samples from lymph nodes. The surgeon may do an excisional biopsy, which removes all of a lymph node. In some cases, doctors may use an incisional biopsy to remove part of a lymph node.

A core needle biopsy may be used for some types of tumours, such as a large tumour in the chest or a tumour in the bone. The surgeon may use a CT scan to guide the needle to the tumour during the biopsy.

Find out more about a surgical biopsies and core needle biopsies.

A skin biopsy may be used to diagnose lymphoma involving the skin. The type of biopsy used often depends on what the growth looks like and its size.

A skin lesion biopsy is a type of surgical biopsy that removes an abnormal area of the skin using a scalpel (knife). When part of the abnormal area is removed, it is called an incisional biopsy. If all of the abnormal area is removed, it is called an excisional biopsy.

A punch biopsy removes a round part of a growth using a sharp tool called a punch. With a punch biopsy, the doctor tries to remove most of the abnormal area of skin including part of the edge. Sometimes the entire growth can be removed.

A shave biopsy shaves off a growth on the skin using a flexible razor blade or a scalpel.

Find out more about excisional biopsies (surgical biopsies), punch biopsies and shave biopsies.

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

A PET scan may be used to look for NHL that has spread from where it started to other areas of the body or to measure how well treatment is working. It is typically combined with a CT scan for a more complete picture and 3D assessment of the disease.

Find out more about PET scans.

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 3D pictures.

An MRI can be used to check for enlarged lymph nodes in the chest, abdomen or pelvis. It can also be used to see if cancer has spread to the brain or spinal cord. Doctors may also use an MRI to rule out or diagnose a type of NHL that starts in the brain or spinal cord, which is called primary central nervous system (CNS) lymphoma.

Find out more about MRIs.

During a bone marrow aspiration and biopsy, the doctor removes cells from the bone marrow so they can be tested in a lab. This test may be used to diagnose and stage NHL that has spread to the bone marrow.

Find out more about a bone marrow aspiration and biopsy.

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). A lumbar puncture 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.

Doctors sometime examine fluid from inside the chest (called pleural fluid) or fluid from inside the abdomen (called peritoneal fluid). They collect the fluid by passing a needle through the skin into the chest or abdomen. The fluid is then looked at under a microscope to check for cancer cells.

A thoracentesis is done to remove fluid from the chest. A paracentesis is used to remove fluid from the abdomen. Find out more about a thoracentesis and a paracentesis.

Doctors can use the following types of cell and tissue studies to diagnose NHL.

Cytogenetics is the analysis of a cell's chromosomes, including their number, size, shape and arrangement. Cytogenetic techniques show chromosomal abnormalities, which help doctors confirm the diagnosis and identify the type or subtype 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 can only be found with a closer analysis using molecular techniques, including the following.

Fluorescence in situ hybridization (FISH) uses fluorescent dyes linked to pieces of DNA that only attach to specific parts of certain chromosomes. It is used to identify specific chromosomal abnormalities and other genetic changes in the lymphoma cells.

Polymerase chain reaction (PCR) is a method used to make many copies of a particular gene segment so that it can be tested in the lab.

Immunophenotyping is the study of proteins expressed by cells. It uses a very specific antigen-antibody reaction to identify proteins in tissues or cells. It uses antibodies marked with a fluorescent label that bind only to specific proteins. The fluorescent label and the pattern of proteins that are expressed allow doctors to identify the lymphoma cells so that they can diagnose the specific type or subtype of NHL.

The following methods are the most commonly used in immunophenotyping.

Immunohistochemistry uses a microscope to view the fluorescent labels. It also allows doctors to look at cells and their surroundings.

Flow cytometry is a technique used to sort and classify cells by the proteins on their surfaces. The cells are labelled with fluorescent tracers and then can be sorted to look at many different proteins at the same time. The cells are exposed to a laser, which makes them give off a light. A computer measures and analyzes the light. This allows the computer to quickly collect data from thousands of cells in a single sample.

Find out more about cell and tissue studies.

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. This test is not needed for all types of lymphoma and may not be needed if a PET scan is used.

Find out more about bone scans.

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