Tests for Lymphoma of the Skin

Medical history and physical exam

When a doctor takes your medical history, you will be asked about your symptoms, possible risk factors, family history, and other medical conditions. The doctor will ask when you first noticed the changes in your skin, if they have changed in size or appearance, and if they are itchy or painful. You may be asked if you have any other symptoms, like fever or weight loss. Because skin lymphomas can be hard to tell apart from allergies and other causes of rashes, you might also be asked if you have any allergies or have recently been exposed to something that could be causing your skin problems, such as a new medicine or a new laundry detergent or any new creams or lotions.

During the physical exam, your doctor will note the size, shape, color, and texture of any area(s) of skin in question. Your body will be checked all over for any other abnormal areas on your skin.

The doctor might also feel the lymph nodes (small, bean-sized collections of immune cells) under the skin in your neck, underarms, or groin, as lymphomas can sometimes cause lymph nodes to become enlarged.

If you are being seen by your primary doctor, you may be referred to a dermatologist (a doctor who treats skin diseases), who will look at your skin more closely.

Skin biopsies

A biopsy is a procedure in which a doctor removes a sample of body tissue for viewing under a microscope or other lab tests. A biopsy is needed to diagnose lymphoma of the skin.

There are several types of skin biopsies, and the doctor’s choice of which one to use is based on each person’s situation. Usually a skin biopsy is done by a dermatologist.

Punch biopsy

For a punch biopsy, the doctor uses a tool that looks like a tiny round cookie cutter. Once the skin is numbed with a local anesthetic, the doctor rotates the punch biopsy tool on the skin until it cuts through all the layers. The piece of skin is then removed. Often the biopsy site is closed with a stitch.

Incisional and excisional skin biopsies

For these types of biopsies, a surgical knife is used to cut through the full thickness of skin (usually in the shape of an ellipse, or oval).

• An incisional biopsy removes only part of the tumor
• An excisional biopsy removes the entire tumor

The piece of skin is removed for testing, and the edges of the cut are sewn together. These biopsies are usually done using a local anesthetic (numbing medicine).

Regardless of the type of skin biopsy, once the samples are removed, they are sent to a doctor called a pathologist, who will look at them with a microscope and might do other tests on them (see below).

Many of the more common forms of skin cancer (and other skin diseases) can be diagnosed just by looking at the biopsy samples. But diagnosing and classifying lymphomas of the skin often requires one or more special lab tests.

Diagnosing some forms of skin lymphoma can be very challenging. Sometimes, especially if the diagnosis is unclear, the skin samples may need to be sent to a dermatopathologist, a dermatologist or a pathologist with additional training in diagnosing skin samples. Even with this expertise, in some cases several biopsies may be need to be done in different areas of abnormal skin and/or at different times before the diagnosis is confirmed.

Lymph node biopsies

Skin lymphomas often spread to lymph nodes, so your doctor may recommend a lymph node biopsy to help confirm the diagnosis or to help determine how widespread the lymphoma is. This is more likely to be done if the doctor detects enlarged lymph nodes, either during a physical exam or with imaging tests (see below).

Excisional or incisional lymph node biopsies

These are the most common types of lymph node biopsy. In these procedures, a surgeon cuts through the skin to remove either the entire lymph node (excisional biopsy) or a small part of a large tumor (incisional biopsy). If the node is just under the skin, this can often be done with local anesthesia (numbing medicine). But if the node is inside the chest or abdomen, the person will need to be in a deep sleep (under general anesthesia) or deeply sedated during the biopsy.

Removing a lymph node almost always provides enough tissue to diagnose the exact type of lymphoma. Most doctors prefer this type of biopsy, if it can be done without too much discomfort to the patient.

Needle biopsy

For a needle biopsy, the doctor uses a thin, hollow needle to remove a small amount of tissue from a tumor. This can be done as a fine needle aspiration (FNA), which uses a very thin needle, or a core needle biopsy, which uses a slightly larger needle.

If an enlarged node is just under the skin, the doctor can aim the needle while feeling the node. If the enlarged node is deep inside the body, the doctor can guide the needle while viewing it with an imaging test such as an ultrasound or a CT scan (see below).

A needle biopsy does not require surgery, but in some cases this type of biopsy (especially an FNA) might not remove enough tissue to make a definite diagnosis of lymphoma. But advances in lab tests (discussed later in this section) and the growing experience of many doctors have improved the accuracy of this procedure.

Other types of biopsies

These procedures may sometimes be done to confirm a diagnosis of lymphoma, but they are more often done to help determine the stage (extent) of a lymphoma that has already been diagnosed. Not everyone with lymphoma of the skin needs these tests.

Bone marrow aspiration and biopsy

These tests are sometimes done after lymphoma has been diagnosed to help figure out if it has spread to the bone marrow (the soft, inner part of certain bones). The two tests are often done at the same time. The samples are usually taken from the back of the pelvic (hip) bone, but sometimes they may be taken from other bones.

In bone marrow aspiration, you lie on a table (either on your side or on your belly). The doctor cleans the skin over the hip and then numbs the area and the surface of the bone by injecting a local anesthetic. This may cause a brief stinging or burning sensation. A thin, hollow needle is then inserted into the bone, and a syringe is used to suck out a small amount of liquid bone marrow. Even with the anesthetic, most people still have some brief pain when the marrow is removed.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is pushed down into the bone. This may also cause some brief pain. Once the biopsy is done, pressure will be applied to the site to help stop any bleeding.

Lumbar puncture (spinal tap)

This test looks for lymphoma cells in the cerebrospinal fluid (CSF), which is the liquid that bathes the brain and spinal cord. Most people with skin lymphoma will not need this test. But doctors may order it if a person has symptoms that suggest the lymphoma might have reached the brain.

For this test, you may be asked to lie on your side or sit up. The doctor first numbs an area in the lower part of the back over the spine. A small, hollow needle is then inserted between the bones of the spine to withdraw some of the fluid.

Lab tests of biopsy or blood samples

Lab tests are done on the biopsy samples (and in some cases, blood samples) to help diagnose lymphoma and determine what type it is. Pathologists can sometimes tell which kind of lymphoma a person has by just looking at the cells under a microscope, but usually these other types of tests are needed to confirm the diagnosis.

Flow cytometry and immunohistochemistry

Cells from the biopsy samples are treated with special antibodies that stick to certain proteins on the cells. For immunohistochemistry, the cells are then looked at with a microscope to see if the antibodies stuck to them (meaning they have these proteins). A special machine (flow cytometer) is used to analyze the cells for a flow cytometry test.

These tests can help tell whether a lymph node is swollen because of lymphoma, some other cancer, or a non-cancerous disease. The tests can also be used for immunophenotyping – determining which type of lymphoma a person has, based on certain proteins in or on the cells. Different types of lymphoma cells have different proteins on their surface.

Chromosome and gene tests

Normal human cells have 23 pairs of chromosomes, which are long strands of DNA that contain our genes. Each chromosome is normally a certain size and looks a certain way . But in some types of lymphoma, the cells have changes in their chromosomes, such as having too many, too few, or abnormal chromosomes. These changes can often help identify the type of lymphoma.

Cytogenetics (karyotyping): Cells are looked at with a microscope to see if the chromosomes have any abnormalities. Getting the results usually takes about 2 to 3 weeks because the cells must grow in lab dishes for a couple of weeks before they can be looked at.

Fluorescent in situ hybridization (FISH): This test looks more closely at lymphoma cell DNA using special fluorescent dyes that only attach to specific genes or parts of chromosomes. FISH can find most chromosome changes that can be seen in standard cytogenetic tests, as well as some gene changes too small to be seen with cytogenetic testing. FISH is very accurate and can usually provide results within a couple of days.

Polymerase chain reaction (PCR): PCR is a very sensitive DNA test that can find gene changes and certain chromosome changes too small to be seen with a microscope, even if very few lymphoma cells are present in a sample.

Molecular tests: Some newer types of sensitive lab tests, which can find changes in the DNA, RNA, or proteins in cancer cells, might also be helpful in some situations.

To learn more about these tests, see Tests Used on Biopsy and Cytology Samples to Diagnose and Classify Cancer.

Blood tests

Blood tests measure the amounts of certain types of cells and chemicals in the blood. They are not used to diagnose lymphoma usually, but they can sometimes help determine how advanced the lymphoma is. They may also be used during certain types of treatment (such as chemotherapy) to monitor how well the bone marrow and other organs are functioning.

• Complete blood count (CBC): This test measures the levels of different cells in the blood, such as red blood cells, white blood cells, and platelets. The CBC is often done with a differential (“diff”), which counts the numbers of different types of white blood cells. If a person’s blood counts are low, it might mean that the lymphoma is growing in the bone marrow and slowing normal blood cell production. People with Sezary syndrome will have Sezary cells in the blood, which can be found on the differential. People getting chemo will have their blood counts checked regularly to see if the treatment is affecting their bone marrow.
• Blood chemistry tests: These tests look at how well organs such as the kidneys and liver are working. These tests are also done regularly in people getting chemo.
• If you have been diagnosed with lymphoma, blood levels of lactate dehydrogenase (LDH) may be checked. LDH levels are often abnormally high in people with widespread lymphoma.
• For some types of lymphoma or if certain treatments might be used, your doctor may also advise you to have tests to see if you’ve been infected with certain viruses, such as hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell lymphotropic virus (HTLV-1), or human immunodeficiency virus (HIV). Infections with these viruses might affect your treatment.

Imaging tests

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to make pictures of the inside of the body. In someone with known or suspected lymphoma, these tests might be done for a number of reasons, including:

• To help find suspicious areas that might be cancer
• To learn how far the lymphoma has spread
• To find out if treatment is working
• To look for possible signs of the lymphoma coming back after treatment

Imaging tests aren’t always needed for people with skin lymphomas who have only a few skin lesions, but they are often done if a lot of the skin is affected, or if lymphoma cells are found in the lymph nodes or blood.

To learn more about any of the imaging tests discussed here, see Imaging (Radiology) Tests.

Chest x-ray

An x-ray of the chest may be done to look for enlarged lymph nodes in this area.

Computed tomography (CT) scan

The CT scan uses x-rays to make detailed, cross-sectional images of your body. Unlike a regular x-ray, CT scans can show the detail in soft tissues (such as internal organs). This scan can help tell if any lymph nodes or organs in your body are enlarged.

CT-guided needle biopsy: A CT scan can also be used to guide a biopsy needle into a suspicious area. For this procedure, you lie on the CT scanning table while the doctor advances the needle through the skin and toward the area. The scans are repeated until the needle is in the right place. A biopsy sample is then removed and sent to the lab to be looked at under a microscope.

Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. MRI scans are very helpful in looking at the brain and spinal cord, but they are not often used to evaluate skin lymphomas unless a CT scan can’t be done for some reason.

Ultrasound

Ultrasound can be used to look at lymph nodes near the surface of the body or to look inside your abdomen for enlarged lymph nodes or organs such as the liver and spleen. (It's harder to use it to look at organs or lymph nodes in the chest because the ribs block the sound waves.)

This test is easy to have, and it uses no radiation. You simply lie on a table, and a technician moves the transducer over the part of your body being looked at.

Ultrasound-guided needle biopsy: Ultrasound can also be used to guide a biopsy needle into a suspicious area inside the body, such as an enlarged lymph node. A biopsy sample is then removed and sent to the lab.

Positron emission tomography (PET) scan

For a PET scan, you are injected with a slightly radioactive form of sugar, which collects mainly in cancer cells. A special camera is then used to create a picture of areas of radioactivity in the body. The picture isn't detailed like a CT or MRI scan, but it can show possible areas of lymphoma in all areas of the body at once.

A PET scan can help tell if an enlarged lymph node contains lymphoma or is benign. It can also help spot small areas that might be lymphoma, even if the area looks normal on a CT or MRI scan.

PET scans can also be used to tell if an advanced skin lymphoma is responding to treatment. Some doctors will repeat the PET scan after a few courses of chemotherapy. If the chemo is working, the abnormal areas will no longer take up the radioactive sugar.

Doctors often use a machine that does both a PET and CT scan at the same time (PET/CT scan). This lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT scan.