Tests for Lymphoma of the Skin

Because this type of lymphoma affects the skin, it is often noticed fairly quickly. But the actual diagnosis of skin lymphoma can sometimes be delayed because the symptoms often resemble other, more common skin problems.

A skin lymphoma diagnosis can only be confirmed with a skin biopsy (described below). Other tests might be needed as well.

Medical history and physical exam

If you have signs or symptoms of a possible skin lymphoma, your health care team will take your medical history and do a physical exam.

Medical history

Your health care team will ask about your symptoms, possible risk factors, family history, and other medical conditions.

They will ask:

• When did you first notice the skin changes?
• Have they changed in size or appearance?
• Are they itchy or painful?

You may be asked if you have any other symptoms, like fever or weight loss.

Allergies and other causes:

Skin lymphomas can be hard to tell apart from allergies and other causes of rashes.

You might be asked if you have any allergies or if you’ve recently been exposed to something else that could cause skin problems, like new medicines, laundry detergents, creams, or lotions.

Physical exam

During the physical exam, your health care provider 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.

They might also feel the lymph nodes under the skin in your neck, underarms, or groin. Lymph nodes are small, bean-sized collections of immune cells. Lymphomas can sometimes cause them to become enlarged.

Referral to a dermatologist

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

There are several types of skin biopsies. The type of biopsy you have will depend on your 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 stitches.

Incisional and excisional skin biopsies

For these 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 skin are sewn together. These biopsies are usually done using a local anesthetic (numbing medicine).

Testing skin biopsy samples in the lab

After the skin biopsy samples are removed, they are sent to the lab, where a doctor called a pathologist looks at them with a microscope.

The pathologist might do other tests on the biopsy samples as well.

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. (See Lab tests of biopsy or blood samples.)

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
• Hematopathologist: A pathologist with additional training in diagnosing lymphomas

Even with this expertise, several biopsies may 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 help determine how widespread the lymphoma is.

This is more likely to be done if the doctor detects enlarged lymph nodes during a physical exam or imaging tests. (See Imaging tests below.)

Excisional or incisional lymph node biopsies

These are the most common types of lymph node biopsy. In these procedures, a surgeon cuts through your skin to remove either:

• The entire lymph node (excisional biopsy)
• A small part of a large tumor (incisional biopsy)

If the node is just under your skin, this can often be done with local anesthesia (numbing medicine). But if the node is inside your chest or abdomen, you 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.

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 either a:

• Fine needle aspiration (FNA), using a very thin needle
• Core needle biopsy, using 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.

The advantage of a needle biopsy is that it doesn’t require surgery. But sometimes this type of biopsy (especially an FNA) might not remove enough tissue to make a definite diagnosis of lymphoma.

However, 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

Other biopsies are sometimes done to confirm a diagnosis of lymphoma. But more often, these procedures are used 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 is 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 are taken from other bones.

Bone marrow aspiration

For this procedure, you lie on a table (either on your side or on your belly). The doctor cleans the skin over your 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.

Bone marrow biopsy

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 is applied to the site to help stop any bleeding.

Lumbar puncture (spinal tap)

This test looks for lymphoma cells in cerebrospinal fluid (CSF). CSF is the liquid that bathes your brain and spinal cord. Most people with skin lymphoma won’t 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 your lower back, over your spine. A small, hollow needle is then inserted between the bones of the spine to withdraw fluid.

Lab tests of biopsy or blood samples

To help diagnose lymphoma and determine what type it is, lab tests are done on the biopsy samples. In some cases, blood samples are also tested.

Pathologists can sometimes tell which kind of lymphoma a person has just by looking at the cells under a microscope. But usually, they need other lab tests to confirm the diagnosis.

Flow cytometry and immunohistochemistry

For both of these tests, cells from the biopsy samples are treated with special antibodies that stick to certain proteins on the cells.

• For immunohistochemistry (IHC), the cells are then looked at with a microscope to see if the antibodies stuck to them (meaning they have these proteins).
• For flow cytometry, a special machine passes the cells through a laser beam to analyze them.

These tests can help tell whether a lymph node is swollen because of lymphoma, some other cancer, or a non-cancerous disease.

Different types of lymphoma cells have different proteins on their surface, so these tests can also be used for immunophenotyping (determining which type of lymphoma a person has based on certain proteins in or on the cells).

Chromosome and gene tests

Chromosomes are long strands of DNA that contain our genes.

Normal human cells have 23 pairs of chromosomes. Each chromosome is usually 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. The cells need to be grown in the lab first, so results can take a week or more.

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.

Other molecular and genetic tests

Other types of lab tests can also be done on the samples to look for specific gene changes or other changes in the lymphoma cells.

Many of these tests are done using next-generation sequencing (NGS), which can look for changes in many different genes at once. This type of testing usually takes a week or longer to get results.

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 usually used to diagnose lymphoma, but they can sometimes help determine how advanced the cancer is.

Blood tests may also be used during certain types of treatment (such as chemotherapy) to monitor how well the bone marrow and other organs are working.

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 the lymphoma is growing in the bone marrow and slowing normal blood cell production.
• People with Sezary syndrome will have Sezary cells in their blood. These 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. Blood chemistry tests are also done regularly in people getting chemo.

LDH levels in the blood

If you’ve been diagnosed with lymphoma, the levels of lactate dehydrogenase (LDH) in your blood may be checked. LDH levels are often abnormally high in people with widespread lymphoma.

Blood tests to check for infection

For some types of lymphoma, or for certain treatments, your doctor may also suggest 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)
• 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 skin lymphoma, these tests might be done for different reasons, including:

• 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 imaging is often done if a lot of the skin is affected, or if lymphoma cells are found in the lymph nodes or blood.

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

A 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.

When looking for lymphoma in the body, CT scans are often combined with a PET scan (known as a PET/CT scan, see below).

CT-guided needle biopsy

A CT scan can also be used to guide a biopsy needle into a suspicious area.

For this test, you lie on the CT scanning table while the doctor advances the needle through your 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.

Magnetic resonance imaging (MRI)

Like CT scans, MRIs 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 for 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. It can also be used 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 uses sound waves and their echoes to create images, so there is no radiation. You simply lie on a table and a technician moves a small, hand-held device called a 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 your 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 then creates a picture of areas of radioactivity in your body. It can show possible areas of lymphoma in all areas of your body at once.

A PET scan can be used to:

• Help tell if an enlarged lymph node contains lymphoma or is benign
• Spot small areas that might be lymphoma, even if the areas look normal on a CT or MRI scan
• See 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.

PET/CT scan

The picture from a PET scan isn't as detailed as those from a CT or MRI scan. But 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.