How Is Lymphoma of the Skin Diagnosed?

Because this type of lymphoma affects the skin, it is often noticed fairly quickly. But the actual diagnosis of skin lymphoma might be delayed because the symptoms often resemble other, more common skin problems. The diagnosis of skin lymphoma can only be confirmed with tests such as biopsies (described below).

Medical history and physical exam

Usually your doctor first takes your medical history. The doctor probably will ask when the changes in your skin first appeared, 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 recently been exposed to something that could be causing your skin problems, such as if you are taking a new medicine or are using 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. The rest of your body will be checked for other areas of skin involvement.

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

If you are being seen by your primary doctor and skin lymphoma or another type of skin cancer is suspected, you may be referred to a dermatologist (a doctor who treats skin diseases), who will look at the skin more closely.


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.

Skin biopsies

There are several types of skin biopsies, and the doctor’s choice 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 (usually a little more than 1/8 inch across). Once the skin is numbed with a local anesthetic, the doctor rotates the punch biopsy tool on the surface of the skin until it cuts through all the layers of the skin. 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. An incisional biopsy removes only part of the tumor, while 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 under 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 under a microscope. But diagnosing and classifying lymphomas of the skin often requires one or more special lab tests (see below).

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 needed over a period of time 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 biopsy: This is the most common type of lymph node biopsy. In this procedure, 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 is often a simple operation that can be done with local anesthesia. But if the node is inside the chest or abdomen, the patient will be asleep or deeply sedated during the biopsy.

Removing a lymph node almost always provides enough tissue to diagnose the exact type of lymphoma. This type of biopsy is preferred by most doctors, if it can be done without too much discomfort to the patient.

Fine needle aspiration (FNA) biopsy: In an FNA biopsy, the doctor uses a very thin, hollow needle attached to a syringe to withdraw (aspirate) a small amount of tissue from a tumor. If an enlarged node is just under the skin, the doctor can aim the needle while feeling it. If the enlarged node is deep inside the body, the doctor can guide the needle while viewing it with ultrasound or a CT scan (see “Imaging tests” below).

An FNA does not require surgery, but in some cases it doesn’t 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 with FNA have improved the accuracy of this procedure. Some doctors will use FNA in patients already diagnosed with lymphoma of the skin to confirm that an enlarged lymph node also contains lymphoma.

Other types of biopsies

These procedures may sometimes be done to confirm a diagnosis of lymphoma, but they are more often done to help stage (determine the 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 procedures are sometimes done after lymphoma has been diagnosed to help figure out if it has reached the bone marrow. The two tests are often done at the same time. The samples are usually taken from the back of the pelvic (hip) bone, but in some cases 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 patients 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 placed 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 patient has by just looking at the cells under a microscope, but usually these other types of tests are needed to confirm the diagnosis.


In this test, a part of the biopsy sample is treated with special antibodies (man-made versions of immune system proteins) that attach to cells only if specific molecules are on their surface or inside the cells. These antibodies cause color changes, which can be seen under a microscope. This test can be used to help diagnose lymphoma and tell what type it is.

Flow cytometry

Like immunohistochemistry, this test looks for certain substances on the surface of cells that help identify what types of cells they are. But this test can look at many more cells than immunohistochemistry.

For this test, a sample of cells is treated with special antibodies that stick to the cells only if certain substances are present on their surfaces. The cells are then passed in front of a laser beam. If the cells now have antibodies attached to them, the laser will cause them to give off light, which can be measured and analyzed by a computer. Groups of cells can be separated and counted by these methods.

This is the most commonly used test for immunophenotyping – classifying lymphoma cells based on the substances (antigens) on their surfaces. Different types of lymphocytes have different antigens on their surface. These antigens also change as each cell matures.

Flow cytometry can help tell whether a biopsy sample contains lymphoma, some other cancer, or a non-cancerous disease. It has also become very useful in helping doctors determine the exact type of lymphoma so that they can select the best treatment.


Doctors use this technique to evaluate the chromosomes (long strands of DNA) in lymphoma cells. The cells are looked at under a microscope to see if the chromosomes have any changes such as translocations (where part of one chromosome has broken off and is now attached to another chromosome), as happens in certain types of lymphoma. Some lymphoma cells may have too many chromosomes, too few chromosomes, or other chromosome abnormalities. These changes can help identify the type of lymphoma.

Cytogenetic testing usually takes about 2 to 3 weeks because the lymphoma cells must grow in lab dishes for a couple of weeks before their chromosomes can be viewed under the microscope.

Molecular genetic tests

These tests look more closely at lymphoma cell DNA. They can detect most changes that are visible under a microscope in cytogenetic tests, as well as others that can’t be seen. These changes can help doctors decide whether a rash or lesion is due to a benign condition or a skin lymphoma. These tests can also tell the difference between B-cell and T-cell lymphomas.

Fluorescent in situ hybridization (FISH): FISH uses special fluorescent dyes that only attach to specific genes or parts of chromosomes. FISH can find most chromosome changes (such as translocations) that can be seen under a microscope in standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing.

FISH can be used to look for specific gene or chromosome changes. It can be used on regular blood or bone marrow samples. It is very accurate and can usually provide results within a couple of days, which is why this test is now used in many medical centers.

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

Blood tests

Blood tests measure the amounts of certain types of cells and chemicals in the blood. They are not used to diagnose lymphoma, 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 the red blood cells, the white blood cells, and the platelets. The CBC is often done with a differential (or “diff”) which counts the numbers of different types of white blood cells. People with Sezary syndrome will have Sezary cells in the blood, which can be found on the differential.

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.

Blood chemistry tests: These tests look at how well the kidneys and liver are working.

If lymphoma has been diagnosed, another blood test called lactate dehydrogenase (LDH) may be done. LDH levels are often abnormally high in patients with widespread lymphoma.

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 patients with skin lymphomas who have only a few skin lesions, but they are often done in patients with a lot of skin involvement or if lymphoma cells are found in the lymph nodes or blood.

If you’d like 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.

Before the test, you may be asked to drink a liquid called oral contrast. This helps outline certain organs. You may also get an IV line through which a different kind of contrast dye (IV contrast) is injected. The injection can cause some flushing (a warm feeling, especially in the face). Some people are allergic to the dye and get hives or, rarely, have more serious reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have any allergies (especially iodine or shellfish) or have ever had a reaction to any contrast material used for x-rays.

A CT scanner has been described as a large donut, with a narrow table that slides in and out of the middle opening. You need to lie still on the table while the scan is being done. CT scans take longer than regular x-rays, and some people might feel a bit confined by the ring while the pictures are being taken.

CT-guided needle biopsy: CT scans can also be used to guide a biopsy needle into a suspicious area. For this procedure, a person lies on the CT scanning table while the doctor advances a biopsy needle through the skin and toward the area. CT 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 provide 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.

A contrast material called gadolinium is often injected into a vein before the scan to better see details. This contrast material usually does not cause allergic reactions.

MRI scans take longer than CT scans – often up to an hour. You may have to lie inside a narrow tube, which is confining and can be distressing to some people. Newer, more open MRI machines might be another option. The MRI machine makes loud buzzing and clicking noises that some people might find disturbing. Some places provide headphones or earplugs to help block this out.


Ultrasound uses sound waves and their echoes to make pictures of internal organs or masses. For this test, a small, microphone-like instrument called a transducer is placed on the skin (which is first lubricated with a gel). It gives off sound waves and picks up the echoes as they bounce off the organs. A computer then converts the echoes into a black and white image on a screen.

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 can’t be used to look at organs or lymph nodes in the chest because the ribs block the sound waves.) It is sometimes used to help guide a biopsy needle into an enlarged lymph node.

This is an easy test 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.

Positron emission tomography (PET) scan

For a PET scan, a radioactive substance (usually a type of sugar related to glucose, known as FDG) is injected into the blood. The amount of radioactivity used is very low and will pass out of the body within a day or so. Because cancer cells in the body grow quickly, they absorb large amounts of the sugar. You then lie on a table in the PET scanner for about 30 minutes while a special camera creates a picture of areas of radioactivity in the body. The picture is not detailed like a CT or MRI scan, but it can look for possible areas of lymphoma in all areas of the body at once.

PET scans 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 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.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master's-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Medical Review: August 4, 2014 Last Revised: February 24, 2016

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