Lymphomas of the skin can be seen and felt. They often appear as itchy, red to purple patches, lumps, or nodules under the skin.

In addition to skin problems, non-Hodgkin lymphoma of the skin will rarely produce generalized symptoms, such as:

• unexplained weight loss
• fever
• profuse sweating (enough to soak clothing), particularly at night
• severe itchiness

Biopsy

A biopsy is needed to diagnose non-Hodgkin lymphoma of the skin. There are several types of biopsies, and the doctor's choice is based on the unique aspects of each person's situation. Usually a skin biopsy is done by a dermatologist. A dermatologist is a doctor who specializes in diagnosing and treating skin diseases.

All skin biopsy samples are examined under a microscope. The skin sample is sent to a pathologist, a doctor who has been specially trained in the microscopic examination of tissue samples and other laboratory tests for diagnosis of diseases. Often, the skin sample is sent to a dermatopathologist, a dermatologist or a pathologist with additional training in making diagnoses from skin samples.

Many forms of skin cancer can be diagnosed by "routine" examination of the tissue under a microscope. In contrast, diagnosis and classification of lymphomas of the skin will often require one or more special tests to identify the lymphoma cells. For example, the cells will usually be tested for certain substances that are labeled by CD numbers. This is usually done by a method called immunohistochemistry or another called flow cytometry (see below).

Diagnosing some forms of skin lymphoma can be very challenging and it's a good idea to ask your doctor how confident he or she is in the expertise of the pathologist who is responsible for testing your biopsy specimen.

Skin biopsies

Punch biopsy

The doctor uses a punch biopsy tool that looks like a tiny round cookie cutter (usually a little more than 1/8 inch in diameter). 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

Incisional biopsy involves removing only part of the tumor. If the entire tumor is removed it is called an excisional biopsy. A surgical knife is used to cut through the full thickness of skin. A piece of skin is removed for further examination, and the edges of the wound are sewn together. These biopsies can be done using local anesthesia.

Lymph node biopsies

Because skin lymphomas often involve lymph nodes, your doctor may recommend a lymph node biopsy to help determine how widespread your lymphoma is.

Excisional or incisional lymph node biopsy

This is the favored type of biopsy. In this procedure, a surgeon cuts through the skin to remove either the entire node (excisional biopsy) or a small part of a large tumor (incisional biopsy). If the node is near the skin surface, this is a simple operation that can be done with local anesthesia (numbing medication). But if the node is inside the chest or abdomen, general anesthesia is used (the patient is asleep). Removing a lymph node almost always provides enough tissue to diagnose the exact type of non-Hodgkin lymphoma. It is preferred, if it can be done without too much discomfort to the patient.

Fine needle aspiration (FNA) biopsy

FNA uses a very thin needle and a syringe to withdraw a small amount of tissue from a tumor. The doctor can aim the needle while feeling an enlarged node near the surface of the body. If the tumor is deep inside the body, the doctor can guide the needle while viewing a computed tomography (CT) scan (see discussion of imaging tests later in this section).

The main advantage of FNA is that it does not require surgery. The disadvantage is that in many cases the thin needle cannot remove enough tissue for a definite diagnosis of lymphoma. However, advances in performing 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. FNA is also very useful in diagnosing cancers that spread to nodes from other organs and in identifying nodes swollen by infection that don't need to be removed.

Other types of biopsies

These procedures may be done to diagnose lymphoma, but they are more often done to help stage (determine the extent of) a lymphoma that has already been diagnosed.

Bone marrow aspiration and biopsy

Bone marrow aspiration and biopsy are usually done at the same time. An area of the pelvic bone (about 2 inches to the side of the spine) and the skin above it are numbed with local anesthetic. Sometimes a tiny incision is made in the skin -- about one-eighth inch. For the aspiration, a large needle is placed through the incision into the bone. Then, using a syringe, a small amount of liquid bone marrow (about 1 teaspoon) is sucked out. Even with the numbing medicine, this can cause a brief, sudden, sharp pain. Then, for the biopsy procedure, a small sliver of bone with the marrow attached is removed with the needle. The piece of bone that is removed is small -- usually about 1/16 inch across and 1/3 inch long. This procedure is usually done with you lying on your stomach, but it can be done with you lying on your side. These tests can be used for the initial diagnosis and for staging (to see how far the cancer has spread).

Lumbar puncture (spinal tap)

Lymphoma can invade the tissues surrounding the brain and spinal cord. This is not common, but sometimes occurs when the disease has become advanced and is growing in internal organs. When this happens, lymphoma cells can be found in the spinal fluid. Spinal fluid is sampled in a procedure called a lumbar puncture -- also known as a spinal tap. Since it is rare to find lymphoma in this area, this test is only done in people who have symptoms that could be caused by the lymphoma growing in the tissues around the brain and spinal cord. These symptoms include headaches, trouble using certain muscles of the face or body, or numbness in parts of the body.

During a lumbar puncture, the skin in the lower back is numbed and a thin needle is inserted between the bones in the lower spine (below the level where the spinal cord ends) into the fluid that surrounds the spinal cord. This fluid, known as cerebrospinal fluid (CSF), is allowed to flow out the end of the needle into a tube that can be sent to the lab for testing.

Laboratory tests

Immunohistochemistry

In this test, cells are treated in the lab with special antibodies that attach to specific molecules on the cell surface. These antibodies cause color changes which can be seen under a microscope. This test can be done on many different types of tissue samples (biopsies). It may be helpful in diagnosing lymphoma and telling what type it is.

Flow cytometry

The cells being examined by this test are treated with the fluorescent antibodies and passed in front of a laser beam. Each antibody sticks only to certain types of cells. If the sample contains those cells, the laser light will cause them to give off light of a different color, which is measured exactly and analyzed by a computer. This test can look at many more cells than immunohistochemistry.

Flow cytometry can help determine whether lymph node swelling is due to non-Hodgkin lymphoma, some other cancer, or a non-cancerous disease. It has also become very useful in helping doctors determine the exact type of non-Hodgkin lymphoma so that they can select the best treatment.

Cytogenetics

This is a test to look at the chromosomes in the lymphoma cells. The cells are cultured in the lab so that they grow and divide. Then a microscope is used to look at the cells to see if the chromosomes look normal. In certain types of lymphomas, translocations are often seen (a translocation is where part of one chromosome has broken off and is now attached to another chromosome). In addition to translocations, some lymphoma cells may have too many chromosomes, too few chromosomes, or other chromosome problems. These abnormalities can help diagnose the specific type of lymphoma as well as help predict the outlook for survival.

Molecular genetic studies

These tests are another way to look at the chromosomes and DNA in the lymphoma cells. They can detect abnormalities that cannot be seen under a microscope in regular cytogenetic tests. For example, these molecular genetic studies can also detect changes called "rearrangements" in genes that identify whether the lymphoma is a B-cell or T-cell type.

Other molecular tests can also detect certain genes that have been "turned on" and are contributing to the lymphoma cells abnormal growth. In the future, as researchers learn more about lymphomas, these may become the most useful tests for determining what kind of lymphoma is present and predicting which treatments will be most effective.

Blood tests

The complete blood count (CBC) is a test that measures the 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 number of different types of white blood cells that are present. If a person's blood counts are low, that might mean that the lymphoma is growing in the bone marrow and crowding out normal blood cell production. People with Sezary syndrome will have Sezary cells in the blood, which can be found on the differential.

Blood chemistry tests look at how well the kidney and liver are working. Another chemistry test, the LDH level, is often high in the blood of patients with widespread lymphoma. The level goes up higher when larger amounts of lymphoma are present.

Imaging studies

These tests are used to see tumors inside the body. They can help find out if the skin lymphoma has spread. They are not always needed for patients with a few skin lesions, but are often done in patients with a lot of skin involvement. Imaging tests are also done when the lymphoma cells are in the lymph nodes or blood, or when the lymphoma is a type that tends to spread.

Chest x-ray

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

Computed tomography scan

The computed tomography (CT or CAT) scan is an x-ray procedure that produces detailed cross-sectional images of your body. For a CT scan, you lie on a table while an X-ray machine takes pictures. Instead of taking one picture, like a conventional x-ray, a CT scanner takes many pictures as the camera rotates around you. A computer then combines these pictures into an image of a slice of your body. The machine can create many images of the part of your body that is being studied.

Before any pictures are taken, you may be asked to drink 1 to 2 pints of a liquid called "oral contrast." This helps outline the intestine so that certain areas are not mistaken for tumors. You may also receive an IV (intravenous) line through which a different kind of contrast dye (IV contrast) is injected. This helps better outline structures in your body.

The injection can cause flushing -- a brief feeling of warmth that goes through the body. Some people are allergic and get hives or, rarely, have more serious reactions like trouble breathing or low blood pressure. Be sure to tell the doctor if you have ever had a reaction to any contrast material or dye used for x-rays.

CT scans take longer than regular x-rays, but with newer machines the scan may be finished in minutes. During the scan, you must lie still on the table that is part of the scanner.

CT scans can also be used to precisely guide a biopsy needle into an enlarged lymph node or suspected tumor. For this procedure, called a CT-guided needle biopsy, the patient remains on the CT scanning table while a radiologist moves a biopsy needle toward the tumor. CT scans are repeated until the doctors are sure that the needle is within the mass. A fine needle biopsy sample (tiny fragments of tissue) or a core needle biopsy sample (a thin sliver of tissue about ½-inch long and less than 1/8 inch across) is then removed to be looked at under a microscope.

Magnetic resonance imaging scan

Magnetic resonance imaging (MRI) scans use radio waves and strong magnets instead of x-rays to take pictures of parts of the body. The energy from the radio waves is absorbed and then released in a pattern formed by the type of tissue and by certain diseases. A computer translates the pattern of radio waves given off by the tissues into a very detailed image of parts of the body. Not only does this produce cross-sectional slices of the body like a CT scanner, it can also produce slices that are parallel with the length of your body. Sometimes a contrast material (called gadolinium) is injected into a vein to make some structures clearer. This contrast is not the same as the contrast used for CT scans, but allergic reactions can still occur. Again, medication can be given to prevent and treat allergic reactions. MRI scans are especially helpful in examining the brain and spinal cord.

MRI scans are a little more uncomfortable than CT scans. First, they take longer -- about an hour. Also, you have to lie inside a narrow tube, which can upset people with claustrophobia (fear of enclosed spaces). Newer machines known as open MRIs may be helpful if you have this fear. If you have problems with tight spaces, you should let your doctor know before the MRI. Also, the machine makes a loud thumping noise which many people find annoying. Some places may provide earplugs or headphones with music to block this out.

Positron emission tomography scan

Positron emission tomography (PET) scans use glucose (a form of sugar) that contains a very small amount of radioactivity. The radioactive glucose solution is injected into a vein and travels throughout the body. Cancer cells use glucose at a higher rate than normal cells, so cancers take up the radioactive sugar more than normal tissues. A scanner can spot the radioactive deposits. This test can be helpful for spotting small collections of cancer cells. It may also help tell whether a tumor is benign or malignant.

PET is useful to look for lymphoma throughout your body. A PET scan can be more helpful than several different x-rays because it scans your whole body. The PET scan can detect areas of "active" cancer, even when a lymph node or organ in the body looks normal. It can also help tell whether an enlarged lymph node contains cancer (like lymphoma) or whether it is large for some other reason.

PET is also used after treatment in helping decide whether an enlarged lymph node still contains lymphoma or is merely scar tissue. PET scan machines are often combined with CT scanners. This can make it easier to tell exactly where the abnormal areas seen on the PET scan are located.

Gallium scan

During this procedure, the radiologist injects a small dose of radioactive gallium into a vein. The gallium goes to lymph node areas in the body, or to other areas where lymphoma may have spread. A special camera can then detect the radioactivity, showing the location of the abnormal gallium uptake. These tests can find tumors that might be lymphoma in bones and other organs.

The gallium scan will not detect most slow-growing lymphomas but will recognize many fast-growing (aggressive) lymphomas. It was used much more often before PET scans were available. It can still be useful in finding lymphoma deposits that the PET scan may miss. It is also useful in separating infections from lymphomas when the diagnosis is not clear.

Bone scan

For this test, the patient receives an injection of radioactive material called technetium diphosphonate. The amount of radioactivity used is very low and causes no long-term effects. This substance is attracted to diseased bone throughout the entire skeleton. A special camera is used to take a picture of the skeleton. Areas of diseased bone will be seen on the bone scan image as dense, gray to black areas, called "hot spots." These areas may suggest that cancer (such as lymphoma) is present, but arthritis, infection, or other bone diseases can also cause a similar pattern. To distinguish among these conditions, the cancer care team may use other imaging tests or take bone biopsies. This test is not often used for patients with lymphoma.

Ultrasound

Ultrasound uses sound waves and their echoes to take pictures of parts of the body. A small microphone-like instrument called a transducer emits sound waves. These waves are transmitted into the area of the body being studied and echo back. The echoes are picked up by the transducer and converted by a computer into an image that is displayed on a computer screen.

This is a very easy procedure. It uses no radiation, which is why it is often used to look at developing fetuses. To have an ultrasound examination, you simply lie on a table and a technician moves the transducer along the skin over the part of your body being examined. Usually, the skin is first lubricated with gel.

Ultrasound is often used to look at the kidneys, liver, and spleen. This test is not often used in the diagnosis of lymphoma.