Cutaneous T-cell lymphoma (CTCL)

Cutaneous T-cell lymphoma (CTCL) is a rare type of non-Hodgkin lymphoma that starts in the skin. Lymphoma is a cancer that occurs in the lymphatic system, which is part of the immune system that helps your body fight infections. This network of lymph nodes, organs and tissue make and carry immune system cells called lymphocytes throughout the body. These cells travel in a clear fluid called lymph, similar to how the circulatory system transports blood. T-cells are one type of lymphocyte and there are many of them in the skin. They are responsible for fighting germs that try to invade your body through the skin. CTCL occurs when T-cells within the skin become cancerous.

CTCL is not a typical cancer of the skin because the affected cells are not skin cells. Instead, CTCL is a blood cancer.

There are many different types (called subtypes) of CTCL. The two most common are:

• Mycosis fungoides. This is the most common type and makes up about 70 percent of all CTCL cases, according to the U.S. National Library of Medicine. Mycosis fungoides is usually slow-growing and can take many years to spread or progress. It tends to progress in phases, starting with red, scaly patches on the skin that can last for months or years. Over time, these patches may get thick and eventually form raised tumors, called plaques. The rashes may go away and come back for a time, or they may be always there.
• Sézary syndrome. This type of CTCL is far less common. According to the U.S. National Library of Medicine, it makes up about 3 to 5 percent of all CTCL cases. It usually progresses more rapidly and is harder to treat than mycosis fungoides. People with Sézary syndrome develop a red, itchy rash all over the body that may resemble a bad sunburn.

Less than 1 percent of the U.S. population is diagnosed with CTCL every year, according to the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program.

CTCL causes

Doctors know that CTCL occurs when T-cells develop mutations that cause them to grow out of control, but they aren’t sure what causes these changes. Genetics, immune system problems (like having HIV or taking drugs to suppress the immune system after an organ transplant), exposure to certain chemicals, and some types of bacterial or viral infections may play a role in causing CTCL.

CTCL risk factors

While doctors don’t know exactly what causes CTCL, they do know some factors that may increase the risk of developing the cancer, including:

• Gender. Males are more at risk of developing CTCL than females. CTCL is two times more common in males.
• Age. Older people are more likely to develop CTCL. Most cases are diagnosed in adults between 40 and 60 years old. However, people of any age can get CTCL, including children in rare cases.
• Race. Black Americans are twice as likely to develop CTCL than members of other racial groups.

CTCL symptoms

Because CTCL causes visible symptoms, and because it progresses slowly, it’s often diagnosed in the early stages, when it tends to be easier to treat. However, rashes and skin changes caused by CTCL are easily confused with more common skin conditions such as eczema and psoriasis, so it can be hard to diagnose at first.

Skin changes often vary depending on the type of CTCL and the stage of the cancer, or how far it’s spread.

Mycosis fungoides

Symptoms of mycosis fungoides, the most common form of CTCL, may appear in different phases:

• The first sign of mycosis fungoides is a red, scaly rash on parts of the body that aren’t usually exposed to the sun. The rash may be itchy. Mycosis fungoides grows slowly, so these symptoms may persist for months, years or even decades for some patients.
• In the second phase, called the patch phase, patients may develop one or more flat patches of scaly skin.
• In the third phase, called the plaque phase, patients develop slightly raised patches of thicker, scaly skin. Plaques may develop from existing patches or in new areas, and they’re often itchy. Patients may have plaques and patches at the same time.
• The fourth phase is the tumor phase, when raised growths appear on top of the skin. These tumors may look like mushrooms. They tend to occur in areas such as the groin, breasts and armpits. The growths may split open and become infected. Patients may have tumors, plaques and patches at the same time.

The patches, plaques and tumors all contain cancerous T-cells. Patients may not experience all these stages. Some may not develop tumors, while others may have tumors before going through the patch or plaque phases. In some cases, patches may disappear and then come back.

In about 10 percent of mycosis fungoides cases, the cancerous T-cells will spread from the skin to other parts of the body, such as lymph nodes or organs.

Sézary syndrome

Sézary syndrome is a rarer type of CTCL. It tends to grow and spread more quickly than mycosis fungoides. The symptoms are different, too. Most patients develop a large, red rash that tends to cover much of the body and may be thick, scaly, peeling and painful. The rash is usually very itchy. Other potential symptoms include:

• Swollen lymph nodes
• Hair loss
• Swelling of the skin
• Thick skin on hands and feet
• Nail changes
• Lower eyelids turning outward

Patients with Sézary syndrome also have cancerous cells (called Sézary cells) in their blood.

Many other, more common conditions can cause the symptoms associated with CTCL. However, it’s important to see a dermatologist if you notice these kinds of changes in your skin, especially if the problem doesn’t go away or becomes worse.

Diagnosing CTCL

CTCL can be difficult to diagnose because it resembles other, more common conditions. Your doctor or dermatologist will likely start by examining the skin and any lesions or bumps that are present. He or she may also take pictures of the skin and ask questions about your symptoms and health history.

You may undergo different procedures and tests during the diagnostic process, including a biopsy. For this procedure:

• A doctor will remove a small piece of skin.
• The doctor will send the sample to a laboratory, where pathologists (experts in diagnosing diseases) will examine the specimen under a microscope to see if it contains cancerous cells.
• If the pathologist suspects cancer, he or she will conduct various tests on the skin sample to determine the exact type of cancer.

It can be difficult to detect tiny changes in cells that indicate CTCL, so patients may sometimes need multiple biopsies over the course of months or years before being diagnosed with CTCL.

Blood tests, such as a complete blood count (CBC), are often important for diagnosing CTCL and other types of lymphoma. A CBC blood test measures the amounts of different types of blood cells. Lymphoma often changes blood cell counts, particularly in later stages. To diagnose Sézary syndrome, a pathologist will need to examine a blood sample to check for Sézary cells.

Your doctor will consider the results of these and other tests to make a CTCL diagnosis. Your doctor will also need to determine the exact subtype of CTCL and whether the cancer has spread, so that he or she can recommend the right treatment for you.

CTCL can be classified as stage 1, 2, 3 or 4, depending on how far the cancer has spread. To stage the CTCL, you may undergo tests such as:

• Imaging tests, such as a computed tomography (CT) scan or positron emission tomography (PET)/CT scan. These produce detailed images to show whether and where the cancer may have spread.
• A lymph node or bone marrow biopsy to find out if the cancer has spread to the bone marrow or a lymph node. A lymph node biopsy is a surgical procedure that removes a lymph node (or part of a lymph node). For a bone marrow biopsy, a doctor inserts a needle into a bone (such as the hipbone) to take out a small piece of bone and a bone marrow sample. The lymph node or bone marrow is then sent to a laboratory for analysis.

These tests help your care team determine the cancer’s stage and identify potential treatment options. Early-stage cancers are generally easier to treat and have better outcomes than advanced-stage cancers. In stage 1, the earliest stage, cancer cells are found in the skin. In stage 4, the most advanced stage, cancer cells may be found in faraway organs or lymph nodes, or there may be a high number of Sézary cells in the blood.

CTCL treatment

The treatment for CTCL depends on the type and stage of the cancer. In general, the treatment for early-stage disease targets the skin, using options such as topical chemotherapy (medication you apply to the skin), local radiation therapy and photodynamic therapy. In advanced stages, when the cancer has spread beyond the skin, treatment usually requires options that treat cancer throughout the body. Patients with Sézary syndrome need whole-body (systemic) treatment.

Below are some of the main treatment options for CTCL:

• Photodynamic therapy involves injecting a drug into the body that gathers in areas where cancer cells are present. After the injection, a laser is aimed at skin to activate the drug, enabling it to kill nearby cancer cells. Because the drug gathers in cancer cells, it causes less harm to healthy cells.
• Radiation therapy uses high-dose radiation (a type of energy) to kill or damage cancer cells. CTCL patients will likely undergo external radiation therapy, using a machine that gives off high-energy X-rays and targets an area of cancer, or that sends tiny particles called electrons across the surface of the skin (called electron beam radiation therapy).
• Chemotherapy uses drugs to kill or slow the growth of cancer cells. These drugs may be taken by mouth, injected into the bloodstream or applied to the skin. If the cancer is widespread, patients may receive chemotherapy by mouth or via injection, so the medicines can attack cancer cells throughout the body. Some patients may get topical chemotherapy, which is applied to the skin.
• Retinoids are a form of vitamin A that may prevent or slow the growth of cancer. Retinoids come in either a topical cream or gel, which is applied to the skin for a targeted treatment, or in pill form, which is taken orally to help slow cancer growth throughout the body.
• Immunotherapy boosts or guides the patient’s own immune system to help it better fight cancer. Interferon is an immunotherapy, made from a substance that our body makes naturally, that may be used to treat CTCL. Injections of interferon may help strengthen the immune system’s ability to kill cancer cells.
• Targeted therapy uses drugs or substances designed to attack specific types of cancer cells and cause less harm to healthy cells than chemotherapy and radiation therapy. Targeted therapy options for CTCL include brentuximab vedotin and mogamulizumab, both of which attach to targets on the cancer cells and then kill the cells.
• Stem cell transplant allows patients to receive higher doses of chemotherapy or radiation therapy, which can kill healthy blood cells along with cancer cells. With a stem cell transplant, doctors remove immature blood cells (stem cells) from the body before giving you high doses of chemotherapy and possibly radiation therapy. The stem cells are then reinjected to the bloodstream after chemotherapy and radiation therapy is complete so they can grow into healthy blood cells.

Existing treatment for CTCL rarely leads to scans that show no evidence of disease, but it may be especially helpful at managing symptoms. It’s important to know that advanced-stage mycosis fungoides and Sézary syndrome tend to have worse outcomes, but treatment may help patients live longer and have good quality of life.

New treatments for CTCL are being tested and refined in clinical trials. Clinical trials may offer patients access to emerging treatments that may become standard in the future. If appropriate, your doctor will be able to provide more information on clinical trials that may be a good fit for you.