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Cancer Medicine :: Lymphoma of the skin

Lymphoma of the skin

General treatment information

In recent years, much progress has been made in treating skin lymphoma, and several newer types of treatment have come into use.

Once a skin lymphoma is found and staged, your health care team will discuss your treatment options with you. The treatment options for a person with skin lymphoma depend on the kind of lymphoma and its stage, as well as other factors such as your overall health. Of course, no two patients are exactly alike, and treatment options are tailored to each patient’s situation.

Several types of treatment can be used against skin lymphoma. These can generally be divided into:

Treatments directed only at the skin

Treatments that can affect the whole body (systemic treatments)

Sometimes these 2 types of treatments are used together.

Based on your treatment options, you may have different types of doctors on your treatment team. These doctors may include:

A dermatologist: a doctor who treats diseases of the skin

A hematologist: a doctor who treats disorders of the blood, including lymphomas

A medical oncologist: a doctor who treats cancer with medicines

A radiation oncologist: a doctor who treats cancer with radiation therapy

Many other specialists may be involved in your care as well, including nurse practitioners, physician assistants, nurses, nutrition specialists, social workers, and other health professionals.

It is important to discuss all of your treatment options and their possible side effects with your doctors to help make the decision that best fits your needs. It’s also very important to ask questions if there is anything you’re not sure about. You can find some good questions to ask in the section “What should I ask my doctor about lymphoma of the skin?”

If time permits, it is often a good idea to seek a second opinion. A second opinion can provide more information and help you feel confident about the chosen treatment plan.

The next sections describe the different types of treatment for skin lymphomas. This is followed by a discussion of the most common treatment options based on the specific type of lymphoma.

Skin-directed treatments for skin lymphomas

In many cases, the first treatment for skin lymphoma is treating the skin lesions directly, while trying to avoid harmful side effects on the rest of the body. There are many ways to treat skin lesions.


Surgery is rarely the only treatment used for skin lymphoma. It may be used to biopsy a lymph node or other tissue to diagnose and classify a lymphoma. It might also be used to treat some types of B-cell skin lymphomas when only one or a few lesions are present and can be completely removed. Even then, other types of treatment may be used as well.

Radiation therapy

Radiation therapy uses high-energy rays to kill cancer cells. Radiation focused on a cancer from a source outside the body is called external beam radiation. The treatment is much like getting an x-ray, but the radiation is more intense. The procedure itself is painless.

The type of radiation used most often for skin lymphomas is called electron beam radiation. It uses a beam of electrons that only penetrate as far as the skin, so there are few side effects to other organs and tissues. The main side effect of electron beam therapy is a skin reaction similar to sun burn. For mycosis fungoides and Sezary syndrome, electron beam therapy is often given to the entire body. This is called total skin electron beam therapy (or TSEBT). This can sometimes cause loss of all hair on the body, as well as loss of fingernails and toenails.

Some thicker lymphomas that are not widespread (especially single lesions) are treated with high energy radiation (like x-rays or gamma rays) instead of electrons. This kind of radiation can penetrate deeper into the body. Because it can damage internal organs, the treatment is planned carefully so that most of the radiation goes only to the skin.

Phototherapy (UV light therapy)

Ultraviolet (UV) light is the part of sunlight that causes sunburn and skin cancer. Phototherapy uses UV light to kill cancer cells in the skin. This is a useful treatment for some people with skin lymphomas that aren’t very thick.

Two kinds of UV light – ultraviolet A (UVA) and ultraviolet B (UVB) – can be used to treat skin lymphoma. Both UVA and UVB treatments are given with special fluorescent lamps like those used in tanning salons. Treatments are given about 3 times a week.

When UVA is used, it is combined with drugs called psoralens. This combination is referred to as PUVA. Psoralens are given as a pill about 2 hours before the treatment. The drug travels through the blood to reach cells throughout the body (including cells of skin lymphoma). When those cells are then exposed to UVA light, the drug is activated, killing them. Psoralens can cause some nausea. They can also make the skin very sensitive to sunlight (increasing the risk of severe burns), so it is important to protect yourself from sunlight as much as possible in the days after treatment.

UVB is given without any extra medicines, and is generally used for thinner skin lesions.

Just like the UV light in sunlight, these treatments can cause sunburn and may raise the risk of skin cancer later in life, so doctors try to avoid giving too much UV light.

Topical medicines

Applying drugs directly to the skin is called topical therapy. It can be very helpful in treating many early skin lymphomas. When a drug is placed on the skin, its effects are concentrated on that spot, with much smaller amounts reaching the rest of the body. This can help limit side effects, especially for strong medicines such as some chemotherapy drugs.

Topical corticosteroids: These are drugs related to cortisol, a hormone made naturally in the body that can affect immune cells such as lymphocytes. Corticosteroid pills and injections have long been an important part of lymphoma treatment.

These drugs can also be applied directly to the skin in the form of ointments, gels, and creams. This can be very helpful in the treatment of skin lesions. When given this way, less of the drug is absorbed, resulting in fewer side effects. Long-term use of topical corticosteroids may cause the skin in that area to become thinner.

Topical chemotherapy drugs: Chemotherapy drugs are strong medicines often given by mouth or injected into a vein to treat more advanced cancers (including advanced skin lymphomas ).

Some chemo drugs can be used to treat earlier forms of skin lymphoma by placing them directly on the skin (usually in a cream or ointment). The drugs most commonly used to treat skin lymphoma include mechlorethamine (nitrogen mustard) and carmustine (BCNU). Possible side effects include redness, swelling, or irritation where the drug is applied, as well as an increased risk of other types of skin cancer in the area.

Topical retinoids: Retinoids are drugs related to vitamin A. They can affect certain genes in lymphoma cells that cause them to grow or mature.

Some retinoids, such as bexarotene (Targretin) and other drugs, come in a gel that can be applied directly to skin lesions. Possible side effects include redness, itching, irritation, and sensitivity to sunlight at the area where the drug is applied. These drugs can cause birth defects, so they should not be used by women who are or could become pregnant.

Topical immune therapies: Imiquimod (Zyclara) is a cream that causes an immune system reaction when applied to skin lesions, which may help destroy them. This drug is used mainly to treat some other types of skin cancers, but some doctors may also use it to treat early forms of skin lymphoma. It can cause redness, itching, and irritation at the site where the drug is applied.

Whole-body (systemic) treatments for skin lymphomas

Systemic treatments have the potential to affect the whole body. They are most useful for more advanced or quickly growing skin lymphomas. In some cases, a systemic treatment may be combined with a skin-directed treatment or with another systemic treatment.

Photopheresis (photoimmune therapy)

This treatment is also called extracorporeal photopheresis, or ECP. It is sometimes used for T-cell skin lymphomas, especially Sezary syndrome. It is thought to work by killing some lymphoma cells directly and by boosting the body’s immune response against other lymphoma cells.

The procedure is similar to donating blood, but instead of going into a collecting bag, the blood goes into a special machine that separates out the lymphocytes (including lymphoma cells). They are then treated with a psoralen (a light-sensitizing drug) and UVA light before they are mixed back in with the rest of the blood and infused back into the patient. Each procedure usually takes a few hours. Treatments are typically given for 2 days in a row, and then repeated every 4 weeks or so.

Side effects are usually minimal. The most significant side effect from this procedure is sensitivity to sunlight for about a day after each treatment, which might result in sunburn or other problems. It is very important to protect yourself from sunlight as much as possible during this time.

Systemic chemotherapy

Chemotherapy (chemo) uses strong drugs to treat cancer. When the drugs are injected into a vein or a muscle or taken by mouth, they enter the bloodstream and reach all areas of the body.

Systemic chemo is not often used for early skin lymphoma, but it may be used when the disease in the skin is more advanced and no longer getting better with other treatments. It can also be helpful when the lymphoma has spread to lymph nodes, blood, or distant organs and tissues.

Many drugs are useful in the treatment of patients with skin lymphoma, including:


Liposomal doxorubicin (Doxil)








Often a single drug is tried first, but sometimes patients are treated with drug combinations more often used for lymphoma not involving the skin. For example, a chemo regimen called CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) may be used, often along with the monoclonal antibody rituximab (Rituxan), which is described below.

The treatments all have different schedules, but they are usually repeated several times in cycles given 3 or 4 weeks apart. Most chemo treatments are given on an outpatient basis (in the doctor’s office, clinic, or hospital outpatient department), but some require hospital admission.

Patients often receive chemo for 2 or 3 cycles and then have tests to see if it is working. If the first regimen doesn’t seem to be working, different drugs may be tried.

Possible side effects

Chemo drugs attack cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow (where new blood cells are made), the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemo, which can lead to side effects. Side effects depend on the specific drugs used, their dose, and the length of treatment. Some common side effects include:

Hair loss

Mouth sores

Loss of appetite

Nausea and vomiting


Increased chance of infection (from a shortage of white blood cells)

Bleeding or bruising after minor cuts or injuries (from a shortage of platelets)

Fatigue or shortness of breath (from low red blood cell counts)

These side effects are usually short term and go away after treatment is finished. There are often ways to lessen these side effects. For example, drugs can be given to help prevent and reduce nausea and vomiting.

A major concern with chemo is its effect on the patient’s immune system, which is often already damaged by the lymphoma itself. This sometimes limits how intense the chemo treatment can be. Drugs known as growth factors (G-CSF or GM-CSF, for example) are sometimes given after chemo to help the body make new white blood cells to reduce the chance of a serious infection. Antibiotics may also be given at the earliest sign of an infection, such as a fever.

If your white blood cell counts are very low during treatment, you can help reduce your risk of infection by limiting your exposure to germs. During this time, your doctor may advise you to:

Wash your hands often.

Avoid fresh, uncooked fruits and vegetables and other foods that might carry germs.

Avoid fresh flowers and plants because they may carry mold.

Make sure other people wash their hands before they come in contact with you.

Avoid large crowds and people who are sick (wearing a surgical mask offers some protection in these situations).

If your platelet counts are very low, you may be given drugs or platelet transfusions to help protect against bleeding. Fatigue caused by anemia (very low red blood cell counts) can be treated with drugs or with red blood cell transfusions.

Some possible side effects are more common with certain drugs. For example, drugs like doxorubicin can damage the heart. Other drugs can sometimes cause damage to the kidneys, nerves, or other organs. Your doctor or nurse can tell you about the possible side effects of specific drugs you may be getting.

If serious side effects occur, the chemotherapy may have to be reduced or stopped, at least for a while. Although most side effects go away after chemo is stopped, some can be permanent. Before you start chemo, discuss with your cancer team what drugs will be used and what side effects to expect.

Chemotherapy can also cause side effects that might not occur until years after treatment. For example, in rare cases, people may develop leukemia several years later.

Targeted and biologic therapies

In recent years, many newer drugs have been developed to treat skin lymphomas. Some of these drugs target specific parts of cancer cells. Others work by boosting the body’s immune system to attack lymphoma cells.

These drugs work differently from standard chemotherapy drugs, which generally affect all quickly growing cells in the body. They sometimes work when chemo drugs don’t. They also tend to have different (and often milder) side effects than standard chemo drugs.

Vorinostat (Zolinza): This drug is in a class of cancer-fighting drugs called histone deacetylase (HDAC) inhibitors. It is given as a pill, once a day. It is used to treat cutaneous T-cell lymphomas, usually after other treatments have been tried. Side effects tend to be mild, but can include nausea, diarrhea, lowered blood cell counts, and effects on the rhythm of the heart.

Romidepsin (Istodax): Romidepsin is another HDAC inhibitor. It is also used to treat cutaneous T-cell lymphomas, usually after at other treatments have been tried. This drug is given as an infusion into a vein (IV), usually once a week. Side effects are similar to those of vorinostat.

Bortezomib (Velcade): This is a type of drug known as a proteasome inhibitor. It is usually used to treat other cancers of lymphocytes. But it can also be used to treat some skin lymphomas, usually after other treatments have been tried. Bortezomib is given as an IV infusion, typically twice a week for 2 weeks, followed by a rest period. Side effects can be similar to those of standard chemotherapy drugs, including low blood counts, nausea, loss of appetite, and nerve damage.

Denileukin diftitox (Ontak): This drug combines part of an interleukin-2 (IL-2) molecule with diphtheria toxin. The receptor for IL-2 is only found on certain lymphocytes and lymphoma cells. When the drug attaches to that receptor, the diphtheria toxin can kill the lymphoma cell. The drug is given as an IV infusion daily for 5 days in a row. It is used mainly in patients whose skin lymphoma has gotten worse (or come back) after another treatment.

Common side effects during the first day of treatment can include low blood pressure, shortness of breath, back pain, and rash. Patients getting this drug may also feel like they have the flu within the first few days of treatment. This improves with treatment and time. A rare side effect of this drug is problems with vision that may not go away even after treatment is stopped.

Rituximab (Rituxan): This drug is a monoclonal antibody – a man-made version of an immune system protein that has a very specific target. This antibody attaches to a substance called CD20 found on the surface of most B lymphocytes, causing the cells to die.

Rituximab can be used alone or with other drugs to treat B-cell skin lymphomas. Treatments are usually given as IV infusions weekly or at longer intervals.

Common side effects are often mild but may include chills, fever, nausea, rashes, fatigue, and headaches, especially during the first infusion. Side effects are less likely with later doses. Rituximab may also increase a person’s risk of infections. It can cause dormant (inactive) hepatitis B infections to become active again, sometimes leading to severe liver problems or even death. Your doctor may check your blood for signs of hepatitis before starting this drug.

Alemtuzumab (Campath): This monoclonal antibody targets the CD52 protein found on some types of lymphocytes and lymphoma cells. When the antibody binds to this protein, it triggers the immune system to destroy the cell. It is given by injection either under the skin (subcutaneous) or into a vein (IV), usually several times a week.

Alemtuzumab works well against skin lymphoma, but this drug can have serious side effects. Some people have allergic reactions during the first few infusions, which can sometimes be serious. Doctors usually give a low dose at first and gradually increase it to try to prevent this.

In some people, alemtuzumab can severely weaken the immune system. This can lead to serious or even life-threatening infections with germs that aren’t usually a problem for healthy people.

Because of these risks, alemtuzumab is not often used as a first treatment. It may be an option for people with skin lymphoma that has come back after other treatments.

Interferons: The interferons are hormone-like proteins normally made by white blood cells to help the immune system fight infections. Certain types of interferon can be made in the lab and given as medicine. Interferons can cause some types of skin lymphomas to shrink or stop growing. They are given as injections, usually under the skin several times a week.

People getting this treatment often have flu-like side effects, such as fatigue (which can be severe), fever, chills, headaches, muscle and joint aches, and mood changes. The side effects tend to be worse when higher doses are used.

Systemic retinoids

Retinoids are drugs related to vitamin A. Retinoids such as all-trans retinoic acid (ATRA), acitretin, isotretinoin (Accutane), and bexarotene (Targretin) can be used to treat some skin lymphomas, especially mycosis fungoides and Sezary syndrome. Bexarotene can be used as a topical treatment when only a few small skin lesions are present, but retinoids are often taken in pill form for skin lymphomas that are more extensive.

Side effects of systemic retinoids can include headache, nausea, fever, increased blood levels of triglycerides (fats), thyroid problems, and eye problems. Some retinoids can cause more serious side effects, like fluid buildup in the body. These drugs should never be given to a woman who is pregnant or who might become pregnant, as they may cause serious birth defects.

High-dose chemotherapy with stem cell transplant (SCT)

Stem cell transplants are sometimes used to treat lymphoma when standard treatments are no longer working. This type of therapy is used only rarely in patients with skin lymphoma, but it may become more common in the future.

Stem cell transplants allow doctors to give higher doses of chemotherapy (and sometimes radiation) than would normally be tolerated. High-dose chemotherapy destroys the bone marrow, which prevents new blood cells from being formed. This could lead to life-threatening infections, bleeding, and other problems due to low blood cell counts.

Doctors try to get around this problem by giving an infusion of blood-forming stem cells after treatment. Stem cells are very early forms of cells that can create new blood cells. They travel to the bone marrow and start making new cells.

The blood-forming stem cells used for a transplant are obtained either from the blood (for a peripheral blood stem cell transplant, or PBSCT) or from the bone marrow (for a bone marrow transplant, or BMT). Peripheral blood stem cells are collected in a procedure similar to a blood donation, while bone marrow donation is usually done in an operating room with the donor under general anesthesia (in a deep sleep). Bone marrow transplants were more common in the past, but they have largely been replaced by PBSCTs.

Allogeneic stem cell transplant

In an allogeneic stem cell transplant, the blood-forming stem cells come from another person (instead of using the patient’s own stem cells). The ideal donor is a relative (often a brother or sister) whose tissue type (HLA type) matches the patient’s. This lowers the chance of a serious side effect called graft vs. host disease, which is discussed later in this section. If the donor is someone who is a tissue type match to the patient but is not related, the transplant carries more risks.

Allogeneic transplants are often the preferred type of transplant if they can be done, but it is often hard to find a matched donor. Another drawback is that side effects of this treatment may be too severe for most people over 55 years old.

Non-myeloablative (mini) transplant: This is a type of allogeneic transplant in which lower doses of chemotherapy and radiation are used than in a standard SCT. This type of transplant may be an option for some patients who couldn’t tolerate a regular allogeneic transplant because of its side effects. In fact, a patient can receive a non-myeloablative transplant as an outpatient.

The lower dose treatment doses do not completely destroy the cells in the bone marrow. When the donor stem cells are given, they enter the body and establish a new immune system, which sees the lymphoma cells as foreign and attacks them (known as a graft-versus-lymphoma effect).

The major side effect is graft-versus-host disease (discussed later in this section), which can be serious.

Doctors aren’t yet sure exactly how effective these types of transplants are for patients with lymphoma, but studies are now being done to find out.

Autologous stem cell transplant

In this type of transplant, a patient’s own stem cells are removed from his or her bone marrow or peripheral blood. They are collected on several occasions in the weeks before treatment. The cells are frozen and stored while the person gets treatment (high-dose chemotherapy and/or radiation) and are then are reinfused into the patient’s blood.

With some types of lymphoma that tend to spread to the bone marrow or blood, an autologous transplant may not be possible because it might be hard to get a stem cell sample that is free of lymphoma cells. Even after purging (treating the stem cells in the lab to kill or remove lymphoma cells), returning some lymphoma cells with the stem cell transplant is possible.

Practical points

With either type of transplant, blood-forming stem cells collected from the donor or the patient are carefully frozen and stored. The patient then receives high-dose chemotherapy and sometimes whole body radiation treatment as well. This destroys remaining cancer cells, but it also kills all or most normal cells in the bone marrow. After therapy, the frozen stem cells are thawed and returned to the body by infusion into a vein, just like a blood transfusion.

For the next several weeks the patient will likely have very low blood cell counts, so they are given as much supportive therapy as needed. This may include antibiotics, red blood cell or platelet transfusions, other medicines, and help with nutrition. Because of the high risk of serious infections, patients stay in protective isolation (where exposure to germs is kept to a minimum) until their white blood cell counts are at a safe level. In an allogeneic SCT, the patient may be given drugs to keep the new immune system from attacking the body (known as graft-versus-host disease).

A stem cell transplant is a complex treatment that can cause life-threatening side effects. If doctors think a patient might benefit from a transplant, the best place to have it done is at a cancer center where the staff has experience with the procedure and with managing the recovery period. Ask the doctor about the number of times he or she has done this procedure, the number done at their facility, and their results with cases such as theirs.

SCT is very expensive (often costing well over $100,000) and often requires a long hospital stay. Some insurance companies may view SCT as an experimental treatment and may not pay for it. Even if the transplant is covered by your insurance, your co-pays or other costs could easily amount to tens of thousands of dollars. Find out what your insurer will cover before deciding on a transplant so you will have an idea of what you might have to pay.

Possible side effects

Side effects from a stem cell transplant are generally divided into early and long-term effects.

Early or short-term effects: The early complications and side effects are basically the same as those caused by any other type of high-dose chemotherapy and can be severe. They are caused by damage to the bone marrow and other rapidly growing tissues of the body and can include:

Hair loss

Mouth sores

Loss of appetite

Nausea and vomiting


Low blood cell counts (with fatigue and increased risks of infection and bleeding)

One of the most common and serious short-term effects is the increased risk for infection. Antibiotics are often given to try to keep this from happening. Other side effects, like low red blood cell and platelet counts, may require blood product transfusions or other treatments.

Late or long-term side effects: Complications and side effects that can last for a long time or that may occur many years after the transplant include:

Graft-versus-host disease, which occurs only in allogeneic (donor) transplants (see below)

Menstrual changes, early menopause, and loss of fertility in female patients (caused by damage to the ovaries)

Loss of fertility in male patients

Damage to the thyroid gland, causing problems with metabolism

Cataracts (damage to the lens of the eye that can affect vision)

Bone damage called aseptic necrosis. If damage is severe, the patient will need to have part of the affected bone and the joint replaced.

Damage to the lungs, causing shortness of breath

Development of leukemia or another cancer years later

Graft-versus-host disease (GVHD): This is one of the most serious complications of allogeneic (donor) stem cell transplants. It occurs because the donor cells establish a new immune system in the patient. The new immune system then may “see” the patient’s own body tissues as foreign and attack them.

Symptoms can include severe skin rashes, itching, mouth sores (which can affect eating), nausea, severe diarrhea, and damage to the liver and lungs. The patient may also become easily fatigued and develop muscle aches.

GVHD is either acute or chronic, based on how soon after the transplant it begins. Sometimes GVHD can become disabling and, if it is severe enough, can be life-threatening. Usually drugs can be used to help control GVHD, although they can have their own side effects.

However, in some cases mild graft-versus-host disease can be a good thing, because it also leads to graft-versus-lymphoma activity. Since the donor’s immune system also sees the lymphoma cells as foreign, it often kills any lymphoma cells remaining after the chemotherapy and radiation therapy.

Treatment for specific types of skin lymphoma

Most of the time, the treatment of skin lymphoma is based on the type of lymphoma, as well as its location and its stage – how far it has spread in the body. But other factors, such as your overall health, may also affect treatment options. Talk to your doctor if you have any questions about the treatment plan he or she recommends.

The treatments mentioned in this section are discussed in more detail in earlier sections of this document.

T-cell lymphomas

Mycosis fungoides

Many forms of treatment can be used for mycosis fungoides (MF).

Skin-directed treatments: For early stages of MF, treatments are aimed at the skin. Options may include:

Phototherapy with ultraviolet (UV) light (either UVB light or UVA combined with drugs called psoralens, known as PUVA)

Topical chemotherapy with BCNU or nitrogen mustard

Topical corticosteroid ointments or injections

Topical retinoid (vitamin A-like drug), such as bexarotene

Topical imiquimod (Zyclara)

Local radiation treatments if there is only one or a few lesions

Total skin electron beam therapy (TSEBT) if MF covers most of the skin

In some cases, more than one type of skin-directed treatment may be used.

Systemic (whole-body) treatments: Mycosis fungoides may remain localized to the skin for many years. However, the disease can eventually become more advanced, and patients may need systemic treatments.

Several types of therapy may be used, such as:

Retinoids (taken by mouth)

Targeted drugs like vorinostat (Zolinza) or romidepsin (Istodax)



Denileukin diftitox (Ontak)

Low-dose methotrexate (a chemo drug)

Chemotherapy (usually with a single drug), bortezomib (Velcade), or alemtuzumab (Campath) may be other options, but they are often reserved for lymphomas that are no longer responding to other treatments. If single chemo drugs are not effective, combinations of drugs (similar to those used for other types of non-Hodgkin lymphoma) might be recommended. A stem cell transplant might be another option at this point.

More than one type of treatment might be used at the same time. This could include combinations of skin-directed and systemic treatments (such as TSEBT plus photopheresis) or multiple systemic treatments (such as an oral retinoid plus interferon).

Many patients can be helped by these treatments, sometimes for many years, but they rarely cure the lymphoma. In cases where other treatments are no longer working, a stem cell transplant may be an option. Newer treatments are also being studied. If current treatments are no longer effective, patients may want to consider entering a clinical trial.

Sezary syndrome

The systemic treatments used for advanced MF are also used for Sezary syndrome. Since the disease has usually spread beyond the skin at the time of initial diagnosis, treatments directed only at the skin are less useful than in MF.

Photopheresis may be helpful in treating the disease, as may retinoids, such as bexarotene. The targeted treatments vorinostat and romidepsin might also be used, as might interferon or denileukin diftitox. Chemotherapy, bortezomib, or alemtuzumab can also be useful, but these are usually reserved for lymphomas that are no longer responding to other treatments. A stem cell transplant may be another option at this point.

As with advanced MF, these treatments are often helpful for a time, but they rarely produce a cure. Newer treatments are currently being studied, and patients may want to consider entering a clinical trial of one of these.

Primary cutaneous anaplastic large cell lymphoma (ALCL)

This lymphoma usually stays confined to the skin. It seldom spreads internally and rarely causes death. It can often be monitored closely without needing to be treated right away. The lymphoma may even go away on its own, without any treatment.

If treatment is needed, the choices are removing it (with surgery), radiation therapy, or topical chemotherapy. If this lymphoma comes back after treatment and spreads to lymph nodes or (rarely) internal organs, then chemotherapy is often used. Newer targeted drugs such as brentuximab vedotin (Adcetris) and crizotinib (Xalkori) have been shown help some patients with non-skin forms of ALCL. These might also be options for advanced cutaneous ALCL, although more research is needed.

Lymphomatoid papulosis

This disease often comes and goes on its own and usually has such a good outlook that treatment is not needed right away. If treatment is needed, topical therapies are often chosen, such as nitrogen mustard or corticosteroids applied to the skin lesions. Rarely is there any need for systemic chemotherapy.

Subcutaneous panniculitis-like T-cell lymphoma

Patients with this type of lymphoma can live a long time and generally have an excellent outlook. Although chemotherapy and radiation have been used successfully in the past, the disease can also be controlled for long periods with the use of corticosteroids alone.

Primary cutaneous peripheral T-cell lymphoma, unspecified

Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphomas are usually fast growing and are treated with systemic chemotherapy.

Cutaneous gamma/delta T-cell lymphoma tends to grow and spread very quickly. It is treated with systemic chemotherapy or radiation therapy, but generally does not respond well to treatment.

Primary cutaneous CD4+ small/medium sized pleomorphic T-cell lymphoma may be removed with surgery or treated with radiation if there is only a single tumor. If there are many tumors, systemic chemotherapy is often effective. People with this lymphoma generally have a good outlook, especially if they have only one tumor.

Primary cutaneous peripheral T-cell lymphoma, unspecified, is treated with systemic chemotherapy. Although these lymphomas may respond to chemotherapy at first, they often come back later, and long-term survival is not common.

These lymphomas are often hard to treat effectively, so patients may want to consider clinical trials studying newer forms of treatment.

B-cell lymphomas

Primary cutaneous marginal-zone B-cell lymphoma

This type of lymphoma can sometimes be watched without treatment until problems develop. For lymphomas that are in one spot or only a few spots close together, initial treatment is usually radiation therapy or excision (surgical removal). If the lymphoma does not go away completely or keeps growing, further treatment may include surgery; radiation therapy; topical medicines such as corticosteroids, chemotherapy, bexarotene (Targretin), or imiquimod (Zyclara); or injected corticosteroids.

For lymphomas that have spread over larger parts of the skin, treatment options include rituximab (Rituxan), topical medicines (such as corticosteroids, chemotherapy, bexarotene, or imiquimod), radiation therapy, or injected corticosteroids. Systemic chemotherapy (sometimes with rituximab), like that used for other slow-growing B-cell lymphomas, can also be used if there are many lesions.

If the lymphoma has spread to lymph nodes or internal organs, it is treated like follicular lymphomas found in other parts of the body, typically with a combination of chemotherapy and rituximab.

Primary cutaneous follicle-center lymphoma

These lymphomas are treated the same way as primary cutaneous marginal-zone B-cell lymphomas (see above).

Primary cutaneous diffuse large B-cell lymphoma, leg type

These lymphomas may look like they involve only a small area of the skin at first, but the disease is often more widespread than it first appears. The treatment of choice is rituximab along with systemic chemotherapy. Often the regimen called R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is given, but other chemo combinations can also be used. If the lymphoma is in only one or a few areas, radiation therapy directed at the tumors is often used as well. For people who can’t tolerate chemotherapy, radiation therapy alone may be given.

If the lymphoma has spread to the lymph nodes or other organs, treatment is the same as that used for diffuse large B-cell lymphomas found in other parts of the body, which is usually R-CHOP, with or without radiation therapy .

Primary cutaneous diffuse large B-cell lymphoma, other (non-leg)

Patients with this type of lymphoma (which involves sites other than the leg) require systemic chemotherapy, similar to that used for primary cutaneous diffuse large B-cell lymphoma, leg type. This is most often the R-CHOP regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone).

What if the lymphoma keeps growing or comes back after treatment?

Some lymphomas may not respond well to treatment. Most often, other types of treatment can then be tried. But as more treatments are tried, they may be less likely to work or more likely to cause side effects.

When a cancer comes back after treatment it is called recurrent or relapsed. In general, if a skin lymphoma comes back it tends to be in the skin. If this is the case, skin-directed therapies that haven’t been used yet may be effective.

Some skin lymphomas eventually spread to lymph nodes and internal organs as well. Often, lymph nodes are the first site of relapse. After that, it may spread to internal organs such as the liver, spleen, and bone marrow. Chemotherapy is often used in this situation, especially if the patient has not yet received chemotherapy. Other drugs, such as romidepsin (Istodax), bortezomib (Velcade), alemtuzumab (Campath), and denileukin diftitox (Ontak), may also be options at the time of relapse. A stem cell transplant may be another option at some point.

Advanced skin lymphomas are very hard to cure. Different systemic treatments may be effective for some time. But in general, with each type of treatment that is tried, the next treatment has a smaller chance of being helpful. If the lymphoma improves with later treatments, it often comes back sooner than it did before. Over time, treatments tend to provide less benefit, but they can still cause side effects.

At some point, a person may want to consider trying to relieve the symptoms of the lymphoma, rather than trying to get rid of it with more aggressive treatments that have a very small chance of success. This approach is called palliative care.

For example, when lymph nodes become enlarged, they may press on nerves and cause pain. Radiation therapy to these areas may help relieve the pain and can be used if radiation has not previously been given to this area of the body. Treatment with appropriate pain medicines is also important. Help with pain treatment from a palliative care team may be required.

Some symptoms from lymphoma may result from low blood counts. Fatigue may be caused by low red blood cell counts (anemia). Sometimes blood transfusions may be used to increase the number of red blood cells and help a person feel better. Low white blood cell counts (from chemotherapy or from the lymphoma itself) may lead to infections. Certain drugs such as G-CSF (Neupogen) or GM-CSF (Leukine) may be used to increase the white blood cell count.

Nausea and loss of appetite can occur because of the disease or its treatment. These symptoms can also be treated effectively with drugs, as well as high-calorie food supplements. If the lymphoma involves the lungs, patients may get short of breath. Oxygen may be used to help treat this symptom. See the “Physical Side Effects” section of our Web site for more information on side effects from cancer and cancer treatment.

Some people may become depressed. Counseling and medication may be helpful. If depression is a problem, it is important to discuss your feelings with your doctor or nurse, so that appropriate treatment can be started. 

What happens after treatment for lymphoma of the skin?

For some people with skin lymphoma, treatment may remove or destroy the cancer. Completing treatment can be both stressful and exciting. You may be relieved to finish treatment, but find it hard not to worry about the lymphoma growing or coming back. (When cancer comes back after treatment, it is called recurrence.) This is a very common concern in people who have had cancer.

It may take a while before your fears lessen. But it may help to know that many cancer survivors have learned to live with this uncertainty and are living full lives. 

For many people, the lymphoma may never go away completely. These people may get regular treatments with chemotherapy, radiation therapy, or other therapies to help keep the lymphoma in check for as long as possible. Learning to live with lymphoma as more of a chronic disease can be difficult and very stressful. It has its own type of uncertainty.

Follow-up care

Whether you have completed treatment or are still being treated, your doctors will still want to watch you closely with regular physical exams, blood tests, and possibly imaging tests. It is very important to keep all of your follow-up appointments.

You may need to have frequent blood tests to monitor your bone marrow function, to check that you have recovered from treatment, and to look for possible signs of disease recurrence. Rarely, blood cell counts can become abnormal as a long-term side effect of chemotherapy. If chemo damages the bone marrow, a disease called myelodysplasia can occur. In some cases this may even lead to acute leukemia.

The choice of other tests depends on the type, location, and extent of your lymphoma. If lymph nodes or other organs are affected, CT scans may be used to measure the size of any remaining tumor masses. PET scans may be done if your doctors aren’t sure if an abnormal area on a CT scan is an active lymphoma or scar tissue.

Almost any cancer treatment can have side effects. Some may last for a few weeks to several months, but others can be permanent. Tell your cancer care team about any symptoms or side effects that bother you so they can help you manage them.

If the lymphoma does come back at some point, further treatment will depend on where it recurs, what treatments you’ve had before, how long it’s been since treatment, and your overall health. 

If treatment of lymphoma of the skin is no longer working

If lymphoma keeps growing or comes back after one kind of treatment, it may be possible to try another treatment plan that might still cure the lymphoma, or at least shrink the tumors enough to help you live longer and feel better. But when a person has tried many different treatments and the lymphoma has not gotten any better, it tends to become resistant to all treatment. If this happens, it’s important to weigh the possible limited benefits of a new treatment against the possible downsides, including treatment side effects. Everyone has their own way of looking at this.

This is likely to be the hardest part of your battle with cancer – when you have been through many medical treatments and nothing’s working anymore. Your doctor may offer you new options, but at some point you may need to consider that treatment is not likely to improve your health or change your outcome or survival.

If you want to continue to get treatment for as long as you can, you need to think about the odds of treatment having any benefit and how this compares to the possible risks and side effects. In many cases, your doctor can estimate how likely it is the cancer will respond to treatment you are considering. For instance, the doctor may say that more treatment might have about a 1 in 100 chance of working. Some people are still tempted to try this. But it is important to have realistic expectations if you do choose this plan.

No matter what you decide to do, it is important that you feel as good as you can. Make sure you are asking for and getting treatment for any symptoms you might have, such as nausea or pain. This type of treatment is called palliative care.

Palliative care helps relieve symptoms, but is not expected to cure the disease. It can be given along with cancer treatment, or can even be cancer treatment. The difference is its purpose – the main goal of palliative care is to improve the quality of your life, or help you feel as good as you can for as long as you can. Sometimes this means using drugs to help with symptoms like pain or nausea. Sometimes, though, the treatments used to control your symptoms are the same as those used to treat cancer. For instance, radiation might be used to help relieve pain caused by cancer that has spread. Or chemo might be used to help shrink a tumor and keep it from blocking the bowels. But this is not the same as treatment to try to cure the cancer. 

At some point, you may benefit from hospice care. This is special care that treats the person rather than the disease; it focuses on quality rather than length of life. Most of the time, it is given at home. Your cancer may be causing problems that need to be managed, and hospice focuses on your comfort. You should know that while getting hospice care often means the end of treatments such as chemo and radiation, it doesn’t mean you can’t have treatment for the problems caused by your cancer or other health conditions. In hospice the focus of your care is on living life as fully as possible and feeling as well as you can at this difficult time. You can learn more about hospice in our document Hospice Care.

Staying hopeful is important, too. Your hope for a cure may not be as bright, but there is still hope for good times with family and friends – times that are filled with happiness and meaning. Pausing at this time in your cancer treatment gives you a chance to refocus on the most important things in your life. Now is the time to do some things you’ve always wanted to do and to stop doing the things you no longer want to do. Though the cancer may be beyond your control, there are still choices you can make.

What’s new in skin lymphoma research and treatment?

Research into the causes, prevention, and treatment of lymphoma of the skin is being done in many medical centers throughout the world.


As noted in the section “Do we know what causes lymphoma of the skin?” scientists are making progress in understanding how changes in DNA can cause normal lymphocytes to develop into lymphoma cells. Understanding the gene changes that occur in lymphoma cells provides insight into why these cells grow too quickly, live too long, and do not develop into normal mature cells. Once this is understood, drugs may be developed that block or specifically target this process.

Our understanding of these DNA changes has already led to highly sensitive tests for detecting this disease. These tests can identify lymphoma cells based on their gene changes. For example, polymerase chain reaction (PCR) is a very sensitive test that is useful in determining if a lymphoma has been destroyed by treatment and whether a relapse is likely. These tests may help pick out those patients who may need early and more intensive treatment.

Skin-directed treatments

Several newer types of skin-directed treatments are now being studied for the treatment of early stage skin lymphomas.

Photodynamic therapy (PDT)

For this treatment, a light-activated drug called aminolevulinic acid (ALA) is applied to the skin lesions. A special type of laser light is then focused on the lesions. This light causes changes in the drug that has collected inside the lymphoma cells, changing it into a new chemical that can kill them.

The advantage of PDT is that it can kill cancer cells with very little harm to normal cells. But because the chemical must be activated by light, it can only kill cancer cells near the surface of the skin. This limits its use to early stage skin lymphomas that have not grown deeply into the skin. Even then, PDT might only be used if other types of skin-directed therapies are not effective. 

Topical tacrolimus

Tacrolimus is a drug that affects immune system cells such as lymphocytes, the cells that develop into lymphoma cells. Applying this drug to skin lymphomas seems to be about as effective as using topical corticosteroids, but more research is needed to help determine its safety and effectiveness.


Many clinical trials are in progress to study newer chemotherapy drugs. One example is pralatrexate (Folotyn), a drug that is already used to treat some T-cell lymphomas and has shown early promise in treating some skin lymphomas. Another drug that has shown some promise in early clinical trials is forodesine. Research on these and other new drugs continues.

Other studies are looking at ways to use drugs already known to be effective by combining them in new ways or using different doses or different sequences of these drugs.

Targeted drugs

Newer drugs known as targeted therapies have shown clear benefit in certain kinds of skin lymphoma. The drugs vorinostat (Zolinza), romidepsin (Istodax), and bortezomib (Velcade) are forms of targeted therapy that can help treat some skin lymphomas. Doctors are now studying how to use these new drugs most effectively.

Other targeted drugs are also being developed. One example is crizotinib (Xalkori), which has been shown help some patients with non-skin forms of anaplastic large cell lymphoma (ALCL). Others being studied include everolimus (Afinitor) and lenalidomide (Revlimid).

Monoclonal antibodies

Lymphoma cells have certain chemicals on their surface. Special man-made antibodies that recognize these substances can be targeted to destroy the lymphoma cells while causing little damage to normal body tissues.

New monoclonal antibodies are also being developed. One example is zanolimumab (HuMax-CD4), an antibody that has shown promise in early clinical trials.

Another is brentuximab vedotin (Adcetris), an antibody that is attached to a chemotherapy drug. The antibody targets a substance on the surface of some lymphoma cells, bringing the chemo drug directly to these cells. It has already shown good results in treating some other types of lymphomas and is now being studied for certain skin lymphomas.

Stem cell transplant

High-dose chemotherapy followed by a stem cell transplant is sometimes used to treat lymphomas that no longer respond to other treatments. Researchers continue to improve stem cell transplant methods, including new ways to harvest these cells before transplantation.

Autologous transplants (using the patient’s own stem cells) have the risk of reintroducing lymphoma cells back into the patient after treatment. Researchers are testing new and improved ways to remove the last traces of lymphoma from these stem cells before they are returned to the patient. Some of the new monoclonal antibodies developed for treating lymphoma may be helpful in removing these remaining cells.

Much research is focusing on reducing graft-versus-host disease in allogeneic transplants (using stem cells from a donor). This work involves altering the transplanted T-cells so that they won’t react with the patient’s normal cells but will still kill the lymphoma cells.

Lymphoma vaccines

Doctors know it is possible for people with cancer to develop immune responses to their cancer. In rare instances, people’s immune systems have rejected their cancers, and they have been cured. Scientists are now studying ways to boost this immune reaction using vaccines.

Unlike vaccines used to prevent infections, the purpose of these vaccines is to create an immune reaction against the lymphoma cells in patients who have very early disease or whose disease is in remission but could come back or relapse. This is a major area of research in lymphoma treatment, but it is still being tested in clinical trials. You may want to consider enrolling in one of these studies.

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