Most people are aware of the basic types of skin cancer. But not so many have heard of a rare type of lymphoma called cutaneous T-cell lymphoma (CTCL), which is often first noticed because of skin symptoms. 

Though T-cell lymphoma can also involve the blood, lymph nodes and internal organs, it most commonly affects the skin, causing rash-like patches, itching and sometimes even tumors. T-cell lymphoma is not curable but it is treatable. 

Yale Medicine's Department of Dermatology offers expert, multidisciplinary care and advanced treatments, including phototherapy for this unusual type of lymphoma. 

T-cell lymphoma is a rare form of lymphoma that can affect many different parts of the body, including the blood, lymph system and internal organs. Usually, however, CTCL presents with skin symptoms, such as small patches of redness or dry skin that grow or spread very slowly, over long periods of time. Sometimes, however, CTCL is aggressive and moves quickly.

Though cutaneous T-cell lymphoma is chronic, it is treatable. Patients who enter remission should be monitored closely for returning symptoms.

“In the spectrum of non-Hodgkin lymphoma, it’s one of the ones that has a better prognosis,” says Michael Girardi, MD, vice chair and program director of the Department of Dermatology at Yale Medicine. He is also a professor of dermatology at Yale School of Medicine.

CTCL comes in many forms, but the two most common are mycosis fungoides and Sézary syndrome.

• Mycosis fungoides is the most prevalent form of CTCL. Though it can appear differently from person to person, it generally shows up in the skin as a red rash. Sometimes this is barely noticeable, looking like a slightly discolored patch of skin – pink, brownish or slightly whitish. It can evolve into large, thick areas on the skin called plaques, which can be scaly and itchy and sometimes further develops into tumors on the skin. Areas of the skin that are commonly affected are the “bathing trunk” areas, meaning parts that would be covered by a swimsuit – the buttocks and the breasts, for example. But cutaneous T-cell lymphoma is a condition that often defies expectations.

“With CTCL we often say that even though there is a typical story, there are a lot of atypical stories,” says Dr. Girardi. “Meaning it can occur anywhere on the skin. It can end up in whatever spots it wants to come out in.”

• Sézary syndrome is one of the most advanced forms of CTCL. A very close relative of mycosis fungoides that can feature similar skin-related symptoms, this type of CTCL is also present in the blood. Sézary syndrome also often affects the lymph nodes.

CTCL can develop in anyone, regardless of age, race or sex, but is more commonly found in older individuals says Dr. Girardi.

“I have patients in their 20s and 30s, but more patients in their 40s, 50s, 60s and 70s,” he says. “It’s the whole spectrum of ages, but the risk increases with age.”

The underlying causes of CTCL are currently unknown, with ongoing research exploring why it affects some people and not others. Those studies are mostly being done at the genetic level, in the hopes that new insights can help to develop new and better treatments.

CTCL is often misdiagnosed because its symptoms closely resemble those of other skin conditions.

“A lot of patients tell me they’ve had a skin disease and their doctor keeps saying it’s one thing, but it’s not responding to treatments, and it’s getting worse,” says Dr. Girardi. “That’s all too common a story that ends up turning out to be CTCL.”

Diagnosis is made more difficult because CTCL can manifest in a subtle way. Many people initially experience only a few mild symptoms, perhaps small red or dry areas on their skin that grow very, very minimally over a long period of time.

“It can be very slow to develop, even over years," confirms Dr. Girardi, noting that in the early stages, even a biopsy may not reveal the presence of disease. “Depending on the pathologist, early on it might not necessarily be clear that it’s CTCL. It can look like eczema and psoriasis, even under the microscope.”

Experience treating CTCL makes it more likely that a clinician and/or pathologist will recognize the overall picture and correctly identify the condition.  

The diagnostic work-up for a patient with suspected CTCL may include a physical exam and biopsies, as well as other molecular testing of the skin and of the blood. Sometimes several skin biopsies are taken over many months in order to come to a correct diagnosis. When a pathologist has the opportunity to examine the cells multiple times, there’s a better chance that he or she will recognize it as cutaneous T-cell lymphoma.

“We have more treatments for CTCL than we’ve ever had,” says Dr. Girard. Which is right for a particular person depends on how their CTCL manifests. Some treatments are used individually, while others are effective in combination.  

• Topical medications: Creams, gels and ointments can be prescribed and applied directly to the skin. Examples include corticosteroids, which can help relieve itchiness and redness; mechlorethamine, which can slow the rapid growth of cells, and imiquimod, which activates the immune system. Though these medications can cause side effects, they are generally recognized as the safest initial forms of treatment.
• Phototherapy: This targeted light therapy exposes the skin to specific parts of the ultraviolet spectrum. This helps eliminate problematic red patches and plaques on the skin, while helping healthy cells to regenerate. Phototherapy requires several treatment sessions per week, over several weeks to several years. Side effects can range from sunburn to, in some cases, an increased risk of skin cancer.
• Electron-beam therapy: This type of radiation therapy stays in the skin and doesn't reach the inside of the body, which means that it’s less harmful to underlying tissue and organs. Often used when CTCL symptoms haven't responded to other types of treatment, this procedure involves application of a specific type of low-level X-rays and electrons to localized areas or to the entire surface of the skin. Electron beam therapy must be given by a radiation oncologist. Side effects can range from sunburn to dry skin.
• Photopheresis: This treatment can help patients whose CTCL is present in the blood, such as those with Sézary syndrome. In Photopheresis, the patient’s blood is typically removed intravenously. The white blood cells are separated and treated with chemicals and ultraviolet light and are then returned to the body. The treatment is often done over a couple days, and repeated every few weeks for at least several months. This treatment can also help patients with widespread redness of the skin but no blood involvement, though it is less commonly used in such cases. Anemia is a potential side effect of Photopheresis.  
• Internal medications: The two oral drugs that are approved by the Food and Drug Administration for the treatment of cutaneous T-cell lymphoma are Targretin (bexarotene) and Zolinza (vorinostat). Doctors may also consider other pills, such as Trexall (methotrexate), or injections, such as alpha and gamma interferons, both of which activate the immune system. Side effects can range from nausea to flu-like symptoms.

“These all have some efficacy,” Dr. Girardi says. “They can often be leveraged in combination, allowing us to use lower doses of each, so we can get much less toxicity by finding the right cocktail of therapy.”

But when a patient doesn’t respond to those types of treatments, doctors may explore more aggressive options, including treatments administered intravenously, such as Istodax (romidepsin). Like other lymphomas, cutaneous T-cell lymphoma can spread throughout the body and to other organs. If this happens, doctors may consider chemotherapy, or, in rare cases, peripheral blood transplantation.

Treatment of CTCL can help to keep symptoms to a minimum, and even lead to remission. But the disease can recur, and treatments may need to be explored again.

“In general we don’t think we’re curing anyone with a lot of these treatments,” Dr. Girardi says. “We’re just keeping the cells to a minimum and helping as best we can to prevent them from growing and traveling. Patients need to be watched closely over many years.”

Yale Medicine's Department of Dermatology offers a wide range of treatments for CTCL in one convenient location. These include separate units for both phototherapy and Photopheresis, a therapeutic radiology center and an oncology infusion center. Additional treatment options may be available through ongoing clinical trials.

Another important advantage Yale Medicine offers is an interdisciplinary approach that provides a level of care few, if any, other centers can match. At Yale, specialists in dermatology, oncology, therapeutic radiology and dermatopathology regularly come together to look at each patient's pathology studies. Together they discuss the clinical findings and test results, and decide on the best treatment plans.

“Even when a patient is only seeing one of us, he or she is getting the expertise of other doctors here with different perspectives on the disease,” says Dr. Girardi. “Sometimes we have them see everyone, but sometimes their cases are being discussed in a way that can benefit them even if they haven’t seen all these doctors. That approach is important in certain diseases, and CTCL is definitely one of them.”