CTCL stands for cutaneous T-cell lymphoma, a rare cancer of T-lymphocytes (a type of white blood cells) that involves the skin. There are several types of CTCL, but mycosis fungoides and Sézary syndrome are the most common. We’ve provided an overview of the disease, treatment and prognosis.
Mycosis fungoides are the most common form of cutaneous T-cell lymphoma (CTCL). Mycosis fungoides” and “CTCL” are often used interchangeably, which is imprecise, as mycosis fungoides is just one type of CTCL.
Primary cutaneous B-cell lymphomas (CBCLs) are a cutaneous lymphoma (a cancer of white blood cells) that affects B-cells in the skin. Primary cutaneous T-cell lymphomas (CTCL) are part of a group of rare non-Hodgkin lymphomas that arise from the T-cell type lymphocytes.
Primary cutaneous T-cell lymphomas (CTCL) are part of a group of rare non-Hodgkin lymphomas that arise from the T-cell type lymphocytes.
Cutaneous T-Cell Lymphoma
One of the most common forms of T-cell lymphoma is cutaneous T-cell lymphoma (CTCL), a general term for T-cell lymphomas that involve the skin. CTCL can also involve the blood, lymph nodes, and other internal organs.
Symptoms can include dry skin, itching (which can be severe), a red rash, and enlarged lymph nodes. The disease affects men more often than women and usually occurs in men in their 40s, 50s, and 60s.
Most patients with CTCL experience only skin symptoms. Some patients with early-stage CTCL might not progress to later stages at all, while others might progress rapidly with the cancer spreading to lymph nodes and/or internal organs.
The exact underlying cause of cutaneous T-cell lymphomas is unknown. Researchers speculate that genetic and immunologic abnormalities, environmental factors (e.g., exposure to ultraviolet rays, certain chemicals, ionizing radiation [carcinogens]; certain viral infections; bacterial skin infections, etc.), diet, stress, and/or additional factors may play varying contributing roles in causing specific types of cancer. Investigators at the National Institutes of Health (NIH)/National Cancer Institute, across the United States, and around the world are conducting ongoing basic research to learn more about the many factors that may result in cancer.
In individuals with cancer, including CTCLs, malignancies may develop due to abnormal changes in the structure and orientation of certain cells (e.g., T-lymphocytes). As mentioned above, the specific cause of such changes is unknown. However, current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body’s genetic code, are the underlying basis of cellular malignant transformation. Depending upon the form of cancer present and several other factors, these abnormal genetic changes may occur spontaneously for unknown reasons (sporadically), such as due to exposure to certain environmental factors, or, more rarely, may be inherited.
The signs and symptoms associated with cutaneous T-cell lymphomas vary greatly from case to case, depending upon the specific type of lymphoma present and how far the disease has progressed (i.e., staging).
The most common type and classic presentation of CTCL are known as mycosis fungoides and usually progresses slowly over many years. The associated skin symptoms of mycosis fungoides progress through three separate phases. Affected individuals may first develop a red rash or dry, red, scaly patches of skin that most often affect the buttocks and trunk (premyotic phase). These patches may remain unchanged, spontaneously go away, or slowly grow larger. The skin lesions associated with the initial phase of mycosis fungoides are termed “nonspecific” because they cannot be differentiated from skin lesions associated with other, more common, skin disorders such as psoriasis. This initial phase of mycosis fungoides may persist for months, years, or decades.
In the second phase of mycosis fungoides, slightly-elevated, reddish-brown, scaly bumps (plaques) develop on the skin (mycotic stage). These plaques may develop from existing patches or spontaneously in unaffected areas. Eventually, these plaques may expand and grow together (coalesce) forming larger plaques. Any area of the body may be affected.
The skin lesions associated with the first two phases of mycosis fungoides may not be associated with other symptoms (asymptomatic) or may occur along with itchiness (pruritis) and pain. In rare cases, affected individuals may experience difficulty sleeping due to severe itchiness.
The third phase of mycosis fungoides is characterized by the development of mushroom-shaped tumors. In some cases, the tumors may become ulcerated and infected. Some individuals may not progress beyond the plaque phase of mycosis fungoides and do not develop tumors. Other individuals may develop tumors without first developing the patches or plaques associated with the early stages of mycosis fungoides (tumeur d’ emblee variant).
In approximately 10 percent of individuals with the classic mycosis fungoides presentation of CTCL, malignant lymphocytes may spread beyond the skin to affect the lymph nodes and major organs of the body including the liver, spleen and gastrointestinal system. Depending upon specific sites and extent of involvement, disease management, and additional factors, disease progression may eventually lead to life-threatening complications. (For more information on this disorder, choose “mycosis fungoides” as your search term in the Rare Disease Database.)
In rare cases, affected individuals may develop Sezary syndrome, a form of CTCL that is considered the leukemic variant of mycosis fungoides. It is characterized by a widespread red rash that may cover most of the body (generalized erythroderma), the presence of specific malignant lymphocytes (Sezary cells) in the blood, and abnormally enlarged lymph nodes (lymphadenopathy). Individuals with Sezary syndrome may experience intense itchiness (pruritis) and thickening, scaling, and peeling (exfoliation) of the skin. Additional symptoms associated with Sezary syndrome include outward turning of the eyelids (ectropion); abnormally thick, rough skin on the palms of the hands and the soles of the feet (palmoplantar keratoderma); malformation of the nails (onychodystrophy); and abnormal enlargement of the liver and/or spleen (hepatosplenomegaly). General symptoms associated with Sezary syndrome include fevers, weight loss, bald patches on the scalp (alopecia), and a general feeling of ill health (malaise).
Granulomatous slack skin is a rare form of CTCL characterized by areas (folds) of lax, reddened skin. The underarms, groin, and stomach are most often affected. Granulomatous slack skin is usually a benign, slow-growing (indolent) form of CTCL. In some cases, affected individuals may develop a more serious form of CTCL, such as mycosis fungoides, later during life.
Primary cutaneous anaplastic large cell lymphomas represent a subgroup of CTCL characterized by positive expression of the CD30 (Ki-1) antigen. Affected individuals develop tumors on the skin. The tumors may become ulcerated or infected. In some cases, the lesions or tumors go away without treatment (spontaneous regression). However, lesions often return (relapse). In rare cases, other organ systems of the body may become involved.
Lymphomatoid papulosis is a rare skin disorder that some researchers believe is an early from of CD30+ lymphoma. The disorder is characterized by groups of slightly-elevated, reddish-brown bumps (nodules or papules) that most often affect the trunk, face, and arms and legs. These lesions often become crusted or ulcerated, sometimes leaving a scar. Approximately 5-20 percent of individuals with lymphomatoid papulosis develop CTCL. Other researchers believe that lymphomatoid papulosis is a similar, yet distinct, “premalignant” condition and not a form of CTCL.
Subcutaneous pannulitic T-cell lymphoma is a rare variant of CTCL. Affected individuals may have multiple, tender, bumps (nodules) just under the surface of the skin of various areas of the body especially the arms and legs (extremities). These nodules may lead to inflammation of the subcutaneous layer of fat (panniculitis). Affected individuals may also experience weight loss, fevers, and joint pain (arthralgia). Unlike mycosis fungoides, this form of CTCL is often aggressive may lead to the involvement of other organ systems and, potentially, life-threatening complications.
Pagetoid reticulosis (PR), also known as Woringer-Kolopp disease, is a rare skin condition characterized by a solitary lesion that usually affects the arms or legs and may grow slowly. The lesion is similar in appearance to the lesions associated with mycosis fungoides. In addition, there are also microscopic similarities between the skin lesions in mycosis fungoides and pagetoid reticulosis. Consequently, most researchers believe that PR is a slow-growing variant of CTCL.
According to the medical literature, cases have been reported in which individuals developed more than one form of CTCL at the same time.
The symptoms of CTCLs result from abnormal, uncontrolled growth and multiplication (proliferation) of malignant T-lymphocytes, which results in accumulation of these lymphocytes in the skin and, in some cases, other organ systems of the body. There are two types of T-lymphocytes known as CD4 and CD8. CD4s (helper cells) help regulate functions of the immune system. CD8s (killer cells) breakdown or rid the body of foreign substances. In most cases of CTCL, CD4s are the cells that become malignant.
Treatments for cutaneous lymphomas vary based on several factors. These include whether it is CTCL or CBCL, early or advanced, and on prior treatments for the lymphoma. There is no one prescription that fits everyone, and treatments are tailored to each patient’s particular situation.
Goals of Treatment
● Improve the quality of life by relieving symptoms such as pain, itching, burning, and redness
● Clear up skin patches, plaques, or tumors
● Eliminate or reduce the number of cancerous lymphocytes in the skin and blood
● Prevent migration of malignant cells from the skin to other organs
● Restore immune balance and competence
As cutaneous lymphomas are indolent (slow-growing), curing cutaneous lymphomas is very difficult and rarely the goal of treatment.
WHAT ARE THE DIFFERENT TYPES OF TREATMENT?
Skin-directed therapy are treatments that are administered directly to the skin. This includes topical therapies like topical steroids, topical retinoids and topical chemotherapy, phototherapy (light therapy), skin radiation, and surgical removal (excision) of lesions. These kinds of treatments are generally very safe and have limited internal side effects. Skin directed therapies are often used to treat early or limited cutaneous lymphoma, and are also used in conjunction with systemic therapies in more advanced cutaneous lymphoma.
Systemic therapies are treatments given internally, such as orally, intravenously, or subcutaneously (injected under the skin). Systemic therapies can be used a single agents, in combination with skin directed therapies, or in combination with other systemic therapies. There are several different types or classes of systemic therapies.
Targeted cancer therapies are drugs that act specifically against particular molecules needed for cancer growth. Targeted therapies usually have a lower toxicity towards normal cells and therefore may result in fewer side effects. Targeted therapies often require that a certain target be present on the cancer cells in order for the drug to work, and may not be as effective for all patients or types of cancers. Targeted therapies are leading to increasingly individualized treatments where each patient can receive therapy that is specific for their individual disease.
Biologic therapy is a kind of targeted therapy that works with the body’s normal cell functions to fight cancer. These drugs repair, stimulate, or enhance the action of the patient’s healthy immune cells. Specific biologic agents target specific characteristics of cancer cells.
Stem Cell Transplantation
Bone marrow or stem cell transplantation is considered in cases for patients with advanced disease, though most cutaneous lymphoma patients will never need to evaluate this option. Stem cell transplantation refers to a procedure where healthy stem cells are transplanted from one person (including yourself) to another. Sources of stem cells include bone marrow, peripheral blood, or umbilical cord blood. Allogeneic stem cell transplantation, in which a patient receives stem cells from another person, is the recommended transplantation method for cutaneous lymphoma patients. Hematopoietic stem cells can grow into any of the cells found within the bloodstream. They make blood cells and the components that your immune system needs to function. During a transplant, you are first treated with high dose chemotherapy or radiation to treat cancer and eliminate your immune system, then your body is infused with healthy stem cells that then grow and produce all of the different parts of the blood that both your body and your immune system need.
Subtypes of CTCL
CTCL describes many different disorders with various symptoms, outcomes, and treatment considerations:
• Mycosis Fungoides (MF): the most common type of CTCL, accounting for approximately one-half of all CTCLs. MF can look different in each patient, with skin symptoms that can appear as patches, plaques, or tumors.
• Sézary Syndrome: characterized by the presence of lymphoma cells in the blood, patients with Sézary Syndrome often present with extensive thin, red, itchy rashes that typically appear on the skin.