Cutaneous T-cell lymphoma (CTCL)

ALSO KNOWN AS: Anaplastic large-cell lymphoma, cutaneous anaplastic large-cell lymphoma, granulomatous slack skin, lymphomatoid papulosis, lymphoproliferative disorder, pagetoid reticulosis, reticulum cell sarcoma of the skin, Woringer-Kolopp disease

RELATED CONDITIONS: Adult T-cell leukemia and lymphoma, follicular mucinosis, mycosis fungoides, non-Hodgkin lymphoma, peripheral T-cell lymphoma, Sézary syndrome

DEFINITION: Cutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin lymphoma that mainly affects the skin. It is an uncontrolled growth of T cells, a type of white blood cell. “Cutaneous” means that this disease affects the skin. Sézary syndrome is a type of CTCL in which the skin, lymph nodes, and blood are all affected. Mycosis fungoides is another kind of CTCL in which only the skin and lymph nodes are affected. Other CTCL types include Primary cutaneous anaplastic large cell lymphoma, Subcutaneous panniculitis-like T-cell lymphoma, Adult T-cell leukemia/lymphoma, Primary cutaneous gamma-delta T-cell lymphoma, Extranodal NK/T-cell lymphoma, and Hydroa vacciniforme-like lymphoproliferative disorder.

Risk factors: The cause of CTCL is unknown, but several risk factors have been identified. Some people with lymphomas have an acquired gene mutation. However, the exact mutation associated with this type of cancer is still unknown. In some patients, this disease is associated with a preexisting allergic condition or a viral infection. Researchers are investigating whether there is a connection between this disease and viruses and whether environmental factors have any association with it.

Etiology and the disease process: Most types of non-Hodgkin lymphoma do not affect the skin. However, CTCL is different in that it mostly affects skin cells. This disease often starts with a rash that itches, sometimes to the point of interrupting sleep, or very dry skin. It may progress to red, scaly patches on the skin, called plaques, that spread to larger areas of skin. The skin may also have tumors that may become infected or turn into bloody sores. This disease may progress to the lymph nodes and, in advanced cases, can spread to the spleen, liver, and intestines. In some cases, this type of lymphoma may begin to act like a more aggressive Hodgkin lymphoma.

Incidence: CTCL is quite rare. The incidence estimates in the United States are six to eight persons per million people annually. People between the ages of forty and sixty are most likely to get this type of cancer, and children rarely have it. Men are twice as likely as women to develop CTCL, and it is slightly more common in Black Americans than in those of other racial backgrounds. Mycosis fungoides accounts for more than 60 percent of CTCL cases.

Symptoms: Symptoms of CTCL include a rash, red, scaly, itchy skin, skin tumors, enlarged lymph nodes, hair loss, and enlarged spleen.

Screening and diagnosis: A physical examination is helpful in diagnosing CTCL. However, since CTCL’s effect on the skin is similar to that of many other conditions, a diagnosis of CTCL involves a biopsy of the affected skin. This skin is then examined under a microscope to determine if T cells are growing abnormally. Diagnosis may also involve blood tests to determine if the cancer has spread to the blood system. Computed tomography (CT) or magnetic resonance imaging (MRI) scans may be used to look at lymph nodes to determine if the disease has spread to them.

One type of staging of CTCL involves three stages; however, the disease does not always progress through these stages.

• Pretumor stage: Small raised patches appear on the skin, usually on the breast or buttocks, though they may appear anywhere. These patches may resemble eczema. Most patients never progress beyond this stage.
• Plaque stage: Red patches appear on the skin, and sometimes there is no hair growth in these patches. These irregularly shaped patches, called plaques, may appear anywhere on the body but are usually on the face or buttocks or in the skin folds.
• Tumor stage: Tumors, or raised lumps, begin to appear on the skin. These tumors and the plaques may become ulcers (bleeding sores). Sometimes the lymph nodes are affected at this stage, and occasionally, the cancer affects internal organs such as the spleen, liver, or lungs at this stage.

This disease may also be called Sézary syndrome, especially if it progresses to the point of having many abnormal lymphocytes in the blood. Sometimes in Sézary syndrome, the entire skin is red, thick, swollen, and itchy.

Non-Hodgkin lymphomas are often graded into low grade (slow growing) or high grade (fast growing). CTCL is a low-grade non-Hodgkin lymphoma.

Another type of staging of the disease, associated particularly with Sézary syndrome, is as follows:

• Stage I: Only parts of the skin are affected with a red, scaly rash. There are no tumors, and lymph nodes are normal.
• Stage II: The lymph nodes are normal or enlarged but have no cancerous cells, and the skin has red, scaly rash but no tumors, or the lymph nodes are normal or enlarged but do not contain cancerous cells, and the skin has tumors.
• Stage III: Most of the skin is affected by the red, scaly rash, but the lymph nodes, either normal or enlarged, do not contain cancerous cells.
• Stage IV: In addition to the skin rash, either cancer cells are in the lymph nodes or cancer cells have spread to other organs.

Treatment and therapy: Treatments for CTCL involve treating the skin either topically (on the surface), systemically (through the blood), or a combination of both. Treatment may control the disease, but if a patient does not continue treatment, the disease may recur.

If only small areas of the skin are affected, the disease can be treated by radiotherapy or electronic beam radiation. High-energy rays are directed at the affected skin, killing the abnormal lymphocytes while minimizing the damage to the healthy cells. This treatment is most effective during the early stages of the disease. It may also be used on the entire body if the cancer has not spread below the outer layer of the skin.

Another type of topical therapy is UVB (ultraviolet light B) therapy. The patient’s skin is exposed to UVB, which can help slow down the growth of skin cells.

CTCL can also be treated by a type of chemotherapy in which drugs are applied directly to the skin using a cream, gel, or ointment. If the cancer becomes much worse or is not responding to other types of therapy, conventional chemotherapy, where drugs are injected into the bloodstream, may also be used.

Photochemotherapy, a combination therapy, may be used if the cancer affects a large area of skin. A patient takes certain drugs that make the skin very sensitive to a type of ultraviolet light called ultraviolet light A. After the drugs have had time to affect the tumors, the skin is exposed to ultraviolet light A, which kills the tumors in the skin.

Researchers are investigating oral drugs and immunotherapy (therapy that uses the body’s immune system to fight the disease) that may be useful for CTCL patients. Drugs available to CTCL patients include Poteligeo (mogamulizumab-kpkc), approved in 2018, Romidepsin (Istodax), approved in 2009, and Vorinostat (Zolinza), approved in 2006.

Prognosis, prevention, and outcomes: Medical professionals assess the prognosis of CTCL patients using TNMB (tumor, node, metastasis, blood). The impact of the disease on each of these factors determines an individual's likely outcome. CTCL may stay only in the skin for several years, and many patients can lead normal lives for quite some time while controlling the disease with treatment.

Outcomes for CTCL depend on the type of disease the patient has, how quickly the disease is progressing, and how well the patient is responding to therapy.

Prognosis for patients with mycosis fungoides is usually good, as this type of CTCL usually affects only the skin, and patients are generally diagnosed early in the disease process. These patients have a median survival rate of more than twelve years. Those with Sézary syndrome generally have a more limited prognosis with a median survival of five years as this disease extends into the blood system. Patients whose internal organs are affected have a median survival of two to four years.

Bibliography

Toumi, Asma, et al. "Lymphomatoid Papulosis." National Library of Medicine, StatPearls Publishing, 22 May 2023, www.ncbi.nlm.nih.gov/books/NBK532295. Accessed 20 June 2024.

Pinter-Brown, Lauren C., et al. "Cutaneous T-Cell Lymphoma." MedScape, 17 Apr. 2024, emedicine.medscape.com/article/2139720-overview#showall. Accessed 12 June 2024.

Foss, Francine. T-Cell Lymphomas. Humana, 2013.

Hall, John C., and Brian J. Hall. Cutaneous Lymphoma: Diagnosis and Treatment. People's Medical, 2012.

Means, Robert T. Wintrobe’s Clinical Hematology. 15th ed. Lippincott, 2024.

Souhami, Robert, et al., eds. Oxford Textbook of Oncology. 3rd ed. Oxford UP, 2018.

Voorhees, Timothy J, et al. “Cutaneous T-Cell Lymphoma: Mycosis Fungoides and Sézary Syndrome.” Novel Therapeutics for Rare Lymphomas, edited by Christopher Dittus, Springer Cham, 2020, pp. 221–246. Springer Link, doi.org/10.1007/978-3-030-25610-4.

Zackheim, Herschel, ed. Cutaneous T-cell Lymphoma: Mycosis Fungoides and Sézary Syndrome. CRC, 2005.