Cutaneous T-Cell Lymphoma: Patient Guide

Cutaneous T-cell lymphoma (CTCL) is a group of cancers of T lymphocytes, a type of white blood cell. What makes this group unusual is where it shows up. These cancers appear first in the skin rather than in lymph nodes or blood.

Mycosis fungoides is the most common form. Sézary syndrome is the leukemic form, meaning the malignant cells circulate in the blood.

Mycosis fungoides is not a fungal infection, despite the name.

Not every T-cell lymphoma in skin is CTCL. Anaplastic large cell lymphoma, peripheral T-cell lymphoma, and adult T-cell leukemia-lymphoma can all involve skin and are separate diseases with separate treatments.

Symptoms can be present for 2 to 10 years before a biopsy confirms the disease.

Early lesions look like eczema or psoriasis, and they wax and wane. A biopsy taken during a quiet phase can look unremarkable. Several harmless or slow conditions also mimic mycosis fungoides under the microscope.

The NCI is explicit about the fix: have the slides read by a pathologist with expertise in telling these conditions apart. If you were diagnosed on one biopsy at a general lab, a specialist review is reasonable to request.

CTCL uses a TNM system with an extra letter, B, for blood. The skin categories are what patients hear most.

T1 means patches, papules, or plaques covering less than 10% of the skin surface. T2 means the same lesions covering 10% or more. T3 means one or more tumors at least 1 cm across. T4 means erythroderma, redness running together over 80% or more of the body.

Two of those words have exact meanings. A patch is a lesion of any size that is not raised or thickened. A plaque is a lesion that is raised or thickened.

Blood is graded separately. B0 means 5% or fewer of blood lymphocytes are atypical Sézary cells. B1 means more than 5%, but below the threshold for heavier involvement.

Stage IA is T1 with no node or organ involvement. Stage IB is T2. Stage IIB is T3. Stage III is T4. Stage IV involves nodes, blood, or organs.

Pathology reports should also note two features: large cell transformation, defined as more than 25% large cells, and whether the cells are CD30 positive.

The spread between early and advanced disease here is wider than in most cancers.

Median survival with stage IA disease is 20 years or more. Most deaths in that group are not caused by mycosis fungoides. With treatment, stage IA survival matches age- and sex-matched controls.

For stage III through stage IV, more than half of patients die of the disease, with median survival around 5 years. Sézary syndrome carries a median survival of about 4 years.

Retrospective studies found 20% of patients progress from stage I or II to stage III or IV. In one study of 1,422 patients followed for a median of 14.5 years, only 3% progressed from mycosis fungoides to Sézary syndrome.

A review of 1,275 patients found four independent markers of worse survival. They are stage IV disease, age over 60, large cell transformation, and raised lactate dehydrogenase, a blood enzyme. Large cell transformation is the shift from a slow lymphoma to an aggressive one. It happens in under 5% of cases.

Two findings from SEER data are worth knowing. Among 1,798 patients, second cancers were more common than expected, with a standardized incidence ratio of 1.32 and a confidence interval of 1.15 to 1.52, especially Hodgkin lymphoma, non-Hodgkin lymphoma, and myeloma. Among 4,459 patients, the 19.2% who were African American had shorter overall survival, with a hazard ratio of 1.47 and a confidence interval of 1.25 to 1.74.

For early disease, treatment aims at the skin rather than the whole body.

PUVA combines psoralen, a drug that makes skin sensitive to light, with ultraviolet A. Trials report complete remission rates of 80% to 90%, with the best responses in early skin stages. Maintenance at longer intervals is generally needed to hold a remission.

Narrowband ultraviolet B reaches similar figures, 80% to 90% complete remission in early stages.

A Cochrane review compared the two in 778 patients with stage IA, IB, and IIA disease. PUVA produced more complete responses, 73.8% versus 62.2%, with a hazard ratio of 1.68 and a p value of .04. There was no significant difference in side effects.

Topical mechlorethamine is chemotherapy applied to the skin. Complete remission tracks with skin stage: 50% to 80% at T1, 25% to 75% at T2, up to 50% at T3, and 20% to 40% at T4.

Total skin electron beam radiation uses electrons tuned so they stop in the dermis, treating the whole skin surface without systemic effects. Complete response rates reach 80%. It needs a radiation facility with physics support and precise dosimetry, and it is not widely available.

A randomized trial of 103 patients compared total skin electron beam radiation plus combination chemotherapy against sequential topical therapies, with chemotherapy held back for symptomatic disease beyond the skin.

The aggressive arm produced more complete responses. It also produced considerably more toxicity, and there was no difference in disease-free survival or overall survival.

The NCI states there is no curative therapy for stage I and II mycosis fungoides and no clear survival difference among the options. Choice depends on local expertise and available facilities.

Chemotherapy responses in this disease are short. In a review of 198 patients with advanced disease, median time to next treatment after chemotherapy was 4 months.

Interferon alfa did better in the same review, with a median time to next treatment of 8.7 months versus 3.9 months for chemotherapy.

Mogamulizumab is an antibody directed at CCR4, a receptor on the malignant cells. It is FDA-labeled for adults with relapsed or refractory mycosis fungoides or Sézary syndrome after at least one prior systemic therapy. It is worked out from body weight and given by vein over at least an hour, weekly through most of the first 28-day cycle, then twice per cycle after that. Label warnings include skin toxicity, infusion reactions, infections, autoimmune complications, and severe graft-versus-host disease if a stem cell transplant follows.

During the tumor phase, a common cause of death is septicemia, meaning bloodstream infection, arising from chronic skin infection.

The organisms named are staphylococcus species, herpes simplex, herpes zoster, and skin fungi.

Call 911 or go to an emergency department for any of these:

• Temperature of 100.4 degrees F (38 degrees C) or higher while you are having treatment that lowers blood counts, or shaking chills with it. Fever on chemotherapy is treated as an emergency, not as a call that can wait for the clinic to open
• Confusion, feeling faint, fast breathing, or skin that turns blotchy or grey
• Rapidly worsening skin breakdown over a large area

Call the care team the same day for any of these:

• A skin area turning hot, sharply redder, or newly painful
• Pus, yellow crusting, or a spreading red streak
• A cluster of painful blisters, which can mean herpes zoster

• Which exact subtype is this, and did a cutaneous lymphoma pathologist review the slides
• What is my T, N, M, and B stage, and what percentage of skin surface is involved
• Is there large cell transformation, and are the cells CD30 positive
• What is my lactate dehydrogenase level
• Are we aiming at the skin only, or at the whole body, and why
• If phototherapy is planned, PUVA or narrowband UVB, and what maintenance follows
• Who manages my skin infections, and what do I do after hours

https://www.cancer.gov/types/lymphoma/hp/mycosis-fungoides-treatment-pdq https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e53960ab-42a1-40d1-9c7d-eb013fe7f18f https://www.cancer.gov/about-cancer/treatment/side-effects/infection