Red/brown, chronic patches and plaques on the upper thighs of an older adult (hidden from the sun).

CUTANEOUS T-CELL LYMPHOMA or MYCOSIS FUNGOIDES

Mycosis fungoides (MF) and Sézary syndrome (SS) taken together are referred to as Cutaneous T-Cell Lymphoma (CTCL). They represent about 50% of all cutaneous lymphomas. SS is an aggressive, leukemic variant, whereas MF is more indolent.

• Older individuals, e.g., 55-60 years of age at diagnosis, are typical with a male to female ratio of about 2:1.
  
• Most are white.
  
• Patients with CTCL are at higher risk for thromboembolism and a second lymphoma.
  

Clinical

The patient develops red, scaly areas usually in sun-protected parts of the body, e.g., the thighs, buttocks and legs. Later in the course of the disease, infiltrated plaques, figurate lesions, and nodules may form indicating progression. The development of nodules is a clear sign of more advanced disease. The lesions are fixed in MF in contrast to eczema. Ulceration may occur.

Variants include:

• Poikilodermatous
• Subcutaneous, Panniculitis-Like
• Hypopigmented
• Hyperpigmented
• Follicular
• Granulomatous Slack Skin
• Ichthyosiform

Rarely, children may develop MF. Yellow lesions may indicate xanthomatosis. Vesicobullous lesions may rarely occur. Atypical cases should be evaluated for the presence of HTLV-1 and EBV. Prognosis is unfavorable if tumors, lymphadenopathy, or skin involvement by infiltrated plaques greater than 10% body surface area (BSA) are present. Darker-skinned patients may develop leukoderma from CTCL. Serpiginous CTCL has been reported. Rarely, an elderly patient with diffuse itching but normal skin will show CTCL on biopsy--so called invisible CTCL.

Sézary Syndrome vs. Erythrodermic MF

SS has high levels of circulating Sézary cells where as erythrodermic MF (eMF) has low or absent levels. SS arises de novo whereas eMF usually represents progression of MF.

Diagnosis

If there is clinical suspicion of CTCL, a skin biopsy should be done which may be diagnostic. If it is equivocal, lymphocyte immunophenotyping may be done. If this is equivocal, gene rearrangement studies may be helpful. Certain drugs can rarely cause a drug eruption mimicking CTCL, so called pseudo-CTCL. A solitary lesion may represent Woringer-Kolopp disease or a response to an arthropod bite.

Clonality

• Not all methods are equal.
• 63-90% of histologically confirmed MF are positive.
• If clonality is not present in patch disease, give more consideration to MF-like drug reaction.

How to Diagnose CTCL in Diffuse Erythroderma

• Multiple skin biopsies (not just one).
• Make sure that patient has not been applying topical steroids for the 2 weeks prior to any patch or plaque you plan to biopsy.
• Always biopsy the most indurated lesion.
• Always biopsy areas of hair loss or any follicular prominence.
• CBC, LDH, and liver function tests.
• Gene rearrangement.
• Flow cytometry of peripheral blood.
• If advanced stage, body scans as directed by oncologist.

Workup

Workup is usually done in conjunction with an oncologist. For the dermatologist, complete skin exam, calculation of body surface area, and evaluation of lymph nodes should be performed. A biopsy should be taken of any and all morphologies--and certainly of the thickest lesion. The surgical oncologist may want to biopsy any node > 1.5 cm. CXR for limited disease and/or CT scan for widespread/more advanced disease. A drug history should be obtained. On study found hydrochlorothiazide (HCTZ) to be a trigger of CTCL in a small subset of patients. Trial off HCTZ would be in order.

Treatment

Treatment by the dermatologist is usually done only for stage 1a, 1b, or 2a. Beyond that, systemic therapy is usually needed and carried out by an oncologist.

For patch or plaque stage, UVB, PUVA, topical nitrogen mustard, topical steroids and narrowband UVB (office or home) are used. PUVA has been shown to have a higher clearance rate than nbUVB for early-stage CTCL. Referral to oncology should be considered if signs of progression such as positive nodes, tumors or blood involvement develop.

Topical Steroids

• Topical steroids may be used as monotherapy in T1 disease (< 10% BSA).
• Topical steroids may be used in combination with other treatments in the following settings:
  • Privileged sites where phototherapy does not reach.
  • With occlusion for stubborn thick plaques along with systemic agents.
  • Alternating with nitrogen mustard.
• Clobetasol may be used for limited disease, and triamcinolone for widespread disease.

Topical steroids, especially Class I, applied BID are capable of inducing remission in a majority of patients with patch-stage CTCL. For widespread skin involvement, triamcinolone may be used. Intralesional steroids (kenalog 10-40 mg/cc) have been used for focally resistant CTCL, including patches, plaques, papules, and nodules.

Nitrogen Mustard

• Best for limited disease or areas excluded from phototherapy.
• Apply daily to lesions.
• If irritation develops, apply steroid until clear, then 3/week with steroids on alternate days.
• Ointment based formulations are compounded.
  
• FDA-approved gel, Valchlor.
• Irritation is the most common side effect and there is potential for postinflammatory hyperpigmentation in darker-skinned patients.

Mechlorethamine is a nitrogen mustard that was introduced approximately 50 years ago as a treatment for Cutaneous T-Cell Lymphoma. A recent population-based study did not show any increased risk of malignancy in patients who had used nitrogen mustard.

Narrow Band-UVB

• Excellent for more diffuse patch or plaque CTCL.
• May have curative potential. In one study of NB-UVB for CTCL followed after discontinuation of therapy for at least 6 years, 60% were disease free. Younger patients with stage IA disease had a better likelihood of attaining this outcome.
• Efficacy equivalent to PUVA for patch/thin plaques.
• Risk of skin cancer is low/not increased.
• May be combined with topical steroids.
• May not be as good as PUVA for thick plaques or folliculotropic CTCL.
• For example, PUVA has been shown to have a higher clearance rate than nbUVB for early-stage CTCL.

PUVA

• Reaches deep enough to treat folliculotropic CTCL.
• Penetrates deep enough to treat cells in blood.
• Risk of skin cancer, including melanoma, is a concern.
• May be combined with an oral retinoid (RePUVA).
  
• Studies suggest that adding an oral retinoid to PUVA therapy decreases the total number of sessions and the amount of UVA needed in order to achieve a response.

Second Malignancy

Some studies have concluded that patients with CTCL are at higher risk for BCC, SCC, and melanoma while others have not. It does seem clear that PUVA, extracorporeal photopheresis, and electron beam therapy can predispose to secondary malignancies.

Followup

The patient should be seen every 3 months for complete skin exam, lymph node exam, and to rule out organomegaly. Rebiopsy should be done if any new morphologies (e.g., tumors) appear. Even if the skin is clear, a proportion of patients have residual molecular disease. In one prospective study, 21% of patients in complete remission after 1 year displayed molecular residual disease.

Pediatric CTCL

CTCL is rare in children but may occur. The majority present with patch-plaque stage. Seventy-nine percent in one review of patients < 18 years of age had hypopigmented CTCL. In another review, the 5- and 10-year survival was 93% and 74% respectively and no statistically significant difference in disease course between adults and children was found . One study found 85% of children with CTCL to be deficient in vitamin D.

Children with CTCL have been treated with success with topical steroids, narrowband UVB and bath PUVA. Nitrogen mustard is a second-line alternative.

Additional Pictures

CTCL on the upper thigh.

CTCL diffusely of the buttocks.

Erytyrodermic CTCL.

RegionalDerm

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