CUTANEOUS T-CELL LYMPHOMA or MYCOSIS FUNGOIDES

By Gary M. White, MD

Mycosis fungoides or Cutaneous T-Cell Lymphoma Red/brown, chronic patches and plaques on the upper thighs of an older adult (hidden from the sun).


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 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:

Rarely, children may develop MF. Yellow lesions may indicate xanthomatosis. Vesicobullous lesions may rarely occur [BJD 1999;141;164]. 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. A pilotropic form without mucinosis may be seen and is characterized by comedones and epidermal cysts [AD 1996;132;683]. A purpuric form may occur [Cutis 2014;94;297]. Darker-skinned patients may develop leukoderma from CTCL [JAAD 2009;60;359–3750]. Serpiginous CTCL has been reported [JAAD Case Reports 2015;1;82–84]. Rarely, an elderly patient with diffuse itching but normal skin will show CTCL on biopsy--so called invisible CTCL [JAAD 2000;42;324].

Staging

Stage Clinical
Ia Skin only. Patches/plaques <10% BSA
Ib Skin only. Patches/plaques >10% BSA
IIa Lymph node involvement
IIb Tumors or nodules (or histologic signs of folliculotropic or large cell transformation)
III/IV Erythroderma, heavy blood involvement, etc.
T Category Clinical
T1 Patches/plaques <10% BSA
T2 Patches/plaques >10% BSA
T3 At least one tumor > 1 cm
T4 > 80% BSA involved

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 [Arch Dermatol. 1999 Dec;135(12):1543-4, 1546-7].

Clonality

How to Diagnose CTCL in Diffuse Erythroderma

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 [Cancer 2013;119:825]. 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. Referral to oncology should be considered if signs of progression such as positive nodes, tumors or blood involvement develop.

Topical Steroids

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 [J Drugs Dermatol 2015;466].

Nitrogen Mustard

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 [Br J Dermatol. 2014 Mar;170(3):699-704].

UVB

PUVA

Guidelines for phototherapy of CTCL at JAAD 2016;74;27-58.

Topical Bexarotene

Topical bexarotene gel 1% (Targretin) may be used to treat CTCL.

Oral Bexarotene

Tazarotene

Not FDA-approved for CTCL but has been used off-label like Targretin.

Isotretinoin

Isotretinoin has been used for CTCL with variable success as reported in small series and case reports, usually at a dose of 1-2 mg/kg/day. It may be more beneficial when combined with UVB or PUVA.

Acitretin

Acitretin has been used in CTCL with limited success. It may be more beneficial when combined with UVB or PUVA.

Interferon Alfa

Laser

The 308 nm excimer laser resulted in a complete response in 3/6 patients with early stage MF [JAAD 2014:70:1058]. It may be a good consideration for lesions in difficult-to-treat areas.

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.

Prognosis

Skin Stage at Diagnosis 10 year Relative Survival
T1 100%
T2 67%
T3 39%
T4 41%

from JAAD 1999;40;418.

Those with clinical stage Ia have a good prognosis. In one long-term study with treatment, they did not have an altered life expectancy [AD 1996;132;1309 and above]. With Stage Ib, there is 83% ten-year survival.

There is an approximate 42% ten-year survival rate if nodules are present and an approximate 20% ten-year survival rate for nodal involvement.

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 [BJD 2015;173;1015–1023].

Pediatric CTCL

CTCL is rare in children but may occur. The majority present with patch-plaque stage. Seventy-nine percent in one review [Pediatric Dermatology 2014;31:459–464] 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 [Dermatology 1999;199;8]. One study found 85% of children with CTCL to be deficient in vitamin D [JAAD 2014;71;1117].

Children with CTCL have been treated with success with topical steroids, narrowband UVB and bath PUVA [JAAD 2014;71;1117]. Nitrogen mustard is a second-line alternative.

Additional Pictures

Various patches and plaques of CTCL.
Mycosis fungoides or Cutaneous T-Cell Lymphoma Mycosis fungoides or Cutaneous T-Cell Lymphoma

Mycosis fungoides or Cutaneous T-Cell Lymphoma

Papulosquamous lesions, mimicking psoriasis but "hiding" from the sun. Also, the elbows, knees, and scalp were normal.
Mycosis fungoides or Cutaneous T-Cell Lymphoma Mycosis fungoides or Cutaneous T-Cell Lymphoma

Poikilodermatosous CTCL.
Poikilodermatous Cutaneous T-Cell Lymphoma Mycosis fungoides or Cutaneous T-Cell Lymphoma

An ulcerated nodule in CTCL indicating more advanced disease.
Mycosis fungoides or Cutaneous T-Cell Lymphoma Mycosis fungoides or Cutaneous T-Cell Lymphoma

Follicular CTCL
Follicular Cutaneous T-Cell Lymphoma

Erythrodermic CTCL/Sézary syndrome
Sezary Syndrome

Elderly man with annular lesions that mimicked tinea.
Mycosis fungoides or Cutaneous T-Cell Lymphoma Mycosis fungoides or Cutaneous T-Cell Lymphoma Mycosis fungoides or Cutaneous T-Cell Lymphoma

References

The development of nodules in the is patient signaled progression of his disease. Dermatology Online Journal 17(10)

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