Cutaneous T cell Lymphoma

CTCLs primarily present in the skin but can involve lymph nodes, blood, and rarely visceral organs.

Classification includes Mycosis Fungoides, its variants, and the Sezary syndrome, the CD 30+ lymphomas including anaplastic large cell lymphoma of the skin and lymphatic papulosis, and aggressive forms of peripheral T-cell lymphoma, including PTCL unspecified, panniculitis T-cell lymphoma and natural killer T cells lymphomas of the skin.

CD30- positive primary cutaneous T. cell lymphoproliferative disorders include lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma.

Mycosis fungoides represent approximately 70% of cases.

Prevalence estimated at 16,000-20,000.

Approximately 1200 new cases annually.

Incidence of 6-9 /million people.

Approximately 1500 cases per year.

Majority patients between 40-60 years.

Approximately twice as common in men as in women.

Approximately twice as common in blacks as whites.

Level of circulating malignant cells is inversely correlated with prognosis and should be evaluated at initial presentation and routinely during follow-up.

Etiology unknown.

Some relationship to immunosuppression as a risk factor with increased incidence in organ transplant recipients, treated lymphoma patients and in patients with HIV infection.

Epidemiological studies have reported potential associations with environmental and occupational factors, including Agent Orange exposure.

Most cases diagnosed early in the disease at T1, T2 stage.

One fourth patients diagnosed at the tumor or erythroderma stage.

Skin biopsies show epidermotropism and atypical mononuclear cells.

Most cases show expression CD24 antigen and a loss of CD7 and CD26.

Tumor cells show clonal T-cell receptor gene arrangements identified by Southern blot or polymerase chain reaction analysis.

Often have decreased number of normal lymphocytes and impaired T cell activities.

Less than 1% of patients have lung involvement.

In patients with early disease there is a favorable prognosis with skin directed therapy.

The disease is staged  according to the International Society of Cutaneous Lymphomas, and the classification takes into account the extent of skin involvement, lymph node disease, visceral disease, and blood involvement.

T1 or T2 stage disease associated with a median survival of more than 10 years.

Patients diagnosed at the tumor or erythroderma phase have a median survival of 4 years for stage IIB/III disease, 1.2 years for stage IVA disease and nodal involvement and 0.9 years for stage IVB disease with visceral involvement.

Early-stage mycosis fungoides involving 10% or less of the body, the primary treatment is topical steroids with a response rate of around 70% with or without phototherapy.

In patients with more than 10% skin involvement topical steroids may be combined with phototherapy in the form of ultraviolet B radiation or with psoralen plus ultraviolet A radiation.

The initial approach of the patient with mycoses fungoides or Sezary syndrome involves the assessment of the type and extent of skin disease as well as a lymph node examination.

Diagnostic testing includes: skin biopsy for histology, immunophenotyping, and T cell receptor gene rearrangement studies; for Sezary syndrome cell count, circulating T cells subsets anxiety.

Treatment includes a combination of skin directed therapies, radiation therapy, and systemic therapy to control disease, improve quality of life, and minimize infectious complications.

Denileukin diftitox compared to placebo in 144 patients with stage IA-III CD 25 positive cutaneous T-cell lymphoma: 9 or 18 mcg/kg days 1-5 q 21 days or placebo: overall response rate 37.8% vs. 15.9% with placebo, disease progression 21% in DD group vs. 52.3% in placebo group, progression free disease 971 days in 9 mcg/kg group, 794 days in 18 mcg/kg group and 124 days in the placebo group (Prince HM).

In the ALCANZA trial median free survival 16.7 months for brentuximab compared to physicians choice arm for cutaneous t-cell lymphoma (CTCL).

Brentuximab should be a favored agent in the management in CTCL.

Mogamamulizumab use in the MAVORIC phase III trial revealed median progression free survival compared to vorinostat at 3.1 months