CUTANEOUS T-CELL LYMPHOMA I. OVERVIEW
II. CLINICAL VARIANTS AND PRESENTATION
A. Clinical Stages
1. Patch phase (see Figure 4-16)
a. Lesions typically present in non–sun-exposed areas as dusky red, violaceous, single or multiple scaly macules and patches in various sizes.
b. Classic distribution is the buttocks, groin, underneath breasts, and axilla, with persistent pruritus.
c. May be transitory, spontaneously disappearing without scarring.
d. Phase may last months or years; diagnosis at this stage is often difficult.
B. Plaque phase
1. Plaques may occur from patch-stage lesions or arise from de novo.
2. Eruptions are well defined and dusky red and may appear shiny with wart-like infiltrates;
a reddish-blue halo may be observed outside the areas of infiltration.
3. As cells proliferate, lesions become firm, and the plaque varies in surface contour.
4. Lesions may spontaneously regress or coalesce into a large plaque and ulcerate or spontaneously disappear.
5. Associating symptoms are scaly scalp with hair loss, thickened and discolored nails, hyperkeratosis, and scaling/fissuring of the palms and soles; risk of misdiagnosing for eczema or psoriasis at this stage.
6. Patient may present with dermatologic emergency as erythroderma, unstable body temperature, weight loss, insomnia, malaise, vasodilation, and exfoliations, which may cause loss of protein, iron, and electrolytes.
C. Tumor phase (T cells lose their affinity for the skin) 1. May occur in CTCL plaques or de novo.
2. Lesions appear on the face, back, and body skinfolds as dull reddish brown or purplish red with smooth surface; softly palpable nodular lesions that rapidly grow in size and number.
3. Presentation of the lesions may show secondary infection and excoriation due to severe pruritus. Ulceration and necrosis may occur in later stage.
4. In SS, “red man disease” may occur (Figure 16-23)
a. Term relates to generalized exfoliating erythrodermic CTCL patients with leukocytes and peripheral blood appearance of “monster” cells.
b. Intensely pruritic with lymphadenopathy starting either de novo, following premalignant eruption, or after established plaque stage of the disease.
5. Different from SS, erythrodermic condition in MF is a progression from the existing lesions, and it has low or no circulating “monster” cell counts.
6. Tumors gradually appear in infiltrative lesions often at the border; may shrink and disappear leaving a pigmented atrophic scar.
7. Widespread CTCL invasion is evidenced by palpable lymph nodes, bone marrow involvement in advanced stages, pulmonary involvement, and osteolytic lesions in the bone with pathologic fractures.
8. Complications of CTCL and cause of death include viral, fungal, and bacterial infections;
immunosuppression; and vital organ involvement.
FIGURE 16-23. Sézary syndrome. A: Mycosis fungoides patient with cutaneous plaques and a tumor. B: Sézary syndrome patient with diffuse erythroderma. (From DeVita, V. T., et al.
(2008). DeVita, Hellman, and Rosenberg’s cancer: Principles and practice of oncology.
Philadelphia, PA: Wolters Kluwer.)
III. LABORATORY AND DIAGNOSTIC TESTS
A. Combination of clinical examination and biopsy is necessary for establishing accurate diagnosis.
B. Molecular immunotyping can be helpful in diagnosing CTCL (e.g., CD4+ helper T-cell complex lack in expressing T-cell antigens CD7 and Leu-8).
C. Most sensitive test is Southern Blot test for T-cell antigen receptor rearrangements in peripheral blood (T-cell receptor gene rearrangement test).
D. CBC with determination of absolute lymphocytes count, serum chemistries (including liver and renal function tests), uric acid, LDH and quantitative immunoglobulins, human immunodeficiency virus (HIV), and HTLV-1 testing.
E. Depending on extent of disease, Sézary count, chest radiography, CT scans, PET scans, lymph node or bone marrow biopsy, or as suggested by history or physical examination.
IV. DIFFERENTIAL DIAGNOSIS
A. Allergic contact dermatitis B. Atopic dermatitis
C. Irritant contact dermatitis D. Lichen planus
E. Palmoplantar psoriasis F. Parapsoriasis
G. Pemphigus foliaceus H. Plaque psoriasis I. Tinea corporis
V. TREATMENT MODALITIES
A. Skin-directed therapy
1. Topical steroids are the most common treatment, and adjunct treatment with other topicals and systemic therapies at all stages.
2. Phototherapy with UVB.
3. Topical chemotherapy with mechlorethamine (nitrogen mustard HN2).
4. Photochemotherapy.
5. Carbon dioxide laser surgery.
6. Total skin electron beam therapy (limited penetration of electrons spares mucous membranes, bone marrow, gastrointestinal tract, and other vital internal organs). Whole body electron beam irradiation results in 85% complete remission rates with medial survival time of 9 years.
7. Surgical removal of solitary nodule or plaque confined to the skin.
8. Topical or intralesional steroids to control symptoms.
B. Chronic disease (with nodal involvement) 1. Follow protocol for skin-directed therapy.
2. Total skin electron beam therapy followed by topical HN2, phototherapy, or photopheresis to maintain remission. Total skin electron beam therapy is an option for patients with widespread skin lesions or patients who have deficient response to conservative therapies.
3. If necessary, systemic drug such as interferon-α, retinoids, or chemotherapeutic agent such as methotrexate.
C. Postremission maintenance includes topical corticosteroids, nitrogen mustard, interferon (alpha), and phototherapy.
D. Tumors
1. No nodal involvement—as above 2. Histologic nodal involvement
a. Individualized palliative treatment
b. Local radiations to local symptomatic disease c. Photopheresis
d. Retinoids/experimental protocols E. Visceral involvement/Sézary syndrome
1. Individualized palliative treatment
2. Systemic chemotherapy (fludarabine, 2-CDA, chlorambucil, pentostatin)
3. Extracorporeal photopheresis (palliative treatment), whereby leukocytes are selectively removed from peripheral blood by extracorporeal centrifugation technique, exposed to UVA light, and reinfused into the patient.
a. Causes selective destruction of cancerous cells in the blood
b. Has been the only single treatment that has been shown to improve survival in patients with Sézary syndrome
4. Immune boosters such as interferon, interleukin-2, and monoclonal antibodies
5. Bone marrow transplant, currently limited by graft versus host disease, offers greatest potential for disease cure.
6. Combinations of skin-directed therapies and biological response modifiers to improve response rates.
7. Recent developments in CTCL therapy include:
a. Targretin (bexarotene)—a retinoid X receptor–selective retinoid for all stages of CTCL and topical gel formation for the treatment of localized lesions
b. Ontak (denileukin diftitox): fusion toxin proteins selective for specific T cells; targets malignant T-cell clones
c. Systemic chemotherapy development including pegylated liposomal doxorubicin, gemcitabine, and pentostatin appears to have greatest potential.
8. Allogenic stem cell transplantation has curative potential for MF and reserved for advanced disease.
VI. PROGNOSIS
The prognosis of CTCL depends on the stage of disease at the time of diagnosis, age, gender, immunocompetence, and the choice and tolerance of the treatments. While there is no cure for MF and SS, the treatment should focus on controlling and limiting the skin lesions, delay the progression, and minimize the recurrence of the disease. The care for the patients should be directed at quality-of-life consideration by optimally treating pruritus and xerosis and prevention of skin infection.