Mycosis Fungoides
For more than 3 years, a 63-year-old man with a long history of parapsoriasis had multiple hyperpigmented, erythematous plaqueswith scaling on the abdomen, back, feet, and arms.Some lesions had a hypopigmented center. The patient denied systemic symptoms.
A 2-cm supraclavicular lymph node was noted. Other physical findings and laboratory results were normal. Results of punch biopsies of the plaques revealed atypical lymphoid infiltration in the superficial dermis with focal exocytosis and Pautrier microabscesses; these findings are consistent with mycosis fungoides. Immunophenotyping of the biopsy specimens was positive for CD3, CD4, and CD45RO and negative for CD8 and CD30. Bilateral bone marrow examination showed normocellular marrow with absence of tumor involvement.
The patient was instructed to apply mechlorethamine on the entire body 3 or 4 times a week and in the groin area and on the arms every day. On periodic follow-up examinations, he had no tingling sensation or other signs of peripheral neuropathy.
Six years later, the patient presented with new lesions on the arms, feet, and head (B), mild fatigue, and inguinal lymphadenopathy. His white blood cell count was 89,000/µL; hemoglobin level, 16 g/dL; hematocrit, 49.6%; and platelet count, 229,000/µL. These findings indicated slow progression of the disease. Psoralens-UV-A (PUVA) therapy was administered. At 4-week follow-up, the lesions had begun to resolve.
Primary cutaneous T-cell lymphomas encompass a wide variety of malignant lymphomas characterized by malignant lymphocytes in the skin. Mycosis fungoides and Sézary syndrome represent 2.2% of all lymphomas.1 The cause is unknown, although several factors—including chronic antigen stimulation from exposure to various chemicals, cutaneous bacterial infection, viral infection (eg, with human T-cell lymphotropic virus type 1),2 or smoking or long-term sun exposure—have been proposed.
There are 3 classic phases of cutaneous progression.3 Stage I, the plaque stage, is characterized by an erythematous macular eruption, which often originates on non-sun-exposed areas; biopsies are frequently nondiagnostic. This stage can last for months or years before progressing to the patch stage. In stage II, limited patches can resemble eczema or psoriasis; biopsies results reveal cutaneous T-cell lymphoma. Untreated disease may progress to the tumor stage—stage III—or erythroderma. This stage is usually associated with lymphadenopathy; visceral involvement is possible.
Plaque lesions are more erythematous than patch lesions and have well-demarcated margins and scaling. They can arise in areas of previous patches or de novo. Ulceration, with secondary infection of tumors, is a common cause of morbidity. The tumor stage of disease may appear without an antecedent patch or plaque phase (the D'emblee presentation).1
The diagnosis of mycosis fungoides is based on the clinical and biopsy findings. Histopathological findings include a band-like infiltrate that involves the papillary dermis and consists of mononuclear cells with hyperchromatic, cerebriform nuclei without spongiosis. Nonmalignant inflammatory cells are usually found among the malignant cells. When multiple patch and plaque lesions are present, diagnosis may be difficult because of the extensive inflammatory response. A nuclear contour index can differentiate mycosis fungoides from benign lymphoid infiltrates.
Routine evaluation usually includes T-cell receptor gene rearrangement studies to define the clonal population using Southern blot or polymerase chain reaction analysis.4-8Lymph node biopsies can be performed at the initial staging in advanced disease or if lymph nodes are enlarged; results usually show involvement of the paracortical regions. Immunophenotyping and T-cell receptor 3 gene rearrangement analysis are also helpful in the evaluation of lymph nodes.
Relief of symptoms and cosmetic improvement are the main goals of treatment. Skin-directed options consist of PUVA therapy, topical chemotherapy, and radiation therapy. Systemic optionsinclude chemotherapy (usually for patients with relapse or refractory disease), photopheresis, interferon, IL-2 fusion protein, and retinoids.
The level of circulating malignant cells is inversely correlated with prognosis, and thus should be evaluated at the initial presentation and during follow-up. In patients who have plaque-only disease, the median survival is more than 12 years.9 In patients who have tumors, erythroderma, or plaque disease with lymph node or blood involvement, the median survival is 5 years. Visceral involvement or node effacement is associated with a median survival of 2.5 years. Transformation of the disease to a large-cell lymphoma indicates a poor prognosis.10
1. Siegel RS, Pandolfino T, Guitart J, et al. Primary cutaneous T-cell lymphoma: review and current concepts. J Clin Oncol. 2000;18:2908-2925.
2. Poiesz BJ, Ruscetti FW, Gazdar AF, et al. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980;77:7415-7419.
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4. Duncan KO, Heald PW. T-cell technology in the diagnosis & management of cutaneous T-cell lymphoma. Compr Ther. 1998;24:117-122.
5. Weiss LM, Hu E, Wood GS, et al. Clonal rearrangements of T-cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy. N Engl J Med. 1985;313:539-544.
6. Bakels V, van Oostveen JW, Gordijn RL, et al. Di-agnostic value of T-cell receptor beta gene rearrangement analysis on peripheral blood lymphocytes of patients with erythroderma. J Invest Dermatol. 1991; 97:782-786.
7.Guitart J, Kaul K. A new polymerase chain reaction-based method for the detection of T-cell clonality in patients with possible cutaneous T-cell lymphoma. Arch Dermatol. 1999;135:158-162.
8. Russell-Jones R, Whittaker S. T-cell receptor gene analysis in the diagnosis of Sézary syndrome. Acad Dermatol. 1999;41:254-259.
9. Sausville EA, Eddy JL, Makuch RW, et al. Histopathologic staging at initial diagnosis of mycosis fungoides and the Sézary syndrome. Definition of three distinctive prognostic groups. Ann Intern Med. 1998;109:372-382.
10. Dmitrovsky E, Matthews MJ, Bunn PA, et al. Cytologic transformation in cutaneous T cell lymphoma: a clinicopathologic entity associated with poor prognosis. J Clin Oncol. 1987;5:208-215.