Mycosis fungoides

The Authors

M. TARIF ZAIM, M.D. is assistant professor of pathology and dermatology at Case Western Reserve University School of Medicine, Cleveland, and director of the Dermatopathology Laboratory at University Hospitals of Cleveland.

MICHAEL D. GRINKEMEYER, M. D. is currently a first-year resident in anatomic and clinical pathology at Wilford Hall U.S. Air Force Medical Center, Lackland Air Force Base, San Antonio. Dr. Grinkemeyer graduated from Case Western Reserve University School of Medicine.

Most patients with mycosis fungoides are between 40 and 60 years of age. The disease has three clinical stages: (1) the premycotic, or patch, stage, consisting of macular, scaling, faint pink to red pruritic patches, usually on unexposed surfaces; (2) the mycotic, or plaque, stage, consisting of reddish, purple-brown plaques, often annular in shape and symmetric in distribution, and (3) the tumor stage, consisting of red-brown to violaceous, dome-shaped, firm tumors with a predilection for the face and body folds. The Sezary syndrome is a leukemic variant. Treatment depends on the extent of disease and includes topical or systemic chemotherapy, radiotherapy and psoralen plus long-wave ultraviolet light therapy.

Mycosis fungoides is a cutaneous,t-cell lymphoma of thymus-derived helper lymphocytes. First described in 1806, mycosis fungoides occurs in adults of all races; men are affected twice as often as women.(1) The disease generally occurs in persons 40 to 60 years of age,(2) although occasionally it develops in persons under age 20 or over age 70.(3) An estimated 400 new cases are diagnosed in the United States each year.(4)

An increased risk of mycosis fungoides is associated with exposure to environmental toxins, such as petrochemicals, metals, solvents and pesticides. In one study,(5) 30 percent of patients reported exposure to hazardous chemicals or materials. While the incidence of other lymphomas and leukemias may be increased among family members of patients with mycosis fungoides,(5) fewer than ten instances of families with more than one case of mycosis fungoides have been reported.(6)

Clinical Stages

Clinically, mycosis fungoides is divided into three progressive stages: the premycotic, or patch, stage; the plaque, or mycotic, stage, and the tumor stage(7) (Figure 1). A leukemic variant, the Sezary syndrome, also affects some patients.

PREMYCOTIC STAGE

Although mycosis fungoides may begin at any of the three stages, the premycotic stage Figure 2) offers the greatest diagnostic challenge, because the skin lesions-both clinically and histologically-may resemble a number of benign dermatoses, including psoriasis, atopic dermatitis and neurodermatitis.(7)

In the premycotic stage, lesions occur singly or multiply, and have the appearance of macular, scaling, faint pink to red patches. They usually develop on unexposed surfaces.(7,8) Premycotic lesions can persist for months to years and may be accompanied by intense pruritus.(9) The lesions typically do not respond well to conventional therapy for dermatitis; thus, multiple biopsies at three-month intervals should be obtained in patients with therapeutically resistant dermatitis until a definitive diagnosis has been made.(8) In addition, alopecia mucinosa, poikiloderma vasculare atrophicans and large plaque parapsoriasis (parapsoriasis en plaque) are sometimes associated with cutaneous T-cell lymphoma, which suggests that patients with these diagnoses should also be followed closely. (8,10)

MYCOTIC STAGE

The mycotic stage (Figure 3) can arise de novo or from preexisting lesions and consists of reddish, purple-brown, often annular, plaques of varying thickness. Lesions at this stage can be found in most areas of the body and tend to be symmetric.(4,7) The plaques may be accompanied by intense pruritus. When they involve the face, they may rarely produce leonine facies (a lion-like appearance of the face, which may also occur in leishmaniasis and lepromatous leprosy).

TUMOR STAGE

The tumor stage of mycosis fungoides (Figure 3) may also present de novo or may arise from progression of preexisting lesions. It is characterized by the appearance of red-brown to violaceous, domeshaped, firm tumors with a predilection for the face and body folds. These lesions tend to spread and ulcerate, and may become secondarily infected.(4,7,9) The tumors are seldom painful and usually are less pruritic than the lesions of other stages but are considered a poor prognostic sign. They also may cause emotional distress because of their appearance.(7,9) The disease originally acquired its name from the mushroom-like appearance of the lesions in the tumor stage.(4)

As mycosis fungoides progresses, extracutaneous dissemination occurs, with lymphadenopathy and involvement of blood and deeper viscera. The lungs, liver and spleen are most commonly involved.(2,9,11) Extracutaneous dissemination is often not clinically evident during the patient's life, because disseminated disease tends to be microfocal and does not severely compromise organ function.(6) In fact, sepsis from ulcerated, infected tumors, rather than organ failure, is the most common cause of death in patients with mycosis fungoides.(2,6,9)

SEZARY SYNDROME

The Sezary syndrome, regarded by many as a leukemic phase of mycosis fungoides, is characterized by exfoliative erythroderma, generalized lymphadenopathy and T-cell leukemia, with white blood cell counts of 25, 000 to 50, 000 per [mm.sup.3] (25 to 50 x [10.sup.9] per L), consisting of 70 to 90 percent T lymphoblasts (Sezary cells). Splenomegaly or hepatosplenomegaly may or may not be present. (12) The syndrome may arise de novo in the absence of mycosis fungoides lesions or, less commonly, may evolve from the patch and plaque stages of mycosis fungoides. Tumors are rarely present.(4) The Sezary syndrome is associated with a particularly poor prognosis; most patients die of sepsis. At autopsy, nearly all patients with Sezary syndrome have visceral involvement.(12) In contrast, only approximately 70 percent of patients dying of cutaneous T-cell lymphoma have visceral involvement.(9)

Diagnosis

Histologic diagnosis of mycosis fungoides in the premycotic, or patch, stage may be difficult and may require multiple skin biopsies over an extended period.(8, 12,13) The histologic picture consists of a mononuclear infiltrate in the papillary dermis. (14) The diagnosis is based primarily on the finding of mycosis cells (atypical lymphocytes with hyperchromatic, convoluted nuclei) in the dermal infiltrate (Figure 4). The diagnosis is further supported by the additional finding of epidermotropism (migration of atypical lymphocytes surrounded by clear halos into the epidermis without spongiosis).(12)

Histologically, the plaque stage of mycosis fungoides is characterized by a denser, band-like, subepidermal mononuclear infiltrate in which mycosis cells are more easily noted. Epidermotropism of mycosis cells is also present, as are Pautrier's microabscesses, seen as small, intraepidermal groups of of ten tightly aggregated atypical mononuclear cells located within a vacuole (13) (Figure 4).

In the tumor stage of mycosis fungoides, the infiltrate is even denser, with a high percentage of mycosis cells; Pautrier's microabscesses are more common in this stage, of ten preceding ulceration.(12,13) Malignant cells with two nuclei may also be present. They can be distinguished from Reed-stemberg cells by their more hyperchromatic nuclei and by the absence of large, eosinophilic nucleoli. (13)

TNM CLASSIFICATION

After diagnosis of mycosis fungoides is confirmed by skin biopsy, the patient may be assigned to a TNM classification (Table 1), based on the extent of skin involvement (T), the number of clinically involved lymph node sites (N), the presence of atypical lymphocytes in the blood (B), and the presence of visceral involvement (M). Staging (Table 2) follows the TNM classification. (6,15)

The actuarially corrected five-year survival rate is 83 percent for patients with stage I disease, 64 percent for stage 2, 50 percent for stage 3 and 35 percent for stage 4.(6,15)

Treatment

Treatment of mycosis fungoides includes long-wave ultraviolet light treatment combined with psoralen (PUVA), electron beam radiotherapy, topical nitrogen mustard therapy, topical carmustine therapy, local-field radiotherapy and systemic chemotherapy.(16) Pruritus may be partially relieved with systemic antihistamines, topical emollients and/or topical corticosteroids.(6) Therapy is generally more effective, with improved survival and reports of cure, in the earlier stages of disease. Treatment in the later stages is generally less effective.(16)

Because the optimal treatment of mycosis fungoides remains unknown, several approaches are used. With one approach, treatment in stage 1 disease is restricted to the skin and consists of topical nitrogen mustard or electron beam radiotherapy, or both. Topical carmustine is used if these therapies fail or if the patient is allergic to nitrogen mustard. For stage 2, systemic chemotherapy may be added. For stage 3, orthovoltage radiation to thick tumors may be added. Systemic chemotherapy is the primary treatment in stage 4.(6) Recently, extracorporeal photochemotherapy has been used, with promising results, in patients with mycosis fungoides and widespread circulating atypical mononuclear cells.(17)

TABULAR DATA OMITTED

COPYRIGHT 1991 American Academy of Family Physicians
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