Leukemic and lymphomatous infiltrates of the skin

Chapter 46 Leukemic and lymphomatous infiltrates of the skin

A lymphoma is a malignancy of the immune system that is characterized by an abnormal proliferation of lymphocytes and related cell types. Most lymphomas begin in lymph nodes and are divided into Hodgkin’s and non–Hodgkin’s lymphomas. The non–Hodgkin’s lymphomas are further subdivided into T-cell and B-cell subtypes.

Willemze R: New concepts in the classification of cutaneous lymphomas, Arch Dermatol 131:1077–1080, 1995.

Mycosis fungoides

2. Is there a lymphoma that begins in the skin?

Yes. Mycosis fungoides begins in the skin and often remains localized there for many years. Rarely, other T- and B-cell lymphomas also can present with skin lesions.

3. What type of lymphoma is mycosis fungoides?

Mycosis fungoides is a low-grade T-cell lymphoma. Histologically, it has a polymorphous cellular infiltrate with polymorphonuclear leukocytes, eosinophils, lymphocytes, and atypical mononuclear cells. The atypical mononuclear cells are moderately large and have a folded (cerebriform) nucleus. These cells are typically seen within the epidermis either singly or in small clusters (Pautrier’s microabscesses). The mycosis cells are primarily CD4-positive helper T cells.

4. How common is mycosis fungoides?

The incidence of cutaneous T-cell lymphoma (CTCL) in the United States is approximately 1,500 new cases per year. The prevalence of CTCL in the United States ranges from 16,000 to 20,000 cases.

Cutaneous Lymphoma Foundation. CTCL-MF fast facts. Available at: http://www.clfoundation.org/publications/publications.htm. Accessed December 6, 2006.

5. How does mycosis fungoides begin?

Typically, mycosis fungoides begins with persistent scaly patches (Fig. 46-1A) that respond poorly to topical therapy with emollients and topical steroids. In the early stages, skin biopsy is frequently not diagnostic. The average time from onset of skin lesions to diagnosis is 7 years. In this early phase of the disease, a diagnosis of parapsoriasis en plaque is often made. In time, the patches thicken and become plaques. Eventually, skin tumors develop (Fig. 46-1B,C) and the lymph nodes can become involved. Visceral disease is a late occurrence in this low-grade lymphoma. Median survival for persons with patch- and plaque-stage disease is 12 years; for tumor-stage disease, it is 5 years; and for nodal or visceral disease, it is 3 years.

Figure 46-1. Mycosis fungoides. A, A 12-year-old boy with extensive patch-stage mycosis fungoides. B, A patient with extensive patch-, plaque-, and tumor-stage mycosis fungoides. C, Tumor-stage mycosis fungoides. This patient had skin lesions for 18 years before tumors developed and a diagnosis was made.

Epstein E, Levin D, Croft J, et al: Mycosis fungoides: survival, prognostic features, response to therapy, and autopsy findings, Medicine 51:61–72, 1972.

6. What is parapsoriasis?

The skin diseases included under this diagnosis are poorly understood and encompass a morass of confusing terms. The “splitters” have described over a dozen varieties of parapsoriasis, while the “lumpers” limit this designation to only a few types. This discussion supports the “lumpers” viewpoint.

Small-plaque parapsoriasis is characterized by chronic, well-marginated, mildly scaly, slightly erythematous, and round to oval skin lesions measuring <4 to 5 cm in diameter. The long axes of the lesions are arranged in a parallel configuration, and the lesions occur on the trunk and proximal extremities in a pityriasis rosea–like pattern. The lesions have been likened to fingerprints and reported under the descriptive term of digitate dermatoses. This form of parapsoriasis does not progress to lymphoma.

Large-plaque parapsoriasis presents as palm-sized or larger lesions located most frequently on the thighs, buttocks, hips, lower abdomen, and shoulder girdle areas (Fig. 46-2). The lesions may be pink, red-brown, or salmon-colored. They often have fine scale and show epidermal atrophy with cigarette-paper wrinkling. Some patients may have lesions with a netlike or reticular pattern with telangiectasia and fine scale. This clinical type of lesion is referred to as retiform parapsoriasis or poikiloderma atrophicans vasculare. Between 15% and 20% of patients with large-plaque parapsoriasis eventually develop mycosis fungoides.

Figure 46-2. Large-plaque parapsoriasis. The lesion was unresponsive to topical treatment.

(Courtesy of the Fitzsimons Army Medical teaching files.)

Sehgal VN, Srivastava G, Aggarwal AK: Parapsoriasis: a complex issue, Skinmed 6:280–286, 2007.

7. What type of skin lesions are seen in patients with mycosis fungoides?

Although the classic skin lesions are scaly patches, plaques, and tumors, a wide variety of skin lesions have been reported, such as follicular papules and pustules with or without alopecia (alopecia mucinosa). Bullous, erythrodermic, hypopigmented, vasculitic, and hyperkeratotic lesions also have been described.

A rare variant of mycosis fungoides is granulomatous slack skin disease (Fig. 46-3). This disorder is characterized by the slow development of lax erythematous skin that eventually develops large pendulous folds of redundant integument. Histologic examination shows a dense atypical granulomatous infiltrate with destruction and phagocytosis of elastic tissue.

8. Describe the three subtypes of mycosis fungoides.

• Sézary syndrome (Fig. 46-4) presents with the classic triad of erythroderma, lymphadenopathy, and atypical circulating mononuclear cells (Sézary cells). These cells are moderately large mononuclear cells with hyperconvoluted nuclei. They resemble activated T cells, and when >15% of circulating lymphocytes are atypical, it is considered significant, with 10% to 15% being considered borderline. However, the finding of circulating Sézary cells must be evaluated in context with the clinical picture and skin biopsy. Severe pruritus, ectropion, nail dystrophy, peripheral edema, alopecia, and keratoderma of the palms and soles are common associated features. The disease tends to wax and wane and generally progresses faster and is more resistant to treatment than typical mycosis fungoides.

• Pagetoid reticulosis (Woringer-Kolopp disease) is characterized by single or grouped hyperkeratotic skin lesion(s). Skin biopsy shows striking epidermotropism, with numerous atypical mononuclear cells, both singly and in clusters, scattered through all levels of the epidermis. The disease tends to be slowly progressive and responds well to local radiation.

• The tumor d’emblee form was initially thought to be a type of mycosis fungoides that began with skin tumors without the usual progression through a patch-and-plaque stage. Recent reports suggest that some of these cases are B-cell primary cutaneous lymphomas and some represent Ki-1–positive primary cutaneous T-cell lymphomas.