Dermatology Online Journal

Folliculotropic mycosis fungoides
Christopher M Hunzeker MD, William Fangman MD, Jo-Ann M Latkowski MD
Dermatology Online Journal 13 (1): 5

New York University Department of Dermatology

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Abstract

A 72-year-old man presented with a 4-year history of asymptomatic erythematous plaques on his face, neck, and scalp. He had no systemic symptoms or lymphadenopathy. Histopathologic examination of a skin biopsy specimen showed a dense, diffuse infiltrate of lymphocytes and plasma cells, with epidermotropism and folliculotropism. T-cell receptor (TCR) gene rearrangement analysis performed on skin biopsy specimen showed a monoclonal cell population. A diagnosis of folliculotropic mycosis fungoides (MF) was made. This clinicopathologic variant of MF is usually associated with ordinary patch-plaque lesions. The prognosis of folliculotropic MF is best estimated using the TNM staging criteria. Many clinicians feel that this variant of MF portends a worse prognosis; however, there are no studies to support this idea. Folliculotropic MF may be more resistant to superficial therapies because of the depth of the neoplastic T-cells in the follicle.

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Clinical synopsis

A 72-year-old man presented to NYU Dermatologic Associates in January 2005 with a 4-year history of asymptomatic, erythematous plaques on his face. The plaques had increased in size and had begun to involve his neck and posterior scalp. A diagnosis of rosacea had previously been made, but the condition failed to respond to therapy with topical metronidazole. The past medical history includes coronary artery disease and diabetes mellitus, type II. He is otherwise healthy and active. A review of systems was negative.

He failed treatment with topical glucocorticoids and was started on oral acetretin (Soriatane®). After 4 months, his overall improvement was less than desirable, with only a slight decrease in the number and thickness of plaques. He is presently taking oral bexarotene (Targretin®).

Well-demarcated, erythematous-to-violaceous plaques were present on the face, neck, and posterior auricular scalp. There was neither cervical, axillary or inguinal lymphadenopathy nor hepatosplenomegaly.

Figure 1	Figure 2

A complete blood count with differential analysis and a comprehensive metabolic panel were normal with the exception of a glucose of 181 mg/dL (reference range 65-139). A triglyceride level was 287 mg/dL (reference range <150).

Figure 3

Histopathology reveals a dense, lymphoplasmacytic infiltrate in the papillary dermis and upper reticular dermis. Numerous lymphocytes extend into an irregularly hyperplastic epidermis and into the epithelium of the adnexa. The lymphocytes have slightly enlarged, hyperchromatic nuclei with irregular contours. In some foci, the lymphocytes form small collections. Immunohistochemistry stain for CD3 highlights the folliculotropism and epidermotropism of the lymphocytes.

T-cell receptor (TCR) gene rearrangement analysis performed on a skin biopsy specimen showed a monoclonal cell population.

Comment

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma, with an incidence of approximately 0.36 per 100,000 person years [1]. The etiology and pathogenesis of MF remain unclear; however, the various clinical presentations and the typical progression from patch to plaque to tumor stage have been described.

Less common clinical presentations of MF include hypopigmented, bullous, hyperkeratotic, ichthyosis-like, granulomatous, and purely follicular lesions [2, 3]. Follicular MF is a unique clinicopathologic variant that is usually associated with ordinary patch-plaque lesions of MF but may also occur as the sole manifestation of disease [4].

The folliculotropic variant of MF is characterized by infiltrates of neoplastic T-helper cells that involve the follicular epithelium, with minimal or no involvement of the overlying epidermis. Follicular MF is associated with the absence of mucin deposition in contrast to the MF-associated follicular mucinosis variant [4]. A considerable amount of overlap exists histologically, which contributes to the inconsistent and sometimes confusing terminology found in the literature.

Follicular MF is difficult to treat because the reservoir of follicular neoplastic cells is protected from the effects of superficial therapy. Therefore, first line treatments for early stage disease, such as ultraviolet-B phototherapy and topical glucocorticoids, are not effective in treating folliculotropic MF. Systemic treatments such as oral retinoids or PUVA photochemotherapy are more efficacious. Radiation therapy is also an option; the cutaneous lymphoma study group of the European Organization for Research and Treatment of Cancer proposed that total skin electron beam therapy was the treatment of choice for follicular MF [5].

The best studies to date regarding the prognosis of MF classify patients according to the TNM staging system and do not take histopathologic criteria into consideration. In a large, retrospective cohort, analysis of patients with limited skin involvement without extracutaneous disease (Stage IA) have essentially a normal life expectancy, with fewer than 10 percent of patients progressing to more advanced stages and only 2 percent of patients dying from their disease [6]. In a similar study of generalized patch and plaque MF, a worse long-term survival outcome existed when compared with age-, race-, and sex-matched controls. This study found that 24 percent of patients with diffuse disease progress to a more advanced clinical stage, and nearly 20 percent died of MF [7]. Patients with tumors or erythroderma have an appreciably less favorable prognosis [8].

References

1. Girardi M, Heald PW, Wilson LD. The pathogenesis of mycosis fungoides.

N Engl J Med. 2004 May 6;350(19):1978-88. PubMed

2. Monopoli A, et al. Purely follicular mycosis fungoides without mucinosis: report of two cases with review of the literature. J Am Acad Dermatol 2003; 48:448

3. Latkowski, JA, Heald P. Cutaneous T-cell lymphomas. In: Freedberg IM, et al., eds. Fitzpatrick's Dermatology in General Medicine, 6th edition. New York: McGraw-Hill, 2003: 1537

4. Hodak E, et al. Follicular cutaneous T-cell lymphoma: a clinicopathological study study of nine cases. 1999; 141:315

5. Willenze K, et al. EORTC classification for primary cutaneous lymphomas: a proposal from the cutaneous lymphoma study group of the European Organization for Research and Treatment of Cancer. Blood 1997; 90:354

6. Kim YH, et al. Clinical stage IA (limited patch and plaque) mycosis fungoides: a long-term outcome analysis. Arch Dermatol 1996; 132:1309.

7. Kim YH, et al. Clinical characteristics and long-term outcome of patients with generalized patch and/or plaque (T2) mycosis fungoides. Arch Dermatol 1999; 135:26.

8. Weinstock MA, Reynes JF. The changing survival of patients with mycosis fungoides. Cancer 1999; 85:208. PubMed

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