Inflammatory vitiligo-like macules that simulate hypopigmented mycosis fungoides

ARTICLE

Auteur(s) : Thomas PETIT¹, Bernard CRIBIER², Martine BAGOT³, Janine WECHSLER¹

¹ Department of Pathology, Hôpital Henri-Mondor, 51, avenue de Lattre de Tassigny, 94010 Créteil, France.
² Department of Dermatology, Hôpital Universitaire de Strasbourg, France
³ Department of Dermatology, Hôpital Henri-Mondor, Créteil, France

Article accepted on 12/05/2003

The authors report herein 2 inflammatory vitiligo-like cases that histologically simulated mycosis fungoides (MF). Contrasting with a suggestive clinical presentation, vitiligo usually shows unremarkable changes with routine histological staining [1]. Nevertheless, some cases show an inflammatory infiltration [2] made of CD8 [3] or CD4 lymphocytes [4]. A common finding in all studies is the absence or the decreased number of melanocytes within the hypopigmented patches [5].

Case 1

A 70-year old man had spontaneously developed hypopigmented macules on his back for 6 months. Clinical examination revealed multiple irregular hypopigmented macules limited by a discrete erythematous and papular border, strictly localized on the back, from the upper neck to the lumbar area (Fig. 1). The largest macule measured almost 20 cm in length. The clinical aspect was suggestive of vitiligo. No chemical nor traumatic aggression had taken place. There was no treatment. Histopathologically, the first skin biopsy from the border of a hypopigmented macule showed a dense band-like superficial infiltrate (Fig. 2). The papular border was characterized by a remarkable lymphocytic exocytosis (Fig. 3). The infiltrate was made of more than 80 % of CD8 positive cells, especially the intra-epidermal lymphocytes. HMB45 immunostaining and ultrastructural analysis showed the absence of melanocytes in hypopigmented skin. A PCR/DGGE standard technique, performed on DNA isolated from the inflammatory border of a lesion detected no dominant T-cell clone. Because the initial histopathological diagnosis was MF, the patient had been treated by PUVA for 6 months. No improvement of the disease was observed during follow-up at 3 and 6 months. After 6 months, the disease became stable.

Case 2

The patient, a 20-year old man with no previous medical history, consulted for hypopigmented lesions that he had spontaneously developed for 2 years. There was no medical treatment. The physical examination showed hypopigmented belt-like macules located on the abdominal wall. They were multiple, not squamous, neither infiltrated nor atrophic. They showed an annular and erythematous papular border. The largest macule was 17 cm in diameter. The clinical aspect was suggestive of vitiligo. The first skin biopsy, performed on the papular border of a hypopigmented macule, showed a band-like epidermotropic infiltrate. Lymphocytes were small with discrete nuclear atypias. They predominantly expressed CD3, a few cells were CD8 positive. HMB45 immunostaining showed loss of melanocytes. A PCR/DGGE standard technique performed on DNA isolated from a lesion detected no dominant T-cell clone.

Topical steroid applications stopped the extension of the lesions and led to a diminution of the erythema. Sun exposure did not induce repigmentation. A second skin biopsy performed 2 months later showed regression of the infiltrate.

Discussion

Although a post-inflammatory reaction cannot be completely ruled out, we believe that arguments for vitiligo are: the absence of chemical, traumatic or toxic cause, the loss of melanocytes in lesional skin. The concave border of hypopigmented macules, though unusual for vitiligo, are not sufficient to rule out vitiligo.
Inflammation is not exceptional in vitiligo [2], in particular at the stage of macules with an erythematous raised border [6-8]. The histological features found in such cases are very similar to those we observed in the 2 current cases. On conventional microscopic analysis, vitiligo with a raised border showed dermal inflammation, associated with exocytosis and spongiosis [6]. In such cases, marginating lymphocytes were found in the basal layer close to the border of the patch [7]. As the inflammation can be very intense inside the papular border, exocytosis is frequently noted, but it is generally believed that the histological picture is of the spongiotic type [6]. Inflammatory changes in vitiligo are sometimes considered as a sign of “active” disease by some authors, as spreading patches of vitiligo can exhibit interface dermatitis [8]. Nevertheless, others have shown that there is no link between the intensity of the infiltrate at the first examination and the disease activity evaluated after a follow up of 3 to 16 months [2].
The main risk is to diagnose a hypopigmented variant of MF [9]. This form of MF generally responds well to PUVA, but recurrences are common [10]. The MF infiltration is predominantly composed of CD3/CD4 positive lymphocytes. Nevertheless, some cases of hypopigmented MF with CD8 + T-cell phenotype have been reported (11). In the 2 current cases, there was a loss of melanocytes as described in the classic form of vitiligo [5]. Yet, absence of melanocytes has been reported in hypopigmented MF plaques [12]. In vitiligo, it has been proposed that the pathogenesis of the depigmentation might be due to an autoimmune-related destruction of the melanocytes [13]. In the hypopigmented variant of MF, the pathogenesis is still unknown.
To conclude, we present an additional example of an inflammatory condition that may be misdiagnosed as MF. It is widely admitted that dense lymphocytic exocytosis and even clusters of T lymphocytes within the epidermis i.e “Pautrier microabscesses” are not specific to MF, as such features can be observed in a variety of inflammatory diseases [14-17]. In our cases, the erythematous raised border surrounding hypopigmented macules, the CD3/CD8 positive lymphocytic infiltrates, the loss of melanocytes and the absence of T-cell clone favoured the diagnosis of inflammatory vitiligo. n

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