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Mycosis Fungoides: a Dermatological Masquerader D

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Mycosis Fungoides: a Dermatological Masquerader D REVIEW ARTICLE DOI 10.1111/j.1365-2133.2006.07526.x Mycosis fungoides: a dermatological masquerader D. Nashan, D. Faulhaber,* S. Sta¨nder,* T.A. Luger* and R. Stadler Department of Dermatology, University of Freiburg, Hautstr. 7, 79104 Freiburg, Germany *Department of Dermatology, University of Mu¨nster, Mu¨nster, Germany Department of Dermatology, Klinikum Minden, Minden, Germany Summary Correspondence Mycosis fungoides (MF), a low-grade lymphoproliferative disorder, is the most D. Nashan. common type of cutaneous T-cell lymphoma. Typically, neoplastic T cells localize E-mail: [email protected] to the skin and produce patches, plaques, tumours or erythroderma. Diagnosis of MF can be difficult due to highly variable presentations and the sometimes non- Accepted for publication 8 June 2006 specific nature of histological findings. Molecular biology has improved the diag- nostic accuracy. Nevertheless, clinical experience is of substantial importance as Key words MF can resemble a wide variety of skin diseases. We performed a literature clinical subtypes, differential diagnoses, mycosis review and found that MF can mimic >50 different clinical entities. We present fungoides, overview a structured framework of clinical variations of classical, unusual and distinct Conflicts of interest forms of MF. Distinct subforms such as ichthyotic MF, adnexotropic (including None declared. syringotropic and folliculotropic) MF, MF with follicular mucinosis, granuloma- tous MF with granulomatous slack skin and papuloerythroderma of Ofuji are delineated in more detail. Mycosis fungoides (MF), a low-grade lymphoproliferative dis- fungoides’ with ‘differential diagnosis’ and ‘clinical picture’, order, is the most common type of cutaneous T-cell lymph- and ‘mycosis fungoides’ and ‘cutaneous T-cell lymphoma’ in oma. Typically, neoplastic T cells localize to the skin and conjunction with clinically descriptive adjectives. From extrac- produce patches, plaques, tumours or erythroderma. Diagnosis ted articles the related articles and publishing authors were of MF can be difficult due to highly variable presentations and also screened. Further original articles were extracted from ref- the sometimes nonspecific nature of histological findings. erence lists. Molecular biology has improved the diagnostic accuracy. Nev- We thereby present a review of all currently published clin- ertheless, clinical experience is of substantial importance as ical pictures of MF simulating other dermatoses and distinctive MF can resemble a wide variety of skin diseases. clinicopathological features which are in part considered sep- Diagnosis of MF is based on a combination of clinical pre- arately in the new World Health Organization (WHO)—Euro- sentation, histopathology and gene rearrangement.1 None of pean Organization for Research and Treatment of Cancer these factors exclusively determines the diagnosis. Histologi- (EORTC) classification.6 The illustration of MF variants follows cally, MF is characterized by the presence of large atypical in Tables according to clinical signs and under the headings of lymphocytes, a lymphocytic infiltrate in the papillary dermis more distinct subtypes. and thickened collagen fibres. However, in early MF not all of these pathological findings are present and distinction from an 2 Clinically and morphologically unusual inflammatory infiltrate is often difficult. Detection of a mono- variations of mycosis fungoides clonal T-cell infiltrate is not lymphoma specific. Positive poly- merase chain reaction (PCR) results are also found in diseases In early stages of MF (T1N0M0 or T2N0M0) characteristic le- such as psoriasis, pityriasis lichenoides et varioliformis acuta sions consist of erythematous macules or papules, which are (PLEVA) and lichen ruber.3,4 Thus clinical presentation is a primarily superficial and resemble an ‘eczema’ with sharply major factor determining the diagnosis.5 defined borders. Often some degree of scaling is observed, similar to psoriasis. The edges of the lesions might exhibit in- Search criteria creased scaling, corresponding to a growing infiltrate. The configuration can be arciform, annular, semiannular, serpingi- This article emerged from Medline searches, manual searches nous or polycyclic.7 The skin surface can be atrophic, exhibit- in dermatological journals and textbooks, and from personal ing wrinkles. The colour can be orange to bright red or experiences. Electronic key word searches included ‘mycosis can present livid or brown-red components. Spontaneous Ó 2006 British Association of Dermatologists • British Journal of Dermatology 2007 156, pp1–10 1 2 Diversity of mycosis fungoides, D. Nashan et al. Table 1 Differential diagnoses of classical mycosis fungoides (MF) are The descriptive term ‘mycosis fungoides’, chosen in 1806 assembled based on a predominant clinical sign. A representative by Alibert, already suggests the first differential diagnosis of publication with a clinically imitative MF is given for each differential tinea corporis for a typical MF lesion. The coincidence of der- diagnosis matophyte infections and MF has been described.9,10 Further descriptive terms provide hints for the differential diagnosis: Clinical sign Differential diagnosis First author lichenification, lichenoid, eczematous, seborrhoeic, urticarial, Eczematous Seborrhoeic eczema Figure 1 erythematous, hypopigmented, pityriasis-like.11 Thus the dif- 82 Perioral dermatitis Wolf 1992 ferential diagnosis includes nonspecific eczema, nummular Palmoplantar eczema Spieth 200219 eczema, seborrhoeic eczema, contact dermatitis, atopic derma- Dyshidrotic eczema Kempf 200580 Contact dermatitis Spieth 200219 titis, psoriasis, drug reaction, lichen simplex chronicus and 12,13 Atopic eczema Kazakov 200412 lichen planus (Table 1). Scaling Psoriasis Zackheim 200283 Limited involvement of the skin, especially as unilesional Psoriasis palmaris Spieth 200219 typical MF, is not uncommon.14–17 A well-documented, Psoriasis plantaris Figure 2 although not universally accepted, solitary form is the paget- 84 Parapsoriasis Ackermann 1996 oid reticulosis type Woringer–Kolopp, characterized by a sin- Tinea corporis Chaves 200285 86 gle, scaling and erythematous MF lesion with acral Tinea pedis Resnik 1995 18 Erythematous Erythema multiforme Krebs 197887 localization. A challenge for the clinician might be the Kazakov 200412 appearance of typical MF in an atypical localization, e.g. MF Annular erythema Lim 200388 simulating palmoplantar or periorificial eczema, isolated alope- Cogrel 200589 cia or affecting the mucosa (Figs 1 and 2).19,20 45 Alopecia Alopecia areata Burg 1992 At the tumour stage IIB (T3N0/1M0) nodules of various sizes are found. They can be flat or dome-shaped. Their colour For a further overview publications of Zackheim and McCal- mont13—with 23 differential diagnoses—and Kazakov et al.12 is yellow-red or red-blue to brown. The lesions are more can be recommended. prominent and deeper than plaques. MF tumours mainly develop in the course of the disease or in conjunction with eczematous lesions. The surface is soft on palpation, which regression of lesions can occur; this is sometimes limited to distinguishes the lesions from metastases of solid carcinomas. the centre of the lesion. Alopecia may develop in lesional sites Ulcerations are frequently seen, which can develop secondary or even in clinically unaffected skin. The lesions are asymmet- infections. Tumours develop in either pre-existing MF lesions rically distributed and are predominantly located in a ‘swim- or de novo. The location and configuration of these tumours are suit’ distribution, i.e. preferentially on the abdomen, hips, comparable with B-cell lymphoma. Another tumorous lymph- buttocks and breasts. Lesions are also seen on the medial sides oma and possible differential diagnosis is lymphomatoid papu- of proximal extremities. The mucosa can be affected at any losis (LyP). In 1968, Macaulay21 summarized LyP as a stage of disease.8 It is still under discussion whether parapso- chronically recurring papulonodular dermatosis, sometimes riasis with its scattered finger-like striped lesions on the flanks self-limiting. It can be excluded by its brownish-reddish cen- is an entity on its own or is a precursor of MF. trally necrotic papules, spontaneous healing within weeks and Fig 1. Mycosis fungoides imitating seborrhoeic eczema. Ó 2006 British Association of Dermatologists • British Journal of Dermatology 2007 156, pp1–10 Diversity of mycosis fungoides, D. Nashan et al. 3 Table 3 Differential diagnoses of erythrodermic mycosis fungoides Clinical sign Differential diagnosis Erythrodermic Se´zary syndrome Adult T-cell leukaemia Actinic reticuloid Atopic dermatitis Drug reaction Psoriasis Age-dependent erythroderma leukaemic involvement’ describe the difficulty of either delin- eation. SS was defined by Se´zary and Bouvrain in 193823 as a triad of erythroderma, lymphadenopathy and atypically large mononuclear blood cells. It is clinically associated with leo- nine facies, ectropion, alopecia of the scalp, palmoplantar hyperkeratosis and fissures and dystrophy of the nails. Similar but less frequent monosymptomatic forms or new phenomena such as a vitiligo-like leucoderma with MF and SS hamper the diagnosis.24–26 A diagnostic discrimination is presented by the Interna- tional Society for Cutaneous Lymphomas, specifying in add- ition to erythrodermic MF and SS, ‘other erythrodermic cutaneous T-cell lymphoma, not otherwise defined’.27 Fur- ther differential diagnoses include primary and secondary
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