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Vol 66, No. 3;Mar 2013
Mycosis fungoides cached under the diagnosis of chronic eczema
Anca CHIRIAC Department of Dermatology, Nicolina Medical Center, Iasi, Romania Tel: 00-40-721-234-999 E-mail:
[email protected] Caius SOLOVAN “V. Babes” University of Medicine and Pharmacy, Dept. of Dermatology, Timisoara, Romania Tel: 00-40-256-493-725 E-mail:
[email protected] Piotr BRZEZI!SKI 6th Military Support Unit, Dermatological Clinic, Ustka, Poland E-mail:
[email protected] Vasilica TOMA “Gr. T. Popa” University of Medicine and Pharmacy, Surgical Dept. Iasi, Romania Tel: 00-40-742-154-358 E-mail:
[email protected] Anca E. CHIRIAC “Gr. T. Popa” University of Medicine and Pharmacy, Iasi, Romania Tel: 00-40-742-461-814 E-mail:
[email protected] Liliana FOIA (Corresponding author) “Gr. T. Popa” University of Medicine and Pharmacy, Surgical Dept. Iasi, Romania RO-700115, Iasi, Romania Tel: 00-40-744-704-4452 E-mail:
[email protected]
Abstract Mycosis fungoides is considered the most common form of cutaneous T-cell lymphoma. Due to its great variety of clinical features and nonspecific histological findings (especially in early stages) it has been named the "great imitator" mimicking various pathologic conditions and therefore resulting in eroneous diagnosis. We present a case of Mycosis fungoides misdiagnosed as chronic eczema in an attempt to signalize upon the liability of a proper diagnosis when facing chronic atypical eczematous lesions. Keywords: mycosis fungoides, eczema 145
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Introduction Mycosis fungoides (MF) represents the most common form of cutaneous T-cell lymphoma (CTCL) and is characterized by a monoclonal proliferation of epidermotropic CD4+/CD45RO+ T-cells often with aberrant expression of mature T-cell antigens [1,2]. Primary cutaneous T-cell and B-cell lymphomas represents primary cutaneous lymphomas (PCL). PCL are rare forms (2%) of non-Hodgkin's lymphomas with an annual incidence of 0.3-1 per 100,000 [1]. Because of its great variety of clinical features and nonspecific histological grounds (especially in early stages) has been named the "great imitator", many times resulting in false diagnosis [3]. Case report A 68-year-old woman presented with 1-year history of localized, pruritic, erythemateous, with fine scales, small plaques on the external faces of both forearms and dorsal aspect of right index (Figure1). Her lesions had not responded to long-term use of various medications: potent topical steroids (used for more than 6 weeks), emollients and immunosuppressive therapy (Tacrolimus ); no obvious change in clinical aspect after one month of daily use being observed. The patient had no personal history of atopic dermatitis, psoriasis or causative drug intake. She was in good health state, with no contact to chemical substances and no out-doors activities. The general physical examination did not reveal any remarkable sign, nor lymphadenopathy or organomegaly. All the lab parameters were within normal range. She has been tested several times in Allergy Department for standard allergens (results were all negative), IgE were normal, and no personal or heredo-collateral history of allergic events, nor new drugs administration or contact with substances that could induce allergic or irritant contact dermatitis were claimed. The previous diagnosis of eczematous reaction was excluded and a cutaneous biopsy was performed. Based on the histopathological report, a diagnosis of Mycosis fungoides was accepted. Phototherapy (short wave UVB) was immediately initiated, with fully clear up of the lesions within 3 weeks and no recurrences.
Figure1. Erythemateous, with fine scales, small plaques on the external faces of both forearms and dorsal aspect of right index 146
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The histopathology gave us an unexpected result: Mycosis fungoides early stage (Figure 2) and was based on the following observations: •
a band like dermal infiltrate of lymphocytes
•
epidermotropism of mononuclear cells
•
Pautrier microabscess
•
little spongiosis in the epidermis
Figure2: HEx4 :epidermotropism, band like infiltrate composed of lymphocytes Immunohistochemistry showed: CD3+, CD4+ with negative CD8 and CD7.
Figure 3: immunohistochemistry imaging Discussion A confident diagnosis of MF can only be made from a combination of clinical and pathologic findings. Characteristic pathologic features include cytologically atypical lymphocytes with cerebriform nuclei either colonizing the basal layer of the epidermis (epidermotropism) or forming clusters of cells in the epidermis (Pautrier microabscesses) with or without a band of cytologically atypical cells in the upper dermis [4]. In 2005, the two classification systems for cutaneous T-cell lymphoma (CTCL), namely the World Health Organization (WHO) and European Organization for Research and Treatment of Cancer (EORTC), were combined, providing distinct subtypes based on clinico-pathologic criteria (Table 1) [5]. The designation MF can only be used for classic cases characterized by the development of patches, plaques and tumors and for variants with a similar clinical course. MF represents less than 1% of the 147
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total number of non-Hodgkin lymphomas; however, it is the most common cutaneous lymphoma. It usually has an indolent course and good prognosis when identified in its early stages [5,6].
Cutaneous T-cell and NK-cell lymphomas
Mycosis fungoides MF variants and subtypes
• • •
Folliculotropic MF Pagetoid reticulosis Granulomatous slack skin
Sézary syndrome Adult T-cell leukemia/lymphoma Primary cutaneous CD30+ lymphoproliferative disorders
• •
Primary cutaneous anaplastic large cell lymphoma Lymphomatoid papulosis
Subcutaneous panniculitis-like T-cell lymphoma Extranodal NK/T-cell lymphoma, nasal type Primary cutaneous peripheral T-cell • lymphoma, unspecified • •
Cutaneous B-cell lymphomas
Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma (provisional) Cutaneous gamma/delta T-cell lymphoma (provisional) Primary cutaneous CD4+ small/medium-sized pleomorphic Tcell lymphoma (provisional)
Primary cutaneous marginal zone Bcell lymphoma Primary cutaneous follicle center lymphoma Primary cutaneous diffuse large B-cell lymphoma, leg type Primary cutaneous diffuse large B-cell• lymphoma, other
Precursor hematologic neoplasm
CD4+/CD56+ hematodermic neoplasm (blastic NK-cell lymphoma)
Table 1. WHO-EORTC manifestations[5]
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Intravascular large B-cell lymphoma
classification
of
cutaneous
lymphoma
with
primary
cutaneous
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The classic form of MF, which is also referred to as Alibert-Bazin, and three variants, namely, the "folliculotropic", "pagetoid reticuloid" and "granulomatous cutis laxa" variants, are acknowledged in the WHO-EORTC classification and in the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. Other subtypes have been reported in the literature due to their peculiar clinical, demographic or histological characteristics: “hypopigmented/hyperpigmented”, “erythrodermic”, “poikilodermic”, pigmented purpura-like”, “bullous/dyshidrotic”, “papular” and even the “invisible” subtype. The leukemic MF subtype is referred to as Sézary Syndrome, with distinct clinical and evolutive expressions [4,7]. Classic MF follows some clinical stages that are useful to identify the disease and its staging. In the early phases, diagnosis is difficult, and the disease mimics different clinical conditions, such as chronic eczema, psoriasis, parapsoriasis, sclero-atrophic lichen, chronic lichenoid pityriasis, pityriasis alba, atopic dermatitis, leprosy, chloracne (MF follicular subtype). During this phase, clinical and histological expression may be unspecific and the disease evolves for years without a diagnosis [7,8]. The early lesions, when fully established, correspond to patches which are referred to as "plaques" and described as erythematous-scaling plaques. They resemble psoriasis or parapsoriasis, which has led to semantic confusions and difficulty with the definition and characterization of the early stage of MF [79] .Considering the histopathology of MF, in the classic early patchstage MF, microscopic findings are often unspecific and they overlap with those of other inflammatory or non-neoplastic diseases. In the patch stage with well-established lesions, lymphocyte infiltrate on the edges of the basal layer and epidermotropism of isolated cells are histologically obvious. Most of these cells are small and differentiated lymphocytes, with slightly rounded or cerebriform nuclei. The epidermis may display acanthosis, hyperkeratosis or signs of damage in the basal layer (pigmentary incontinence) and edema. There may be prominence of postcapillary venules and infiltrate containing eosinophils, plamocytes, macrophages and dermal dendritic cells. Papillary dermal fibrosis may also be present. Density of the infiltrate is variable and it increases as the lesion develops and clinically resembles plaque lesions [10]. Parker SR described a 42-year-old white male military recruit presented with a 2-year history of painful ulcerations on the skin of his flanks and thighs [7]. Prior skin biopsies were nondiagnostic but raised the suspicion of an infectious etiology due to the presence of a granulomatous infiltrate. His medical history was significant for herpes zoster and eczema, and, upon review of symptoms), he reported) a 1year history of progressive fatigue and night sweats. Thoroughly examination revealed approximately one dozen 1 to 5cm indurated, dusky violaceous plaque on his trunk and lower extremities. Several of the plaques, including one on his right flank, had overlying deep ulcerations. Topf S reported a 18-year old male patient, who had been previously diagnosed with palmoplantar eczema. Clinical, histopathological, immunohistochemical and molecular findings revealed an atypical case of MF [9]. German scientists analyzed in their study the clinical and histological features of three adult patients with preexisting nonclassified chronic palmoplantar eczema poorly responding to standard therapies. Onset of cutaneous lesions with broad clinical variation was experienced 2-10 years prior to diagnosis and, palmar and/or plantar MF was eventually diagnosed [11]. Conclusions Taking into consideration the chronic evolution and the progression to more aggressive forms (with internal involvement), diagnosis of MF becomes a challenge and early therapeutic decision is of great importance in terms of prognostic significance. Therefore, in any patient with chronic atypical eczematous lesions with no response to classic medication, we strongly recommend long-term followup with repeated skin biopsies to rule out mycosis fungoides. References 1. Thomas BR, Whittaker S. A practical approach to accurate classification and staging of mycosis fungoides and Sézary syndrome. Skin Therapy Lett. 2012;17(10):5-9. 149
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2. Brzezi"ski P, Sanaei-Zadeh H, Shane T, Bonifaz A, Arenas R, Royer-Bégyn M. Dermatology eponym – phenomen / sign – Dictionary (B). N Dermatol Online. 2011; 2(1): 35-45. 3. Brzezi"ski P, Wass J, White K, Daboul MW, Arlt W, van den Hombergh P, Parker S, Khamesipour A: Dermatology eponyms phenomen / sign – Dictionary (A) –continued N Dermatol Online. 2011; 2(1): 27-34. 4. Wain EM, Orchard GE, Whittaker SJ, Spittle MF, Russell-Jones R. Outcome in 34 patients with juvenile-onset mycosis fungoides: a clinical, immunophenotypic, and molecular study. Cancer. 2003;98(10):2282–2290. 5. Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005; 105(10):3768-85. 6. Kannangara AP, Fleischer AB, Yosipovitch G: The Sparing Phenomenon. A case series of the inverse Koebner and related phenomena. Our Dermatol Online. 2013; 4(1): 35-39. 7.Parker SR, Traywick C, Arbiser JL. Ulcerative granulomatous mycosis fungoides Skinmed. 2010; 8(3):188-90. 8. Wei Li, Ying Liu, Quan Luo, Xue-Mei Li, Xi-Bao Zhang Off-label dermatology Our Dermatol Online 2012; 3(Suppl.1): 259-278. 9. Topf S, Lüftl M, Neisius U, Brabletz T, Simon M Jr, Schuler G, Schultz ES Mycosis fungoides palmaris et plantaris-an unusual variant of cutaneous T-cell lymphoma. Eur J Dermatol. 2006; 16(1):84-6. 10. Furmanczyk P, Wolgamot GM, Kussick JS, Sabath DE, Olerud JE, Argenyi ZB. Diagnosis of mycosis fungoides with different algorithmic approaches. J Cutan Pathol. 2010; 37(1):8-14. 11. Spieth K, Grundmann-Kollmann M, Runne U, Staib G, Fellbaum C, Wolter M, Kaufmann R, Gille J. Mycosis-fungoides-type cutaneous T cell lymphoma of the hands and soles: a variant causing delay in diagnosis and adequate treatment of patients with palmoplantar eczema. Dermatology. 2002; 205(3):239-44.
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