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Defining Early Mycosis Fungoides

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Defining Early Mycosis Fungoides View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Florence Research Defining early mycosis fungoides Nicola Pimpinelli, MD,a Elise A. Olsen, MD,c Marco Santucci, MD,b Eric Vonderheid, MD,d Andreas C. Haeffner, MD,e Seth Stevens, MD,f Guenter Burg, MD,e Lorenzo Cerroni, MD,g Brigitte Dreno, MD,h Earl Glusac, MD,i Joan Guitart, MD,j PeterW.Heald,MD,i Werner Kempf, MD,e Robert Knobler, MD,k Stuart Lessin, MD,l Christian Sander, MD,m Bruce S. Smoller, MD,n Gladys Telang, MD,o Sean Whittaker, MD,p Keiji Iwatsuki, MD, PhD,q Erik Obitz, MD,r Masahiro Takigawa, MD,s Maria L. Turner, MD,t and Gary S. Wood, MD,u for the International Society for Cutaneous Lymphoma Florence, Italy; Durham, North Carolina; Baltimore, Maryland; Zurich, Switzerland; Thousand Oaks, California; Cleveland, Ohio;GrazandVienna,Austria;Nantes,France; New Haven, Connecticut; Chicago, Illinois; Philadelphia, Pennsylvania; Munich, Germany; Little Rock, Arkansas; Providence, Rhode Island; London, United Kingdom; Okayama and Hamamatsu, Japan; Aarhus, Denmark; Bethesda, Maryland; and Madison, Wisconsin This editorial review summarizes the results of 5 meetings sponsored by the International Society for Cutaneous Lymphoma at which the clinicopathologic and ancillary features of early mycosis fungoides were critically examined. Based on this analysis, an algorithm was developed for the diagnosis of early mycosis fungoides involving a holistic integration of clinical, histopathologic, immunopathologic, and molecular biological characteristics. A novel aspect of this algorithm is that it relies on multiple types of criteria rather than just one, for example, histopathology. Before its finalization, the proposed diagnostic algorithm will require validation and possibly further refinement at multiple centers during the next several years. It is anticipated that a more standardized approach to the diagnosis of early mycosis fungoides will have a beneficial impact on the epidemiology, prognostication, treatment, and analysis of clinical trials pertaining to this most common type of cutaneous lymphoma. ( J Am Acad Dermatol 2005;53:1053-63.) he early diagnosis of mycosis fungoides features with benign dermatoses or discordance (MF), the major subtype of cutaneous T-cell between clinical and pathologic findings. Despite T lymphoma (CTCL), has important ramifica- extensive clinicopathological and investigational tions for therapeutic options, determination of prog- studies of MF and its putative precursors, as well as nosis, and outcomes in clinical trials. However, the strong biases toward particular histologic criteria, diagnosis of MF in its patch or early plaque phase there has been no consensus on the key clinical and is often difficult, either because of overlapping pathologic criteria that would ultimately facilitate From the Department of Dermatological Sciencesa and Depart- Dermatology, Okayama Universityq; Department of Dermatol- ment of Human Pathology and Oncology,b University of ogy, University of Aarhusr; Department of Dermatology, Florence; Division of Dermatology, Duke University, Durhamc; Hamamatsu Universitys; Dermatology Branch, National Cancer Department of Dermatology, Johns Hopkins University, Balti- Institute, Bethesdat; and Department of Dermatology, Univer- mored; Department of Dermatology, University of Zuriche; sity of Wisconsin and Veterans Affairs Medical Center, Amgen, Inc, Thousand Oaksf; Department of Dermatology, Madison.u University of Grazg; Department of Dermatology, CHU Nantesh; Funding sources: Research funding provided by the Department Department of Dermatology, Yale University, New Haveni; De- of Veterans Affairs and National Institutes of Health grant AR-02136 partment of Dermatology, Northwestern University, Chicagoj; (to G. S. W.). Division of Special and Environmental Dermatology, Medical Conflicts of interest: None identified. University of Viennak; Division of Dermatology, Fox Chase Parts of this work have been presented at international meetings. Cancer Center, Philadelphial; Department of Dermatology, Reprint requests: Gary S. Wood, MD, Department of Dermatology, University of Munichm; Department of Pathology, University University of Wisconsin, One South Park, 7th Floor, Madison, of Arkansas, Little Rockn; Department of Dermatology, Brown WI 53715. E-mail: [email protected]. University, Providenceo; St John’s Institute of Dermatology, 0190-9622/$30.00 guys and St Thomas’ Hospital NHS Trust, Skin Cancer Unit, ª 2005 by the American Academy of Dermatology, Inc. Division of Skin Sciences KCL, Londonp; Department of doi:10.1016/j.jaad.2005.08.057 1053 1054 Pimpinelli et al JAM ACAD DERMATOL DECEMBER 2005 dermatosis that was part of a larger spectrum of Abbreviations used: eczematoid, psoriasiform, or lichenoid skin disor- CI: confidence interval ders (‘‘les parapsoriasis’’) whose nosology has been CTCL: cutaneous T-cell lymphoma reviewed elsewhere.2 The relation between PEP and DGGE: denaturing gradient gel electrophoresis 3 ISCL: International Society for Cutaneous MF was first specifically addressed by Civatte Lymphoma (Brocq’s disciple) and other groups, including those MF: mycosis fungoides of Osmundsen,4 Samman,5 Bonvalet et al,6 and OR: odds ratio 7 PCR: polymerase chain reaction Binazzi who made careful clinicopathologic cor- PEP: parapsoriasis en plaques relations from series of patients with PEP followed over time. A ‘‘small’’ lesion variant, now commonly termed small-plaque parapsoriasis, was distin- collaborative multicenter research studies of early guished from a ‘‘large’’ lesion variant, now referred disease. to as large plaque parapsoriasis, on the basis of size, Recognizing this persistent need to develop preferential distribution of lesions, and the presence standardized diagnostic criteria for early MF, the or absence of atrophy and/or poikiloderma.2 The International Society for Cutaneous Lymphoma skin lesions of both small-plaque parapsoriasis and (ISCL) sponsored meetings in Zurich, Switzerland large-plaque parapsoriasis are flat patches rather on May 28-31, 1999; in Napa, California on March 9, than infiltrated plaques, consistent with the fact that 2000; in Bethesda, Maryland on March 1, 2001; in the French term plaque equates to the English term New Orleans, Louisiana on Feb 21, 2002; and in patch. Therefore these two conditions would be Washington, DC on Feb 5, 2004 with the following termed most appropriately ‘‘small-patch parapsoria- goals: (1) to facilitate discussion on this topic among sis’’ and ‘‘large-patch parapsoriasis,’’ except that these clinicians and scientists with extensive experience terms incorporating the word ‘‘plaque’’ are embed- in CTCL; (2) to develop a working proposal for ded in the literature.8,9 diagnostic criteria for early MF, taking into account The lesions of small-plaque parapsoriasis are clinical, histologic, and ancillary (particularly immu- generally on the upper trunk, sometimes with a nophenotypic and genotypic) criteria; and (3) to test digitate appearance (so-called ‘‘digitate dermatosis’’) the validity of these criteria in an international and without atrophy or poikiloderma.2 Lesions are collaborative forum. We are confident that meeting usually 2 to 6 cm in diameter; however, the long axis these goals will help to better evaluate the true of digitate lesions may be up to 10 to 20 cm, imparting incidence of MF, to potentially discriminate among a ‘‘fingermark’’ appearance. Histologically, small- prognostic subsets of MF, to advance the under- plaque parapsoriasis has been characterized by standing of factors involved in the pathogenesis of nonspecific changes (focal spongiotic and/or psori- MF and its progression, and to aid in the development asiform and/or lichenoid dermatitis with exocytosis of differential therapeutic approaches likely to im- of small lymphocytes). Small-plaque parapsoriasis prove current remission and survival rates. The has been judged to have little, if any, potential to meetings noted above accomplished the first goal. evolve to typical MF.8 This article summarizing the meetings’ proceedings In contrast, the lesions of large-plaque parapsori- addresses the second goal and creates a framework asis are usually larger than 6 cm in diameter and for achieving the third objective through future col- localized to the buttocks, lower trunk, upper thighs, laborative studies. inner upper arms, and inframammary areas (ie, non- sun-exposed regions) and frequently manifest atro- phy and/or poikiloderma. Histologically, the pattern RELATIONSHIP BETWEEN MF AND of lymphoid infiltration in large-plaque parapsori- PARAPSORIASIS EN PLAQUES: asis is similar to small-plaque parapsoriasis, but the HISTORICAL PERSPECTIVE AND infiltrates often contain lymphocytes with cerebri- CURRENT IMPLICATIONS form nuclei called Lutzner cells (synonymous with Part of the difficulty in establishing threshold Se´zary cells) similar to that seen in MF. Large-plaque criteria for the diagnosis of early MF stems from the parapsoriasis has been long regarded to be difficult existence of established terminology for reputedly to distinguish from patch-phase MF, with progres- benign dermatoses, such as parapsoriasis en plaques sion to frank MF in 7.5% to 14% of cases.2,5-7 (PEP), that have overlapping clinical and/or histo- In 1979, Sanchez and Ackerman10 suggested that logic features with early MF. By utilizing clinical instead of large-plaque psoriasis evolving into frank findings only, PEP was defined by Brocq1 in 1902 MF only in selected cases,
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