The symposium discussed the pathobiology, classification, and treatment of cutaneous lymphomas. Drs. Burg and Kadin commented on the pathophysiology of mycosis fungoides/Sézary syndrome and cutaneous CD30+ lymphoproliferative disorders, respectively. A proposed classification of primary cutaneous lymphomas from the EORTC was presented by Drs. Kerl and Sterry. Dr. Jaffe presented a classification of cutaneous lymphomas based on the REAL classification. All speakers agreed that primary cutaneous lymphomas are usually distinctive in their clinical behavior and biology, and differ from their nodal counterparts. The symposium concluded with remarks from Drs. Vonderheid and Hoppe on the therapeutic approach to primary cutaneous lymphoid malignancie

Burg, G.

Jaffe, E. S.

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Annals of Oncology 8 (Suppl. 1): S83-S84, 1997.© 1997 Kluwer Academic Publishers. Printed in the NetherlandsOriginal articleReport of the Symposium on Cutaneous Lymphomas: Sixth InternationalConference on Malignant Lymphoma*E. S. Jaffe1 & G. Burg2^Hematopathology Section, Laboratory of Pathology, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD, USA; 2Clinic ofDermatology, University Hospital, Zurich, SwitzerlandSummaryThe symposium discussed the pathobiology, classification, andtreatment of cutaneous lymphomas. Drs. Burg and Kadincommented on the pathophysiology of mycosis fungoides/Sezary syndrome and cutaneous CD30+ lymphoproliferativedisorders, respectively. A proposed classification of primarycutaneous lymphomas from the EORTC was presented by Drs.Kerl and Sterry. Dr. Jaffe presented a classification of cutaneouslymphomas based on the REAL classification. All speakersagreed that primary cutaneous lymphomas are usually dis-tinctive in their clinical behavior and biology, and differ fromtheir nodal counterparts. The symposium concluded with re-marks from Drs. Vonderheid and Hoppe on the therapeuticapproach to primary cutaneous lymphoid malignancies.Key words: cutaneous lymphoma, T cell, B cell, lymphocytebiology, skinA symposium chaired by Prof. Gunter Burg and Dr.Elaine S. Jaffe focused on the pathophysiology, classifica-tion, and treatment of cutaneous lymphomas. Primarylymphomas of the skin differ in many ways from theirnodal counterparts, and these malignancies require spe-cial consideration from the specialist. The program beganwith a review of the pathogenesis of cutaneous T-celllymphoma (CTCL) or mycosis fungoides/Sezary syn-drome (MF/SS) by Gunter Burg. He noted that thepathologic and clinical manifestations of CTCL followfrom complex interactions between the neoplastic T cellsand the cells of the cutaneous microenvironment, mainlykeratinocytes and dendritic cells. An important factormay be a switch from TH (T helper) 1 cells to TH 2 cellsduring tumor development. The cytokines elaborated bythe neoplastic cells and bystander cells play a role both intumor development and the ensuing clinical manifesta-tions. CTCL, like most other malignancies, goes throughstages of tumor evolution. Tumor progression may beexplained by stepwise accumulation of mutations involv-ing DNA repair- and tumor-suppressor genes. The riskfor the accumulation of gene mutations increases with thenumber of cell divisions, which normally is limited by celldeath owing to apoptosis or senescence of the cell. Theseevents depend on bcl-2 expression and telomerase activ-ity, both of which are increased in CTCL and, therefore,may be important factors in promoting unlimited cellproliferation, driven by persistent antigenic stimulation.CD30+ lymphoproliferative disorders (LPDs) of theskin include lymphomatoid papulosis (LyP) and primarycutaneous anaplastic large-cell lymphoma (ALCL). Thesedisorders, which were reviewed by Marshall Kadin, ex-hibit a spectrum in both their pathologic features and* The US Government right to retain a non-exclusive, royalty-freelicence in and to any copyright is acknowledged.clinical behavior. Multiple cytokines (TNF-a and TGF-(3)produced by the T-cell clone appear to influence thehistologic features and clinical regression of the cutane-ous lesions. CD30+ cutaneous LPDs appear distinct fromclassical ALCL, and lack the t(2;5)(p23;q35) of the lattermalignancy. The most common cytogenetic abnormal-ities involve chromosomal breakpoints at Ip36 and10q24-26. Although the disease typically remains con-fined to the skin for many years, extracutaneous diseaseis seen in 25% of patients and is associated with a moreaggressive clinical course.The symposium proceeded to a discussion of theclassification of primary cutaneous lymphomas. TheEORTC, noting that cutaneous lymphomas differ fromnodal lymphomas in clinical behavior and functionalmarkers, has proposed a classification for these diseases(Table 1). Helmut Kerl presented an overview of cutane-ous B-cell lymphomas and Wolfram Sterry presented theEORTC perspective on T-cell malignancies. The tumorsare classified according to their usual clinical behavior,indolent or aggressive. In addition, some entities havebeen identified as provisional, and still others are under-going continued discussion regarding their inclusion. TheEORTC group identifies a primary cutaneous lymphomaas one presenting solely with cutaneous disease, withoutdetected extracutaneous spread for at least six months.Elaine Jaffe presented a classification of cutaneouslymphomas based on the principles of the revised Euro-pean-American lymphoma (REAL) classification pro-posed by the International Lymphoma Study Group(ILSG). She noted that the premise of the REAL classi-fication is the identification of disease entities, based onpathologic, immunophenotypic, genetic and clinical fea-tures. Therefore, if cutaneous involvement is a uniqueaspect of a disease entity, this clinical fact is consideredintegral to disease recognition. Indeed, there are a num-84Table 1. EORTC classification of primary cutaneous tymphomasPrimary cutaneous T-celllymphomasPrimary cutaneous B-celllymphomasIndolentMycosis fungoidesSezary syndromePagetoid reticulosisLymphomatoid papulosisLarge-cell CTCL, CD30+, includ-ing anaplastic, immunoblastic,pleomorphicAggressiveLarge-cell CTCL, CD30- , includ-ing immunoblastic pleomorphicProvisionalGranulomatous slack skin diseaseCTCL pleomorphic small/medium sizedCD8+ CTCLIndolentFollicle center cell lymphoma ofhead and trunkImmunocytomaIntermediateLarge B-cell lymphoma of the legProvisionalIntravascular CBLMarginal-zone B-cell lymphomaPlasmacytomaFor discussion: angiocentricity, gamma/delta CTCL, marginal-zoneB-cell lymphoma, and subcutaneous lymphoma.Abbreviations: CTCL - cutaneous T-cell lymphoma; CBL - cutaneousBcell.ber of T-cell malignancies for which cutaneous involve-ment is essential (Table 2). B-cell lymphomas restricted tothe skin are rare, with the possible exception of cutaneousfollicle-center lymphoma. It differs from its morphologi-cally similar nodal counterpart clinically, immunopheno-typically, and at the genetic level (bcl-2 rearrangement-negative). So-called cutaneous immunocytoma is felt tobe an extranodal marginal-zone lymphoma of MALT-type. Cutaneous large B-cell lymphoma is usually asso-ciated with a good prognosis, but it is not clear whetherthis clinical behavior is related to low stage or to anintrinsically different biology.Dr. Jaffe concluded that the principles of the REALclassification are applicable to cutaneous lymphomas,and that organ-specific classification schemes are notrequired. Indeed, such schemes may impede the recogni-tion of features common to diseases involving multipleanatomic sites; e.g., MALT-type lymphomas. Neverthe-less, primary cutaneous lymphomas are frequently dis-tinctive in their clinical behavior and biology.The symposium concluded with an overview of thetreatment of primary cutaneous lymphomas from thedermatologist's perspective by Eric Vonderheid, and fromthe oncologist's perspective by Richard T. Hoppe. Dr.Vonderheid reaffirmed the principles presented by Dr.Burg, that MF/SS represent a continuum with respectto tumor aggressiveness and risk for transformation. Bothparapsoriasis en plaques and patch-stage MF are con-sidered part of this continuum, with plaque- and tumor-stage MF representing the opposite extreme. In patientswith limited cutaneous disease, skin-directed chemother-apy and/or radiotherapy may be curative in 30%-50% ofpatients. Such approaches are also useful in palliatingTable 2. Classification of cutaneous lymphomas based on the REALclassification.Cutaneous T-cell lymphomasMycosis fungoides/ Sezary syndromePagetoid reticulosis (oc/p and y/6)Granulomatous slack skin diseaseFollicular mucinosisCD30+ cutaneous lymphoproliferative diseaseLymphomatoid papulosisCutaneous anaplastic large cell lymphomaSubcutaneous panniculitis-like T-cell lymphomaOther T-cell lymphomas with cutaneous involvement (nearly all)T-PLL/T-CLLAggressive NK-cell leukemiasNK/T-cell 'angiocentric' lymphomasAngioimmunoblastic T-cell lymphomaPeripheral T-cell lymphoma, NOSAdult T-cell leukemia/h/mphomaClassical anaplastic large-cell lymphomaCutaneous B-cell lymphomasCutaneous follicle-center lymphoma(Usually bcl-2 rearrangement/expression—negative)Cutaneous marginal-zone B-cell lymphoma (cutaneous MALT-typelymphoma)So-called 'cutaneous immunocytoma'Large B-cell lymphomaIntravascular large B-cell lymphomaPrecursor B-lymphoblastic lymphomaAbbreviations: T-PLL/T-CLL - T-cell prolymphocytic leukemia/T-cellchronic h/mphocytic leukemia; NK - natural killer; NOS - not other-wise specified; MALT - mucosal-associated lymphoid tissue.patients with more advanced disease. Biological responsemodifiers and cytotoxics or immunotoxins targetedagainst T cells hold promise for the future.Dr. Hoppe confirmed the effectiveness of topicaltherapies in control of disease. Because systemic diseaseat presentation is rare, only limited staging is required(chest radiographs, hematological evaluation with Sezarycell counts, and routine chemistries). If significant lym-phadenopathy is present, lymph node biopsy may beindicated. Electron beam and topical nitrogen mustardsare both effective. Visceral disease requires systemic che-motherapy, but chemotherapy generally has not beeneffective. Interferon has shown some promise, and otherinvestigational approaches are indicated in patients withadvanced disease. Primary localized cutaneous B-ceLllymphoma is often treated successfully with localizedradiation therapy.In conclusion, all speakers agreed that primary cuta-neous lymphomas differ significantly from nodal and mostextranodal lymphomas, and that these malignancies re-quire specialized diagnostic and therapeutic approaches.The site of presentation must be taken into considerationby both the pathologist and the clinician.Correspondence to.Dr. Elaine S. JaffeHcmatopathology SectionLaboratory of PathologyDivision of Clinical SciencesNational Cancer InstituteBethesda, MD 20892, USA

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