Ong, S. T.

Stupp, R.

Ultmann, J. E.

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Annals of Oncology 8 (Suppl. 2): S1-S2,1997.IntroductionThe Sixth Lugano Conference: Basic science papersS. T. Ong,1 R. Stupp2 & J. E. Ultmann11 Section of Hematology I Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA; 2 Center for Oncology, University Hospital,Lausanne, SwitzerlandThe Lugano conferences have in the past stressed bothclinical and basic science research in the study of lym-phomas. This year has been no exception, and we wit-nessed an obvious increase both in the number and scien-tific content of the presentations and abstracts in themeeting. Herein we include some of the interesting pre-sentations in the basic sciences and pathological classifi-cation of lymphomas.Since the last meeting in 1993, an important new clas-sification of lymphomas has emerged. Originally pub-lished in Blood in 1994, the REAL classification is anattempt by the International Lymphoma Study Group todevelop a consensus list of currently recognizable lym-phoid neoplasms that can be diagnosed with availablemorphologic, immunologic, and genetic techniques, andwhich have distinct clinical features. Certainly, the REALclassification is an excellent review of the known lympho-ma entities and, significantly, directs our thinking towardtreating each lymphoma as a different disease, with itsown distinctive genotype and biologic behavior, each ofwhich may require a specific therapy. However, as theauthors pointed out in their original article, this is only aninterim classification, and remains as imperfect as ourknowledge of lymphomas. Ongoing efforts are beingmade to improve the clinical relevance of biologicallybased classifications by consensus meetings betweenpathologists and clinicians. With better understanding ofthe underlying causes of malignancy, and the additionalgenetic 'hits' that confer more aggressive behavior andresistance to chemotherapy, we may actually find our-selves adopting even more detailed classifications in thefuture. The explosion of research in molecular oncologyis the force driving us in this direction. The question atpresent is to determine if such a classification betterserves the patient in terms of improved assessment ofrisk factors and improved treatment. Such questions arebeing answered with retrospective analyses, such as thosethat were presented by Fisher and Armitage at the 1996conference, and ongoing prospective trials.One distinctive entity, MALT lymphoma, is a partic-ularly instructive example. The recognition of this lym-phoma by Isaacson in the 1980s and its association withH. pylori infections paved the way for the astoundingregressions that are seen when the associated H. pyloriinfections are treated. A number of papers confirmedthat early-stage and low-grade disease can be effectivelytreated in 90% of cases with a combination of antibioticsand anti-ulcer therapy. The relapse and long-term sur-vival rates have yet to be described. The recognition ofMALT lymphoma as a distinct clinicopathologic entity,its association with H. pylori, and the disease-specifictherapy have been a remarkable advance encouraged bycareful pathologic and epidemiologic studies. A specialissue of Annals of Oncology that includes many of thepresentations at the 1996 conference on MALT lympho-mas has been published recently.Since the last conference yet another infectious agent,Kaposi's sarcoma-associated herpes virus, or humanherpes virus 8, has been strongly associated with a rarebut clinicopathologically distinct lymphoma: the primaryeffusion lymphomas. The studies by Knowles, in whichSouthern blotting or PCR-based techniques were usedto look for KSHV, demonstrated the specificity of thisvirus in body cavity-based lymphomas but not in AIDS-and non-AIDS-related lymphomas or Hodgkin's lym-phoma. These findings are obviously important, de-scribing a new infectious agent and its possible role inthe etiology of these rare lymphomas. Ultimately theymay also herald a cause-directed therapeutic approachthat combines antiviral therapy and conventional chemo-therapy.The 1996 conference also witnessed the more carefulcharacterization of known proto-oncogenes in lympho-ma: bcl-\, bcl-2, bcl-3, and bcl-6. The recognition ofmantle-cell lymphomas (within the REAL classification)and the realization that these lymphomas overexpress thecyclin Dl gene, at the bcl-\ locus, in the majority of cases,further justifies its recognition as a distinct biologic entity.We also learned that the transformation to diffuse large-cell lymphoma by follicular lymphoma is associated withsomatic mutations of the bcl-2 gene. Whether this isresponsible for the more aggressive behavior of the large-cell lymphomas has yet to be shown. Falini and othersshowed us using immunohistochemical techniques thatnormal germinal centers express bcl-6, as well as follicu-lar, large-cell, and Burkitt's lymphomas. Interestingly, itwas also demonstrated that the protein is also expressedin L & H cells of lymphocyte-predominant Hodgkin'sdisease.Two presentations suggested answers to long-standingquestions regarding the biology of Hodgkin's disease: thecell of origin of the Reed-Sternberg cell and the role,if any, of eosinophils in the pathogenesis of Hodgkin's proliferation by way of its CD30 ligand. This paper sug-disease. Rajewksy et al. presented data for the B-cell gests a role for the eosinophil in the pathogenesis oforigin of the Reed-Sternberg cell. These elegant data Hodgkin's disease, and suggests another potential thera-were derived from single-cell PCR studies in which they peutic target in this disease.showed VH gene rearrangements in Reed-Sternberg cells As evidenced by the following selection of papers, thefrom 12 out of 13 patients with classical Hodgkin's dis- quality of the science presented at the Lugano confer-ease. Furthermore, these cells demonstrated a high level ences continues to be of the highest standards. The inter-of somatic mutations, suggesting an origin from the ger- actions between basic scientists and clinicians are one ofminal center cell. A paper by Pinto et al., investigating the most valuable aspects of these conferences, and willthe role of eosinophils in Hodgkin's disease, suggested in future ensure both the success of the meetings andthat they-were capable of promoting Reed-Sternberg cell their important role in the battle against lymphoma.

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