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New Approach to Classifying Non-Hodgkin's Lymphomas: Clinical Features of the Major Histologic Subtypes By James 0.Arrnitoge and Dennis D. Weisenburger for the Non-Hodgkin's Lymphoma Classification Project . Increasing knowledge about the biology of the nonHodgkin's lymphomas has led to new approaches in classification. Rather than grouping lymphomassimply based on cell size, cell shape, and growth pattern, it is now possible to identify distinctive clinicopathologic entities. Inmanycases, the existenceof specific immunologic and/or genetic features has confirmed the existence of these distinctive types of lymphoma. Since patients will be given these diagnoses by pathologia, it is important that clinicians be knowledgeable w& regard to their clinical characteristics. The findings & ' the 13 most common lymphoma types that will encountered in clinicalpractice are presented hem. J Clin Oncol 16:2780-2795. o 1998 by Societyof ClinicalOncology. * $, t NON-HODGKIN'S LYMPHOMAS are increasing in incidence and will be diagnosed in more than 55,000 patients this year in the United States." These malignancies have been increasing in incidence at a rapid pace, approximately 4% per year since 1950.' and the mortality rate has been increasing in a parallel manner. The classification of non-Hodgkin`s lymphoma has been modified several times in this century and has often been a source of confusion and frustration for clinicians. Gall and Mallory3proposed the first widely used lymphoma classification. but this classification was not useful clinically. In the 1950s, Rappaport et a14 recognized the inlportance of lymphoma-cell growth pattern and subdivided the nonHodgkin's lymphomas based on this characteristic. which led to the clinically relevant classification that bears Rappaport`s name. In the 1970s. it became apparent that nonW g k i n ' s lymphomas were tumors of the immune system and were derived from T or B lymphocytes. This knowledge led to the classifications of Lukes and Collins5 and Lennert et a P 7 (Kiel classification). The Working Formulation was proposed in 1982 in an attempt to unify the complex and confusing lymphoma terminology and improve communication between pathologists and clinicians in different parts of the world.* The Working Formulation became the most popular ciaisification used in North America, whereas the Kiel classification dominated clinical practice in Europe. The 1980sand 1990s have been a time of rapid increase in our knowledge of the biology of the immune system. New From the Departments of Internal .Medicine and pa tho log^, Lhiversic of Nebraska Medical Center. Omtrha.NE. Submitted Junuuc 7, 1998; accepwd April 24. 1998. Address reprint requests to James 0.Armitage. MD. Depanmen?-of lnfenral Medicine, L`niversir).of Xebraska Medical Center, 600S 42nd St. Omaha. NE 68/98-3332. C 1998 bv American Socien of Clinical Oncology 0732- I 8 3 x / 9 8 / I 6 O 8 - O 0 ~ 8 $ ~ . ~ / O insights into immunology and genetics have allowed &e recognition of a number of previously unrecognized typesaf ' nomHodgkin's lymphoma: In some cases, biologic observations confirmed the existence of entities that were suspected on clinical and/or morphologic grounds. In 1994, International Lymphomas Study Group recognized the existence of these new entities and proposed a new c l a s s i f i c a h that has been referred to as the Revised European-American Lymphoma (REAL)classifi~ationT.~hese observations will form the basis for a new World Health Organization classification of lymphomas that will soon become available. A recent retrospective study of the REAL classification confirmed the clinical relevance of this approach.1 This study was performed in eight countries throughout the world and demonstrated that this new approach could be applied more accurately than previous classification systems.1 The data from that study form the basis of this report. METHODS OF THE INTERNATIONAL LYMPHOMA CLASSIFICATION PROJECT The methods used have been published in detaillo and an summarized here. Nine institutions in eight countries were chosen to provide up to 200 consecutive cases of previously untreated non-Hodgkin's lymphoma that were represents- -tive .of the geographic region- during the time. between January 1. 1988 and December 3 I . 1990.The first 200 cases at each site that fultilled the following criteria were selected for the study. In all cases. tissue biopsy samples that wen? adequate for diagnosis and classification were required and all diagnostic pathology materials obtained before initial therapy, including positive bone marrow specimens. were ~IIcluded in the pathology review. Immunologic characterization8s to B- or T-cell origin. by whatever means in use at the ktituthk was also required in all cases. Clinical data were also requiredin all cases.The nine study sites provided a total of 1.403cases. At each institution. the pathology slides and reports for each case were carefully reviewed by a designated site 2780 Journal of Clinical O n c o l o g ~Vol 16, No8 (August), 1998: pp 2780-2795 CLINICAL FEATURES OF THE NON-HODGKIN'S LYMPHOMAS pathologist. Five expert hematopathologists then traveled as a group to each of the nine sites to review and classify each case in each of the three major classifications.'-' In each case, the expert was then presented with the immunophenotypic profile, along uith any available cytogenetic and molecular genetic data, and the immunostains andor flow cytometry report. After review. a second diagnosis was rendered in each classification. In addition to the independent diagnoses rendered by each of the expert pathologists. a consensus diagnocis mas also reached in each case. The International Prognostic Index" was used to stratify patients within the various disease entities. Treatment outcome was measured using failure-free sunival and overall survival. Failure-free survival was defined as the time from diagnosis to the first occurrence of progression. relapse after response. or death from any cause. Follow-up evaluation of patients who did not experience one of these ekents was censored at the date of last contact Overall survival was measured from diagnosis to death from any cau$e. uith surviving patient follou -up data censored at the lact contact date. Estimates of failure-free survival and overall survival distribution were calculated wing the method of Kaplan and Meier." Time-to-event distributions were compared using the log-rank test." MAJOR LYMPHOMA SUBTYPES The I3 most frequent clinical entities that are recognized in the new lymphoma classification are diffuse large B-cell lymphoma, follicular lymphoma, small lymphocytic lymphoma. mantle cell lymphoma, peripheral T-cell lymphoma, marginal zone B-cell lymphoma of mucosa-associated 1) mphoid tissue (MALT) type, primary mediastinal large B-cell lymphoma. anaplastic large T-/null-cell lymphoma, lymphoblastic lymphoma (TB), Burkitt-like lymphoma, marginal zone B-cell lymphoma of nodal type. lymphoplasmacytic lymphoma. and Burkitt's lymphoma. These are the diagnoses that uill be provided by pathologists to clinicians who care for patients with lymphoma for the ensuing years. Therefore, it is important that clinicians be acquainted mith 278 the clinical characteristics of these lymphoma types. Summaries of their frequency. clinical characteristics, biologic characteristics, and clinical course are presented in the following tables for easy reference. The lymphomas are presented in order of their frequency of occurrence. Composite lymphomas are excluded, resulting in a total of less than 100%.A previous study has shown that expert hematopathologists can diagnose most subtypes accurately (ie, > 8 5 9 ) when adequate material. inimunophenotype. and clinical information are available.'0 The excep[ions are Burkitt-like lymphoma: nodal marginal zone lymphoma. and lymphoplasmacytic lymphoma. In these subtypes. lack of clear definitions are probably at fault. Burkitt-like lymphoma is probably a mixture of Burkitt's lymphoma and a variant more closely related to diffuse large B-cell lymphoma. with the former more frequent in pediatric cases and the latter more likely in older adults. In conclusion. it is extremely important that cliniciaq recognize that the correct diagnosis of each of these lymphoma entities is only one of many important pieces of information necessary for planning patient care. The clinical prognostic characteristics as identified in the International Prognostic Index" are also vitally important. since the prognosis of any particular patient is related to the biology of the specific lymphoma type and the patient's clinical prognostic characteristics. Combining this information will facilitate an accurate estimate of the prognosis and makes possible the development of a rational treatment plan for an individual patient. This progress is not the last change in the classification of lymphomas we will see. New insights into the biology of lymphoma will continue to elucidate new clinicopathologic entities. Certainly, the large group of diffuse large B-cell lymphomas will be subdivided into more specific entities. The future for clinical investigation in the non-Hodgkin's lymphomas is promising. Hopefully, new insights into the biology of this group of disorders will lead to improved therapies. APPENDIX Study Participants 1s and c/iniciaiu at each iiistirution were as follows Wing C Chan and James 0 Armitage (Owaha, NE). Rand) Gascoyne and Vancouver, Canada). Pauline Close and Peter Jacobs (Capetown, South Afnca), Andrew Norton and T. Andreu Lister (London, . Ennio Pednnis and Franco Caval11(Locarno, Switzerland), Francoise Berger and Bertrand Coiffier (Lyon, France). Fiuth Ho and Hong Kong). German OttIAlfred Schauer and Uolfgang Hiddemann (Wurzbur@Gottingen.Germany ) 1 m g expert heinatopathologisrs were asfollows Jacquec Diebold (Pans.France). KennethA MacLennan ( k e d s . United Kingdom),H er-Hermelink (Wurzburg. Germany). Bharat N Nathsani C o s Angeles. CA). and bennis D Weisenburger (Omaha, NE) ancy L Hdms (Bo5ton. MA) participated as a consultant regarding application of the International Lymphoma Stud) Group classification James nderson (Omaha. NE) and Pascal Ro! (Lyon. France) pro\ided statistical expertise regarding the study design and data analysis 2702 ARMITAGE AND WEISENBURGER c DIFFUSE LARGE B-CELL LYMPHON This is the most frequently occurring non-Hodgkin's lymphoma. It contains predominantly lymphomas classified as diffuse large cell, diffuse mixed cell, or immunoblastic in the Working Formulation and lymphomas classified as diffuse centroblastic, diffuse centroblastic/centrocytic, and immunoblastic in the Kiel classification. In the Non-Hodgkin's Lymphoma Classification Project using histology, immunophenotyping, and clinical information, diffuse large B-cell lymphoma was diagnosed accurately 87% of the time. Immunophenotyping improved the accuracy of diagnosis by 14%. Diffuse large B-cell lymphoma is a chemotherapy-curable lymphoma. I 1 1 ( I Frequency b e , years Median Range Mole Stage I IE I1 IIE Ill IV B symptoms ElevatedLDH Kamahky score 5 70 ..b Tumor bulk, cm : 25 k 10 Any extranodalsite > 1 extranodal sik Bone marrow involved GI tract i n 4 . d IPI score o/ 1 1 2/3 ._ 4/5 Typical immunophenotype Characteristic cytogenetics Oncogenesfrequently invdved 31% (n = 422) 64 14-98 55% 12% 1 3% 1 3% 16% 1 3% 33% 33% 53% 24% 76% 30% 71% 29% 16% 1 8% Abbreviatims.LDH, lactotedehydrogenase;GI,gashointesthal;IPI,!nkrna- tionol PrognosticIndex . 012345670 Years -. .. . .- . NICAL FEATURES OF THE NON-HODGKIN'S LYMPHOMAS 2783 FOLLlCUlAR LYMPHOMA The combined group of follicular lymphoma makes up the second most frequent type of nonn's lymphoma.These lymphomas are classified as follicularsmall cleaved cell, follicular mixed cell, and ular large cell lymphoma in the Working Formulation and predominantly as follicular centroblastic/ yt~cor follicular centroblastic lymphoma in the Kiel classification. In the Non-Hodgkin's Lymphoma ification Project using histology, immunophenotyping, and clinical information. follicular lymphoma was iosed accurately 94% of the time. However, subtyping of follicular lymphomas was less accurate. Immuenotyping improved the accuracy of diagnosis by only 1%. Although there was an overall 5-year survival of approximately 72%,patients with a high International Prognostic Index score had a poor survival. ---- CAS 22% (n = 306) 1 1 3 4 5 6 7 a 8 Years ARMITAGE AND WEISENBURGER ' SMALL LYMPHOCYTIC LYMPHOMA Small lymphocytic lymphoma makes up 6% of all non-Hodgkin's lymphomas. Since this often is the tissue manifestation of chronic lymphocyte leukemia, if patients who present with leukemia and predominantly blood and bone marrow involvement are included, the actual incidence would be higher. It contains predominantly lymphomas classified as small lymphocytic in the Working Formulation, but is called chronic lymphocytic leukemia in the Kiel classification. In the Non-Hodgkin's Lymphoma Classification Project using histology, immunophenotyping, and clinical information, small lymphocytic lymphoma was diagnosed accurately 87% of the time. Immunophenotyping added only 3% to the diagnostic accuracy. Frequency Age, years Median Range Male Stage I IE II IIE 111 . IV Bsymptoms ?', ElevatedLDH . Kornofskyscore 5 70 Tumor bulk, crn 25 z 10 ~ n eyxtranodal site > 1 extranodolsite b e marrow involved GI tract involved IPI score o/ 1 2/3 4/5 Typical immunophenotype Characteristiccyiugenetics Oncogenes involved 6%In = 88) 65 21 -91 53% 4% 0% 2% 3% 8% 83% 33% 41% 11% 59% 13% 80% 29% 72% 3% - .. 23% 64% 13% CDZO', CD3- CDl 0 -,CD5' CD23 + dd(l3qL -12 Unknown -- 0. 0 1 2 3 Ye4- 5 6 7 8 )BURGER 1 is the ia and higher. on. but phoma . mphoF to the :UNICAL FEATURES OF THE NON-HODGKIN'S 1YMPHOMAS MANTLE CELL LYMPHOMA 2785 Mantle cell lymphoma is among the most frequent of the newly recognized subtypes of ion-Hodgkin's lymphoma. In the Working Formulation, mantle cell lymphoma is classified as diffuse ;mall cleaved cell lymphoma most frequently, but also as follicular small cleaved cell lymphoma, small ymphocytic lymphoma, diffuse large cell lymphoma, and lymphoblastic lymphoma. In the Kiel :lassification, this lymphoma is most frequently classified as centrocytic lymphoma or centrocytoid gcentroblastic lymphoma. In the Non-Hodgkin's Lymphoma Classification Project using histology, mmunophenotyping, and clinical information, mantle cell lymphoma was diagnosed accurately 87%of he time. Immunophenotyping added 10% to the accuracy of diagnosis. Patients with mantle cell . ymphoma have a striking male predominance, usually advanced disease, and a poor overall and 'ailure-free survival, which belies the good survival usually anticipated with small cell lymphomas. -- i _--- 78 --CY 9%yeor5 Median hnge ble b i f I HE 1 N WPtoms ?uted LDH d k y score 5 70 m ~ brulk, cm 0/1 2/3 4/5 ricd imrnunophenotype I w r i s t i c cytogenetics involved -- k I. A is 6%(n = 83) 63 37-02 74% 10% 3% 6% 1% 9% 71% 28% 40% 21% 69% 25% 81% 51% 64% 9% 23% 54% 23% CD20+,CDCDlO-,CD5' CD23-, PRADIA r(l1;14)(q13;q32) BCl-l(PRAD1) .. 04 1 Oi2545678 Years I 20. 10. P<.OOl O\ I-- 1 -I- - 1I b---. -1 , 012345670 Years Years 2786 ARMITAGE AND W E I S E N B ~ 1 PERIPHEJUL-T-CELL LYMPHOMA The subgroup of peripheral T-cell lymphoma not otherwise specified represents the largest T-cell lymphomas in the REAL classification. For this report, angiocentric nasal lymphomas an T-lymphotropic virus type 1 (HTL.V-l)-associated lymphomas were excluded, which makes the r typical for those seen in most western countries. Peripheral T-cell lymphoma includes lymphomas w wide variety of histologic appearances. Tumors in this subgroup were classified as diffuse small cl cell, diffuse mixed cell, diffuse large cell, and immunoblastic in the Working Formulation. In Non-Hodgkin's Lymphoma Classification Project using histology, immunophenotyping, and cliN information, peripheral T-cell lymphoma was diagnosed accurately 86% of the time. However, this only true when immunophenotyping was available. Immunophenotyping improved the acc diagnosis by 45%. Peripheral T-cell lymphomas have one of the lowest overall and failure-fre rates. lOOk i i t -F f Frequency stose I IE II IIE I1 igr 6 syhptoms Elevated LDH Kamofsky score 5 70 Tumor bulk, cm 25 2 10 h y extrancdal site > 1 extranodalsite Bone marrow involved GI hod involved IPI score o/ 1 2/3 4/5 Typical immuncphenotype Characteristic Cytogendics Oncogenes involved 6%(n = 76) 61 17-90 ,55% 1% 7% 6% 6% 1 5% 65% 50% 64% 32% 65% 12% 8% 45% 36% 15% 17% 52% 31% CD20 ,CD3' Variable Unlvlown ! i E i i ! i c 4 1 1 , 1 I L CLINICAL FEATURES OF THE NON-HODGKIN'S LYMPHOMAS 2707 MARGINAL ZONE B-CELL LYMPHOMA, MALT TYPE This is among the most frequent of the newly recognized subtypes of non-Hodgkin's lymphoma. In this report, only low-grade MALT lymphomas are included. In the Working Formulation, MALT lymphomas were most commonly diagnosed as small lymphocytic lymphoma or small lymphocytic lymphoma with plasmacytoid characteristics, although some were called diffuse small cleaved cell lymphoma. In the Non-Hodgkin's Lymphoma Classification Project using histology, immunophenotyping. and clinical information, marginal zone lymphoma of the MALT type was diagnosed accurately 86%. of the time. Immunophenotyping added only .2% to the accuracy of the diagnosis. MALT lymphomas have one of the highest survivals of any subtype and even patients with a high International Prognostic Index score have a 5-year overall survival rate of 40%. Frequency Age. parr . Medion XI. Range Mole SW I IE II IIE 111 N B symptoms k k d LDH kmfsky score 5 70 Tumor bulk, cm =5 5 10 Any extranodalsite > 1 extranodal site 5one marrow involved GI 1r0ctinvolved PI score o/ 1 2/3 4/5 Typical irnmunophenotype Characteristic cytogenetics Quogenes in& 5%(n = 72) 60 19-91 48% 0% 39% 0% 28% 2% 31% 19% 27% 15% 68% 8% 98% 31% 14% 50% 61% 48% 8% CD20-, CD3- CDlO-,CD5- CD23- 1(11;18)(q21;q21) -3,118 Unknown . 20 * lo' , O\ + 01234567E Years .) 0 12345670 Years '"100% I IPI w1 f 401 I 2788 ARMITAGE AND WEISENBUW - LPRIMARY MEDIASTINAL LARGEB CE L LYMPHOMA Primary mediastinal large B-cell lymphoma represents a diffuse large B-cell lymphoma that cannot be distinguished histologically, but presents as a clinical syndrome due to the presence of a large mediastinal mass. This syndrome is clinically distinctive in that it occurs predominantly in young* patients and has a female predominance. In the International Non-Hodgkin's Lymphoma Classification Project using histology, immunophenotyping, and clinical information, mediastinal large lymphoma was diagnosed accurately 85% of the time. Immunophenotyping added 7% to the acc diagnosis. The clinical course of these patients differed little from that of other patients with diffuse B-cell lymphoma, although mediastinal radiotherapy may play an important role in their treatment. C. . R' ha ar let an SI in In lY fa Frequency Age, years Median Range hie %e I IE II IIE 111 IY! 8 iy+toms ElevatedIDH Karnohky score 5 70 Tumor bulk, cm a5 t 10 Any extranodal site. > 1 e x t r a d l sik Bone marrow involved GI trod invobed IPI score o/ 1 2/3 4/5 Typical immunophenotype Characteristiccytogenetics Oncogenes invoked 2% (n = 33) 37 21 -84 34% 10% 0% 34% 22% 3% 31% 38% 81% 228 90% 52% 56% 19% -3% 0% ._ 52% 37% 11% CD20.. CD3Variable Unknown P<.Wl + o i 2345671 Ym CUNICAL FEATURES OF ME NQN-HODGKIN'S LYMPHOMAS 2789 ANAPLASTIC LARGE T-/NULL-CELL LYMPHOMA Anaplastic large T-hull-cell lymphoma represents the'second most common T-cell lymphoma in the REAL classification. Patients with anaplastic large T-hull-cell lymphoma were often classified as having anaplastic carcinoma or an undifferentiated malignant neoplasm before staining for the CD30 antigen and discovery of the characteristic chromosomal translocation between chromosomes 2 and 5 led to its recognition as a distinctive non-Hodgkin's lymphoma. In the REAL classification, only anaplastic large-cell lymphomas with T or null immunophenotype are included in this category. In the Non-Hodgkin's Lymphoma Classification Project using histology, immunophenotyping, and clinical information, anaplastic large T-hull-cell lymphoma was diagnosed accurately 85% of the time. Immunophenotyping contributed 39% to the accuracy of diagnosis. Patients with this subtype of lymphoma have a young median age and a male predominance, and have the best overall and failure-free survival rates of any large cell lymphoma. Frequency Age, years Median Range kle %e I IE II IIE 111 IV B symptoms Elevated LDH Karnokky score I70 Tumor bulk, cm 25 2 10 Any axtronodal site > 1 extranodalsite Bone marrow invdved GI tract invdved IPI scwe 011 2/3 A/5 $pica1 immunophenotype Chomcteristic cytogenetics Oncogwrinvdved 2%(n = 33) 34 10-100 69% 16% 3% 22% n10% 100 10% 90 -39% 80 553% 70 AS% .$ 6C a26% 5c 76% 17% 59% 28% 1 3% 9% =pe4 c 3c O 2( 1( P=.97 Ir 012345678 YOiUS 61% 1 8% 21% CD20 ,CD3' CD30+,CD15EMA', AK' N2,5)(p23;q351 AM .O \ 012345678 Years 2790 ARMITAGE AND WEISENBUR- *' ., 1 LYMPHOBIASTIC L Y M P H O(T~/B) The lymphoblastic lymphomas make up a small proportion of all non-Hodgkin's lymphomas a associated with a low median age, male predominance, and advanced stage. In the Non-Hod Lymphoma Classification Project using histology, immunophenotyping, and clinical info lymphoblastic lymphomas were diagnosed accurately 89% of the time. Immunophenotyping con uted 35% to the accuracy of diagnosis. This is an aggressive lymphoma with low overall and failure survival rates. c c a d tt 1: Frequency Age, years Median Range Mole Stage I IE II IIE 111 IV B symptoms Elnokd LDH K a ~ f s k yxore 5 70 Tumor bulk, crn 25 2 10 Any extranodal site > 1 extranodal site b e marrow invoked GI tract involved IPI score o/ 1 2/3 4/5 Typical immunophenotype (T-cell only) Characteristic cytogenetics Oncogenesinvolved(T-cell only) 2% (n = 26) 20 4-65 64% 0% 0% 11% 0% 14% 75% 21% 70% 29% 06% 32% 02% 43% 50% A% -_ 33% 41% 26% CD20-, CD3. Tdt* Variable r c ~I -3 04 c 1 2 3 4 5 3 7i Yean F A N st B El Kc TL Ar > Bc. GI IPI c TY E Chc On, - 3URGER c CLINICAL FEATURES OF THE NON-HODGKIN'S LYMPHOMAS 2791 nd are gkin's lation. mtrih- BURKIlT-LI'KE LYMPHOMA urkitt-like lymphomas could not be diagnosed accurately in the Non-Hodgkin's Lymphoma fication Project. Using histology, immunophenotyping, and clinical information, the diagnostic cy was only 53%. The problem was the lack of precise definitions to separate this group from the e large B-cell category or true Burkitt's lymphoma. The median age and clinical characteristics of t 01 23438 Years 78 100 - 90 80 70 f 60 3 50 u) =eg a 3c I I O 2c L- 3 IPI 4/5 1c I P<.OOl cI I -. 112345678 Years . 012345676 Years 2792 ARMITAGE AND WEISENBURGER .i ;i I MARGINAL ZONE B-CELL LYMPHOMA, NODAL TYPE Marginal zone B-cell lymphoma of the nodal type is one of the new forms of-non-Hod&&* lymphoma not recognized in the Working Formulation. In the Working Formulation, these l y m p h o m were most commonly found in the small lymphocytic subcategory, but were also sometimes diagnosed as diffuse small cleaved cell lymphoma, small lymphocytic lymphoma with plasmacytoid charactens tics, or diffuse mixed cell lymphoma. In the non-Hodgkin's Lymphoma Classification Project u s b histology, immunophenotype, and clinical information, marginal zone B-cell lymphoma of the n type was diagnosed accurately 63% of the time. Immunophenotyping added 8% to the accurac diagnosis. These patients had an overall and failure-free survival similar to small lymph lymphoma. These lymphomas are often currently diagnosed as monocytoid B-cell lymphoma. E' Pi L! !I C( th Frequency Age, years &ion Range Mole stage I IE II IIE 111 IV B symptoms Elyokd LDH Ka%fsky score 5 70 Tumor bulk, cm 25 2 10 Any extranodo1sik > 1 extronodol site h e marrow invoked GI tract involved IPI score o/ 1 2/3 4/5 Typicol imrnunophenotype Chorocteristiccytogenetics Oncogenes involved 1%(n = 20) 58 27-90 42% 1 3% so% 13% 0% 34% 40% 37% 40% 7% 36% 0% 47% 16% 32% 5% 60% 27% 1 3% CDX)', CD3CDlO .CDSCD23+3,+18 Unknown 2r,, 10 9\ i 0123055 78 Years - Fr Ac M' stc 8. Ele Kc Tu ~ Ar BO. GI IPI -. TY Ck On - P CLINICAL FEATURES OF THE NON-HODGKIN'S LYMPHOMAS `. 2793 LYMPHOPWSMAC~LY~MICPHOMA Lymphoplasmacytic lymphoma is an uncommon diagnosis in the REAL classification, and includes patients that might also be diagnosed with Waldenstrom's macroglobulinemia. In the Non-Hodgkin's Lymphoma Classification Project using histology, immunophenotyping, and clinical information, lymphoplasmacytic lymphoma was diagnosed accurately 56% of the time. Immunophenotyping contributed 3% to the diagnostic accuracy. The clinical characteristics of this lymphoma were similar to those of small lymphocyticjymphoma. Frequency Age, years & Median Range Male %e I IE II IIE 111 IV B symptoms E~evotedLDH Karnofskyscore 5 70 Tumor bulk, crn 25 2 10 Any extranodalsite > 1 extranodal site Bone marrow invdved GI h c t invdved IPI score o/ 1 2/3 4/5 Typical irnrnunophenotype Characteristiccytogenetics Oncogenes involved l % ( n = 15) 63 37-81 53% 7% 0% 0% 1 3% 7% 73% 13% 1 5% 27% 50% 25% 100% 40% 73% 7% 16% 69% 1 5% CD20+,CD3CDl 0-, CD5- CD23-, cytalg+ t(9;14)lpl3;q32) del 6(q23) Unknown Abbreviation:cyt0.19, cytophsmicirnmu?ogIobuIin. - -. , 3 "/i_CO i Years 10 k . 2 8 0 . I. . 012345670 Years -- - -IPI 4/5 ;-----e---- IPI 2l3 I 8 012345678 Years 2794 ARMITAGE AND WEISENBU&EQ CLIb BURKITS LYMPHOMA This is a rare lymphoma in a clinical series that includes predominantly adults. Although this i highly aggressive and clinically distinctive lymphoma requiring unique treatment approaches, overall and failure-free survival rates are similar to diffuse large B-cell lymphoma. ,UT\ t 4 re-e' hdWJ 5 Frequency Age, years Median Range hle stose I IE II IIE Ill IV B symptoms Elevated LDH Karyfsky score 5 70 hr&bulk, cm 2 5r 10 ~ n eyxtranodal site < 1 extranoda~sik Bone marrow in& GI tract involved ' IPI scare . 0/1 2/3 4/5 Typtcal immunophenotype Charockristic cytogenetics Oncogenes involved < I % ( n = 10) 31 2-60 89% 25% 12% 13% 1 2% 0% 38% 22% 75% M% 56% 22% 78% 56% 33% 11% 57% 29% 14% CD20'. CD3CDlO+,CD5Tdt(8;14)(q24;q32) ~ 2 , w p2i;q24) 1(8;22)(q24;qll) c-Mrc CLINICAL FEATURES OF THE NON-HODGKIN'S LYMPHOMAS 2795 REFERENCES 1. Weisenburger DD: Epidemiology of non-Hodgkin's lymphoma: Recent findings regarding an emerging epidemic. Ann Oncol 5:19-24. 1994(suppl 1 ) 2. Landis SH. Murray T.Bolden S. et al: Cancer statistics. 1998.CA: A Cancer Journal for Clinicians 48:6-29.1998 3. Gall EA. Mallory TB:Malignant lymphoma. A clinicopathologic survey of618cases.Am J Pathol 18:381-415, 1942 4. Rappaport H, Winter W1.Hicks EB: Follicular lymphoma: A re-evaluation of its position in the scheme of malignant lymphoma. based on a survey of 253 cases. Cancer 9:792-821.1956 5. Lukes RF, Collins RD: Immunologic characterization of human malignant lymphomas. Cancer 34:1488-1503.1974 .!- ' '-6L.erlhert K; Mohri- N. Stein H, et al: The histopathology malignant lymphoma. B r J Haematol31:193-204. 1975(suppl) of 7. Lennen K: Malignant Lymphomas Other Than Hodgkin's Dis- ease. New York. NY, Springer-Verlag. 1978 8. The Non-Hodgkin's Lymphoma Classification Project: National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphqmas. Summary and description of a working formulation for clinical usage. Cancer 4921 12-2135. 1982 9. Harris NL. laffe ES.Stein H. et al: A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood 84:1361-1392.1994 IO. The Non-Hodgkin's Lymphoma Classification Project: A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. Blood 89:3909-3918.I997 I I . The International Non-Hodgkin's Lymphoma Prognostic Factors Project: A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med 319:987-994.I993 . 12. Kaplan EL. Meier P Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457-481.1958 13. Cox DR: Regression models and life-tables. J R Stat Soc 34:187-202.1972 .. ..