Strategies to distinguish anaplastic large cell lymphoma (ALCL) from Hodgkin's disease (HD)

58 CURRENTDIAGNOSTICPATHOLOGY shoe-shaped nuclei with prominent nucleoli, and tend to form nodules often surrounded by thick collagen bands. Reed-Sternberg-like cells are rare. Intrasinusoidal diffusion is usually encountered as opposed to HD, where it represents an exceptional finding. On phenotypic grounds, the tumour carries the same molecular expressions as other types of ALCL (CD30 = 100%, CD45 = 65%, CD15 = 20%, T-cell markers: 55%; B-cell markers: 15-20%; null-phenotype: 25-30%; hybrid phenotype: 1-2%). As nodularity and fibrosis are common features with nodular sclerosing Hodgkin's disease (NSHD), the new term ALCL, Hodgkin's like (ALCL-HL) has been proposed (Harris et al, Blood, in press). In REALC, ALCL-HL represents a provisional entity, as further clinical, phenotypic and genotypic data are required for its definitive validation. Within this scope, some recent observations can be of interest. Firstly, a report on a large series of prospectively studied ALCLs has shown that ALCL runs the same course as ALCLcommon type (ALCL-CT) and high-grade non-Hodgkin's lymphomas other than ALCL, when third generation chemotherapy regimes are applied (Pileri et al, Br J Haematol, 86:513, 1994). Furthermore, the tumour usually occurs in young adults, presents aggressively with hugh mediastinal masses, and tends to easily achieve and to maintain complete remission. Secondly, ALCL-HL shows quite distinctive molecular expression, which significantly differ from the ones observed in typical HD. In this respect, by testing 100 cases (15 examples of HD, mixed cellularity (MC-HD); 35 cases of nodular sclerosis HD (NS-HD); 15 ALCLs-CT; 35 ALCL-HL), it has become evident that, while there is no differenence between ALCL-CT and ALCL-HL, as well as between MC-HD and NS-HD, ALCL and HD are characterized by distinct algorithms (Pileri et al, Leukemia and Lymphoma, in press). In particular, neoplastic cells of ALCL are CBF.78+, CD45+/-, EMA+/-, CD15-/+, p53-/+, EBV (EBER1/LMP-1)-/+, and are not surrounded by CD3+ T-cell rosettes; on the other hand, Hodgkin's and Reed-Sternberg cells of HD are CBF.78-, CD45-, EMA-/+, CD15+/-, p53+, EBV+, and are usually surrounded by rosettes of CD3+ T-lymphocytes.

Strategies to distinguish anaplastic large cell lymphoma (ALCL) from Hodgkin's disease (HD) M. C. Kinney, R. S. Larson, W. R. Macon and R. D. Collins, Vanderbilt University Medical Center, Nashville, TN, USA Most cases of ALCL and HD are readily distinguished, but there are overlap cases that are difficult to categorize into one or other lymphoma group. ALCL is defined by morphologic and immunologic criteria and possibly by a karyotypic abnormality, the t(2;5)(p23;q35). ALCL is usually a pleomorphic large cell lymphoma with a paracortical and sinus growth pattern. Virtually all tumor cells show strong expression of Ki-1 (CD30). Most cases are T cell originated and have EMA positivity. The cytologic spectrum is hetero-

geneous. Large cell variants include monomorphic, sarcomatoid and Hodgkin-related. We have recently described a small cell prominent variant (SCV) that extends the histologic and clinical spectrum of ALCL. A novel translocation t(2;5)(p23;q35) has been associated with ALCL and SCV. Cloning of the translocation has demonstrated involvement of the NPM gene on chromosome 5 and ALK (anaplastic lymphoma kinase) gene on chromosome 2. Studies are underway to evaluate the specificity of t(2;5) for ALCL. The term HD is now applied to a group of neoplasms having certain common features but remarkable heterogeneity as well. This inherent heterogeneity raises questions as to the nature of HD and confuses our separation of HD from other large cell lymphomas, including ALCL. The potential difficulty in such separation is exemplified by our recent studies: (1) confirming the diagnosis of lymphocyte depleted HD, reticular variant (LDHDr) in only 39%) of cases diagnosed at Vanderbilt from 1972-1989 (Kinney et al, Lab Invest 64:75A, 1991), (2) demonstrating the variation in immunoreactivity in those cases of HD with many large tumor cells (types of LDHD and NSHD)(Larson et al, Lab Invest 70:113A, 1994). In the latter study, cases of HD were compared to ALCL using a broad panel of antibodies reactive in paraffin-embedded tissue. All cases of HD were negative for EMA, T cell related markers (CD45RO and CD43), and BNH9, but the other markers were heterogeneous: CD15 (94%), CD30 (69%), BLA.36 (69%), CD20 (25%), CD15s (25%). The results for ALCL were heterogeneous and overlapped those for HD: CD30 (100%), CD15 (20%), BLA.36 (40%), CD15s (50%), BNH9 (25%), CD45RO (70%) CD43 (70%), CD45 (70%); CD20 (0%), EMA (65%). From these studies, it seems unlikely that paraffin immunoperoxidase studies will be a specific discriminant amongst CD30+ large cell lymphomas (LCL) including HD in the near future. Therefore, our strategy at Vanderbilt to categorize these neoplasms more precisely is as follows: (1) CD30+ ALCL will be divided into three groups, primary ALCLs of T cell type (including the SCV), B cell, or null type; CD15+ cases will be diagnosed as ALCL only if there is CD45 and T cell marking; (2) Cases with large numbers of tumor cells will be classified as HD only if they have the appropriate growth pattern and are CD45-, CD15+ and/or CD30+, and T cell antigen negative; (3) CD30 and/or LeuMl+ cases not meeting these criteria will be called LCL, not otherwise specified (NOS). Each of these groups will be studied with recently available markers, including a molecular probe for the t(2;5)(p23;q35) and antibodies directed against adhesion molecules. These studies should refine the diagnostic criteria for ALCL and HD, and show if other entities exist in the CD15+, CD30+ LCL, NOS group.

A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group N. L. Harris (for the International Lymphoma Study