Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma characterized by the CD30+ large neoplastic cells and sometimes carries a t(2;5)(p23;q35). Recently, we found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in ALCLs with t(2;5). Subsequent cDNA cloning showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al, Science 263:1281, 1994). Meanwhile, the clinicopathologic features of p80-carrying ALCLs have remained unclear. Paraffin sections of 105 cases of ALCL were immunostained using anti-p80 antibody, and 30 of them were shown to express p80. Clinicopathologic comparison between p80-positive and -negative ALCLs showed that p80-positive cases occurred in a far younger patient age group (16.2 +/- 12.9 years; p80- negative cases, 51.0 +/- 22.3 years; P < .0001) and the patients showed a far better 5-year survival rate (79.8%; p80-negative group, 32.9%; P < .01). These data showed that p80-positive ALCL is a distinct entity both clinically and pathogenetically and should be differentiated from p80-negative ALCL.

756 CLASSLFICATION OF MALIGNANT LYMPHOMA Acta Path. Jap.form no clear-cut pattern but rather monotonous diffuse masses of round cells which appear to differ only in size. It should be a great hazard not only for treatment of the patients but also for statistical, epidemiological and various other studies on lymphomas that the diagnosis on one tumor would vary according to pathologists who examine it or hospitals where a patient is treated.It is therefore very important to evaluate the general situation on lymphoma diagnosis, to investigate the cause of diagnostic diversity, and to find objective measures to improve the accuracy and reproducibility of lymphoma diagnosis.As seen in the other reports of this symposium, new theoretical and technical approaches based on the recently acquired knowledges on basic immunology have greatly advanced the study of malignant lymphoma.50 It is now apparent that the Rappaport classification (AFIP Atlas, 1966)45 whose clinical usefulness had been widely recognized has some theoretical as well as practical drawbacks. Several different new classifications for non-Hodgkin's lymphomas have been proposed by leading scholars of this field in U.S.A. and E~rope,4,~~,16,16,~~35 and they are a t present being critically evaluated in the project for the international classification of non-Hodgkin's lymphoma sponsored by the National Cancer Institute of U.S.A.It was established through the U.S. -Japan seminars on malignant diseases of hematopoetic system held twice in 1967 and 19712, that the geographic difference between U.S.A. and Japan in various aspects of malignant lymphoma notably in the relative incidence of its subtypes was quite a p~a r e n t .~~~~' In order to contribute to the clarification of the problems of lymphoma diagnosis, and to obtain useful findings for a new classification suited for the lymphomas in Japan, a collaborative study was made by organizing a study group consisting of 16 members of different schools and different length of experience in the pathology of lymphoma. This study consisted of two parts namely I) the study of the consistency and reliabily of the histopathological diagnosis, and 11) the correlation between histological appearances and immunological characters of the lymphoma cells.

Alkaline phosphatase (ALP) activity was evaluated histochemically and cytochemically in concert with immunologic technics in 60 cases of non-Hodgkin's lymphomas and lymphocytic leukemias. Surface membranes of neoplastic cells were positive for ALP only in certain B-cell malignancies: 3 of 6 lymphocytic lymphomas of intermediate differentiation, 4 of 13 nodular lymphomas, and 1 of 7 Burkett's lymphomas. All other B-cell tumors, including chronic lymphocytic leukemia, well-differentiated lymphocytic lymphoma, and diffuse "histiocytic" lymphoma, were ALP-negative. The neoplastic cells of Sezary syndrome and lymphoblastic lymphoma were also consistently negative for ALP. In control lymph nodes ALP-positive lymphocytes were present only in primary follicles and in mantle zones of secondary follicles. ALP-positive lymphomas appear to be neoplastic counterparts of these normal lymphocytes, not only cytochemically, but also with respect to their morphologic and immunologic characteristics. Furthermore, histochemical inhibition tests suggested that the ALP activity demonstrated may reflect a newly recognized, unique isoenzyme.

In 14 cases of hairy cell leukemia unique vascular lesions not previously reported were observed in surgically resected spleens and hepatic biopsies. In all 14 spleens there were variably prominent distended spaces filled with erythrocytes and resembling dilated sinuses. These structures appeared to be lined by hairy cells,and studies utilizing histochemical and enzymatic methods confirmed that they were in fact pseudosinuses lacking the endothelial cells and ring fibers of normal splenic sinuses. These changes were not present in normal spleens or in spleens involved by other types of chronic leukemia, and appear to be qualitatively specific for hairy cell leukemia. In three of five hepatic biopsies similar angiomatous lesions were present in multifocal clusters resembling hemangiomas. Their pathogenesis may be related to possible adherence of hairy cells to reticulum fibers in involved tissues.