Studies on nasal T/natural killer (NK)-cell lymphoma have been hampered by its tendency to cause necrosis. Thus, the establishment of cell lines of this neoplasm would seem to be valuable. This study attempted to establish cell lines from primary lesions of this tumor, and successfully obtained 2 novel Epstein-Barr virus (EBV)-positive cell lines, SNK-6 and SNT-8, by means of highdose recombinant interleukin 2. Flow cytometry showed that SNK-6 had an NK-cell phenotype, CD3 ؊ CD4 ؊ CD8 ؊ CD19 ؊ CD56 ؉ Tcell receptor (TCR) ␣/␤ ؊ TCR ␥/␦ ؊ , whereas SNT-8 was CD3 ؉ CD4 ؊ CD8 ؊ CD19 ؊ CD56 ؉ TCR ␣/␤ ؊ TCR ␥/␦ ؉ . These were consistent with immunophenotypes of their original tumors, and the cell lines had monoclonal EBV clones identical to ones in their original tumors. Thus, the cell lines developed from cells forming the primary lesions. Genotypic analysis showed that SNK-6 had unrearranged TCR and immunoglobulin heavy-chain genes, supporting the conclusion that SNK-6 was of NK-cell lineage. On the other hand, SNT-8 had rearranged TCR ␤-, ␥-, and ␦-chain genes, and together with its phenotype, SNT-8 proved to be a ␥␦ T-cell line. This is the first report of the establishment of cell lines from primary lesions of nasal T/NK cell lymphomas, and the results demonstrated that there are at least 2 lineages, NK-and ␥␦ T-cell, in this neoplasm. Moreover, it has been suggested that nasal T/NK cell lymphomas of these lineages may belong to the same clinicopathologic entity because both types of cases shared common clinical and histopathologic features. IntroductionNasal T/natural killer (NK)-cell lymphoma is a distinct clinicopathologic entity characterized by progressive necrotic lesions in the nasal cavity, nasopharynx, and palate. 1 It has been called angiocentric lymphoma, lethal midline granuloma, or polymorphic reticulosis. 2 It is a relatively rare disease associated with a poor prognosis and more often seen in Asia than in the United States and Europe. 3-14 Nasal T/NK-cell lymphomas can exhibit a broad histologic spectrum and usually show invasion of the vascular walls, which is associated with prominent ischemic necrosis of both tumor cells and normal tissue.The most characteristic feature of the disease is a consistent and strong association with the Epstein-Barr virus (EBV); indeed, almost all cases are positive for EBV irrespective of ethnic difference, [15][16][17][18][19][20][21][22] yet the precise role of the virus in the etiology of the disease is poorly understood. The cellular origin of the nasal T/NK-cell lymphoma has been controversial. It was initially thought to originate from the T-cell lineage based on immunophenotype. [23][24][25][26][27] Later studies using combined immunophenotypic and genotypic analysis have suggested that most nasal T/NK-cell lymphomas are of NK-cell lineage, being CD56 ϩ , negative for surface CD3 (Leu4), and unassociated with rearrangements of the T-cell receptor (TCR) genes. 11,[28][29][30] On the other hand, some studies have reported the existence of T-cell lymphomas that...

Summary. In this study, we describe the cytological and cytogenetic features of six Epstein-Barr virus (EBV)-infected natural killer (NK) cell clones. Three cell clones, SNK-1, -3 and -6, were derived from patients with nasal T/NK-cell lymphomas; two cell clones, SNK-5 and -10, were isolated from patients with chronic active EBV infection (CAEBV); and the other cell clone, SNK-11, was from a patient with hydroa vacciniforme (HV)-like eruptions. An analysis of the number of EBV-terminal repeats showed that the SNK cell clones had monoclonal EBV genomes identical to the original EBV-infected cells of the respective patients, and SNK cells had the type II latency of EBV infection, suggesting that not only the cell clones isolated from nasal T/NK-cell lymphomas but also those isolated from CAEBV and HV-like eruptions had been transformed by EBV to a certain degree. Cytogenetic analysis detected deletions in chromosome 6q in five out of the six SNK cell clones, while 6q was not deleted in four control cell lines of T-cell lineage. This suggested that a 6q deletion is a characteristic feature of EBV-positive NK cells, which proliferated in the diseased individuals. The results showed that EBV-positive NK cells in malignant and non-malignant lymphoproliferative diseases shared common cytological and cytogenetic features.

The prevalence of adult T-cell-leukemia virus (ATLV) infection was examined in Japanese monkeys living naturally in various parts of Japan and in other species of non-human primates imported into and kept in Japan. Sera of 2,650 Japanese monkeys from 41 troops throughout Japan were tested. High incidences of anti-ATLV-associated antigen (ATLA)-positive monkeys were found in most troops, not only in the endemic area of human ATL(Southwestern Japan), but also in non-endemic areas. The incidence of sero-positive individuals increased gradually with age, reaching a maximum when the animals became adult, indicating age dependency, like that found by epidemiological studies on humans. Anti-ATLA antibodies were also detected in 90 of 815 sera of imported non-human primates of 33 species other than Japanese monkeys. All the anti-ATLA sero-positive monkeys were Catarrhines (Old World monkeys), mainly macaques of Asian origin. Some sero-positive monkeys were also found among animals of African origin, but no antibody was detected in Prosimians and Platyrrhines (New World monkeys). The clear-cut difference between the geographical distribution of sero-positive simians and that of humans indicates the improbability of direct transmission of ATLV from simians to humans.