Hisamitsu Suzuki

Clinicopathologic study of CD56 (NCAM)-positive angiocentric lymphoma occurring in sites other than the upper and lower respiratory tract.

The expression of the neural cell adhesion molecule (NCAM) (CD56, NKH-1) is a rare phenomenon in malignant lymphoma. Recently, several authors, including our group, described the clinicopathologic, phenotypic, and genotypic features of NCAM-positive tumors as a unique subgroup within a larger category of hematolymphoid malignancies. Ten cases of CD56+ angiocentric lymphoma occurring in sites other than the upper aerodigestive tract were studied for evaluating their characteristics. The disease occurred in six men and four women varying from 24 to 85 years (mean age, 53 years) who often exhibited a striking predilection for extranodal sites of involvement, such as the skin, gastrointestinal tract, and muscle, usually in the absence of peripheral lymphadenopathy. Although the cytologic appearances and immunophenotypic profile varied from case to case, these tumors often exhibited azurophilic granules, an angiocentric growth pattern, and surface CD3−, T-cell receptor (TCR) antigens−, and CD56+ phenotype without B-cell phenotype, except for a single case of CD3+, TCRα/β+, and CD56+ phenotype. Genotypic investigation exhibited germline configuration of the TCR β and γ chain genes and the immunoglobulin heavy chain gene in all five cases of surface CD3− phenotype examined, whereas the case of CD3+ phenotype showed rearrangement of TCRβ. They seem to constitute a distinct entity of the lineage spectrum spanning from natural killer (NK) cell to NK-like T cell.

Molecular and immunological dissection of diffuse large B cell lymphoma: CD5+, and CD5- with CD10+ groups may constitute clinically relevant subtypes.

Diffuse large B cell lymphoma (DLBL) constitutes the greatest percentage of adult non-Hodgkin’s lymphomas and represents a diverse spectrum of lymphoid neoplasms. Clinicopathologic, phenotypic and genotypic findings were correlated and compared for 63 DLBL cases to investigate whether they represent clinically relevant subtypes. They were all cyclin D1 negative and were phenotypically divided into three groups, ie group I (CD5+ type, n = 11), group II (CD5− CD10+ type, n = 19), and group III (CD5− CD10− type, n = 33). Data were correlated by observing the respective gene rearrangement and expression of BCL2 and BCL6. In clinical aspects, the group I cases demonstrated a significantly inferior survival than those of the other two groups (log-rank test, P = 0.016). Although rearrangement of BCL2 and BCL6 did not show any inclination to a specific subgroup, the immunohistochemical detection of BCL2 was less frequent, at a statistically significant level (P = 0.011), in group II (50%) than in group I (82%) and III (82%) cases. This appears to confirm the unique aspect of the CD5− CD10+ type DLBL, indicating a certain relationship with the normal germinal center cells which usually lack BCL2 expression. The BCL6 protein expression was detected in most of the present DLBL cases (92%) irrespective of this grouping. These data suggest that the phenotypic delineation by the detection of CD5 and CD10 will improve our understanding of DLBL and be helpful in a future subgrouping of DLBL.

Clinicopathologic study of large cell anaplastic lymphoma (ki‐1‐positive large cell lymphoma) among the japanese

The clinical, prognostic, phenotypic, and genotypic findings of 30 patients with large cell anaplastic lymphoma (Ki‐1‐positive large cell lymphoma) were analyzed. There were 13 male and 17 female patients (male‐female ratio, 0.8) whose ages ranged from 3 to 81 years of age (mean, 28 years of age; 67% of the patients younger than 30 years of age). The 5‐year survival rate was 52%; this was better than that of other types of high‐grade peripheral T‐cell lymphoma. Histologic examination showed distinctive morphologic features such as tumor cell pleomorphism, sinus infiltration, fibrosis, partial lymph node involvement, sparing of B‐cell regions, and occasional plasma cell infiltrates. Eighty percent of the cases were of T‐cell phenotype, and others expressed neither B‐cell nor T‐cell markers. The tumors were frequently positive for a histocompatibility antigen (HLA‐DR), CD25 (the interleukin‐2 receptor), and epithelial membrane antigen. Rearrangements of the T‐cell receptor beta gene were observed in nine of 13 cases (69%). These findings indicated that many of the tumors had the phenotype and genotype of activated T‐cells. This study also showed that large cell anaplastic lymphoma has a survival figure intermediate between Hodgkins disease and low‐grade peripheral T‐cell lymphoma.

Malignant lymphoma of mucosa‐associated lymphoid tissue arising in the thymus of a patient with sjögren's syndrome

A 59‐year‐old woman with Sjögrens syndrome had an anterior mediastinal tumor. The tumor had epithelium‐lined thymic cysts. Histologically, centrocyte‐like (CCL) cells were present as clusters intermingling with small lymphocytes and plasma cells, invaded the epithelium, and formed characteristic lymphoepithelial lesions; the tumor was identified as malignant lymphoma arising in mucosa‐associated lymphoid tissue (MALT). Within the tumor, trapped Hassalls corpuscles were recognized. Immunohistochemical staining demonstrated monotypic cytoplasmic kappa light chains in a small portion of the CCL cells. Furthermore, Southern blot hybridization studies showed rearrangements of immunoglobulin heavy chain, immunoglobulin kappa light chain, and T‐cell receptor beta genes. The findings are consistent with thymic low‐grade B‐cell MALT lymphoma. Cancer 1992; 69:1347‐1355.

Phenotypic analysis of peripheral T cell lymphoma among the Japanese

From 1980 to 1990, 174 peripheral T cell lymphomas were studied morphologically and immunophenotypically with a panel of monoclonal antibodies which were reactive with T cell differentiation antigens in cryostat sections and/or cell suspensions. Histologically, 57% of the lymphomas were categorized into low‐grade tumors according to the updated Kiel classification, while 41% were high‐grade tumors. By immunologic studies, 50% of the lymphomas were of helper/inducer (CD4) phenotype, 6% were of cytotoxic/suppressor (CD8) phenotype, 3% expressed both CD4 and CD8, 3% lacked both CD4 and CD8, and 36% were phenotypically undetermined because of an admixture of a fairly even number of CD4 and CD8‐positive cells. The phenotypically undetermined cases were more frequently noted in the low‐grade groups than in the high‐grade group, and the latter often showed a loss of pan‐T antigens, although there was no definite correlation between the histologic category and the immunophenotype. CD25, which is strongly manifested in anti‐HTLV‐1 antibody‐positive cases, was negative or only weakly expressed in anti‐HTLV‐1 antibody‐negative cases. Anaplastic large cell lymphomas (LC‐Ana) strongly expressed CD30, which was also detectable in only large blast‐like cells in the low‐grade tumors. Seventy‐one per cent of the lymphomas expressed la antigens. In this series, the clinical data were available on 154 patients. For individual markers, the expression of CD30 and HLA‐DR were associated with a longer actuarial survival (P< 0.01 and P < 0.05 by the generalized Wilcoxon test). The absence of CD25 or the presence of CD3 on tumor cells correlated with a relatively favorable prognosis, but not significantly. The detection of CD4 and CD8 had relatively little prognostic value. In the cases excluding LC‐Ana, a significant difference was also recognized between the groups with and without CD25, CD30 and HLA‐DR (P < 0.05 by the generalized Wilcoxon test). These results suggest that the immunophenotypic analysis of peripheral T cell lymphoma provided its use as an adjunct to a histopathologic diagnosis and was related to prognostic prediction.

Clinicopathologic study of 212 cases of peripheral T-cell lymphoma among the Japanese

Background. Postthymic/peripheral T‐cell malignancy shows significant histopathologic and clinical diversity, even in its prognosis, and the correlations remain to be debated.

Hodgkin's disease expressing follicular dendritic cell marker CD21 without any other B-cell marker: a clinicopathologic study of nine cases.

Reed-Sternberg (RS) and Hodgkins (H) cells are considered to be the neoplastic cells in Hodgkins disease (HD). Although most data suggest their lymphoid origin, the nature of these cells still remains a subject of controversy. Recently, a number of RS cells have been found to express an antigen that is also present on follicular dendritic cells (FDCs), asserting FDCs as the possible progenitor cells of H-RS cells. This prompted us to investigate whether these CD21-positive cases had distinct clinicopathologic characteristics. In a series of 94 examined cases of HD, we identified 9 CD21-positive ones (4 of 37 cases of nodular sclerosis, 1 of 41 mixed cellularity, and 4 of 12 lymphocyte depletion HD) without any other B-cell marker on paraffin sections. The patients varied in age from 16 to 82 years (median, 50 years) and included six men and three women. They had superficial or mesenteric lymphadenopathy without hepatosplenomegaly. Peripheral blood leukocytosis was seen in three patients. The clinical course was indolent, and all patients but one achieved an initial complete response with HD-based treatment regimens, although three of them relapsed. Morphologically, two subgroups could be delineated. Six of the cases were characterized, besides by the classic RS cells, by a varying number of the cells with the distinctive walnutlike or cerebrumlike nuclei and cytologically with cytoplasmic processes. Their fine structural examination also revealed villous processes, but no desmosomes. The other three cases had multinucleated RS cells often with triangular nuclei, but not cytoplasmic processes. The percentage of CD21-positive tumor cells ranged from less than 10% to 60% among the H-RS cells. These RS cells were positive for CD30 (9 of 9), CD15 (7 of 9), CD68 (1 of 8), fascin (8 of 8), S-100 protein (1 of 7), and epithelial membrane antigen (2 of 8) on paraffin sections. Notably, of eight cases examined on frozen sections, two showed immunostaining for DRC1, CD35, R4/23, and Ki-M4p. Only CD35 was also detected in the other two cases. Genotypic investigation showed germline configuration of the T-cell receptor beta and gamma chain genes and the immunoglobulin heavy chain gene in all eight cases examined. In situ hybridization showed Epstein-Barr virus sequences in four cases, three of which were examined by the terminal region analysis and showed the Epstein-Barr virus to be monoclonal. We concluded that in a small proportion (9.6%) of HD, H-RS cells might be derived from FDCs and that they appear to represent a distinct pathologic variant based on morphologic and phenotypic traits within the framework of HD.

Differences in prognostic factors between leukemia and lymphoma type of adult T-cell leukemia

Prognostic factors affecting the survival of adult T‐cell leukemia (ATL) patients were analyzed in three groups: total cases, leukemia type cases, and lymphoma type cases. Factors found to be important overall, i.e. for total cases, were leukocyte count, ATL cell ratio in the peripheral blood, serum calcium levels and lactate dehydrogenase (LDH) level. Of those, LDH level proved not significant when evaluated separately for leukemia type or lymphoma type cases. Leukocyte count and ATL cell ratio were significant in leukemia type patients, whereas it was serum calcium level that was significant in lymphoma type; there were mutually exclusive sets of factors for the two groups. Thus, prognostic factors for ATL patients should be considered separately for each type of the disease.

Cancer superimposed on adult T-cell leukemia.

Forty‐three patients with adult T‐cell leukemia (ATL), admitted to the hospital from 1982 to 1987, were studied. Five of those were found to have additional cancer; two of the five had two additional kinds of cancers besides ATL. During the same period, in contrast, the authors encountered only three patients with some superimposed cancer among 155 cases of hematologic malignancies which had no association with human T‐cell lymphotropic virus type I (HTLV‐I). These facts strongly suggest that HTLV‐I infection is not only associated with ATL, but it is likely to increase the incidence of other types of malignancy as well.

Phenotypic and genotypic characterization of 14 leukemia and lymphoma cell lines with 11q23 translocations.

11q23 translocation is the most popular chromosomal abnormality in infant leukemia. In adults, it is often encountered in non-Hodgkins lymphoma (NHL). In this study, we analyzed the phenotypic and genotypic characteristics of 9 acute leukemic cell lines with 11q23 translocations and one with deletion of the 11q23 locus, nine of which were established by researchers in this group, together with 4 NHL cell lines with 11q23 translocations. All lines were considered to belong to the B-cell lineage at different stages. All 10 leukemic lines showed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene: two corresponded to the B-precursor stage (CD19+, cytoplasmic mu-), while the other 8 corresponded to the pre-B stage (cytoplasmic mu+). All 4 NHL lines showed rearrangements of both the IgH and Ig kappa genes with three expressing surface Ig; specifically, mature B-cell phenotype. As for myelocytic-monocytic markers, at least one out of 4 antigens examined were positive in 8 of the 10 leukemic cell lines, while only one of the 4 NHL lines was reactive. There were essentially no clear phenotypic or genotypic differences between t(4;11) and t(11;19) cell lines, supporting the view that both diseases have similar clinicopathological characteristics. These cell lines are also valuable for cloning genes at the chromosomal breakpoints.