Mantle cell lymphoma (MCL) is a low grade B-cell lymphoma; patients with this lymphoma have widespread nodal disease at the time of diagnosis, although local extranodal disease has also been reported in some cases. It is uncertain whether these two disease are identical. To determine the relationship between MCL and extrnodal lymphoma with a morphology similar to that of MCL, we compared clinical and immunohistological findings of 17 patients with MCL to those of 54 patients with other low grade B-cell lymphoma including 15 patients with extranodal lymphoma. The overexpression of PRAD1 gene and the expression of immunoglobulin shared idiotypes were also studied in these lymphomas. The patients with MCL had advanced disease with generalized lymphadenopathy on admission, a CD5⁺CD10^-IgD⁺ phenotype, and PRAD1 gene overexpression. In contrast, the patients with extranodal lymphoma had localized disease on admission, a CD5^-CD10^-IgD^- phenotype, and lack of PRAD1 expression. The patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL) also showed findings indicating a distinctive disease entity. The expression of shared idiotypes, which may be a serologic marker for little or no somatic mutation, were detected in only 4 of 27 FL patients, 10 of 13 MCL, 4 of 6 CLL, and 9 of 14 extranodal lymphomas. These finding suggest that 1) MCL is nodal disease and differs from extranodal lymphoma, 2) there are four distinctive disease entities within low grade B-cell lymphoma: MCL, CLL, FL, and extranodal lymphoma, and 3) MCL, CLL, and extranodal lymphoma are derived from pre-germinal center cell or cell non-entering germinal center, although FL is derived from germinal center cell.

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In order to characterize whether a recently proposed monocytoid B-cell lymphoma (MBCL) is a distinct clinicopathologic entity, cases were collected from the two lymphoma files (K.N. and H.N.). The diagnosis of MBCL was based primarily on the described criteria, but several other limitations were also applied to increase the accuracy of case selection. By clinicopathologic features of 47 cases collected together with review of the literature, it is confirmed that a low-grade non-Hodgkin's lymphoma (NHL) which is difficult to be characterized based on the currently used classification systems does exist. However, the clinicopathologic features of MBCL were more heterogeneous than initially thought. Although MBCL and low-grade B-cell NHL arising from the mucosa-associated lymphoid tissue should be separated for the managements of patients with these NHLs, several lines of evidence indicate that these two NHLs are hematopathologically identical. It is stressed that NHLs should be classified based on the cells of origin, but not on the organs or systems involved.

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The distinctive low-grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma) of the extranodal lymphoid tissue has been well characterized in recent years. One hundred cases of gastrectomized primary gastric lymphomas, 30 cases of surgically resected primary intestinal lymphomas and five cases of autopsied pulmonary lymphomas were examined clinicopathologically. Fortyone cases of gastric lymphomas, nine cases of intestinal lymphomas and four cases of pulmonary lymphomas were classified as MALToma by using Isaacson's classification. Morphological feature of MALToma was lymphoepithelial lesion. All of gastric MALTomas were found out in advanced stage. Pulmonary lymphoma cases were not diagnosed correctly during life. Metastasis in gastrointestinal tract and serous membrane were seen in four cases of pulmonary MALToma. Tumor cells of MALTomas share an identical phenotype with splenic marginal zone B-cells. We examined the experimental gastric ulcer of rat by using immunohistochemistry. Centrocyte-like cells foci were observed in the ulcer bed, which express the phenotypical characters as same as splenic marginal zone B-cells. We discussed the cytopathological features of MALToma from the viewpoint of B-cell lineages.

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We have recently shown that two-color analysis with fluorescein isothiocyanate (FITC)-anti-CD38 antibody could clearly distinguish myeloma cells (plasma cells) from other hematopoietic cells in the bone marrow. Myeloma cells (plasma cells) alone were located at CD38^{strong positive(+++)} fractions. We also identified two subpopulations among these myeloma cells: VLA-5^-MPC-1^- myeloma cells and VLA-5⁺MPC-1⁺ myeloma cells. Morphological examination showed that VLA-5^- myeloma cells were mostly immature and VLA-5⁺ cells were mature myeloma cells. Furthermore, VLA-5^- myeloma cells proliferated markedly in vitro and responded to interleukin 6 (IL-6), while VLA-5⁺ myeloma cells showed very low proliferation and no response to IL-6 but secreted higher amounts of M-protein in vitro significantly. Therefore, we could clarify heterogeneity of human myeloma cells in the bone marrow with regard to the expression of VLA-5; VLA-5^- myeloma cells were proliferative immature cells and VLA-5⁺ cells were mature myeloma cells. To further distinguish normal plasma cells from mature myeloma cells phenotypically, we examined immunophenotypes of normal plasma cells and myeloma cells by two-color flow cytometry with FITC-anti-CD38 antibody and phycoerythrin (PE) staining with a given antibody. Normal plasma cells in the bone marrow, tonsil, spleen and lymph node were all CD19⁺CD56^-. On the other hand, mature myeloma cells were mostly CD19^- and most of them were CD56⁺, and there were no myeloma cell with the CD19⁺CD56^- phenotype. According to this findings, we investigated the expression of CD19 and CD56 on plasma cells (CD38⁺⁺⁺ fractions) in benign monoclonal gammopathy (BMG). Both CD19⁺CD56^- and CD19^-CD56⁺ plasma cells were detected, and were suggesting that BMG consisted of phenotypically normal plasma cells and myeloma cells. In order to investigate from where myeloma cells (plasma cells) originate, the phenotypes of B cell lineage in tonsils, lymph nodes and peripheral blood were analyzed by two-color analysis. In the tonsils and lymph nodes, germinal center B cells (GC-B cells) revealed CD38⁺VLA-5^-MPC-1^-CD24^-CD10⁺ CD5^-, while the phenotype of mantle zone B cells (MZ-B cells) were CD38^-VLA-5⁺ MPC-1⁺CD24⁺CD10^-CD5⁺. On the other hand, we found CD38^{moderately positive(++)} cells in the peripheral blood and they revealed VLA-5^-MPC-1^-CD24^-CD10⁺CD5^-. Morphological examination showed that these cells were plasmacytoid. Therefore, we regarded the cells as precursor plasma cells. In conclusion, we could present here that 1) myeloma cells consisted of VLA-5^- immature and VLA-5⁺ mature myeloma cells, 2) normal plasma cells were clearly distinguished from mature myeloma cells phenotypically, 3) plasma cells in BMG contained both normal plasma cells and myeloma cells, 4) precursor plasma cells were identified in the peripheral blood.

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The authors report a 28-year-old man who showed recurrent liver dysfunction and the clinical features of so-called malignant histiocytosis. Autopsy findings revealed this case is a peripheral T-cell lymphoma. Its differential diagnosis and the possible causes of liver dysfunction were discussed.

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