Accumulating evidences suggest that some of extranodal malignant lymphomas develop in the sites of chronic inflammation. In this review, we describe the results of our study on the extranodal lymphomas developing from chronic inflammation, including pyothoraxassociated lymphoma (PAL), and lymphoma of thyroid gland, salivary gland, and gastrointestinal tract. PAL had developed over 20 years history of chronic (tuberculous) pyothorax. Histologically, all were non-Hodgkin's lymphoma with diffuse large cell type being the most common. Immunologic and immunohistochemical studies revealed that PAL have immunophenotype of exclusively B-cell. Epstein-Barr virus (EBV) genome was detected in the lymphoma cells in all PAL cases, which suggested the etiological role of EBV for the development of PAL. We established two cell line from two PAL cases (OPL-1, 2), in which monoclonal latent infection of EBV was identified. We characterized the profile of expression of EBV latent genes and cytokine including interleukin (IL)-6, and IL-10. To investigate the escape mechanism of latent gene expressing PAL cells from host immune surveillance, HLA-A allotype of patients and mutation of EBNA-4 gene were examined. The results suggested that mutation of EBNA-4 gene play a role for PAL development. Thyroid lymphoma and salivary gland lymphoma are closely associated with Hashimoto's disease and Sjögren's syndrome, respectively, known as autoimmune diseases. Our epidemiological study revealed the relative risk for the development of thyroid lymphoma in patients with Hashimoto's disease was 80 times higher than that in general population. Both type of lymphomas showed a female preponderance. The frequencies of lymphoma showing proliferation of small lympoid cells with irregular nucleus and relatively rich cytoplasm, so-called centrocyte-like cells, were relatively high in both type of lymphomas. This type of lymphoma is termed by Isaacson as low-grade lymphoma of mucosa-associated lymphoid tissue (MALT). The frequencies of low grade MALT lymphma in stomach, small intestine, and rectum is 47%, 0%, and 42%, respectively, in our series. Low- grade MALT lymphoma was closely associated with reactive lymphoid hyperplasia in the gastrointestinal tract. Clinicopathologic findings together with EBV status in nasal lymphoma were summarized. Our epidemiological study revealed the clustering of patients with polymorphic reticulosis, a type of nasal lymphoma and constitute lethal midline granuloma syndrome, in the East Asian countries including Japan, Korea, and China.

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The clinical and biological differences between Japanese and Caucasian chronic lymphocytic leukemia (CLL) characterized by a progressive accumulation of immunologically incompetent mature-appearing lymphocytes with CD5⁺ B-cell immunophenotype have been reviewed.
The following four items have been discussed; 1) the quite different incidence of CLL morbidity in Japanese and Caucasian, approximately 0.1 vs 15 per millions; 2) the different frequency of CLL subtype, atypical CLL of CLL/PL and CLL mixed inclusive of cases with aberrant immunophenotypes such as CD5 negative are relatively high in Japan; 3) the different autoimmune complications in race such as hemolytic anemia with positive antiglobulin test; and 4) biomolecularly characterization of CLL cells derived Japanese and Caucasian cases, suggesting different usage of IgH VH genes in race.
Conclusively, little differences of CLL between different races but the incidence were able to be pointed out. Elucidating its different incidence would provide a new insight to disclose carcinogenesis of CLL.

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Human T-lymphotropic virus type 1 (HTLV-1) is etiologically associated with adult T-cell leukemia/lymphoma (ATL), and the diverse clinical features of this disease have led to its subclassification. The incidence of ATL is rather low among HTLV-1 carriers, and those who develop the disease usually have a 40-to 60-year latency period from the time of infection to proggression to ATL. The tumor suppressor genes such as p53, p15 and p16, are abnormal in aggrassive ATL. Sometimes, the abnormalities appear at the time of crisis. However, the precious mechanism of multi-step leukemogenesis in ATL remains unknown.
In all types of ATL, the monoclonal integration of the HTLV-1 provirus into tumor cells can be detected by Southern blotting. The integration patterns of the provirus have clinical implications for ATL. The multiple, complete and defective types in that order are apparently associated with prognosis from good to bad. Sequential Southern blotting for the HTLV-1 and T-cell receptor beta genes disclosed frequent clonal change at crisis from indolent ATL. This change is a peculiar phenomenon, in contrast to the clonal evolution characteristic of the multistep carcinogenesis of most human malignancies, probably reflecting the emergence of multiple premalignant clones in viral leukemogenesis as suggested in Epstein-Barr virus associated lymphomagenesis in the immunocompromised host.

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The antigenic heterogeneity of the reticular framework in the lymphoid tissues is well documented in mice and rats. In the present study, the reticular framework of the human lymphoid tissues was examined with special references to heterogeneity.
Surgically resected human spleens, lymph nodes, and tonsils were investigated. Thymi were obtained from autopsy cases. Formalin-fixed materials were embedded in paraffin and serial sections were prepared for hematoxylin-eosin, silver staining, and immunohistochemical examination. Immunoelectron microscopy was also applied. The reticular framework of malignant lymphoma was also examined.
The reticulum cells and reticulin fibers in the framework of the spleen, lymph node, tonsil and thymus were immunostained for type IV collagen, laminin and fibronectin. In the spleen, lymph node and tonsil, α-smooth muscle actin (α-SMA)-positive reticulum cells formed the reticular framework of the T-lymphocyte area and ensheathed the reticulan fibers. Interdigitating cells (IDCs) were scattered throughout the framework and some were attached to the reticulum cells. In the B-lymphocyte area, reticulum cells were α-SMA-negative. The reticulan fibers were involved in the mesh of the follicular dendritic cells (FDCs) in some areas and were covered by the cytoplasm of the FDCs. The reticular framework was heterogeneous in the T- and B-lymphocyte areas. In the thymus, reticulum cells were keratin-positive and their immunohistochemical character was different from those in the T-lymphocyte area of the peripheral lymphoid tissues. In the reticular framework of malignant lymphoma, reticulum cells/fibers showed positive reactivity for type IV collagen, laminin and fibronectin. The heterogeneity of the reticular framework was also found in the T- and B-lymphocyte areas of malignant lymphoma.
The reticular framework is specialized into heterogeneous components in T- and B-lymphocyte areas and may play a role in the formation of the distinct microenvironment specific for lymphoid subclasses.

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