We performed immunohistochemical and molecular genetic (bcl-1, bcl-2 and bcl-3 gene) studies on specimens from 87 patients with low garde B cell lymphoma (28 patients with FL, medium-sized cell; 17 patients with FL, mixed; 6 patients with DL. small cell; and 36 patients with DL. medium-sized cell) to clarify the cellular origin and characteristics of medium-sized cell lymphoma. FL. medium-sized cell showed a phenotype of follicular center cells (FCC) of secondary follicles (CD10⁺, SIgD^-, CD5^- and ALPase^-) and a relatively high frequency of bcl-2 rearrangements (54%). Follicular lymphomas with CD10 expression showed a very high frequency of bcl-2 rearrangements (κ^2., 0.01, 1). On the other hand, almost all the cases with DL. medium-sized cell displayed a phenotype of mantle zone (MZ) B lymphocytes of secondary follicles (SIgD⁺, CD5⁺, ALPase⁺ and CD10^-) and always expressed at least one or more of these four markers. The neoplastic cells occasionally showed bcl-1 rearrangements (24%) but never bcl-2 rearrangements. DL. medium-sized cell with CD5 expression showed a trend toward a higher frequency of bcl-1 gene rearrangements. Low grade B cell lymphomas examined in this study showed no rearrangement bands of bcl-3 gene. These data indicate the following: (1) FL. medium-sized cell is derived from FCC of secondary follicles, (2) DL. medium-sized cell is derived almost from MZB lymphocytes of secondary follicles and (3) Almost all the cases with DL. medium-sized cell do not represent a diffuse counterpart of FL. medium-sized cell. The proliferative rate measured by Ki-67 positivity was closely related with survival of low grade B cell lymphoma (p<0.05).

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Malignant lymphoma (ML) of low grade malignancy includes small lymphocytic lymphoma and follicular lymphoma other than large cell type. Recent study revealed intermediate lymphocytic lymphoma (ILL) and monocytoid B-cell lymphoma (MBCL) to be new types of ML of low grade malignancy. These two types of ML are fundamental elements of ML developing in so-called mucosa associated lymphoid tissue (MALT). In this report, results of our study on ILL and MBCL of extranodal organs were described.
ILL is composed of small lymphoid cells with morphologic features between those of well-differentiated lymphocytic lymphoma and poorly differentiated lymphocytic lymphoma of follicular center cell origin. The frequency of ILL in nodal and extranodal non-Hodgkin's lymphoma was almost same. The frequency was high in salivary gland and thyroid lymphoma. Histologic features of chronic lymphocytic thyroiditis (CLTH) are constantly observed in cases with thyroid lymphoma. Histologic findings suggestive of Sjogren's syndrome such as formation of lymphoid follicles and myoepithelial islands were observed in one third of cases with salivary lymphoma. These findings suggested that autoimmune diseases such as CLTH and Sjogren's syndrome played an important role in the etiology of thyroid and salivary lymphoma.
MBCL shows the proliferation of the atypical lymphoid cells with abundant and pale cytoplasm and reniform nucleus. The high incidence of Sjogren's syndrome in cases with MBCL was evident suggesting the etiologic role of Sjogern's syndrome for development of MBCL. Six cases of MBCL developing in extranodal sites such as thyroid, stomach, and rectum were described below. Two of three patients with thyroid lymphoma presented with positive serum antithyroid antibodies, and one had CLTH. In all three patients with gastric or rectal lymphoma, reactive lymphoid hyperplasia was present near the tumors. These findings suggested the important role of long-standing inflammation for development of MBCL as well as ILL.

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The clinical and cytological features of 73 patients with chronic (mature) B-cell leukemias were studied. Large lymphocytes or cleft cells were often seen in patients referred to us as chronic lymphocytic leukemia (CLL). Immunophenotypical and histopathological studies were performed and the diagnosis of leukemic phase of non-Hodgkin's lymphoma (follicular lymphoma; FL and intermediate lymphocytic lymphoma; ILL) was made in a significant portion of the patients and only ten cases were diagnosed as CLL including mixed cell type.
Although hairy cell leukemia (HCL) is quite rare in Japan, a disproportionally large number of patients were referred to our laboratory. Typical HCL seen in Western countries, was found in nine cases. On the other hand, most (29 cases) showed cytologic features distinct from typical HCL and were classified into HCL-Japanese Variant (HCL-J). Morphology of HCL-J cells in May-Giemsa stained films resembled large CLL lymphocytes, but several features shared by typical HCL and HCL-J including typical hairy morphology under phase contrast microscopy, CD11c⁺, L30^- phenotype and the histology distinguished the disease from CLL and other B-cell leukemias. In two cases, the cells displayed prominent nucleoli and surface villi, the features consistent with those described for HCL Variant (prolymphocytic variant). Some patients were differentiated from HCL and were diagnosed as leukemic phase of ILL with large spleens or splenic lymphoma with villous lymphocytes (SLVL). Under phase contrast, fine cytoplasmic processes were obseved in ILL cells. Surface morphology of SLVL cells considerably varied from cell to cell; some displayed prominent cytoplasmic projections similar to those of hairy cells, while others had a few, short villi or lacked villi even by phase contrast microscopy. The spleen histology showed prominent involvement in the white pulp with the features of lymphoplasmacytic lymphoma.

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We analyzed 113 cases of low-grade lymphoma including follicular medium-sized cell type, follicular mixed type and diffuse small cell type of B-cell origin in the LSG classification. Diffuse medium-sized cell type of B-cell origin corresponding to diffuse small cleaved cell in working formulation and intermediate lymphocytic lymphoma, both of which are classified in indolent lymphoma by national cancer institute, was excluded because our study showed poor prognosis of this type. Chemotherapy was done as the primary therapy in 89 patients and anthracycline was used in 63 patients. Analysis of survival rate revealed better prognosis of the chemotherapy with anthracycline from 5 -to 10-year survival, although CR ratio was less than that of the chemotherapy without anthracycline. Significant differences in prognosis were found in clinical stage (I vs II), primary sites (nodal vs exnodal), serum LDH (normal vs high) and therapeutic response (CR vs PR). Follicular medium-sized cell type showed almost the same survival as that of diffuse small cell type within 5 years after onset. Ten patients with follicular medium-sized cell type, however, died more than 5 years after onset and all of 4 patints of 10-year survival were under recurrent disease. In contrast, none of patients with diffuse small cell type died after 4-year survival and all of 4 patients of 10-year survival were disease-free. Improvement of long-term survival of follicular lymphoma is a major problem in chemotherapy of low-grade lymphoma, and a more intensive chemotherapy and/or combination with radiotherapy will be necessary in the near future.

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A rare autopsy case of granular lymphocyte proliferation disease (GLPD) accompanied by hemophagocytic histiocytosis and systemic lymph node swelling due to metastasis from prostatic carcinoma, was reported.
An 87-yr-old man was admitted because of general fatisue, loss of consciousness and paresthesia of the right foot. General clinical examination revealed systemic lymphadenopathy without splenomegaly and mild hepatic dysfunction. Hematological examination showed leucocytosis with a marked increase of large granular lymphocytes (LGL) and a decrease of T cells in the peripheral blood. Upon immunological examination, CD3^- CD57⁺ CD16⁺ LGL were numerically dominant which was suggestive NK-type GLPD.
After a two months' asymptomatic course, sudden severe repiratory distress and mild jaundice appeared, and the patient died 3 days later.
Autopsy revealed enlargement of the systemic lymph nodes due to cancer metastasis, central liver cell necrosis, and bleeding and marked congestive edema of the lungs with pleural effusion. Microscopic exmination disclosed well differentiated adenocarcinoma of the prostate with lymph node involvement. However, there were no metastatic lesions in the other organs and tissues examined. Prominent distribution of hemophagocytic histiocytosis was recognized in the lymph nodes, spleen and liver.
Immunohistochemically, T cells were decreased in number in the lymphoid tissues, and also CD57⁺ LGL were decreased in the lymph nodes involved with cancer cells. The CD57⁺ LGL in lymph nodes failed to express HLA-DR (LN 3).
In this case, it was considered that latent prostatic carcinoma might be have undergone rapid growth with widespread lymph node involvement within a short period under condition of disturbed immunoregulation due to GLPD, decrease of T cells and hemophagocytic histiocytosis. And also, it was possible that metastatic cancer involvement caused proliferation of LGL.

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Three-dimensional morphology of follicular dendritic cells (FDC) in vivo was studied with fluorescent microscopy and electron microscopy.
FDC are specialized cells found within primary and secondary lymphoid follicles of lymphoid tissues. They retain antigen-antibody complexes on their surface and may play the leading role in the induction of immunological memory and the maintenance of long-term immunity. The author observed their unique distribution with the aids of their characteristics to retain immune complexes and new type of fluorescent microscope, confocal scanning laser microscope. Detailed structure of cytoplasmic processes was described by ultrastructural observation of serial ultrathin sections.
Twelve days after human serum and red blood cells were injected to the Sprague-Dawley (SD) rats intravenously or peritoneally, FDC in the spleen were detected by surface human IgG with FITC-conjugated antibody using confocal scanning laser microscope. FDC had long cytoplasmic processes and formed complex labyrinth-like structures. FDC-clusters were not observed. S-100 protein was also a useful marker to detect FDC of the rat.
Ultrastructural study on human tonsils with follicular hyperplasia showed that the nucleus was irregularly shaped, with well-defined nucleolus and prominent fibrous lamina. The cytoplasm had rough-surfaced endoplasmic reticulum, mitochondria, Golgi apparatus, polysomes, and bundle of microfilaments along the cell membrane. Extracellular dense materials were common findings. Observation of serial sections showed that the processes of FDC were ruffled dendritic processes with extensive branching and anastomoses. Lymphocytes also came in active contact with FDC.
Author also made an observation on the S-100-positive cells in the rat lung, and found that reticular cells in the lymphoid follicles of bronchus-associated lymphoid tissue (BALT) have similar features to FDC ultrastructurally, although their cytoplasmic processes were not developed as those in the spleen. These dendritic cells may also play an important role to local defense of respiratory tract.

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Pulmonary complications in 132 patients with adult T cell leukemia (ATL) autopsied in Kagoshima prefecture from 1975 to 1989 were studied histopathologically.
By the study the following results were obtained:
1) In 101 (76.5%) out of 132 patients, pulmonary infections were recognized. Cytomegalovirus (CMV) pneumonia was detected in 44 out of the patients, Pneumocystis carinii (P. carinii) pneumonia in 23, cryptococcal pneumonia in 9, other fungal pneumonia in 30 was found.
2) Infections in more than 3 organs including the lung were seen in 25 of them (18.9%). CMV infections were seen in 16 patients, candidiasis in 5 patients, crytococcosis in 3, and aspergillosis in 2.
3) An increased number of patients with P. carinii pneumonia seen at the beginning of this study has been reduced by the introduction of the oral administration of trimethoprim-sulfamethoxazole.

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