A 82-year-old male developed asymptomatic lymphadenopathy gradually increasing in submandibular region in 1985. Lymph nodes biopsied in 1987 showed massive proliferation of histiocytes with abundant clear cytoplasm, round nucleus, and occasional emperipolesis. Foci of marked plasmacytic infiltration and fibrosis were also seen in medullary and paracortical region. Immunohistochemically, most of the histiocytes were positive for S-100 protein, and a few were positive for lysozyme, α₁-antitrypsin, and α₁-antichymotrypsin. Ultrastructurally, the large histiocytic cells exhibited many lysosomes and marked interdigitation of cytoplasmic processes, but these cells lacked Birbeck granules. The patient had IgG antibodies to EBVCA and HTLV-I p 19. RA test and skin test with PPD were positive. No microorganism was detected by culture using biopsied lymph node and pharyngeal swab specimens. Histiocytic proliferation seen in this case resembled sinus histiocytosis with massive lymphadenopathy, though histogenesis was undetermined. A possible association of immunoresponses to EB virus and HTLV-I with unique differentiation and proliferation of histiocytes awaits further study.

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Infiltration of dendritic cells, macrophages and lymphcytes into tumor tissues was immunohistochemically investigated using new monoclonal antibodies ID-1 for dendritic cells and CD68 for macrophages in 68 patients with gastric cancer. A serial section technique and double staining method were used for the phenotypic analysis. In the normal musosa, ID-1⁺ cells were located under the surface epithelium, while CD68⁺ cells were widely distributed in the lamina propria. Most of ID-1⁺ cells and CD68⁺ cells in the normal mucosa were negative for ICAM-1 and activated markers of CD25 and HLA-DR antigens. In cases of mucosal cancer, the numbers of ID-1⁺ cells and CD 68⁺ cells in the cancer tissue were similar to the normal mucosa. When cancer cells invaded the submucosa, ID-1⁺ cells and CD68⁺ cells were significantly increased in the cancer tissue except for the cases of signet ring cell carcinoma. The increased ID-1⁺ cells were positive for ICAM-1, HLA-DR, CD25 and CD11c, while most of CD68⁺ cells were negative for ICAM-1 and CD25 antigans. Further, ID-1⁺ cells were predominantly distributed adjacent to the tumor tissues with a marked infiltration of CD3⁺ cells. Conversely, CD68⁺ cells were distributed in the cancer stroma and necrotic tissues without CD3⁺ cell infiltration. These findings suggested that ID-1⁺ dendritic cells play a crucial role in the immune response agaist the cancer tissue.

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Immunohistochemical studies were performed on formalin-fixed and paraffin-embedded specimens of 28 cases of primary B-cell type gastric malignant lymphomas. Avidin-biotin complex method was employed to detect peanut agglutinin (PNA) binding sites, lysozyme, and S-100 protein. PNA-binding characteristics similar to those in the nodal lymphomas were also observed in the gastric lymphomas. Lymphoid follicles or lymphoid follicle-like cell aggregation coexistent with gastric lymphomas can be classified into 4 categories according to the morphology and staining patterns. They showed morphological transition from typical secondary follicle to lymphoma cell aggregation according to the distance from lymphoma lesion. It is suggested that lymphoma lesions expand by invading neibouring lymphoid follicles and that some gastric lymphomas grow and spread in the germinal centers of the associated lymphoid follicles. And from these points of view, it is suggested that lymphoid follicles associated with gastric lymphoma play an improtant role as supportive structure for the growth or expansion of lymphomas rather as a defense mechanism of the hosts.

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Angiodestructive lymphoma (ADL) is defined as a T-cell non-Hodgkin's lymphoma (NHL) with the destruction of blood vessels by lymphomatous cells and the resulting necrotic foci. Review of pathology slides of the one hundred twentythree cases with head and neck extranodal NHL treated from 1975 through 1989 in the Department of Radiology, Chiba University Hospital discovered seven cases of ADL. The primary site of the ADL was the nasal cavity in five cases and the antrum in two cases. The clinical stage was I in six cases and the remaining one belonged to stage IV. Three cases were diagnosed as diffuse mixed cell lymphoma and the remaining four was classified to diffuse large cell lymphoma. All but one were shown to be of T-lineage with immunohistochemical staining. Only one case showed surface antigens with features of B-cell, although DNA analysis was not performed. Six cases were mainly treated by radiation therapy and one was treated by CHOP. Out of the seven cases, three could not be induced into complete remission, whereas another two recurred after the attainment of complete remission. Presently only two cases are alive without disease. Recurrence in the primary site was seen most frequently, although always accompanied by the spread to distant sites. Cervical lymph node recurrence was seen only in one case. The treatment result indicates that radiation therapy alone is not adequate to sterilize even locally confined angiodestructive lymphoma and administration of systemic therapy is strongly recommended.

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An unusual case with Epstein-Barr virus (EBV) infection accompanied by large granular lymphocytosis, hemophagocytic syndrome and aggressive clinical course was described. The phenotype of the large granular lymphocytes in the peripheral blood were as followed: CD2⁺, CD3^-, CD4^-, CD8^-, CD16⁺, CD25^-, CD45RA⁺, CD56⁺, CD57^- and HLA-DR⁺. These cells also showed natural killer activity. The terminal clinicopathological features were quite similar to those of malignant histiocytosis. The autopsy showed extensive proliferation of lymphoid cells and erythrophagocytic macrophages in the almost all organs especially in the spleen (1800g), liver (3300g) and bone marrows. We consider that EBV infection accompanied by large granular lymphocytosis has an important position in hemophagocytic syndrome.

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When mouse femoral bone was subcutaneously implanted after the cutting of both ends into the abdominal wall of syngeneic mouse, bone marrow tissue regenerated in the medullary cavity of the bone. We removed the implanted bones at 1-week intervals and evaluated the regenerative process. The medullary cavity underwent necrosis after 1 week. Regeneration of the stromal components appeared in the epiphyses after 2 weeks and progressed with resorption of the necrotic tissue. After 3-4 weeks, myxomatous stroma rich in matrix components formed resulting in enlodgement and proliferation of hematopoietic cells. Marrow graftment was nearly completed after 6 weeks. Immunohistochemical examination showed a large amount of chondroitin sulfate proteoglycan (PG) and large PG in the myxomatous stroma that formed after 3-4 weeks. Biochemical analysis of the glycosaminoglycan chain primarily revealed low-sulfated chondroitin sulfate. Formation of myxomatous stroma rich in chondroitin sulfate PG and large PG seemes to play an important role in the regeneration of hematopoietic tissue.

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Three cases of histiocytic sarcoma were reported. Neoplastic cells in these cases posessed cytoplasm which was S100 protein and α₁ antitrypsin positive but lysozyme negative, suggesting T zone histiocyte origin. Interdigitation was observed electron microscopically in case 2. However different results in immunohistochemical staining were observed among these cases. For example, LCA and OKT4 positive tumor cells were observed only in case 2 and Ki-1 positive cells in case 1 and 2. Erythrophagocytosis was observed only in tumor cells of case 3 obtained at autopsy. The patients were young (16, 48 and 19 years old respectively), and had multiple metastases involving extranodal organs.

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Proliferative activity of neoplastic and non-neoplastic cells in 123 lymphoma cases [non-Hodgkin's lymphoma (NHL) 70 cases, Hodgkin's disease (HD) 53 cases], as well as 18 control reactive lymphadenopathies, was estimated by employing immunohistochemical procedures [avidin-biotin complex (ABC) method] with a monoclonal antibody against proliferating cell nuclear antigen (PCNA) which is synthesized during the late G1 and S phases. Immunostaining of PCNA was achived using sections of formalin fixed and paraffin embedded lymphoma tissue stored in the pathology files of our departments snd of some affiliated institutions. PCNA positive rates (positive cells/total cells) were determined, and relationship between these rates and pathological parameters were investigated. There was a positive correlation between the PCNA positive rates and a Working Formulation in NHL (P<0.05). In HD, Reed-Sternberg (RS) cells were highly positive (44%). No relationship was found, however, between the PCNA positive rates and a Rye classification. This finding may be explained either by speculating the cell cycle of RS cells derranged in a manner that G1-S phases are prolonged or, altematively, that proliferated RS cells destroyed by host reaction. These results indicate that PCNA immunostain is a useful method to analyse malignant lymphomas in formaldehyde fixed, paraffin embedded materials.

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