Intraepithelial lymphocyte (IEL), which is a member of gut-associated lymphatic tissue (GALT), takes an important role as a mucosal barrier in gastrointestinal (GI) tracts. The function of IEL has not been fully elucidated. We examined the IEL in intact mucosal tissues from one case of esophageal cancer, fifteen of gastric cancer, five of colon cancer and three of malignant lymphoma of the stomach. Those secimens were fixed by PLP fixative and frozen. The cryostat sections were stained with the ABC method. In the intact mucosas, the number of the IEL was the highest in the stomach. The IEL was mainly composed of T cell. B cells were seldom noticed in the IEL. By the immunohistochemical characterization of IEL, CD8 phenotype was more predominat than CD4. Many γδ cells, positive for δ1, were also seen in the IEL of the colon, but seldom found in the esophagus and stomach. On the other hand, in some pathological conditions, the number of the IEL-positive for CD8 was decreased in the intestinal metaplasia. Mild increase of the IEL in the chronic gastritis was observed. The prominent increase in the number of γδ cells was noticed in the antrum of the stomach with chronic gastritis and in the body of the stomach with intestinal metaplasia. In the malignant lymphoma, especially T cell type, distinct increase in the number of γδ cell was identified. These results suggested the γδ cells may play a very important immunological role in the defence mechanism in the mucosa of GI-tracts, especially in the stomach.

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11 cases received operation for primary B cell lymphoma of the gastrointestinal tract were studied immunohistochemically to clarify vascular endothelial cell (EnC) function in extranodal lymphoma tissues. Microvasculature in primary B cell lymphoma of the gastrointestinal tract, based on the morphological characteristics, were devided into high endothelial cell vessels (HEV) and flat endothelial cell vessels (FEV). HEV were characterized as HLA-DR^- OKM1^- OKM5^- F VIII RAg⁺ IL-1^-, accompanied by the cluster of non-neoplastic T lymphocytes, and FEV were HLA-DR^- OKM1^- OKM5⁺ F VIII RAg⁺ IL-1^- not by T lymphocyte infiltration. In contrast, microvascular EnC in the surrounding non-lymphoma tissue, normal gastric and ileal tissues showed HLA-DR⁺ IL-1⁺. Our results suggest that microvascular EnC in primary B cell lymphoma of the gastrointestinal tract lack a fuction as antigen presentation, and that HEV regulate non-neoplastic T cell migration.

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A group of 62 B-cell malignant lymphomas and 6 cases of reactive lymphoreticular hyperplasia (RLH) in the gastrointestinal tract were investigated with morphological and immunohistochemical methods, and one-stage silver staining technique of nucleolar organizer regions.
Sixty-two cases of non-Hodgkin's lymphomas were reclassified using the updated Kiel classification, which was modified to include the categories low-and high-grade mucosa-associated lymphoid tissue lymphoma. There were 13 low 1-1 grade non-Hodgkin's lymphomas and 49 high 1-1 grade tumors. Low 1-1 grade lymphomas comprised mucosa-associated lymphoid tissue (MALT) lymphoma, three centrocytic (CC) lymphoma, six centroblastic-centrocytic (CB-CC) lymphoma and one plasmacytic lymphoma. High 1-1 grade lymphoma comprised 40 centroblastic, three immunoblastic, one lymphoblastic or Burkitt, four high 1-1 grade mucosa-associated lymphoid tissue (High 1-1 MALT) lymphoma, and one large cell anaplastic lymphoma (LCAL).
The presence of intracytoplasmic and/or surface immunoglobulins were studied by the immunoperoxidase technique using polyclonal antibodies. A monoclonal staining pattern as revealed by light chain restriction, was found in 10 cases (77%) of the low 1-1 grade non-Hodgkin's lymphomas, and in 43 cases (88%) of the high 1-1 grade lymphomas. MALT lymphomas were composed of cells containing intracytoplasmic or surface immunoglobulins that was exclusively IgM·κ. In addition, monoclonal antibodies, Ki-B3 and L26 gave positive staining of about 80% of B-cell lymphomas. MALT and CC lymphomas showed positive reaction with LN-2.
Using a silver staining technique, nucleolar organizer region-associated proteins (AgNORs) have been studied in paraffin sections of 6 RLH and 62 non-Hodgkin's lymphomas. Our data demonstrated that the mean number of AgNORs is related to the histological grade of non-Hodgkin's lymphoma. In addition, the mean AgNORs number of centroblast in RLH was greater than those of CC and MALT lymphomas. Therefore, this study showed that the AgNORs score which is an indicator of cellular proliferation may reflect the cell size. Furthermore, the mean number of AgNORs in the MALT lymphoma was similar to those of mantle zone and interfollicular lymphocytes in RLH. And this result may be closely related to the histogenesis of MALT lymphoma.

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We studied clinical and pathological features of gastrointestinal (GI) lesions in patients with adult T cell leukemia (ATL) by examining 84 ATL patients treated in our department from September 1977 to May 1990, and 134 ATL patients autopsied in Kagoshima prefecture from November 1976 to December 1988.
We found the following results:
1) Abnormal mucosal pattern throughout the GI tract was demonstrated by radiography using barium meal and enema in most of the patients.
2) Endoscopy demonstrated edematous and reddish mucosa in stomach and/or colon in many cases. Multiple ulcer and erosion were frequently found. Usual endoscopy failed to discriminate granular lesions in stomach and colon which were demonstrable by radiography, but spreading methylene blue on the mucosa surface enabled to discriminate the lesions.
3) In biopsied specimens, ATL cells were found to be invaded into mucosal area of stomach in 28 out of 48, and colon in 5 out of 7 patients examined.
4) In autopsied patients, infiltration of ATL cells into the GI tract was found to be evident in 59 out of 134 patients (44.0% of total). Among the 48 patients that GI lesions were examined thoroughly, 24 patients had the cell invasion in the GI tract except for esophagus. ATL cell invasions were found to be in stomach, small intestine, and colon in 13, 16, and 13 out of 48 patients, respectively. In 5 patients, simultaneous invasions into the three lesions were observed.
5) ATL cell invasion was also frequently found around lymph vessels. In small intestine, invasion into lymph follicles and resulting tumor formation was characteristic.
6) HML-1, a monoclonal antibody produced from small intestinal mucosal lymphocytes, reacted with ATL cells from peripheral blood. The reactivity was higher in the cells from the patients having cell invasion in GI tract as compared with patients without the invasion.
7) In immunohistochemical study, HML-1 reacted with invaded ATL cells in lymph nodes, skin, stomach and tonsil.
In conclusion, GI lesions were observed in most of ATL patients. Characteristic views demonstrated by radiography and endoscopy were present.
Pathologically, ATL cell invasions were evident in mucosal area and around lymph vessels. ATL cells from peripheral blood and several organs reacted with a novel monoclonal antibody HML-1.

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We analyzed 446 patients of malignant lymphomas that had admitted in our hospital for latest ten years, and gave the special reference on the extranodal lymphoma (ENL) including primary stomach site.
Four hundred and forty-six patients with malignant lymphoma were registered in this study (non Hodgkin's lymphoma (NHL): 400 cases, Hodgkin's disease (HD): 46 cases), in which ENL patients were 115 cases (25.7%). Most of ENLs were not HD (4 cases) but NHL (111 cases). The frequent initial sites of ENLs included Gastrointestinal tract 40.8% (47 cases) and Waldeyer's ring 23.5% (27 cases).
In 47 patients of primary Gastrointestinal tract lymphomas, 35 cases had primary lesions in stomach.
ENL of stomach was morphologically classified in five types according to Sano's macro-pathological classification with some modifications. Among them, 17 cases were ulcer-forming type and 8 cases were superficial-spreading type. Histopathologically, diffuse large cell type of LSG (Lymphoma Study Group) lymphoma classification were more than a half (19 cases). Twelve cases out of 14 cases examined for lymphoma cell surface markers had B cell-lineage antigens. The ratio of the patients with ENL in Japan relatively higher than in western conutries since most of malignant lymphoma in Japan are diffuse type whose initial sites are often in extranodal sites, while Hodgkin's lymphomas or follicular lymphomas are less frequent in extranodal sites.
Recently, it has been reported that Gastrointestinal tract has a special lymphatic architecture called GALT (Gut associated lymphatic tissue) and its lymphocytes has a special function called “Homing phenomenon”.
It is important to clarify the role of these special Gastrointestinal lymphatic systems and the relations between these systems and the other extranodal lymphatic tissues for the diagnosis and the therapy of ENL in future.

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One hundred patients with primary gastric lymphoma treated at the National Cancer Center Hospital during a period from 1962 to 1989 were analyzed retrospectively to evaluate the treatment strategy and the prognostic factors of survival.
I) The patients were divided into two groups, one consisting of 48 patients treated systematically with combination chemotherapy following gastrectomy after 1978 and another consisting 52 patients treated non-systematically before 1978. Comparison was made of the survival after treatment according to the Naqvi's clinical staging classification between the two groups.
(1) Stage I:
Among forty five patients with complete resection and four patients treated with combination chemotherapy after incomplete resection or no resection, relapses were not observed during a period from 14 to 310 months. On the other hand, two patients treated without combination chemotherapy after incomplete resection had a relapse and died of lymphoma after 104 months and 108 months, respectively.
(2) Stage II:
Of the 17 patients treated systematically with combination chemotherpy following gastrectomy, fourteen are alive without relapse. On the other hand, of 12 patients treated non-systematically, seven died of lymphoma. The median survival time was not less than 127 months in the former group, but 32 months in the latter group. Significant differences (p<0.05) in survival were observed between the two groups.
(3) Stage III and Stage IV:
Six patients in the systematic treatment group and 14 patients in the non-systematic treatment group died within 18 months regardless of gastrectomy and/or chemotherapy. The median survival was only five months for both groups.
II) Prognostic factors infulencing patient's survival was analyzed using the stepwise proportional hazards general liner model in the SAS program.
Stage (p=0.0000), age (p=0.0016), and leucocyte (P=0.0020) were identified as the significantly important factors in primary gastric lymphoma.

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The functions of alveolar macrophages where evaluated in healthy subiects and patients with sarcoidosis, idiopathic interstitial pneumonitis (IIP), interstitial pneumonitis with collagen vascular disease (IP-CVD), and hypersensitivity pneumonitis (HP). Chemotactic indices were significantly higher in patients with sarcoidosis, IIP, and HP than in healthy subjects. Phagocytotic indices were higher in patients with sarcoidosis, IIP, and HP than in healthy subjects, however they were lower in patients with IP-CVD. Acid phosphatase activity was lower in patients with IIP, IP-CVD, and HP compared with healthy subjects. Beta-galactosidase activity was lower in patients with sarcoidsis and IP-CVD compared with healthy subjects. From the aspect of surface markers, in patients with sarcoidosis, IIP, and HP CD15-positive macrophages were increased, but there were no significant differences in CD14 and HLA-DR antigens in these patients compared with those in healthy subjects. These results indicate that the recruitment of peripheral blood monocytes to the lung is increased in patients with sarcoidosis, IIP, and HP, and alveolar macrophages play an important role in the pathogenesis of interstitial lung diaeases.

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A 65-year-old man who presented with adrenal insufficiency was admitted on Feburuary 9, 1988. CT scan showed bilateral swelling of adrenals; open biopsy of the tumor revealed non-Hodgkin's lymphoma. The serum level of catecholamines and calcitonin was elevated. A combination chemotherapy was started. After 3 courses of the treatment remission was achieved, following recovery from adrenal insufficiency. In November, 1988, he had pulmonary infiltration and high fever, resolved by the administration of antibiotics and antifungal drugs. On January 27, 1989, he underwent emergency operation because of perforation of gastric ulcer. In Feburuary, tumor increased in size, and the disease became progressive. On April 2, 1989, he died of respiratory failure. Autopsy revealed a definite diagnosis of malignant lymphoma, diffuse large cell type. Immunohistological studies revealed B cell origin of the cells based on positive LCA and pan B markers.

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Twenty six cases diagnosed as Non-Hodgkin's lymphoma in patients under 15 years of age between 1980 and 1989 were reviewed and reclassified histopathologically and immunohistochemically.
There were 21 boys and 5 girls with a mean age of 9.0 years. Major primary sites were head and neck (50.0%) and abdomen (23.0%). Non-localized type (stage III and IV) were 76.9% of the patients and localized type (stage I and II) were 23.1% at the time of diagnosis according to the Murphy's classification.
Histopathologically, 26 cases divided into three major subtypes: lymphoblastic type (30.8%), large cell type (34.6%), and Burkitt type (30.8%).
Immunohistochemically, it was demonstrated that 13 cases of 26 cases were T cell origin and 11 cases were B cell origin. There was no case of non-T non-B.
In lymphoblastic type and Burkitt type, histology was found to correlate strongly with immunophenotype and biologic behavior, but in the cases of large cell type they were heterogeneous.
In 9 cases of large cell lymphoma, 4 cases were T cell lymphoma, 2 cases were B cell lymphoma and 3 cases were Ki-1 positive lympoma.
Complete remission was obtained in 23 of 26 cases (88.5%), 100% in lymphoblastic type, 75.0% in large cell type and 87.5% in Burkitt type. Two-year-survival rate was 100% in lymphoblastic type, 56.3% in large cell type and 83.3% in Burkitt type. Seven-year-survival rate was 75.0%, 56.3%, and 83.3%, respectively. Large cell type lymphomas had the worst prognosis.

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