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In an effort to settle the conflicting views on the proliferation kinetics of Kupffer cells (Kc), we performed 2/3 partial hepatectomy on rats injected with Pelikan ink. Using an anti-rat macrophage monoclonal antibody, ED 2, we evaluated the numerical changes in total, carbon-positive ED 2+ cells and carbon-negative ED 2+ cells in the portal and central area. We also analyzed the ultrastructure and peroxidase cytochemistry of various types of cells observed during regeneration. The total numbers of ED 2+ cells in the remaining liver increased rapidly from day 2 to 5, and the number of dividing ED 2+ cells reached a maximum on day 2. Thus, the numerical increase in ED 2+ cells corresponded to the division phase. In contrast, the carbon-labeling experiment showed a continuous increase of carbon-negative ED 2+ cells from day 2 to 7. In the central area where division was less frequent, the proportion of carbon-positive cells decreased markedly to 50% on day 7, as against 97% in control rats. These findings suggest the possibility of an influx of carbon-negative Kc in addition to cell division. Ultrastructurally, the presence of carbon-negative "small Kc" and "immature Kc" with morphological features different from those of carbon-positive Kc was demonstrated. Such carbon-negative Kc with a high nucleus-to-cytoplasm ratio and rather few phagosomes, were not observed in control rats. Furthermore, we demonstrated two types of possible precursor cell, i.e. "transitional" forms between monocytes and Kc, and "immature macrophages". The former showed peroxidase activity in some lysosomes as well as in the rough endoplasmic reticulum and nuclear envelope. Our result indicated that the proliferation kinetics of Kc depend upon both local proliferation and influx.

Seventy-nine cases of non-Hodgkin malignant lymphoma were light and electron microscopically evaluated with special reference to intercellular correlationship comparing with non-neoplastic lymph nodal cells and cultured B cells. Reticulum cells and histiocytes are regarded as an independent cell unit. Reticulum cell sarcoma shows a fibrosarcomatous proliferation with abundant reticulin fibers, while histiocytic sarcoma is confined to a pleomorphic neoplasm with valid phagocytization. Lymphoid cells are divided into large, intermediate and small lymphocytes. Under inflammation and cultivation they, especially intermediate and large, preferentially proliferated clustering in a reticular fashion, which are designated as reticular lymphocytes, in contrast with nonreticular lymphocytes individually separated. The desmosome-like junctions are found among reticular lymphocytes not only in but also outside germinal centers as well as in vessels and among cultured B cells. Lymphocytic sarcomas, either nodular or diffuse, are classified into reticular and nonreticular types in association with their cellular sizes. The desmosome-like junctions are predisposedly disclosed in reticular lymphoma irrespective of proliferating patterns, nodular or diffuse, and of membrane character, B or T. And the junctions are not regarded as a hallmark for follicular or nodular lymphomas of germinal center cell origin. ACTA PATHOL. JPN. 30: 195 approximately 217, 1980.

An autopsied case of acute megakaryoblastic leukemia is described in a 20 months old, Japanese female infant with Down's syndrome. She presented spontaneous remission of transient abnormal myelopoiesis in her neonatal period, which was followed by acute megakaryoblastic leukemia 1 year later. The clinical picture of acute megakaryoblastic leukemia was initially characterized by peripheral pancytopenia with a few blasts, the absence of hepatosplenomegaly, but ended in overt leukemia characterized by increase of blasts, marked hepatosplenomegaly, and elevated LDH. She died 6 months after the onset at 20 months of age. Autopsy findings revealed widespread leukemic infiltration comprised of megakaryoblasts and megakaryocytes, and extramedullary tumors in the left tibia, the liver, both kidneys, and the endocardium of the heart. Identification of the megakaryocytic cell line was performed in immunohistochemistry and electron microscopy. Chromosomal analyses of peripheral blood disclosed 47, XX, +21, in her neonatal period but disclosed 48, XX, +G, +G, in acute megakaryoblastic leukemia.

Tumor forming acute promyelocytic leukemia (APL) is rare and only three cases have been documented. However, there are no reports on either the chloromatous character or electron microscopical analysis. The present paper dealt with a light, electron microscopic and histochemical study of the tumor of APL in a 55-year-old Japanese male. The tumors found in the anterior mediastinum and right lower extremity. He died from respiratory disturbance and hydrothorax due to obstruction of the pulmonary truncus by the mediastinal tumor. In electron microscopy, the tumor cells showed dilatation, colloracious pattern and honey-comb-like structure of rough endoplasmic reticula (RER) and parallel array-arrangement of smooth endoplasmic reticula (SER). These abnormalities of ER are the same as those recently recognized in leukemic cells in APL. Furthermore, the intercellular junctions composed of opposing dense patches of the cytoplasmic plasmalemma were frequently found between the more immature tumor cell of the mediastinum.

The present paper deals with immunohistochemical and ultrastructural study of the lymph nodes of sinus histiocytosis with massive lymphadenopathy (Rosai and Dorfman, SHML) of a 12-year-old Japanese boy. This is the fourth case in Japan. Osseous manifestation was also found in the bilateral ulnae. With hallmarks of S-100 protein and interdigitating cytoplasmic extensions, the phagocytizing histiocytes proliferating in the sinuses were considered to be derived mostly from interdigitating cells in the paracortex or T cell dependent area, which have heretofore been regarded as nonphagocytizing. Furthermore, it is most interesting that lymphoid cells bearing thymic cortical cell-antigen (OKT 6) were increasingly recognized in the patient's peripheral blood. These results suggested that SHML is a specialized reactive histiocytosis analogous to histiocytosis X and histiocytic medullary reticulosis.

A case of WDHA syndrome accompanied by a pancreatic tumor in a 44-year-old Japanese male is presented, the 6th case in Japan. Clinically, the patient suffered from unremitting watery diarrhea, hypokalemia and achlorhydria with marked anemia and jaundice. The patient died of emaciation, dehydration and bronchopenumonia, and an autopsy was performed. Autopsy examination revealed a hen's egg-sized tumor in the tail of the pancreas with metastases in liver, lungs and lymph nodes. In addition, bronchopneumonia and diabetic nephrosclerosis were present. Histologically, the tumor had the characteristics of an islet cell tumor, and histochemically the tumor cells were positive to Grimelius' stain which revealed non-B-islet cell features. Electron-microscopically, the tumor cells had electron dense round membrane-bounded granules resembling non-B-granules of pancreatic islet cells. With the immunoperoxidase procedure (PAP method), tumor cells nearly almost reacted to anti-vasoactive intestinal polypeptide (VIP) serum, which suggested that the tumor of the present case had the capability to produce VIP.

Histiocytosis X of the stomach of a 47-year-old Japanese woman, who underwent subtotal gastrectomy following a clinical diagnosis of scirrhous carcinoma, was studied by light and electron microscopy as well as by immunohistochemistry. The histiocytoid cells proliferated monotonously in the lamina propria mucosae of the atrophied mucosa covering the body and fornix. They were arranged in a sheet- or pavement stone-pattern and included some giant cells. The histiocytoid cells had a reniform to irregularly indented nucleus and conspicuous cytoplasm. Ultrastructurally, they were characterized by interdigitating cytoplasmic extensions and abundant tubulovesicular structures including Langerhans granules. S-100 protein, alpha 1-antitrypsin, and alpha 1-antichymotrypsin were immunohistochemically identified in the cytoplasm. Endoscopic biopsies of the extragastric digestive tract, a biopsy of the lymph node, and bone marrow aspiration excluded a systemic disorder. The case is regarded as benign localized histiocytosis X of the stomach, a previously undescribed gastric lesion.

An autopsy case of systemic histiocytosis with excessive deposition of kappa-type light chain crystals was reported in a 58 year-old man who had consistently showed kappa-type light chain paraproteinemia, Bence Jones proteinuria and hypogammaglobulinemia for about 10 years until his death. However, no bony destruction was found by repeated X-ray examinations. At autopsy, extensive hyperplasia of crystal-storing histiocytes was observed in the bone marrow, spleen, liver, lymph nodes, interstitial tissues of visceral organs and loose connective tissues. In the bone marrow and some other tissues, mild proliferation of plasmocytoid cells containing small crystals were found. Histochemically the crystals positively stained with various methods for amino acids and proteins, especially with Weigerts' method for fibrin. Ultrastructurally intralysosomal crystal deposition was confirmed in the storage histiocytes and derivation of the crystals from Golgi's sacculi in the plasmocytoid cells was suggested. Biochemically the crystals were regarded as mainly consisting of dimers of a variable half of light chain immunoglobulin and immunochemically and immunohistochemically reacted to anti-kappa type light chain serum. Such a generalized storage histiocytosis may be secondarily induced by immunoglobulin synthesized in plasmocytoid cells.

In 11 of 18 spleens surgically removed from patients with idiopathic thrombocytopenic purpura (ITP), the occurrence of sea-blue histiocytes or foam cells were observed. In a few cases, sea-blue histiocytes were found in the lymph nodes or bone marrow. Histochemically the sea-blue histiocytes were proved to contain ceroid or ceroid-like pigments in their cytoplasm. Ultrastructurally numerous intracytoplasmic membrane-bound inclusions, mostly containing tightly laminated materials and intermingling electron-dense amorphous materials or osmiophilic lipid droplets, were present in these cells. In the foam cells, accumulation of excess amounts of phospholipids was histochemically demonstrated in frozen sections, often accompanied by deposition of cholesterol, particularly in advanced cases. Electron microscopically, vacuolar membrane-bound inclusions were found to predominate in their cytoplasm, most of which contained irregularly or loosely laminated materials. Transitional cells between both types of cells were also found light or electron microscopically and ultrastructural transition of sea-blue histiocytes to foam cells was traced. Enhanced phagocytosis of blood cells, including platelets, by sea-blue histiocytes, and gradual transition of the ingested blood cells to the inclusions were confirmed.

Smears of bone marrow aspiration from 82 patients with leukemia and major hematopoietic organs, such as bone marrow, spleen, liver and lymph nodes, obtained from 97 autopsy cases of the disease, were light-microscopically examined. As the results, occurrence of either sea-blue histiocytes or Gaucher-like cells, or of both, was observed in bone marrow smears of 23 patients and in the hematopoietic tissues of 44 out of the examined cases, particularly marked in those of chronic myelogenous leukemia. In acute myelogenous leukemia, these lipid storage cells were also confirmed though less in frequency or degree. Histochemically, the sea-blue histiocytes were substantiated to contain ceroid-like pigments in their cytoplasm uhile the lipid materials stored in the Gaucher-like cells were presumed to be glycolipids. Ultrastructural morphology of the inclusions in the sea-blue histiocytes uas almost consistent with that of ceroid previously reported, but showed more marked variegated and heterogeneous features. Intracytoplasmic inclusions of the Gaucher-like cells differed from those of Gaucher cells seen in Gaucher's disease and were dominated by fibrillar or linear deposits. Transitions from phagocytized leukemic cells to the inclusions characteristic of each type of the cells were traced.

A new monoclonal antibody, designated UFT-4, reacting with rat Kupffer cells, was produced using sinusoidal liver-cell fraction as an immunogen. Immunohistochemically, UFT-4 reacted with Kupffer cells, interdigitating cells (IDCs), sinus endothelial cells of the spleen, a proportion of reticulum cells, smooth muscle fibers, choroid plexus epithelia and some macrophages. Immunoelectron microscopy disclosed two types of intracytoplasmic positivity: a striated type and a diffuse type. Both appeared to depend on variations in the quantity and distribution of the same antigen. On the other hand, UFT-4 gave a negative result for blood monocytes and most macrophages in lymphatic sinuses, lymphoid follicles, splenic red pulp and loose connective tissue. Cells positive for UFT-4 were mostly considered to belong to a narrow spectrum of the classical reticuloendothelial system, explaining the close relationship existing between some endothelia and some macrophages or reticulum cells. SDS-PAGE analysis of immunoprecipitates showed that the antigen reacting with UFT-4 was of molecule of 36-42 kDa under reducing conditions in the presence of 2-mercaptoethanol. The present results suggest that UFT-4 will be very useful for the study of Kupffer cells and for reconsidering their origin and destination.

Antibody-containing cells in lymph nodes, expecially in germinal centers, and in thoracic duct of rats sensitized by injection of horseradish peroxidase were studied with the immunoperoxidase method. In the primary response the large germinal center cells began to produce antibody on the 9th day and predominated thereafter in germinal centers ,added by intercellular antibody deposition in its late stage. The "ordinary" medium-sized germinal center cells were a minor component. In the secondary response, the intracellular antibody positivity disappeared immediately after the antigenic rechallenge but reappeared from 6 hours later in the large germinal center cells which further transformed from 48 to 72 hours into the "specifically differentiated" medium-sized germinal center cells that disappeared by 96 hours after the secondary injection to enter the thoracic duct. Antibody-containing cells outside the germinal centers appeared 5 to 6 days after the primary injection and were mainly comprised of plasmocytic cell series which was classified into interfollicular large cells, proplasmocytes and plasmocytes. Some results conflicting with the cytological identity of both cell series were presented.

Localization of IgG, IgA and IgM in human palatine tonsils, especially in germinal centers, was studied with the electron microscopical enzyme-labeled antibody method. The large germinal center cells differentiate into two kinds of cells within the germinal center; one was the medium-sized germinal center cells not engaging in intracytoplasmic production of immunoglobulins and another was the immature cells producing at least one of the three classes of immunoglobulins, especially IgM. The latter continued to maturate and developed into the intermediate-matured cells and probably into the plasmocytes. The three classes of immunoglobulins were also deposited in the form of admixtures in the intercellular spaces among the constituent cells of the germinal centers, mainly attaching on the cell membrane of desmodendric cells. In addition, some of the deposits were found freely in the intercellular spaces. Some differences between the immunoglobulin-containing cells outside and within the germinal centers were pointed out.

A case of malignant fibrous histiocytoma of the tibia of a 49-year-old Japanese farmer was presented. The patient was diagnosed as malignant hemangiopericytoma by biopsy, whereas the amputated material showed a marked pleomorphism representing features of malignant fibrous histiocytoma. Ultrastructurally, undifferentiated mesenchymal cells, intermediate cells between the undifferentiated mesenchymal cells and fibroblastic cells, fibroblastic cells and histiocytoid cells including bizarre giant cells were confirmed in a broad modulating spectrum. The hemangiopericytomatous lesion was predominated by intermediate cells, the ultrastructure of which bore a close resemblance to that of pericytes, and was regarded to be resulted from a differentiation of undifferentiated mesenchymal cells towards the pericyte.