T-zone Histiocytes Research Articles

Primary histiocytic sarcoma of the epididymis in B6C3F1 mouse.

A case of histiocytic sarcoma developed primarily in the epididymis of B6C3F1 mouse at 109 weeks old was reported. Metastases were observed in the liver and adipose tissue of the abdominal cavity. Tumor cells showed atypism, pleomorphism and active erythrophagocytosis. Touton type giant cells, which were PAS positive after diastase digestion, were seen in the tumor. Electronmicroscopically, the tumor cells had many slender processes forming interdigitation with the adjacent cells. However, no junctional complex or basal lamina was observed in the tumor cells. Tubular autolysozomes in the cytoplasm were characteristic feature of tumor cells of the present case. The vacuoles containing finger print membranes similar to the structures observed in human eosinophilic granuloma of the bone were found in some of the tumor cells. The structures similar to Birbeck's granule of the T-zone histiocyte were also observed. This case seems to be the first report on histiocytic sarcoma developed in the epididymis of B6C3F1 mice. Since fibrohistiocytic proliferative lesion developed in the epididymis of B6C3F1 mice. Since fibrohistiocytic proliferative lesions were known to develop occasionally in the epididymis of B6C3F1 mice, differential diagnosis from this proliferative lesions is important. Further immunohistological analysis for elucidating the origin and pathogenesis of this neoplastic lesion will be needed. (J Toxicol Pathol 7: 95`102, 1994)

High endothelial venule and immunocompetent cells in typical medullary carcinoma of the breast.

The characteristics of immunocompetent cells and their role in killing tumour cells in typical medullary carcinoma of the breast (TMC) have been investigated morphologically. Formation of high endothelial venule (HEV)-like vessels in tumour cell nests, the distribution of macrophages, T-zone histiocytes, T- and B-lymphocytes, the ratios of CD4+/CD8+, and natural killer (NK) or NK-like T-cells were examined in five cases of TMC. These results were compared with controls which consisted of three cases of ductal carcinoma with intense lymphocytic infiltration (control I) and four cases of ductal carcinoma with scanty lymphocytic infiltration (control II). An increased incidence of HEV-like vessels with migration of lymphocytes and a higher number of CD8+ lymphocytes with interleukin-2-receptor expression, as well as numerous CD57 cells, were noted in the tumour nests of TMC as compared with those of control groups. Furthermore, large granular lymphocytes, large lymphocytes invaginating tumour cells and necrotic tumour cells were observed electron microscopically. These findings indicate that infiltrating lymphocytes in TMC are activated and become effector cells that can kill the tumour cells by mechanisms similar to those of NK cells. The activities of immunocompetent cells in TMC appear to contribute to a favourable prognosis in TMC of the breast.

Langerhans Cells Related to Prognosis in Patients With Laryngeal Carcinoma

Intratumoral and peritumoral infiltration of T-zone histiocytes, mainly of mature Langerhans cells, was investigated in 88 patients with squamous cell carcinoma of the larynx by immunohistochemical methods using polyclonal antibodies against S100 protein and lysozyme. Granulocytic and lymphoid inflammatory infiltration and its relationship to the presence of Langerhans cells were also evaluated. Langerhans cells were present within the cancer tissues and showed a relationship with lymphoid infiltrate. No significant correlation was present among the density of Langerhans cells and the site of neoplastic growth (supraglottic or subglottic), granulocytic inflammatory infiltration, histological tumor grade, or clinical stage. Patients with high or intermediate density of Langerhans cells survived longer than those with low density (mean survival, 61%, 62%, and 0%, respectively). The number of Langerhans cells was relevant in patients with evident infiltration of lymphocytes and plasma cells, according to their ability to present antigens to sensitized T cells. Our results indicate that the presence of high or intermediate density of Langerhans cells and of marked lymphoid inflammation may be considered favorable prognostic factors for patients with squamous cell carcinoma of the larynx.

顎骨嚢胞におけるＴ‐ｚｏｎｅ組織球の分布に関する研究

In order to investigate the potential role of the cell-mediated immune system in jaw cysts, the presence and distribution of T-zone histiocytes (Langerhans cells and indeterminate cells) were studied immunohistochemically using antisera to S-100 protein in the walls of six different groups of jaw cysts in relation to the degree of inflammatory cell infiltration (macrophages, MT-1 positive lymphocytes, MB-1 positive lymphocytes, plasma cells and neutrophils) and the thickness and type of covering epithelium. Materials consisted of 42 radicular cysts, 19 odontogenic keratocysts, 9 dentigerous cysts, 8 postoperative maxillary cysts, 7 nasopalatine duct cysts and 7 cysts of unknown diagnosis. Twenty samples of oral mucosa served as control.In contrast to 95% in the control oral mucosa, intraepithelial T-zone histiocytes were found in only 37% of 75 cysts having epithelial lining. The value in the supporting connective tissue was 74% and T-zone histiocytes were found more often in cysts with inflammatory cell infiltration. The mean numbers of T-zone histiocytes in a given field of the connective tissue for radicular cysts, odontogenic keratocysts, dentigerous cysts, postoperative maxillary cysts, nasopalatine duct cysts, cysts of unknown diagnosis and oral mucosa were 1.2, 1.2, 4.9, 0.2, 1.3, 2.6 and 2.5, respectively. A tendency to decreased T-zone histiocytes was observed in radicular cysts with little to very mild or severe inflammatory cell infiltration, but like in oral mucosa, the number in the odontogenic keratocyst-dentigerous cyst group was related to that of inflammatory cells, whereas there was no such correlation in the postoperative maxillary cyst-nasopalatine duct cyst group. A significant correlation was also observed between the number of T-zone histiocytes and the thickness of the covering epithelium in all cysts but those of unknown diagnosis. In addition to the thickness of covering epithelium, MT-1 and MB-1 positive lymphocytes were the factors related to the number of T-zone histiocytes in radicular cysts and odontogenic keratocyst-dentigerous cyst group in the multiple regression analysis.In conclusion, T-zone histiocytes were found to be contributing in the induction of immune response in the presence of adequate inflammation except when it is too mild or too severe to cause extensive damage of cyst wall tissues. However, further study is needed to clarify their contribution in cysts with epithelial lining of respiratory origin.

Immunophenotyping of cutaneous lymphoid infiltrates in frozen and paraffin-embedded tissue sections: A comparative study

A panel of antibodies reactive in routinely fixed, paraffin-embedded tissue sections was compared with a panel of antibodies reactive in frozen sections for the immunophenotyping of cutaneous lymphoproliferative disorders. Three T cell-associated markers (UCHL1, MT-1, MT-2, six B cell-associated markers (MB-1, MB-2, LN-1, LN-2, L-26, 4KB5), immunoglobulin heavy and light chains, anti-LCA antibody, two markers for Reed-Sternberg cells (Ber-H2, Leu-M1), one marker for macrophages (Mac-387) and anti-S-100 protein antibody were tested on normal skin, inflammatory skin diseases, and cutaneous lymphomas and pseudolymphomas. On the basis of the results in frozen sections, 12 inflammatory T cell diseases, 14 T cell lymphomas and pseudolymphomas, and 10 B cell lymphomas and pseudolymphomas were identified. In addition, two cases of specific skin infiltrates of Hodgkin's disease have been examined. Among T cell markers, the greatest sensitivity was exhibited by UCHL1, which stained all but one specimen of T cell infiltrate; it was negative in one specimen of mycosis fungoides that progressed into a T-immunoblastic lymphoma. The combined use of MB-2, LN-2, and 4KB5 identified all B cell proliferations. LN-1 marked germinal centers in all cases of follicular lymphoma and pseudolymphoma. Ber-H2 stained the Reed-Sternberg cells in both cases of Hodgkin's disease and the large cells in the histiocytic type of lymphomatoid papulosis. Mac-387 and anti-S-100 protein antibody recognized macrophages and T-zone histiocytes (Langerhans cells and interdigitating cells), respectively. A panel of antibodies reactive in routinely fixed, paraffin-embedded tissue sections is proposed that facilitates the identification of most B and T cell infiltrates in the skin.

Ｆａｍｉｌｉａｌ ｈｅｍｏｐｈａｇｏｃｙｔｉｃ ｌｙｍｐｈｏｈｉｓｔｉｏｃｙｏｓｉｓと考えられる４兄弟の剖検例

Four cases of familial hemophagocytic lymphohistiocytosis(FHL) occurring in a Japanese family are reported. They presented with typical fever, hepatosplenomegaly, and convulsions in the first year of their lives. These children were products of unconsanguineous marriage, and all children in that family were affected by FHL. Family history was otherwise unremarkable. Pertinent laboratory findings included pancytopenia, liver dysfunction and hypofibrinogenemia in all four cases. Hypertriglyceridemia was recorded in the fourth child. Clinical course was fulminant in all four cases. They died between 30 and 78 days after the onset of the disease. Autopsy revealed maked hepatosplenomegaly, marked atrophy of systemic lymphoid organs, and varaible degrees of lymphohistiocytic infiltration in many internal viscera. The infiltralion was noted in almost every organ, but was most prominent in spleen, bone marrow, and central nervous system. Many of these histiocytes showed variable degrees of hemophagocytosis. Immunohistochemical studies of proliferating histiocytes have shown following results: Leu M1(+), Leu 4(-), Leu 8(-), HLA-DR(+), Leu-M5(+), S-100 protein (-), α-1-antichymo-trypsin (+), lysozyme (+), and epithelial membrane antigen (EMA) (-). These data indicate that proliferating histiocytes are carrying markers similar to those of sinus histiocytes in reactive lymph nodes, and that they do not carry markers of T-zone histiocytes. Lack of cellular atypia as well as negative staining patterns for EMA suggest benign nature of these histiocytes. However, a possibility of malignancy cannot be ruled out with certainty, as these histiocytes infiltrated and destroyed the parenchyma of brain in all four cases.

男児陰茎にみられた Histiocytosis X の1例

A case of localized histiocytosis X of the penis was reported. The patient was a 9-year-old boy who had several tumor lesions on the glans penis and inner layer of prepuce. Biopsy specimens were studied by H-E staining and immunohistochemical staining for S-100 protein (S-100), lysozyme (Lys), leucocyte common antigen (LCA), and Leu-M1. They revealed diffuse infiltration of many atypical histiocytes, which were shown to be S-100+, Lys+, LCA- and Leu-M1-. This indicates that these cells were derived from T-zone histiocyte system. After complete remission of these tumors, the other one arose from anal mucosa. In the literature we could find only one case of a primary penile lesion reported by Myers and others.

皮膚科領域の組織球増殖性疾患

Histiocyte proliferating diseases that we often experience in the dermatologic clinics include histiocytosis-X particularly Letterer-Siwe disease, non-X histiocytosis such as xanthogranuloma, multicentric reticulohistiocytosis, xanthoma disseminatum, and verruciform xanthoma, and fibro-histiocytic tumors represented by dermatofibroma, dermatofibrosarcoma protuberans, and malignant fibrous histiocytoma, as well as malignant histiocytosis. The other diseases, for example, congenital self-healing reticulohistiocytosis and generalized eruptive histiocytoma may be observed in very rare instance. We investigated cell types by using immunohistochemical markers for the prolifearting histiocytic cells on the paraffin sections from 40 cases. A clear result was obtained that S-100 positive cells belonging to T-zone histiocyte lineage are proliferating in histiocytosis-X, while lysozyme positive mononuclear phagocytes are the major cell type in malignant histiocytosis. Although in the rests of the diseases cells are positively reacted for α1-antichymotrypsin, α1-antitrypsin and vimentin, differentiation of the diseases by such immunomarkers was not enabled. There was a tendency that non-X histiocytosis represented by xanthogranuloma showed stronger reactivity for α1-antichymotrypsin and α1-antitrypsin, whereas the cells in fibro-histiocytic tumors are rather strongly positive for vimentin. Further studies are required for the proliferating cells positive for α1-antichymotrypsin, α1-antitrypsin and vimentin.

Involution of lymph node histiocytes in AIDS.

Lymph nodes of human immunodeficiency virus (HIV)-infected patients were studied histologically and immunohistochemically to elucidate the pattern of involution of various histiocytes in AIDS. Specimens consisted of one node with hyperplasia, five with atrophy, and three with severe atrophy. Antibodies such as L25, ID1, My4, 12, anti-Leu 3a, KiM4, OKT6 and anti-S100 protein were used for identification of the histocytes. Another antibody, VAK5, was used to demonstrate HIV antigen. T-zone histiocytes were mildly decreased in the hyperplastic node, but considerably decreased in the atrophic nodes. My4+ sinus histiocytes were unchanged in number and enlarged in the hyperplastic node, but not decreased in the atrophic nodes. Follicular dendritic cells (FDCs), defined by KiM4, were mostly depleted in the atrophic nodes. The T4 antigen was detected in some of the sinus histiocytes of the atrophic nodes. T6-positive cells were not found in any of the nodes. HIV antigen was detected only in FDCs. It is therefore suggested that various histiocytes respond differently to HIV, and that T-zone histiocytes and sinus histiocytes persist up to the late stage of AIDS.

T-zone histiocytes and recurrence of papillary urothelial bladder carcinoma.

We have studied the histologic distribution and prognostic significance of T-zone histiocytes (TZH) in 89 papillary urothelial bladder carcinomas (PUC), 3 cases of nonspecific cystitis (NC) and 4 cases of follicular cystitis (FC) by immunohistochemical determination of S-100 protein. Nineteen (21.37%) of the PUC cases have been found to have TZH S-100-positive with a variable density intratumor, along the papillary axis, or in the lymphoid aggregates of the vesical wall. All four FC cases were also TZH-positive, with a distribution and density similar to those of follicular dendritic cells of lymph nodes, although none of the 3 NC cases presented TZH. The recurrence-free period was significantly (p less than 0.05) longer in TZH-positive patients.

悪性組織球症様病変をきたした重篤蚊刺過敏症の1剖検例

An autopsy case of an 18-year-old Japanese girl with a malignant histiocytosis-like disorder that developed during the course of a hypersensitive reaction to mosquito bite is reported. Episodes of hypersensitive reactions to mosquito bite had been repeated since she was 12 years old and at the age of 18 years she died of acute respiratory failure only 11 days after a mosquito bite. On autopsy, the dermal reaction to the last mosquito bite had already calmed down, and 'poorly differentiated histiocytes', which were presumed from their histochemical characteristics, had remarkably infiltrated into multiple organs, appearing like leukemic infiltration. Only a small number of them were noted in the lymph nodes and the bone marrow. The results of histochemical examination of 'poorly differentiated histiocytes' was as follows: (1) Neither markers for granulocytes (peroxidase and naphthyl AS-D Cl esterase) nor markers for lymphocytes and plasma cells (leukocyte common antigen and immunoglobulins) were detected. (2) Some markers for histiocytes (peanut lectin agglutinin and lysozyme) were positive in some of the proliferated cells. (3) A marker for T-zone histiocyte (s-100 protein) was negative. These results suggested that the proliferated cells included cells of the monocyte-macrophage system. These cells morphologically showed no phagocytic activity and were suggested to be immature histiocytes. Jurco et al. reported (poorly differentiated) malignant histiocytosis consisting of immature histiocytes without phagocytic activity, by using histochemical methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Histopathologic prognostic factors in adenocarcinomas of the peripheral lung less than 2 cm in diameter.

The histologic prognostic factors of pulmonary adenocarcinomas of the lung less than 2 cm in diameter were analyzed in 75 patients who had undergone surgical resection. The pathologic stage, lymph node involvement, and pleural involvement were found to be the major determinants of prognosis (P less than 0.01). In addition, other single factors, such as tumor differentiation (P less than 0.01), vascular invasion (P less than 0.01), the degree of collagenization in the fibrotic focus (P less than 0.01), the standard deviation (SD) of nuclear areas (P less than 0.05), and mitotic index (P less than 0.05) correlated significantly with prognosis by the log-rank test on the Kaplan-Meier survival curves of these factors. Patients with dense infiltration of "T-zone histiocytes" survived significantly longer than those with less infiltration (P less than 0.05). Cox's proportional hazard general linear model analysis showed the importance of factors, such as lymph node or pleural involvement and the SD of nuclear area, when the pathologic stage was excluded, and of the mitotic index when all four factors were excluded to emphasize the cellular characteristics. It is possible to predict the postoperative prognosis of patients with small pulmonary adenocarcinoma more precisely by combination of the above histopathologic factors.

Immunohistochemical distribution of s-100 protein in tumors and tumor-like lesions of bone and cartilage

Various tumors and tumor-like lesions of bone and cartilage were examined for S-100 protein using the avidine-biotin-peroxidase complex (ABC) immunostaining method. The most intense reactivity for S-100 protein was found in well-differentiated chondrocytes of enchondromas, osteochondromas and chondrosarcomas, and in normal epiphyseal cartilage. S-100 protein was positive in both polygonal stromal cells and chondrocytes of chondroblastomas and in chondrocytes of mesenchymal chondrosarcoma. In osteosarcomas not only chondroblastic areas but also osteoblastic areas showed positive cells. Reticulum histiocytic cells of eosinophilic granulomas and chordoma cells were positive for S-100 protein. The study yielded three main conclusions: (1) S-100 protein could be the marker for tumors of cartilaginous origin and differentiation, notochord origin, and T-zone histiocyte origin; (2) chondroblastoma can be distinguished from other histologically confusing giant cell lesions by using ABC to detect S-100 protein; and (3) S-100 protein has some relationship with tumoral calcification not only in cartilaginous tumors but also in osteosarcoma.

Immunohistochemical Study on Cutaneous Histioproliferative Lesions

Immunohistochemical examinations were performed using five kinds of histiocytic markers [S100 protein, lysozyme, non-specific cross reacting antigen with carcinoembryonic antigen (NCA), alpha 1-antichymotrypsin (alpha 1-ACT) and alpha 1-antitrypsin (alpha 1-AT)] in biopsied tissues from histiocytosis X, juvenile xanthogranuloma, xanthoma tuberosum, xanthoma disseminatum, reticulohistiocytic granuloma and multicentric reticulohistiocytoma, all of which have been classified as histiocytic proliferative disorders. Our results suggested that xanthomatous lesions of the skin to be composed of the histiocytic proliferation of two different cell lineages, i.e. S100+lyso-NCA- T-zone histiocytes and S100-lyso+NCA+ tissue macrophages. Only lesions of histiocytosis X were composed of the former cells. It is suggested that these markers will be useful in determining the delineation of the histiocytic system on the basis of functional heterogeneity.

Induction of Lymphokine-Activated Killer Activities in Peripheral Blood Lymphocytes and Regional Lymph Node Lymphocytes Against PC-9 Cultured Adenocarcinoma and Autologous Pulmonary Adenocarcinoma Cells

The cytotoxic activities, of the peripheral blood lymphocytes (PBL) and regional lymph node lymphocytes (LNL) generated by incubation with recombinant IL-2 (rIL-2) in vitro, have been studied to assess their effects on autologous pulmonary adenocarcinoma cells from 21 patients with lung cancer. The lymphokine-activated killer (LAK) activities of PBL were 22.9 +/- 14.8% for autologous pulmonary adenocarcinoma cells and 44.9 +/- 20% for PC-9 cells. A previous coculture of autologous tumor cells with PBL (ATS-LAK) showed no increase in induction of cytotoxicity to autologous tumor cells. The LAK activities of LNL were significantly lower than those of PBL. The cytotoxicities of rIL-2 activated lymphocytes seemed lower in well differentiated pulmonary adenocarcinoma than in moderately and poorly differentiated adenocarcinoma, and higher in patients with lymph node metastasis than in those without; they appeared, however, not to be related to clinical stage or degree of infiltration of T-zone histiocytes into the cancer stroma. The cytotoxicity to autologous tumor cells was not significantly different in the presence of the Ia antigen expressed on tumor cells, but the cytotoxicity to Ia positive PC-9 cells was significantly higher for rIL-2 activated lymphocytes from patients with lung cancer cells which were Ia positive than from those where they were Ia negative. The presence of Ia antigen on tumor cells seemed important for antitumor activity.

Biochemistry and Biology of the Langerhans Cell

Langerhans cells mainly present in the normal epidermis and are thought to be identical to the proliferating cells in the lesions of histiocytosis-X. The Langerhans cell is positive not only for ATPase, esterase, and acid phosphatase, but also for S-100 protein. Since these findings are similar but distinct from those of monocytes and macrophages, the Langerhans cell may be a cell line independent of the monocyte-macrophage system, designated as T-zone histiocytes. Immunologically, the Langerhans cell has Fc and C3 receptors and Ia-like antigen. Thus, the Langerhans cell may be a member of the immune network, as antigen-presenting cells, in the epidermis. One hypothesis is that Langerhans cells activated by external stimuli induce a local immune reaction by activation and proliferation of T-cells, with the interaction of keratinocytes and macrophages. Because of cytochemical and immunologic similarities between Langerhans cells and histiocytosis-X cells, histiocytosis-X may be a proliferative disorder of immature or neoplastic Langerhans cells.

T-Zone histiocytes in adenocarcinoma of the lung in relation to postoperative prognosis

T-Zone histiocytes in adenocarcinoma of the lung in relation to postoperative prognosis

Histiocytes in nasopharyngeal carcinoma in relation to prognosis.

Forty-nine biopsy specimens of nasopharyngeal carcinoma and 20 biopsy specimens of nasopharyngeal mucosa obtained from non-cancer patients were studied for the presence of T-zone histiocytes (Langerhans' cells and their precursors) and macrophages by immunohistochemical methods with the use of antibodies against S-100 protein and lysozyme (lys), respectively. Patients with dense infiltration of T-zone histiocytes in the primary sites survived longer than those without such infiltration (mean survival times, 8, 39, and 72 months in the patients with the density of -, +, and ++, respectively; P less than 0.005). In contrast, there was no relationship between patient prognosis and density of lys+ macrophages in the tumor tissue (P = 0.33). The distribution of T-zone histiocytes in the tumor tissue was different from that of macrophages. T-zone histiocytes may play an important role in the immune reaction against cancer, probably acting through mechanism different from that of macrophages.

S-100-protein-positive dendritic cells in nodular vasculitis.

We investigated the distribution of S-100-protein-positive dendritic cells in 20 cases of nodular vasculitis (erythema induratum Bazin). The cells were identified by immunohistochemical demonstration in paraffin sections. S-100-protein-positive dendritic cells were present in all cases and comprised up to 11% of the infiltrating cells in lymphohistiocytic areas (mean 3.7%). Because of the dendritic shape and the association with lymphocytes the cells are considered to represent T-zone histiocytes. Our findings suggest a possible role of delayed-type hypersensitivity in nodular vasculitis.

T-zone histiocytes in adenocarcinoma of the lung in relation to postoperative prognosis.

Infiltration of T-zone histiocytes (Langerhans' cells and their precursors) and macrophages was investigated by immunohistochemical methods with the use of anti-S100 protein and anti-lysozyme antibodies in 40 Stage Ia cases of adenocarcinoma of the lung. Varying population densities of S100+ T-zone histiocytes were demonstrated in 31 (77.5%) of 40 adenocarcinomas; however, lysozyme+ macrophages were found in almost equal quantities in all cases of adenocarcinoma. The distribution of T-zone histiocytes was clearly different from that of macrophages. Namely, the former was mainly interspersed among the tumor cells, whereas macrophages were found in the stroma and around necrotic foci. The prognosis of Stage Ia adenocarcinoma cases was related to the density of T-zone histiocytes in tumor tissues. Patients with marked infiltration of T-zone histiocytes survived longer than those without or with only slight infiltration (P less than 0.05). Such relationship was not observed with regard to macrophages. This indicates that T-zone histiocytes infiltrating within the tumor and regional lymph nodes may play a role in host defense mechanisms against tumor in the early stage of adenocarcinoma of the lung.