Interdigitating Reticulum Cells Research Articles

Immunohistochemical study of 22 cases of thymoma.

The histological and clinical features of 22 thymomas were reviewed. Immunohistochemical studies were performed using antibodies to cytokeratins (CAM 5.2 and S29) and to desmosomal protein. The heterogeneity of staining patterns seen in the epithelial cells supported the concept of separating thymomas into cortical, medullary, or mixed groups. Interdigitating cells were identified by antibody to S100 protein, and these varied in number between different tumours. Clustering of interdigitating reticulum cells occurred in association with foci of mature lymphocytes which were shown by staining of the leucocyte common antigen (CD45). The extent to which this occurred was used to assess the degree of medullary differentiation within the thymomas and this was correlated with the histological and clinical features. The lymphocyte population of six of the thymomas was studied using a range of antibodies to T and B cells; this showed the presence of B lymphocytes in thymomas.

Characterization of Extracellular Matrix in Non-Hodgkin's Lymphomas

Basement membrane proteins laminin, type IV collagen and aminoterminal propeptide of type III collagen (type III pN-collagen) are important components of extracellular matrix of normal lymph nodes; they are present in reticular fibres and in the walls of blood vessels and sinuses. We have studied the distribution of these proteins in 45 cases of non-Hodgkin's lymphomas representing different types of Kiel classification. Light microscopic immunohistochemistry was used on sections from formalin fixed, paraffin embedded biopsy specimens. Reticular cells were identified by using antibodies against S-100 protein, a marker for dendritic and interdigitating reticulum cells, and against cystatin A for the demonstration of follicular dendritic reticulum cells. The findings of the immunohistochemical stainings were generally similar in the different lymphoma types. Thus the method for the demonstration of extracellular matrix proteins could not give obvious aid for lymphoma classification. BM stainings proved to be efficient in the demonstration of sinuses. Marginal and medullary sinuses of the nodal cases were either totally or partly spared and open also in the cases in which there was extracapsular growth. The fibre content was variable, but generally the distribution of all the three extracellular matrix proteins was comparable with each other and mainly corresponded with the pattern seen in conventional Gomori's reticulin stain. This also holds for the tumor tissue infiltrated through the capsule and for extranodal cases. Areas of sclerosis of some cases contained only type III pN-collagen. Reticular fibres were at places seen to be closely associated with cells of spindle or dendritic shape. A few reticulum cells could be found to show cytoplasmic staining for laminin, type IV collagen and type III pN collagen. This finding suggests that the cells are synthetizing these proteins. The amount of cells staining for cystatin A or S-100 protein did not generally correlate with the amount of fibres, and most of the stained cells were not closely associated with fibres. The results show that in non-Hodgkin's lymphomas basement membrane proteins and type III pN-collagen are important components of reticular fibres. Results also indirectly support the main role of fibroblastic reticulum cells in the production of the fibres.

A novel B cell line established from Ki-1-positive diffuse large cell lymphoma.

A novel cell line, designated KIS‐1, was established from a patient with Ki‐1‐positive diffuse large cell lymphoma. Multiple phenotypic analysis of the KIS‐1 cells was carried out with a total of 22 monoclonal antibodies defining hematopoietic cell subsets and lineages. The KIS‐1 cells were positive for Ki‐1, B4, HLA‐DR, and 2D1 (common leucocyte) antigens, but were negative for the antigens reportedly specific for T cells, natural killer cells, granulocytes, monocytes, interdigitating reticulum cells and dendritic reticulum cells. The genomic analysis of the KIS‐1 cells showed not only the rearrangement of JH and Jk genes but also the probable rearrangement of Cγ genes. Moreover, the cells produced immunoglobulin γ chains. Thus, KIS‐1 was considered to be of B‐cell lineage. The lymphoma‐cell derivation of KIS‐1 was based on the following facts. The cytochemical, immunologic, cytogenetic properties and the results of the molecular genomic analysis in the KIS‐1 cells were essentially the same as those of the original tumor cells, and the KIS‐1 cells were negative for Epstein‐Barr virus‐associated nuclear antigen. KIS‐1 is the only known B‐cell line derived from Ki‐1‐positive diffuse large cell lymphoma, and should be useful for defining the biological implications of Ki‐1 antigen.

Hodgkin cells in freeze-fracture replicas.

Lymph nodes from six patients with Hodgkin's disease (three with the nodular sclerosing subtype, one with mixed cellularity and two with the lymphocyte-predominant subtype) were analysed by electron microscopy in freeze-fracture replicas and thin sections. Two main variants of Hodgkin cell could be identified in the nodular sclerosing and mixed cellularity subtypes. (1) Hodgkin cells with wide cytoplasm and short, smooth- and rough-surfaced tubular profiles of endoplasmic reticulum (ER) unevenly scattered in the cytoplasm. (2) Hodgkin cells with well developed rough ER. In freeze-fracture replicas the ER was seen to consist of both short and long tubules, some of the latter forming anastomoses with each other. Both cell types possessed branching cytoplasmic processes. A P-face rich in intramembrane particles (IMP) and an E-face with few IMP were common to both Hodgkin cell types. These cells do not, therefore, possess the membrane features characteristic of interdigitating reticulum cells, thus refuting the previously held belief that Hodgkin cells, in particular lacunar cells, are related to interdigitating reticulum cells. The cytoplasmic structures and membrane characteristics of Hodgkin cells in the lymphocyte-predominant subtype (L & H cells) are similar to other Hodgkin cells in that they may show a high content of rER, and the P-face of these cells contains more IMP than the E-face. Both characteristics support the theory put forward in the literature (based on immunohistochemical findings) that these are lymphoid cells (immunoblasts or immature plasma cells).

Interdigitating reticulum cells in dermatopathic lymphadenitis: freeze-fracture and ultrathin-section morphology.

Dermatopathic lymphadenitis is a non-neoplastic lesion found with various chronic skin lesions and associated with hyperplasia of the thymus-dependent (T) areas. These areas consist chiefly of interdigitating reticulum cells (IDC's), which are known to be accessory cells for T-cell-dependent immune reactions. The most characteristic features of IDC's are the bizarre-shaped cell nucleus, numerous cytoplasmic processes, deep cytoplasmic invaginations, and a close topographical relationship to surrounding (T) lymphocytes. The cytoplasmic processes of IDC's do not interdigitate with adjacent lymphocytes, as previously reported in the literature, but show close interdigitations with the processes of neighboring IDC's. With the freeze-fracture technique it can be seen that IDC's exhibit a characteristic distribution of intramembranous particles (IMP). While, for example, macrophages, epithelioid cells and lymphocytes display a clearly greater number of IMP on the P face than on the E face, IDC's show an equally high particle density on both the P face and the E face. The organelle content of IDC's in dermatopathic lymphadenitis varies considerably. Tubular profiles, the Golgi apparatus and vesicles may be increased in number. Birbeck granules are also found in IDC's, but only rarely. Variations in the numbers of the different cytoplasmic organelles may be a reflection of varying degrees of metabolic activity of IDC's.

Plasmacytoid T cells: A cell population normally present in the reactive lymph node: An immunohistochemical and electronmicroscopic study

Plasmacytoid T cells (PTCs) are medium-sized cells characterized by abundant rough endoplasmic reticulum. They occur in the thymic-dependent area in human lymph nodes. PTCs are hardly identified in routinely stained sections. We studied their occurrence in 100 reactive lymph nodes with the use of monoclonal antibodies MB2, MT1, LN1, LN2, reactive on paraffin-embedded tissue, and with electron microscopy in nine selected cases. PTCs strongly reactive with MT1 and LN2 were found in 87 of 100 lymph nodes. They were observed in clusters, loose aggregates, and as singular cells. An association between PTCs, postcapillary venules, small T lymphocytes, and interdigitating reticulum cells (IDRCs) was found. Our results indicate that PTCs are normally present in the human lymph node. Their immunophenotype suggests a relationship with a monocyte/macrophage lineage, but does not rule out a T cell origin. If the various distribution patterns represent the morphologic substrate of functional stages of PTCs it can be assumed that PTCs play a role in T cell-mediated immune response.

Clinical, ultrastructural immunohistochemical and DNA content analysis of lymphomas having features of interdigitating reticulum cells

Interdigitating reticulum cells (IRC) are dendritic, nonphagocytic histiocytes found in thymus-dependent areas of lymphoid tissues. We report two cases of large cell lymphoma having features of IRC in patients 13 and 17 years old. In each case the diagnosis was suggested by light and electron microscopic features, positive immunoperoxidase staining for S-100 protein, and additional immunoperoxidase findings. Both patients presented with aggressive lymphomas and were treated with intensive combination chemotherapy. Each patient achieved a complete clinical remission, then rapidly relapsed and died with disseminated disease 3 and 9 months after presentation. Novel findings included strong staining of specimens with an antibody to epithelial membrane antigen, staining of one specimen with peanut agglutinin in the pattern previously described in normal IRC, and a DNA content analysis that showed aneuploid stem cell lines in both patients.

Primary gastric peripheral T-cell malignant lymphoma with helper/inducer phenotype.First case report with a complete histological ultrastructural and immunochemical study

Primary gastrointestinal T-cell malignant lymphomas (T-ML) are very rare. In this case report we describe a primary gastric tumor with local lymph node involvement. On the basis of histologic, immunohistochemical, and electron microscopic studies, the authors classified this tumor as a pleomorphic T-ML, large cell variant with peripheral helper/inducer T-cell phenotype (Leu1/CD5+, Leu4/CD3+, Leu5/CD2+, Leu9/CD7+, and Leu3/CD4+). The extreme pleomorphism of lymphoma cells, the numerous giant cells, and the presence of tumor nodules with two or three concentric layers were the three striking morphologic features of our case. Tumor cells showed an inconstant but true positive staining with anti-LeuM1/CD15 and LeuM3/CD14 antibodies. Vimentin positivity could be related to the presence of intermediate filaments at ultrastructural level. Neuron-specific enolase reactivity was a peculiar but unexplained feature. Furthermore, the positivity of the surface markers Ki-1/CD30, anti-Tac/CD25 and HLA-DR, and the nuclear marker Ki-67 suggested an activation state and a high proliferative activity of the tumor cells. This study emphasizes the usefulness of combined pathologic methods in order to rule other diagnoses such as undifferentiated carcinoma, malignant melanoma, malignant histiocytosis, B-cell lymphoma and interdigitating reticulum cells sarcoma, in view of an extremely polymorph tumor proliferation. This is apparently the first completely documented case report of a primary gastric pleomorphic T-ML of peripheral T-cell origin.

Thymus in myasthenia gravis. Isolation of T-lymphocyte lines specific for the nicotinic acetylcholine receptor from thymuses of myasthenic patients.

The thymus is believed to play a central role in the pathogenesis of Myasthenia gravis (MG). According to a previous hypothesis, MG is initiated within the thymus by immunogenic presentation of locally produced nicotinic acetylcholine receptor (AChR) to potentially autoimmune T cells. Data of 10 consecutive MG patients demonstrate two critical features of MG thymuses that support the concept of intrathymic activation of autoreactive, AChR-specific lymphocytes. Morphologically, the thymuses showed lympho-follicular hyperplasia in nine cases and benign thymoma in one case. The paramount feature revealed by immunohistological double marker analyses was the intimate association of myoid cells (antigen producing) with interdigitating reticulum cells (potentially antigen presenting cells), both of which were surrounded by T3+ lymphocytes in thymus medulla. All 10 thymuses contained T lymphocytes reactive with AChR. This was in contrast to the peripheral immune compartment (blood) where in only 3 of 10 patients, significant T cell responses to AChR were observed. AChR-specific T cell lines could be established from 8 of 10 thymuses, all members of the helper/inducer subset as indicated by the expression of markers T3 and T4.

Immunoelectronmicroscopic demonstration of S-100 protein in hairy cell leukemia cells.

Hairy cell leukemia (HCL) is generally considered a neoplastic proliferation of B-cell lineage. Among immunocompetent cells, however, S-100 protein is also demonstrated in "dendritic" cells (i.e., interdigitating reticulum cells, Langerhans cells, follicular dendritic cells) and in a small percentage of T8-cells. This study reports the surprising detection of S-100 protein in peripheral blood HCL cells of B-cell type, using immunofluorescence and immunoelectronmicroscopy. However, negative results for S-100 protein staining were obtained in paraffin splenic sections of HCL cases. This report stresses the need for caution in the interpretation of immunocytochemical methods and results, and emphasizes the diagnostic ambiguity of the S-100 protein.

Expression of sialylated Leu-M1 antigen in histiocytosis X.

The purpose of this study is to determine the versatility of the monoclonal antibody anti-Leu-M1 in histiocytosis X diagnosis. This antibody recognizes an unsialylated lacto-N-fucopentaose III (hapen X) carbohydrate moiety that is linked to the cell membrane protein in interdigitating reticulum cells and Langerhans' cells. Previously, the authors have shown that anti-Leu-M1 can be used to stain Reed-Sternberg cells, which are likely related to interdigitating reticulum cells. In this study, the authors tested the usefulness of anti-Leu-M1 in staining formalin-fixed and paraffin-embedded tissue sections from eight patients with histiocytosis X. For staining of histiocytosis X cells, unlike Reed-Sternberg cells in Hodgkin's disease, neuraminidase treatment was required for removal of sialic acid residues from the Leu-M1 antigen. The staining characteristics of anti-Leu-M1 in histiocytosis X cells resembled those of normal Langerhans' cells and lymphocyte and histiocyte variants (L & H cells) in the lymphocyte-predominant type of Hodgkin's disease. The significance of sialylation of Leu-M1 antigen in histiocytosis X cells has yet to be determined in order to correlate the prognosis of the disease. The authors suggest that anti-Leu-M1 used together with neuraminidase treatment is a valuable tool in the diagnosis of histiocytosis X when electron microscopy or frozen sections for OKT6 immunostaining are not available.

Solitary Cutaneous Reticulum Cell Tumor

We herein report a case of solitary cutaneous reticulum cell tumor not associated with any other organ involvement. The enzyme-immunohistochemical and electron-microscopic features of the cellular infiltrate are the same as those of interdigitating reticulum cells (IDRC), which can give rise to neoplasms in lymphoid organs; they are also similar to those of Langerhans cells and "indeterminate" cells, which are usually thought to give rise only to systemic disorders. The authors support the hypothesis that such neoplasms may represent the cutaneous counterpart of IDRC neoplasms of lymphoid organs.

Interdigitating reticulum cells in the dermal infiltrate of mycosis fungoides. An ultrastructural and immunohistochemical study.

In order to provide insight into the role of accessory cells in lymphoproliferative neoplasms, 7 cases of mycosis fungoides at various clinical stages--patches, plaques and nodules--were studied ultrastructurally and immunohistochemically. The aim was to establish whether interdigitating reticulum cells are a constant finding in the dermal infiltrate. Their possible relationships with mycosic cells were also investigated. This study revealed that interdigitating reticulum cells were present in all the skin lesions examined, were present in considerable number in the patches and plaques and became sparse in the nodules. Furthermore, in the lesions at various clinical stages these cells showed varying ultrastructural features, probably related to different developmental stages. The close contacts between interdigitating reticulum cells and mycosic cells, the expression of antigenic markers of activation by mycosic cells and the morphological and immunohistochemical signs of progressive de-differentiation of mycosic cells in the more advanced stages suggest that interdigitating reticulum cells are involved in stimulating proliferation and--possibly--neoplastic progression of mycosic cells. A role for the T-cell microenvironment created in the dermis by lymphoid infiltrate in inducing the differentiation of interdigitating reticulum cells from their precursors is proposed.

S-100 protein detection in "follicular macrophages" of mouse lymphoid organs by ABC immunoperoxidase method.

The distribution of S-100 protein was investigated in normal or reactive lymphoid organs from adult mice, rats and humans by the avidin-biotin complex ABC) immunoperoxidase method. In mouse lymph nodes and spleen the protein appeared to be confined to the "tingible-body macrophages" and occasionally in sinus histiocytes in the lymph nodes. No immunoreaction product was detected in the other cell types present inside or outside the follicles. In the thymus the immunostained cells were located in the medullary area and corresponded morphologically to mononuclear PAS-positive cells with histiocytic appearance. By contrast, in rat and human organs S-100 protein was detected in interdigitating reticulum cells and dendritic reticulum cells. The present findings indicate that S-100 protein is located differently in mouse lymphoid organs and in other mammalian species.

Epithelioid granulomatosis with initial and predominant manifestation in spleen. Morphological and immunohistochemical analysis of six cases.

In six patients with systemic symptoms, four of which had lymphoplasmacytic infiltrates in the bone marrow splenectomy was performed because of suspected malignant lymphoma, with resolution of clinical symptoms. The spleen showed epithelioid granulomas, and neither splenic tissue nor clinical follow-up revealed evidence of malignant lymphoma. Immunohistochemical analysis documented an identical phenotype in epithelioid and giant cells as well as in large numbers of CD4 + lymphocytes and S100 + interdigitating reticulum cells within the granulomas. These cases are interpreted to represent epithelioid granulomatosis with primary and/or predominant manifestation in the spleen.

Distribution and morphology of macrophages in palatine tonsils.

The distribution and morphology of macrophages were studied by immunohistochemical and electronmicroscopic methods in three diseases of the palatine tonsils: tonsillar hypertrophy, recurrent tonsillitis and tonsils with focal infection. We confirmed the presence of two types of macrophages in the tonsils, a monocyte-macrophage cell line and dendritic cells with subtypes, Langerhans' and interdigitating reticulum cells. In the lymphoepithelial symbiosis area and in the subepithelial area, the monocyte-macrophage cells and the dendritic cells had similar distributions and densities. Since these two types of cells were sometimes in contact with each other, they may function in close cooperation. In tonsils with focal infection, there were fewer dendritic cells in the lymphoepithelial symbiosis area, and the germinal centers were less well developed than in the other tonsillar diseases. These findings suggest that in tonsils with focal infection, insufficient amounts of antigen may be presented by the dendritic cells to helper T-lymphocytes.

Syngeneic transplantation of rat pancreatic islets into the spleen. Light and electron microscopical findings.

An islet transplantation model was established with the two congeneic Lewis rat strains LEW.1W and LEW.1A, which were made diabetic by a single i.p. injection of 50 mg/kg b.w. streptozotocin. Isolated neonatal islets of the two strains served as a graft. Syngeneic transplantation into the spleen resulted in permanent graft survival and in normoglycemia of streptozotocin diabetic rats of the two strains. 200 days after transplantation functionally intact islets were demonstrable in the spleen by histological, histochemical and electron microscopical investigations. Histochemical findings indicate an activation of interdigitating reticular cells in the white pulp and of macrophages in the red pulp of the spleen as consequences of the islet transplantation. In addition a few electron microscopical findings concerning possible interactions between host plasma cells, lymphocytes and transplanted beta cells of islets are described and discussed.

Diversity of the human monocyte/macrophage system as detected by monoclonal antibodies.

Four monoclonal antibodies against the human monocyte/macrophage system, termed Ki-M1, Ki-M6, Ki-M7, and Ki-M8, are described with regard to their immunohistochemical tissue distribution pattern and their subcellular reactive sites. The differences found applying these analyses are also reflected by the various molecular weights of the recognized antigens. Based on these data it is proposed that the monocyte/macrophage system can be divided into the phagocytosing compartment on one hand and the immune accessory compartment on the other hand; the latter constitutes the interdigitating reticulum cells, the indeterminate dendritic cells, and the Langerhans cells, as well as the follicular dendritic cells (dendritic reticulum cells) as the accessory cells for T- and B-cell immune response, respectively.

Interdigitating reticulum cells in lymph nodes of Sézary syndrome. Freeze-fracture and ultrathin-section morphology.

Lymph nodes with extensive leukemic infiltration from three patients with the Sézary syndrome were examined in ultrathin sections and in freeze-fracture replicas. Sézary cells (SC) and interdigitating reticulum cells (IDC) were the predominant cell types in the lymph nodes. Both were closely connected with each other by apparently interdigitating cytoplasmic processes. The projections between these cells were, in the main, processes from the IDC. In freeze-fracture replicas these cellular processes did not appear as interdigitations but were more bubble-like, and for this reason these cells are imprecisely described by the term "interdigitating." The SC were seen to possess only short cytoplasmic processes. The frequent polar grouping of cell organelles in SC in the region of the contact zone with IDC and the high organelle content of IDC ('activated IDC') could be the morphologic expression of intense interaction between IDC and SC. IDC displayed three features in freeze-fracture which are not specific to the Sézary syndrome, but should be applicable to IDC in general: (1) they exhibited an approximately equal density of intramembrane particles in both the E-face and the P-face, (2) some of the intramembrane particles in the P-face were assembled in clusters and (3) the surface showed bubble-like formations of the cytoplasmic processes. On the basis of these properties it was possible to distinguish IDC from macrophages and lymphocytes in freeze-fracture replicas.

Reed-Sternberg cells and their cell microenvironment in Hodgkin's disease with reference to macrophage-histiocytes and interdigitating reticulum cells.

Fifty-eight paraffin-embedded lymph node biopsies from patients with Hodgkin's disease (36 nodular sclerosis, 14 mixed cellularity, five lymphocyte depletion, and three lymphocyte predominance) were immunostained with a panel of monoclonal (anti-Leu-M1, antileukocyte common antigen) and polyclonal (to lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and S-100 protein) antibodies by using the avidin-biotin immunoperoxidase technique. Both the immunostaining features of the Reed-Sternberg (R-S) cells and their variants, and the numbers of immunostained accompanying cells morphologically corresponding to macrophage-histiocytes (M-H) and to interdigitating reticulum cells (IRC) were analyzed. Variable numbers of R-S cells and their variants were positive for Leu-M1 in 83% of the cases, for alpha 1-antitrypsin in 40%, for alpha 1-antichymotrypsin in 30%, and for leukocyte common antigen in 3.4%; they were constantly negative for lysozyme and S-100 protein. Whereas the average numbers of accompanying cells immunostained for Leu-M1 were very low, the numbers of S-100-positive IRC were relatively high in all the Hodgkin's subtypes. The average numbers of M-H were lower (P less than 0.1 for lysozyme; P less than 0.001 for alpha 1-antichymotrypsin) in the nodular sclerosis than in the other pooled subtypes. In the nodular sclerosis subtype, however, R-S cells and their variants that stained positive for Leu-M1 appeared to express more frequently the lineage markers of M-H (alpha 1-antitrypsin and/or alpha 1-antichymotrypsin). These data appear to suggest that there is not an apparent qualitative correspondence between the immunostaining features of the cellular microenvironment composed of M-H and IRC and the features of the R-S cells.