muramidase and Histiocytosis--Langerhans-Cell

Langerhans cell histiocytosis (LCH) is a neoplastic disorder that results in clonal proliferation of cells with a Langerhans cell (LC) phenotype. The pathogenesis of LCH is still poorly understood. In the present study, serial analysis of gene expression (SAGE) was applied to LCs generated from umbilical cord blood CD34+ progenitor cells to identify LC-specific genes and the expression of these genes in LCH was investigated. Besides the expression of several genes known to be highly expressed in LCs and LCH such as CD1a, LYZ, and CD207, high expression of genes not previously reported to be expressed in LCs, such as GSN, MMP12, CCL17, and CCL22, was also identified. Further analysis of these genes by quantitative RT-PCR revealed high expression of FSCN1 and GSN in all 12 LCH cases analysed; of CD207, MMP12, CCL22, and CD1a in the majority of these cases; and CCL17 in three of the 12 cases. Immunohistochemistry confirmed protein expression in the majority of cases. The expression of MMP12 was most abundant in multi-system LCH, which is the LCH type with the worst prognosis. This suggests that expression of MMP12 may play a role in the progression of LCH. These data reveal new insight into the pathology of LCH and provide new starting points for further investigation of this clonal proliferative disorder.

Topics: Antigens, CD; Antigens, CD1; Biomarkers; Carrier Proteins; Chemokine CCL17; Chemokine CCL22; Chemokines, CC; Gelsolin; Gene Expression; Gene Expression Profiling; Gene Library; Histiocytosis, Langerhans-Cell; Humans; Immunohistochemistry; Immunophenotyping; Langerhans Cells; Lectins, C-Type; Mannose-Binding Lectins; Matrix Metalloproteinase 12; Metalloendopeptidases; Microfilament Proteins; Muramidase; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction

Involvement of the thyroid gland by Langerhans' cell histiocytosis is quite rare. We describe the case of a 58-year-old man referred for treatment of a progressively enlarging goitre. The trachea was severely stenotic and adjacent structures such as the left carotid vein and the thyroid cartilage were also involved. Central diabetes insipidus and severe combined immunodeficiency were associated. Although fine needle aspiration biopsy of the thyroid was initially interpreted as papillary carcinoma, anaplastic thyroid cancer was suspected. Treatment with prednisolone, doxorubicin and irradiation controlled the tracheal compression. A diagnosis of thyroid Langerhans' cell histiocytosis was finally made on the basis of the presence of Birbeck granules and CD1a and CD4 antigen in the thyroid tumour cells. Furthermore, positive staining for CD68 and lysozyme suggested that the tumour cells may have had the character of phagocytic cells in addition to their dendritic cell nature. This is the first case of thyroid involvement by malignant histiocytosis of Langerhans' cell type with unusual phagocytic markers.

Topics: Antigens, CD; Antigens, CD1; Antigens, Differentiation, Myelomonocytic; Biomarkers; Biopsy, Needle; CD4 Antigens; Diagnosis, Differential; Histiocytic Sarcoma; Histiocytosis, Langerhans-Cell; Humans; Male; Microscopy, Electron; Middle Aged; Muramidase; S100 Proteins; Thyroid Gland; Tomography, X-Ray Computed

The clinicopathological and immunohistochemical features of four patients with systemic multicentric reticulohistiocytosis (MR) were compared with five cases of solitary and one case of multiple reticulohistiocytoma (RH), which were confined to the skin only. The MR cases mostly affected the limbs of older women, while RH affected young male adults without preference to site. Characteristically, both entities consisted of oncocytic mononuclear histiocytes (with granular eosinophilic cytoplasm similar to oncocytic thyroid cells) and multinucleated histiocytes with a ground-glass appearance, which appeared to be much larger (> 200 microns) and bizarre in cases of RH compared with cases of MR (50-100 microns). In RH a variable number of vacuolated, spindle-shaped, and xanthomatized mononuclear histiocytes were also present. Immunohistochemical profiles showed positivity of mononuclear histiocytes with HHF35, factor XIIIa, and LN3 (HLA-DR), with a variable number of multinucleated histiocytes in RH showing binding with peanut agglutinin. In mono- and multinucleated histiocytes in both entities macrophage markers KP1 (CD68), KiM1P, HAM56, lysozyme, and alpha 1-antitrypsin were positive. However, macrophage markers MAC387 (L1 antigen) and Leu-M1 (CD15) were negative. Vimentin was universally positive in both conditions, with all other markers (S100, desmin, smooth muscle-specific actin, and QBEnd 10 [CD34]) negative. This study shows that histology supplemented by immunocytochemistry delineates MR from RH and immunohistochemical profiles indicate a cell lineage relationship between RH and adult xanthogranuloma.

Topics: Adolescent; Adult; alpha 1-Antitrypsin; Cell Nucleus; Child; Child, Preschool; Cytoplasm; Female; Granuloma; Histiocytes; Histiocytosis, Langerhans-Cell; Histiocytosis, Non-Langerhans-Cell; HLA-DR Antigens; Humans; Immunophenotyping; Macrophages; Male; Middle Aged; Muramidase; Skin Diseases; Transglutaminases; Vimentin; Xanthomatosis

Topics: Adolescent; Adult; Antigen-Antibody Complex; Biopsy; Diagnosis, Differential; Ferritins; Fever of Unknown Origin; Histiocytic Sarcoma; Histiocytosis, Langerhans-Cell; Humans; Interferons; Iron; Leukocytes, Mononuclear; Liver; Middle Aged; Muramidase; Phagocytes

Immunohistochemically, the presence of lysozyme (LZ) has been detected by the antibody against human LZ in cytoplasm of cells from granulomatous and histiocyte-proliferative skin diseases. To detect LZ in these cells morphologically, I have done electron microscopic observations of the following skin diseases; sarcoidosis, lupus vulgaris, lupus miliaris disseminatus faciei (LMDF), tattoo granuloma, lichen nitidus, foreign body granuloma, granuloma annulare, xanthelasma, xanthoma tuberosum, xanthoma planum, juvenile xanthogranuloma, giant cell tumor of tendon sheath, dermatofibroma, malignant fibrous histiocytoma, dermatofibrosarcoma protuberans, granulation tissue of burn, hypertrophic scar, and histiocytosis X. From both the immunohistochemical and the electron microscopic features it was concluded that a) immunohistochemically LZ-positive cells from lesions of sarcoidosis, lupus vulgaris, LMDF and tattoo granuloma had a number of electron-lucent bodies (ELB) or microvesicles in their cytoplasm, b) lichen nitidus and xanthoma tuberosum had few LZ-positive cells and the ELB were not observed, and c) the other diseases were LZ-negative, and the ELB were also absent. It is suggested that LZ is present in the ELB which are observed electron microscopically.

Topics: Granuloma; Histiocytes; Histiocytic Sarcoma; Histiocytoma, Benign Fibrous; Histiocytosis, Langerhans-Cell; Humans; Immunohistochemistry; Microscopy, Electron; Muramidase; Skin Diseases; Skin Neoplasms

In order to determine the antigenic phenotype of the proliferating cells in Langerhans cell histiocytosis (LCH), we studied 15 such examples by using formalin- and B5-fixed, paraffin-embedded tissues. We used a panel of antibodies that are known to react with lymphocyte- and histiocyte-associated antigens. These included LN-1, LN-2, and LN-3 monoclonal antibodies (MoAbs), MoAbs to leukocyte common antigen (LCA), Leu-M1 antigen, vimentin, and epithelial membrane antigen (EMA), as well as polyclonal antibodies to lysozyme and S100 protein. The antigens encountered most frequently in LCH cells were S100 protein (93% of cases), vimentin (86%), and those detected by LN-2 (80%) and LN-3 (82%). Lysozyme was detected focally in two cases and diffusely in one case. The LCH cells were negative for LN-1, LCA, Leu-M1, and EMA. There was only one specimen in which S100 protein was not demonstrated; in this case, LN-3, vimentin, and T6 on frozen section were positive. The phenotype of LCH cells is similar to that of Langerhans' cells and interdigitating histiocytes. Our results demonstrate the value of using a panel of antibodies, including anti-vimentin MoAb, LN-2, and LN-3 for the immunophenotypic diagnosis of LCH in addition to an antibody to S100 protein.

Topics: Antibodies, Monoclonal; Antigens; Antigens, Differentiation; Antigens, Differentiation, Myelomonocytic; Histiocytosis, Langerhans-Cell; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Langerhans Cells; Leukocyte Common Antigens; Lewis X Antigen; Membrane Glycoproteins; Mucin-1; Muramidase; Phenotype; S100 Proteins; Vimentin

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.

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Biopsy; Bone and Bones; Carcinoembryonic Antigen; Eosinophilic Granuloma; Histiocytoma, Benign Fibrous; Histiocytosis, Langerhans-Cell; Humans; Immunohistochemistry; Lymphatic Diseases; Muramidase; S100 Proteins; Skin; Skin Neoplasms; Xanthogranuloma, Juvenile

Recent evidence suggests that the proliferative cells of idiopathic histiocytosis may be derived from Langerhans cells. In this study, antisera to S-100 protein, HLA-DR (la-like) antigen, muramidase, and alpha 1-antichymotrypsin were tested on formalin-fixed, paraffin-embedded tissue from nine cases of idiopathic histiocytosis using an immunoperoxidase technique. Tumor cells were positive for S-100 protein and HLA-DR antigen but negative for muramidase and alpha 1-antichymotrypsin. Mononuclear phagocytes were positive for HLA-DR antigen, muramidase, and alpha 1-antichymotrypsin but negative for S-100 protein. The immunohistochemical staining pattern of the tumor cells in these cases of idiopathic histiocytosis is similar to that seen for normal Langerhans cells. When these results are coupled with electron microscopic and histochemical data, it would appear that the origin of cells in idiopathic histiocytosis is from the Langerhans cell or its precursor. Thus, this condition might be better designated "Langerhans cell disease."

Topics: alpha 1-Antichymotrypsin; Chymotrypsin; Histiocytosis, Langerhans-Cell; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Langerhans Cells; Mandibular Diseases; Maxillary Diseases; Muramidase; Phagocytes; S100 Proteins; Staining and Labeling

Fourteen cases of disseminated histiocytosis x (HX) from a 15 year period were studied clinicopathologically. Morbidity and mortality were comparable to that of previous reports on disseminated HX. S-100 protein, recently established as a HX marker, was demonstrated immunohistochemically in the cytoplasm and the nuclei of the HX cells of 12 examined cases. Neuron specific enolase (NSE) positive material was found in a minority of the cells of 2 cases. Cytoplasmic lysozyme was present in the mononuclear cells accompanying the HX cells in all examined cases. These results show that immunohistochemical demonstration of S-100 protein and lysozyme can be successfully applied to formalin-fixed, paraffin embedded tissue after storage at room temperature for as long as 15 years. The presence of cytoplasmic NSE positivity in the lesions from 2 patients was surprising and has not previously been observed in HX. This finding suggests an antigenic heterogenicity between cases with the disease of unknown prognostic significance. Nor did the presence of lysozyme in the lesions from patients with acute as well as chronic disease yield any prognostic information.

Topics: Autopsy; Biopsy; Bone Marrow; Carboxylesterase; Carboxylic Ester Hydrolases; Child; Child, Preschool; Female; Histiocytosis, Langerhans-Cell; Histocytochemistry; Humans; Immunoenzyme Techniques; Infant; Lymph Nodes; Male; Muramidase; Retrospective Studies; S100 Proteins; Skin

Topics: alpha 1-Antichymotrypsin; Biopsy; Chymotrypsin; Diagnosis, Differential; Histiocytes; Histiocytosis, Langerhans-Cell; Histocytochemistry; Humans; Immunochemistry; Immunoglobulins; Lymph Nodes; Muramidase; Phagocytosis

The cellular nature of the proliferating histiocytes in 6 cases of histiocytosis X was studied immunohistochemically and ultrastructurally. Immunohistochemically, S-100 protein was detected both in the cytoplasm and the nuclei of histiocytosis X cells as well as Langerhans cells in normal oral epithelium. These cells were always negative for lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin and immunoglobulins. S-100 protein was not detected in lysozyme-positive histiocytes and multinucleated giant cells often showed the signs of phagocytosis. Thus, S-100 protein appears to be a useful immunohistochemical marker for histiocytosis X cells. Ultrastructurally, Birbeck granules noticed in histiocytosis X cells were never seen in the phagocytic histiocytes with numerous lysosomes and phagosomes. These results emphasized the heterogeneous nature of the proliferating histiocytes involved in the lesions. Since histiocytosis X cells share characteristics, not only ultrastructurally but also immunohistochemically, with Langerhans cells, the hypothesis that histiocytosis X may be fundamentally an abnormal proliferation of Langerhans cells has been further supported.

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Cell Division; Chymotrypsin; Histiocytes; Histiocytosis, Langerhans-Cell; Histocytochemistry; Humans; Immunoenzyme Techniques; Immunoglobulins; Muramidase; S100 Proteins

Topics: Adolescent; Antigens, Neoplasm; Cell Adhesion Molecules; Diagnosis, Differential; Female; Glycoproteins; Histiocytosis, Langerhans-Cell; Humans; Immunoenzyme Techniques; Male; Middle Aged; Muramidase; S100 Proteins; Skin Diseases; Xanthomatosis

Topics: Antigens; Antigens, Neoplasm; Cell Adhesion Molecules; Glycoproteins; Histiocytes; Histiocytosis, Langerhans-Cell; Humans; Immunoenzyme Techniques; Lymphatic Diseases; Muramidase; S100 Proteins; Skin; Skin Diseases; Skin Neoplasms; Xanthogranuloma, Juvenile

Eight cases with malignant histiocytosis (MH), two cases with systemic Letterer-Siwe disease, and one case with sarcomatous variant of MH were studied clinicopathologically. Characterization of neoplastic histiocytes was performed by immunohistochemical staining for S100 protein, lysozyme, and nonspecific cross reacting antigen with carcinoembryonic antigen (NCA). The immunohistochemical characteristics of histiocytes were S100+lys-NCA- in eight MH and two Letterer-Siwe disease cases and S100-lys+NCA+ in the sarcomatous variant of MH. MH and Letterer-Siwe disease were considered to have derived from a specific S100+ histiocytic cell lineage (T-zone histiocyte with S100 protein) independent of the monocyte--macrophage system, from which a sarcomatous variant was derived. Leukemic change of MH was discussed with special reference to the maturation and differentiation of T-zone histiocytes.

Topics: Adult; Antigens, Neoplasm; Cell Adhesion Molecules; Child; Child, Preschool; Female; Glycoproteins; Histiocytes; Histiocytosis, Langerhans-Cell; Histocytochemistry; Humans; Infant; Infant, Newborn; Lymphatic Diseases; Male; Middle Aged; Muramidase; S100 Proteins

Histiocytosis X, multicentric reticulohistiocytosis, juvenile xanthogranuloma, the "fibrous" type of dermatofibroma, dermatofibrosarcoma protuberans, and malignant fibrous histiocytoma are all characterized by dermal and/or subcutaneous infiltrates composed at least partially of cells having morphologic features suggestive of histiocytes. Paraffin-embedded tissues representing these conditions were stained for lysozyme (muramidase) with a peroxidase-antiperoxidase technic. The cells of juvenile xanthogranuloma were rich in lysozyme. Some of the cells of histiocytosis X showed a positive pattern, and the cells of the other three conditions were essentially negative. This study confirmed the histiocytic nature of juvenile xanthogranuloma and multicentric reticulohistiocytosis, supported the interpretation that there is a histiocytic component in the lesions of histiocytosis X, and cast some doubt on the alleged histiocytic nature of "fibrous" dermatofibroma, dermatofibrosarcoma protuberans, and malignant fibrous histiocytoma.

Topics: Fibroma; Granuloma; Histiocytes; Histiocytoma, Benign Fibrous; Histiocytosis, Langerhans-Cell; Humans; Immunoenzyme Techniques; Lipoma; Lymphatic Diseases; Muramidase; Skin Diseases; Skin Neoplasms

Topics: alpha 1-Antichymotrypsin; Chymotrypsin; Diagnosis, Differential; Histiocytes; Histiocytoma, Benign Fibrous; Histiocytosis, Langerhans-Cell; Humans; Immunoenzyme Techniques; Lymphatic Diseases; Muramidase

Topics: Brain Neoplasms; Cerebrospinal Fluid; Female; Glioma; Histiocytosis, Langerhans-Cell; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Meningitis; Muramidase; Neoplasm Metastasis

Topics: B-Lymphocytes; Cell Migration Inhibition; Cells, Cultured; Fibroblasts; Histiocytosis, Langerhans-Cell; Humans; Immunologic Deficiency Syndromes; Lectins; Lymphocyte Activation; Lymphocyte Depletion; Macrophage Migration-Inhibitory Factors; Muramidase; Serum Albumin, Bovine; Serum Albumin, Radio-Iodinated; Skin; Skin Tests; T-Lymphocytes