Monomorphous histiocytoma in a child. Report of a case with ultrastructural features suggestive of dendritic cell differentiation

The authors describe a rapidly growing soft tissue tumor of predominantly histiocytic composition in an 8-year-old child. The tumor cells were identified as elements of the mononuclear phagocyte system by histologic, histochemical, immunologic, and electron microscopic study. Despite the presence of a minor fibroblastic component, the tumor did not conform to established criteria for a diagnosis of malignant fibrous histiocytoma. Formation of frequent desmosome-like intercellular junctions raised the possibility of dendritic reticulum cell differentiation, since the latter cells seem to be the only elements of the mononuclear phagocyte system that display such specialized cell junctions. The results of immunostaining were discrepant with those reported for normal dendritic reticulum cells, but the currently available information makes it doubtful that the entire neoplastic spectrum of dendritic cell differentiation can currently be diagnosed in surgical pathology.     

Multiple marker studies on a malignant fibrous histiocytoma with primary cutaneous localization

Continuing controversy exists concerning a possible relation between neoplastic cells of malignant fibrous histiocytoma (MFH) and the mononuclear phagocyte system. The aim of this study was to investigate the membrane and cytoenzymatic phenotype of a primary cutaneous MFH, storiform pleomorphic type, and to compare these data with ultrastructural observations. Cytoplasmic proteins (acid phosphatase, non specific esterase, alpha-1 antitrypsin, and lysozyme) suggestive of a mononuclear phagocyte origin were demonstrated in varying amounts in neoplastic cells infiltrating the dermis. Consistent with these data, two (LeuM3 and OKM5) out of four (OKM1 and LeuM1) monoclonal antibodies directed against mononuclear phagocyte antigens stained most of the neoplastic cells. Class II MCH antigens (DR and DQ) were variably expressed on distinct groups of neoplastic cells, suggesting different activation/differentiation states. The results favor the view that the present case of primary cutaneous MFH was of mononuclear phagocyte origin. However, the observed phenotypic profile was expressed on neoplastic cells irrespective of their ultrastructural morphology (histiocytic or fibroblastic). Together with previous data in the literature, the latter finding corroborates the view that distinction between these two cell types in MFH is likely to reflect divergent growth and differentiation patterns rather than histogenesis.     

In situ immunologic characterization of cutaneous involvement in Hodgkin's disease

The current study assesses in situ the antigenic phenotype of cutaneous infiltrate in two cases of Hodgkin's disease affecting the skin. Immunostaining utilized monoclonal antibodies for T-lymphocyte and B-lymphocyte and mononuclear phagocyte markers. The same immunophenotypic pattern of cutaneous infiltrate was observed in both cases, despite a different histopathologic subtype (mixed cellularity in case one, nodular sclerosis in case two). The majority of infiltrating cells expressed T-lymphocyte markers, with a predominance of CD8+ phenotype. Few cells bore B-lymphocyte markers or had DRC-1+ phenotype. No CD1a+ dendritic cell was found in the dermal infiltrate. Variable numbers of cells reacted with mononuclear phagocyte markers. The authors believe that the antigenic phenotype of cutaneous Hodgkin's disease has not previously been reported. The immunophenotypic pattern of skin infiltrate is different from that described in lymphoid tissues. Such findings could be related to the previous therapy or to the possible influence of skin microenvironment.     

Promotion of tumor growth in vivo by antimacrophage agents.

Various attempts were made to assess the role of the mononuclear phagocyte system in tumor resistance of rats in vivo. The growth of sc inoculated, weakly immunogenic, carcinogen-induced, syngeneic tumor cells was modestly reduced by ip injection and, more impressively, by local injection of peptone-induced, activated, nonimmune macrophages. A single iv injection of silica particles or carrageenan on the day of sc tumor cell inoculation greatly enhanced tumor growth. When these agents had been given a few days before or after tumor cell inoculation, the tumor-promoting efficiency was distintly diminished or even cancelled. The enhancing effects of silica and carrageenan on tumor growth were nulified by the macrophage-stabilizing agent, poly-2-vinylpyridine N-oxide, To assess the in vivo consequences of silica administration, various cellular, biochemical, and functional macrophage parameters were determined at different intervals. Results indicated the complexity of events elicited after the mononuclear phagoycte system was damaged, which made the interpretation of such results difficult.     

Immunohistochemical assessment of splenic lymphocyte and macrophage subpopulations in patients with gastric cancer

In order to assess the effects of malignant tumors on the immune system, 25 spleens from patients with gastric carcinoma were studied by in situ immunohistochemical methods for lymphocyte subsets and cells of the mononuclear phagocyte system. Highly significant reductions of CD4+ T cells (P less than 0.001), Ki M2+ and Ki M-3+ MPS cells (P less than 0.02 and P less than 0.05), and a stage-dependent reduction of Ki 67+ B cell proliferation activity (P less than 0.05) were seen in spleens of patients with gastric cancer. These results, which were obtained by morphologic methods in a noninvolved lymphatic organ, reflect the systemic immunosuppressive and immunodepleting effects of malignant tumors that are probably mediated by tumor-associated cytokines.     

Epidermal Langerhans' cell densities influence survival in mycosis fungoides and Sézary syndrome

Because Langerhans' cells (LC) (CD1a-positive epidermal cells) have been discussed to be involved in the pathogenesis of mycosis fungoides and Sézary syndrome, the authors examined the influence of densities of Langerhans' cells and, concurrently, of other phenotypes retrospectively on survival of 35 patients. Cell densities were assessed on cryostat sections (alkaline phosphatase antialkaline phosphatase-technique) of the respective diagnostic biopsy specimens. Additionally, two clinical parameters (age, stage of disease) were evaluated. CD1a-positive epidermal cells were demonstrated to be the only cell population being significantly associated (P = 0.011) with survival. Death resulting from mycosis fungoides and Sézary syndrome was significantly (P = 0.003) less frequent in patients with epidermal CD1a-positive cell densities higher than 90 cells/mm2 (optimal break point) as compared with patients with lower numbers. These results suggest that Langerhans' cells have a significant impact on prognosis of patients with mycosis fungoides and Sézary syndrome. They play an important role in the host defense mechanisms against these lymphomas rather than to favor their progression as proposed recently.     

Langerhans' cells and macrophages in eosinophilic granuloma. An enzyme-histochemical, enzyme-cytochemical, and ultrastructural study

Biopsy material of six patients with eosinophilic granuloma (EG) was investigated by electron microscopic and enzyme-histochemical methods for acid phosphatase (AcP), leucyl-beta-naphthylamidase (LA), adenosine triphosphatase, and alpha-naphthyl-acetate esterase (NE). Paraplast sections were used for demonstration of lysozyme with an immunoperoxidase method. Results of staining for these different enzymes suggested the existence of two separate sets of histiocytic cells: one type with "dot-like" AcP staining and negative for NE and lysozyme; and the other with diffuse AcP staining, positive for NE and lysozyme, and often showing signs of phagocytosis. The first type presumably represented Langerhans' cells and also often showed positive staining for LA. Macrophages were generally negative for LA. Electron microscopic study confirmed the impression gained from enzyme-histochemical studies. No intermediate cell types between Langerhans' cells and genuine macrophages were seen. From these results it is concluded that in EG no transformation exists between Langerhans' cells and macrophages. The latter are presumably of reactive nature.     

Langerhans' cell histiocytosis with thyroid involvement masquerading as thyroid carcinoma

A 28-year-old woman was admitted to our Hospital with a chief complaint of progressive gingival swelling and loosening of teeth over about a year. According to past history, she had received total thyroidectomy 2 years previously due to thyromegaly. The thyroidectomy specimen was at first interpreted as 'poorly differentiated carcinoma of the thyroid'. One year ago, she began to be aware of gingival swelling and loosening of teeth. A gum biopsy was taken and the pathologic features were similar to her 'thyroid carcinoma'. Subsequent investigations, including immunohistochemical stain, showed the gum was heavily infiltrated with histiocyte-like Langerhans' cells which were positive for S-100 protein. Ultrastructural examination of the cells under electron microscope revealed many typical intra-cytoplasmic Birbeck granules. Langerhans' cell histiocytosis was diagnosed. Langerhans' cell histiocytosis with thyroid involvement is extremely rare and may run a relatively indolent course. Even on a retrospective examination, it may easily be confused with poorly differentiated carcinoma of the thyroid. We suspect that this error may have been made on other occasions and that the occurrence of this condition may be underreported.      

Cytochemical and immunocytochemical characterization of Yoshida ascites sarcoma cells

Some cytochemical and immunocytochemical investigations were carried out on actively growing Yoshida ascites sarcoma cells. These cells displayed an intense granular alpha-naphthylacetate esterase (ANAE) staining while the alpha-naphthylbutyrate esterase (ANBE) reaction was in part fluoride-sensitive and marked particularly in the large-size malignant cells. Acid phosphatase as well as peroxidase activities were not detected. The lack of immunoreactive lysozyme and alpha 1-antitrypsin suggested a poor differentiation of the above-mentioned tumor cells, but fibronectin and S-100 protein where highly expressed, as in tumors arising from the mononuclear phagocyte system.     

“sternberg-reed” giant cells of hodgkin's disease: Cultivation in vitro,heterotransplantation, and characterization as neoplastic macrophages

Cells from the involved spleens of 25 patients with Hodgkin's disease have been grown in long-term culture and compared with normal spleen macro-phage cultures from control cases. The Hodgkin's spleen cell culture contained mono-, bi-, and multinucleate giant cells, many closely resembling Sternberg-Reed cells, which were adherent, phagocytically active and neoplastic by the dual criteria of aneuploidy and heterotransplantability. Lysozyme secretion was consistently observed in all Hodgkin's cultures tested. The giant cells possessed both Fc and complement (C_3b) receptors, and lacked lymphocyte markers such as C_3d receptors, surface IgM, and the capacity to form E-rosettes. Binucleate and multinucleate cells, as well as mononuclears, were capable of active DNA synthesis, and binuclear mitotic figures were observed. It is concluded that these cells are the in vitro descendants of the Sternberg-Reed and Hodgkin neoplastic cell population, and that they are derived from macrophages or closely related cells of the mononuclear phagocyte system.     

YAC-Lymphoma bearing induces functional changes in bone marrow derived mononuclear phagocytes

Bone marrow derived mononuclear phagocytes (BMDMP) differentiated in vitro from bone marrows of YAC-lymphoma bearing mice and Corynebacterium parvum (CP)-inflamed mice shown to differ in several functional parameters from those derived from bone marrows of control mice. The former 2 BMDMP populations expressed: (a) an increased level of acid phosphatase activity; (b) an increased degree of zymosan-induced chemiluminescence reaction; (c) a lower sensitivity of the proliferative capacity to prostaglandin E2 (PGE2), as compared to the BMDMP population from normal mice. These data suggest that YAC-lymphoma bearing in A/J mice induces similarly to inflammatory stimuli changes in the functional capacity of bone marrow mononuclear phagocyte precursor cells.     

Allogeneic bone marrow transplantation for Langerhans' cell histiocytosis

A group of proliferative diseases of the epidermal Langerhans' cells are commonly referred to as Langerhans' cell histiocytosis (LCH). A small number of the patients with this disease face an unfavorable disease course despite chemotherapy and radiation therapy. In LCH patients with a poor prognosis, allogeneic bone marrow transplantation (BMT) could be the appropriate treatment with proven antiproliferative effects and may be able to repopulate the recipient with stem cell-derived Langerhans' cells from the donor or correct the presumed underlying immunodeficiency. An LCH was diagnosed in a 15-year-old boy with multiple osteolytic lesions, anemia, and diabetes insipidus centralis. Repeated flare-ups of the disease had necessitated several courses of conventional chemotherapy including cyclophosphamide (CY), prednisolone (P), 6-mercaptopurine (6-MP), vincristine (VCR), and additional local irradiation without stable remission. Three years after first being diagnosed with LCH the patient underwent high-dose chemotherapy-radiation therapy followed by allogeneic BMT from his human lymphocyte antigen (HLA)-identical brother. Currently, he is alive and well and has been disease-free for more than 41 months after BMT.     

Malignant histiocytosis X. Report of a rapidly fatal case in an elderly man

A 71-year-old white man developed an increasing number of 1-to-10 mm, erythematous nodules, many with central ulceration, most prominent on the head and trunk. Biopsy of a nodule showed infiltration of the dermis and epidermis by large cells with multilobulated nuclei and numerous mitoses. Electron microscopy showed that most tumor cells contained Langerhans' cell granules. Immunohistochemical studies demonstrated a pattern of antigen expression similar to that of Langerhans' cells including Ia and Leu-6 (T6) antigens. Chest x-ray showed diffuse pulmonary infiltration and similar tumor cells were present in the sputum and urine. He developed increasing dyspnea and jaundice despite chemotherapy, and died 6 months after the onset of the disease. Autopsy showed massive tumor infiltration of the lungs, liver, spleen, and lymph nodes, and focal involvement of the myocardium, skin and bladder. Clinical and cytologic features indicated this case to be a rare example of highly malignant histiocytosis X in an elderly man.     

Synchronous bilateral carcinoma of the breasts occurring in a young woman with a history of Langerhans' cell histiocytosis in infancy

We report the case history of a 28-year-old woman who developed synchronous bilateral carcinoma of the breasts, having been diagnosed with multisystem Langerhans' cell histiocytosis in infancy. She had been treated with vinblastine and corticosteroids for 3 years and made a full recovery without late sequelae. We review the association of Langerhans' cell histiocytosis and its treatment with subsequent malignancy, with particular reference to carcinoma of the breast, and discuss the possible causes.     

Calprotectin expression and mononuclear phagocyte subpopulations in peripheral blood and bronchoalveolar lavage

BACKGROUND AND AIM OF THE WORK: The phenotype of human alveolar macrophages (AM) can be affected by the process of maturation/differentiation and by multiple factors from the local environment. The aim of our study was to assess the expression of selected phenotypic markers characteristic for subsets of mononuclear phagocytes in bronchoalveolar lavage fluid (BAL) and peripheral blood with special attention to calprotectin (27E10), a marker of acute inflammatory macrophages. METHODS: The expression of calprotectin and 13 other phenotypic markers was evaluated by an immunoperoxidase slide assay and computer image analysis. RESULTS: We consider calprotectin (27E10 antigen) to be a marker of freshly recruited, monocyte-like, mononuclear phagocytes, being expressed in 84 +/- 13% PBM and only 10 +/- 11% of AM, p < 0.001. Computer image analysis confirmed that calprotectin-positive mononuclear cells in peripheral blood and BAL are morphologically very similar in contrast to the much larger calprotectin-negative AM. On the other hand, 25F9 antigen, the transferrin receptor (CD71), KiM8 (CD68), RFD1 (marker of dendritic cells), RFD7 (marker of mature macrophages), RFD9 (marker of epithelioid cells and macrophages of germinal centers), and RM3/1 (macrophages of late phase inflammation) were restricted preferentially to mature AM. CONCLUSIONS: Our study demonstrates phenotypic differences between mononuclear phagocytes derived from BAL and their peripheral blood precursors, and indicates markers useful for assessing the stages of maturation/differentiation of these cells. The percentage of calprotectin (27E10) positive AM might represent a parameter for assessing mononuclear phagocyte influx from peripheral blood to the lung in the very early stage of inflammatory reactions.     

The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology

The origin and nature of osteoclast-like multinucleated giant cells (OMGCs), in extraskeletal neoplasms, is uncertain. The ultrastructure, antigenic phenotype and function of OMGCsm in a breast carcinoma were studied in order to clarify the relationship between OMGCs, osteoclasts and other cells of the mononuclear phagocyte system (MPS). OMGCs resorbed cortical bone in a manner similar to osteoclasts. However, unlike osteoclasts, OMGCs did not possess a ruffled border or clear zone, and expressed HLA-DR and Fc receptors and CD14, CD16, CD18 and CD11 (p150,95) antigens. In addition, OMGCs failed to respond morphologically to calcitonin and were directly stimulated by parathyroid hormone (PTH) to increase bone resorption. These findings suggest that OMGCs are a specific type of macrophage polykaryon distinct from both osteoclasts and other types of inflammatory polykaryon. Occasional smaller (20-25 microns) macrophage-like cells were also associated with resorption pits. Bone resorption by OMGCs isolated from the breast indicates that a cell of the MPS can be transplanted to a new tissue location and perform a highly specialised function appropriate to an MPS cell of that tissue (i.e. the osteoclast). PTH stimulation of bone resorption by OMGCs suggests that PTH or a PTH-like protein, may be involved in the bone resorption and consequent hypercalcaemia associated with metastatic breast cancer.     

DEL cell line: a "malignant histiocytosis" CD30+ t(5;6)(q35;p21) cell line

A new cell line DEL, established in vitro, was isolated from a pleural effusion of a boy who died of malignant histiocytosis. Its principal characteristics are: strong positivity with monoclonal antibodies (MAbs) to CD25, CD30, CD45R, KiM7, EMA, HLA Cl I and II; constant presence of acid phosphatase, ANAE, alpha-anti-trypsin, alpha-anti-chymotrypsin and NBT reductase activity; rearrangement of the immunoglobulin heavy-chain gene (JH) and a germ-line configuration of the T-chain gene; and finally a translocation between chromosomes 5-6 with a breakpoint in 5q35. The DEL cell line is appropriate for studying the role of the 5q localized c-fms oncogene and of the genes of the mononuclear phagocyte growth factor (CSFI) and of their receptors in the dynamics and etiology of malignant hemopathies associated with a 5q35 breakpoint.     

Tartrate-resistant acid phosphatase as a differentiation marker for the human mononuclear phagocyte system

Human blood monocytes (BM) were stimulated with various immune modulators in short-term cultures. Tartrate-resistant acid phosphatase (TAcP) activity was demonstrated with an enzyme cytochemical method. Other members of the mononuclear phagocyte system (MPS), such as peritoneal (PM) and alveolar macrophages (AM), were also tested. Unstimulated BM and physiologic functional forms of macrophages, with the exception of AM, were invariably TAcP negative. On appropriate stimulation, particularly with media containing lymphokines, cultured BM became TAcP positive. The results suggest that TAcP is an inducible differentiation marker that indicates transformation of monocytes into cells belonging to a distinct subset of the MPS.     

Immunohistochemical evaluation of squamous cell carcinoma antigen and S-100 protein-positive cells in human malignant esophageal tissues

Localization and intensity of squamous cell carcinoma-related antigen (SCC-Ag) and infiltration of Langerhans' cells (LC) were investigated immunohistochemically, using anti-SCC-Ag and anti-S-100 protein antisera, respectively, in 36 cases of squamous cell carcinoma of the human esophagus. The SCC-Ag was an indicator of histologic differentiation of squamous cell carcinoma but not of malignant potential. The population density of LC correlated well with the histologic stage, vessel invasion, and postoperative survival time. In patients with a marked infiltration of LC, survival time was longer than for those in whom the infiltration was slight (P less than 0.05). The density of the LC can serve an indicator of defense of the host against the carcinoma. There was no correlation between SCC-Ag and S-100 protein-positive cells.