Cells In Malignant Histiocytosis Research Articles

Bisphosphonates significantly increase the activity of doxorubicin or vincristine against canine malignant histiocytosis cells

Canine malignant histiocytosis (MH) is an aggressive neoplasm of macrophages and dendritic cells. It carries a poor prognosis because of the development of widespread metastasis and poor sensitivity to chemotherapy. Thus, there is a large need for new treatments for MH. We hypothesized that bisphosphonates might be useful to increase the effectiveness of cytotoxic chemotherapy against MH. To address this question, we conducted in vitro screening studies using MH cell lines and a panel of 6 chemotherapy and 5 bisphosphonate drugs. The combination of clodronate with vincristine was found to elicit synergistic killing which was associated with a significant increase in cell cycle arrest. Second, zoledronate combined with doxorubicin also significantly increased cell killing. Zoledronate significantly increased the uptake of doxorubicin by MH cells. On the basis of these findings, we conclude that certain bisphosphonate drugs may increase the overall effectiveness of chemotherapy for MH in dogs.

Bone marrow findings in malignant histiocytosis and/or malignant lymphoma with concurrent hemophagocytic syndrome.

We examined bone marrow specimens from 19 patients with malignant histiocytosis (MH) and/or malignant lymphoma (ML) with concurrent hemophagocytic syndrome (HS) who suffered from high fever, hepatosplenomegaly, liver dysfunction, profound cytopenia, and erythrophagocytosis. There was little lymph-node enlargement or no tumor formation. The neoplastic cells in 3 patients exhibited histiocytes/macrophages phenotype with positive reactions for fluoride-sensitive nonspecific esterase, lysozyme and CD68 (KP1). Twelve other patients showed a T-cell (CD3) phenotype, in which 5 patients expressed CD30 (BerH2) as well. B-cell characteristics with CD20 (L26), CIg. nu lambda and gamma kappa were manifest in 2 patients, but indeterminate markers were found in the 2 remaining patients. Eighteen patients showed an infiltration of large neoplastic cells mainly with noncohesive interstitial growth pattern, ranging from 1.7% to 74.2% of the nucleated cells in the bone marrow. A large number of histiocytes/macrophages and dendritic cells was diffusely observed in 15 patients. Severely decreased hematopoiesis in all three series of hematopoietic cells was found in 16 patients. Bone marrow infiltration by the neoplastic cells and numerous reactive cells with erythrophagocytosis appears to be an important factor of profound cytopenia in patients of MH and/or ML with HS. The infiltrating pattern of the neoplastic and reactive cells in the bone marrow of MH and/or ML with HS was different from that of other types of peripheral T-cell ML, B-cell ML in high grade malignancy, and Hodgkin's disease. Cell characteristics and lineage of the neoplastic cells in MH and/or ML with HS are also discussed in this study.

Malignant histiocytosis: A study on clinicopathological features and cell origin

Thirty-one autopsy cases previously diagnosed as malignant histiocytosis (MH) were studied by means of immunohistochemical staining. Antibodies detecting the formalin resistant epitopes on T-cells, B-cells and those of histiocyte/monocyte origin were used. It was shown that the malignant histiocytes reacted only to the cell markers derived from histiocyte/monocyte, and only a part of lymphocytes showed positive reaction to the T and B cell markers. It is suggested that the histiocyte/monocyte lineage is the possible origin of the malignant proliferating cells in MH. The clinicopathological features and the differentiation of MH from familial erythrophagocytic lymphohistiocytosis, virus-associated hemophagocytic syndrome and malignant lymphoma are described. The pathogenesis, the causes of death and the points for attention in the treatment of MH are also discussed.

Malignant histiocytosis presenting as lethal midline granuloma: immunohistological study.

Recent advances in immunology have revealed that the "histiocytic" lymphoma of Rappaport is a proliferation of transformed lymphocytes rather than true histiocytes, and that the malignant cells in malignant histiocytosis (MH) are truly transformed histiocytes. We previously reported cases of MH presenting as lethal midline granuloma (MH-LMG) utilising fresh tissue specimens for the detection of cytological markers in a small number of cases. The results showed the true histiocytic nature of the proliferating cells. In this study, paraffin-embedded specimens from 16 cases with MH-LMG were processed for immunoperoxidase procedures to confirm the true histiocytic nature of the proliferating cells. Five cases with nasal and paranasal lymphomas (ML) were also stained to test the usefulness of immunoperoxidase procedures for distinguishing the MH-LMG from ML. Results were as follows; proliferating cells in MH-LMG were histiocytic in nature, staining positive for lysozyme in MH-LMG in contrast to the negative staining in ML.

Leukemic phase of malignant histiocytosis (arguments in favour of the histiomonocytic origin of the abnormal cells)

A 15-year-old female was treated for malignant histiocytosis. The occurrence of a leukemic phase (178,000 blasts/cu mm) during the follow up provided the opportunity of studying a large number of malignant cells by cytochemical electron microscopic, and cell membrane markers techniques. Acid phosphatase reaction was strongly positive and totally inhibited by tartaric acid. Nonspecific esterase reaction was moderately positive with inhibition by sodium fluorid. Electron microscopy revealed the presence of surface membrane pseudopods and the phagocytic activity of the cells. The leukemic cells had a receptor for the Fc fragment of IgG. These findings support the histiomonocytic origin of the abnormal cells in malignant histiocytosis.