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[The role of lymphocytes and histiocytes as mechanism of action of BCG for bladder cancer].

Antitumor activity of BCG for transitional cell carcinoma of the urinary bladder was evaluated in 103 patients from October, 1983 to October, 1989 at Hirosaki University Hospital. At the same time, the role of various inflammatory cells infiltrating in the bladder wall after intravesical BCG instillation as mechanism of action of BCG was studied. Of 72 patients with superficial bladder cancer, 19 showed a complete response and 28 showed a partial response. The effective rate was 65.3 percent. Significant efficacy was obtained in patients received more than 5 times instillation of BCG. Before intravesical BCG instillation, a small number of lymphocytes or plasma cells infiltrated in the stroma of the tumor. But histiocytes, neutrophils or eosinophils were hardly found. After BCG instillation, the degree of infiltration of each of them tended to increase. The mean degree of infiltration of those inflammatory cells almost all significantly increased in the stroma of the tumor, while only lymphocyte and histiocyte counts significantly increased in both the basal areas of the advancing margin of tumor cells and the tumor free submucosa after BCG instillation. Epithelioid granulomas were recognized almost in the basal areas of the advancing margin of tumor cells and the tumor free submucosa after BCG therapy. Langhans' giant cells were occasionally found within these lesions. In 2 patients marked central necrosis (caseation) was noticed in epithelioid granulomas. In BCG effective cases with superficial bladder cancer lymphocytes and histiocytes increased significantly in all of the stroma of the tumor, the basal areas of the advancing margin of tumor cells and the tumor free submucosa. On the other hand, in BCG noneffective cases they increased significantly only in the stoma of the tumor. Subsets of lymphocytes which increases after intravesical BCG instillation were mainly T pan cells with the predominance of T helper/inducer cells (Th/Ts ratio always > 1).

Administration, Intravesical↗

Bleomycin, adriamycin, cyclophosphamide, vincristine, and prednisone (BACOP) combination chemotherapy in the treatment of advanced diffuse histiocytic lymphoma.

A new combination chemotherapy program for patients with diffuse histiocytic and mixed histiocytic-lymphocytic lymphoma was designed to prevent tumor recurrence during the recovery period of each treatment cycle. A myelosuppressive phase consisting of adriamycin, cyclophosphamide, and vincristine was followed by the nonmyelosuppressive agents bleomycin and prednisone to suppress regrowth of lymphoma while allowing for a return in bone marrow function. Twelve of 25 patients (48%) with advanced, previously untreated, diffuse histiocytic lymphoma achieved a complete remission as determined by restaging 1 month after discontinuation of treatment. The median duration of complete response after completion of therapy is in excess of 1 year (range, 5 to 30 months), and no patient has relapsed. Based on previous experience, it is anticipated that the majority of these patients will achieve an extended disease-free survival for what had previously been regarded as an invariably fatal disease.

Adult↗

Comparison of the response of primary murine peritoneal macrophages and the U937 human histiocytic cell line to challenge with in vitro generated clinically relevant UHMWPE particles.

The response of primary murine macrophages and the U937 human histiocytic cell line to challenge with clinically relevant UHMWPE wear debris of known particle size and dose was evaluated. Particles with mean sizes of 0.24, 0.45, 1.71, 7.62 and 88 microm were co-cultured with cells for 24 hours prior to assessment of cell viability and production of the osteolytic mediators IL-1beta, IL-6, TNFalpha and, in supernatants from murine phagocytes, PGE2 and GM-CSF. All particle fractions were evaluated at particle volume (microm3) to cell number ratios of 10 : 1 and 100 : 1 (and, additionally, 0.1 : 1 and 1 : 1 for U937 cells). These ratios had previously been identified as the most stimulatory and clinically relevant. Although the results for the cell line were highly variable, stimulation with phagocytosable particles (range 0.1 to 15 microm) resulted in enhanced levels of cytokine secretion by both murine macrophages and U937 histiocytes. The most biologically active particles were sub-micrometre in size. However, U937 cells responded to wear debris at much lower particle volume to cell number ratios (>0.1 microm3 per cell) than the murine cells (> 10 microm3 per cell). No GM-CSF was produced by particle or LPS stimulated murine macrophages. Similarly, U937 histiocytes failed to secrete any IL-1beta. Neither macrophage population responded to stimulation with the largest (88 microm) particles. These results confirm earlier findings and suggest that the size of UHMWPE wear particles is a critical factor in macrophage activation. Moreover, primary murine macrophages have been demonstrated to be a suitable model for studying cell-particle interactions in vitro.

Animals↗

[A case of systemic lupus erythematosus with hemophagocytic syndrome and cytophagic histiocytic panniculitis].

A 23-year-old man, admitted because of high fever, polyarthralgia, butterfly rash and chest pain, was diagnosed as systemic lupus erythematosus (SLE) from the findings of positive antinuclear antibody and anti-DNA antibody. He was treated with 60 mg prednisolone daily, but as reducing the dose, white blood cell counts and platelet counts were decreased and fever, polyarthralgia, decrease of complements, increase of ferritin, hepato-splenomegaly and liver dysfunction were observed. Bone marrow specimen revealed phagocytosis of blood cells by histiocytes and he was diagnosed as hemophagocytic syndrome(HPS) due to active SLE. Methylprednisolone pulse therapy was effective temporarily, HPS recurred while reducing steroid, and cyclosporin was added. After a temporary remission, marked extensive swelling in the face appeared suddenly. Facial skin biopsy showed necrosis of fat cells and hemophagocytosis by histiocytes. Accordingly, he was diagnosed as panniculitis due to HPS and was treated successfully with intravenous cyclophosphamide pulse therapy and high dose of gammaglobulin. Several cases of HPS due to SLE have been reported recently, but this is a rare case of cytophagic histiocytic panniculitis (CHP) due to SLE.

Adult↗

Subcutaneous panniculitic T cell lymphoma mimicking histiocytic cytophagic panniculitis in a child.

Subcutaneous panniculitic T-cell lymphoma is a very rare malignancy in the pediatric age group, its association with hemophagocytic syndrome had been described but the association with the skin lesions mimicking histiocytic cytophagic panniculitis which is characteristic of hemophagocytic syndrome has not, to our knowledge, been described in children. We report a child with panniculitic T-cell lymphoma associated with bone marrow hemophagocytosis and subcutaneous histiocytic infiltration with active phagocytosis simulating histiocytic cytophagic. We stress the importance of searching for T-cell lymphoma in patients with panniculitis and hemophagocytic syndrome.

Biopsy, Needle↗

Clinical spectrum of histiocytic tumors of the orbit.

Histiocytic tumors of the orbit comprise an unusual group of lesions characterized by the infiltration of the orbital tissues by xanthomatous cells. Recently, there have been a number of new observations regarding the various histiocytic tumors that can affect the orbit. The condition previously referred to as histiocytosis X is believed to represent a proliferation of Langerhans cells and the term Langerhans cell histiocytosis is often used instead of histiocytosis X. Juvenile xanthogranuloma has been demonstrated to affect the orbit without involving the skin or the iris. The Erdheim-Chester disease is a condition of adults characterized by infiltration of bone, retroperitoneum, heart, lungs and other tissues by xanthoma cells. This condition has recently been recognized to produce a classic ophthalmological picture of bilateral xanthelasmas and bilateral proptosis. The authors review their personal experience with several patients with histiocytic tumors of the orbit and stress the clinical spectrum of these conditions.

Histiocytosis↗

Microcinematographic and electron microscopic study of the death of human tumor cells induced by histiocytic cells.

The cells from a malignant fibrous histiocytoma were enzymatically isolated and cultured in vitro. The cultures were observed by microcinematography and with an electron microscope after fixation and embedding. The interactions between histiocytic and tumor cells resulted in tumor cell death. The microcinematographic study revealed that filiform projections of the histiocytic cell protrude toward the tumor cell surface making contacts for varying periods of time. The tumor cell then contracts and almost simultaneously some granules (lysosomes?) appear in the tumor cell cytoplasm. These granules eventually fuse with each other thus increasing in volume. The resulting granulation heads for the periphery of the tumor cell at a site previously touch by a projection of a histiocytic cell; at this site the membrane bursts and the tumor cell dies leaking amorphous cytoplasmic material. Before bursting the tumor cell does not show any noticeable morphological changes.

Cell Survival↗

Epithelial membrane antigen staining patterns of histiocytic lesions.

Epithelial membrane antigen (EMA) appears to be a marker of activation, proliferation, and/or neoplasia in some epithelial and nonepithelial cells, including histiocytes. We performed immunoperoxidase stains for EMA on a variety of histiocytic lesion specimens, including specimens from two cases of interdigitating reticulum cell lymphoma, 12 cases of histiocytosis X, seven cases of sarcoidosis, five cases of granuloma annulare, 13 juvenile xanthogranulomas, two reticulohistiocytomas, five xanthelasmas, three dermatopathic lymph nodes, and three foreign body reactions. Only the two cases of interdigitating reticulum cell lymphoma and two of the 12 cases of histiocytosis X exhibited significant EMA positivity. These findings may prove useful in the differential diagnosis of histiocytic lesions.

Diagnosis, Differential↗

Histiocytic lymphoma of B cell origin.

A histiocytic lymphoma with a terminal leukemic phase occurred in a 50-year-old man. Immunologic studies indicated that neoplastic cells from the peripheral blood sample, bone marrow aspirate, and lymph node carried surface immunoglobulin. Cytochemical and immunohistochemical analysis of this histiocytic lymphoma and its subsequent leukemic phase displayed a profile consistent with a lymphocytic rather than a histiocytic origin of the neoplastic cell.

B-Lymphocytes↗

Predictive model for prognosis in advanced diffuse histiocytic lymphoma.

The purpose of this study was to examine the validity of a predictive model for response to treatment and survival in advanced diffuse histiocytic lymphoma. One hundred twenty-seven consecutive patients with Ann Arbor stage II-IV diffuse histiocytic lymphoma, who completed treatment between 1974 and 1984 in one of four different Memorial Hospital combination chemotherapy protocols, were reviewed. The median follow-up time was 66.9 months for survivors (range, 21-153.1 months). Factors studied included: age; sex; Ann Arbor stage; prior therapy; B symptoms; serum lactic dehydrogenase (LDH); sites of initial disease; and tumor bulk. LDH was grouped accordingly (units/liter): low, less than 225; medium, 225-500; high, greater than 500. Each patient was assigned an overall level of site involvement (LSI) from the following mutually exclusive groups: group I, peripheral lymph node (PLN) (including +/- Waldeyer ring involvement, +/- spleen); group II, extranodal disease (EN) +/- PLN; group III, retroperitoneal lymph node (RLN) +/- PLN; group IV, bulky mediastinal disease (MED) +/- any other disease; group V, EN with RLN +/- PLN. The Ann Arbor staging system failed to dissect patient groups differing significantly in their prognosis. Serum LDH, LSI, and age were the only factors important for predicting response and survival after multivariate logistic regression and a parametric Weibull survival analysis. Using three levels of serum LDH and correlating them with the different LSI, four tentative "stages" differing significantly in their survival at 48 months were defined: stage I, low LDH, any LSI (80% alive); stage II, medium LDH, PLN, and/or EN (50% alive); stage III, high LDH, PLN, and/or EN or medium LDH, RLN +/- PLN +/- EN, and/or MED (35% alive); stage IV, high LDH, RLN +/- PLN +/- EN, and/or MED (15% alive). Identification of prognostic stages on the basis of LDH level and LSI will allow more accurate comparison of clinical trials for patients with advanced diffuse histiocytic lymphoma.

Adult↗

Frequent immunoglobulin and T-cell receptor gene rearrangements in "histiocytic" neoplasms.

The authors have analyzed the DNA of immunoglobulin and T-cell receptor genes in a series of 6 malignancies which were judged to be of histiocytic derivation on the basis of morphologic criteria. They found that 4 of these cases showed rearrangements of the beta T-cell receptor genes in spite of the lack of any specific immunohistochemical markers for B or T cells. One case showed rearrangements of both heavy and light chain immunoglobulin genes and probably represents either a sinusoidal large cell lymphoma or a B-cell lymphoma with activation of histiocytes simulating malignant histiocytosis. A single case lacked both immunoglobulin and T-cell receptor rearrangements consistent with immunologic analyses that suggested its origin from an interdigitating reticulum cell. The result of this study in conjunction with the authors' previous immunologic observations suggests that many presumed histiocytic malignancies actually represent T-cell lymphomas. Alternatively, beta T-cell receptor rearrangement may be a common feature of tumors that show monocyte/histiocytic differentiation.

Antibodies, Monoclonal↗

Immunohistochemical characterization of histiocytic tumours.

Immunohistochemical labelling of histiocytic tumour cells in formalin-fixed paraffin-embedded material was usefully applied to malignant fibrous histiocytoma (MFH) and to malignant histiocytosis (MH). Not all cases of MFH showed a positive reaction, in contrast with the obligatory positive staining in MH. In general, histiocytic tumour cells stained more intensively with alpha 1-antichymotrypsin than with lysozyme. False positive results can be due to intermingled non-neoplastic histiocytes or degenerating neoplastic cells in any mesenchymal tumour.

Chymotrypsin↗

Sputum cytodiagnosis of disseminated histiocytic lymphoma. A case report.

Cytohistologic evidence of pulmonary involvement with histiocytic lymphoma was discovered in a patient nine years after the original clinical diagnosis was made. The positive sputum cytologic diagnosis confirmed the radiologic impression of pulmonary involvement, which was substantiated by an open lung biopsy. This case report demonstrates the value of periodic sputum cytology in the diagnosis and management of histiocytic lymphoma. Sputum cytology should be utilized more frequently in the monitoring of pulmonary histiocytic lymphoma.

Biopsy↗

[Primary histiocytic lymphoma of the liver. Study of 2 cases and review of the literature].

The authors report two cases of primary histiocytic malignant lymphoma of the liver successfully treated by right hepatectomy. The first case, was free of secondary spread with a follow-up of ten years, although he received no adjuvant therapy. The second patient developed skin, bone and brain metastases, which disappeared after chemotherapy and radiotherapy. He has been free of recurrence for four years. Such primary liver tumors are very rare and are worth knowing because of the efficiency of treatment and of their rather good prognosis. Evolution is different from that observed in histiocytic malignant lymphomas developed in other sites. It is suggested that, in the liver, this tumor might originate and grow from Kupffer's cells. This histologic origin might explain the particular clinical and evolutive features of primary histiocytic malignant lymphomas of the liver.

Adult↗

Nodular histiocytic lymphoma: an aggressive nodular lymphoma with potential for prolonged disease-free survival.

Nodular histiocytic lymphoma (NH) is uncommon, and its natural history is not well defined. Of 473 patients with non-Hodgkin's lymphoma, we found 16 (3.4%) with NH. Most patients (13/16) presented with pathologic stage (PS) III or IV disease, including 7 with liver involvement. One patient (PS III) was initially treated with cyclophosphamide alone, and 4 patients received only radiotherapy, and none were long-term survivors. Eleven patients received combination chemotherapy, and 8 achieved complete remission. Only one of these patients relapsed and died at 19 mo; the other 7 continue in complete remission without maintenance therapy with a minimum followup of 4.5 yr. The survival of the entire group of patients with NH is intermediate between that of the other nodular lymphomas and diffuse histiocytic lymphoma. Nine of 16 patients had either a repeat lymph node biopsy during the course of their disease or lymph node examination at autopsy. Lymph node histology in the majority converted to a diffuse, less differentiated subtype of lymphoma. NH has a natural history similar to that of diffuse histiocytic lymphoma and should be approached with the same therapeutic strategy.

Humans↗

True histiocytic lymphoma.

An 86-year-old man had true histiocytic lymphoma of the skin. Diagnosis was established by the following findings: (1) typical histological features, (2) lack of receptors on tumor cells for immunological surface markers, and (3) active phagocytic function. Electron microscopic studies indicated cytoplasmic multivesicular bodies in the tumor cells. Multivesicular bodies have been reported in histiocytic proliferative disorders and may be of diagnostic value in cases of true histiocytic lymphoma.

Aged↗

Histiocytic lymphoma (reticulum-cell sarcoma) of bone. Current strategy for orthopaedic surgeons.

We retrospectively reviewed the cases of eight patients with histiocytic lymphoma (reticulum-cell sarcoma) appearing as a primary bone lesion. Histological findings were classified according to the criteria of Rappaport. Lesions were staged as suggested by the Ann Arbor Conference. After thorough staging, four of the eight patients were shown to have more extensive disease than was initially thought, which altered the therapeutic approach used. Thorough staging is necessary for improved survival of patients with histiocytic lymphoma of bone. We suggest a diagnostic strategy for patients with histiocytic lymphoma presenting in bone that leads to appropriate therapy.

Adult↗

Morphometric characterization of diffuse large-cell (histiocytic) lymphomas.

From 28 large-cell lymphomas, defined by marker studies, enzyme histochemistry, and electron microscopy as large noncleaved follicle center cell tumors (lnc FCC), B-immunoblastic or true histiocytic lymphomas, morphometric cell parameters, including nuclear size and shape, cytoplasmic area, and cytoplasm-to-nucleus ratio, were measured. Moreover, size, number, and location of nucleoli in the nuclei of the characteristic cells of lnc FCC and B-immunoblastic lymphoma were determined. Statistical evaluation of the data showed the nuclear shape to be the most sensitive parameter in the differentiation of true histiocytic lymphoma from lnc FCC and B-immunoblastic lymphomas. With nucleolar parameters lnc FCC could be differentiated from B-immunoblastic lymphoma: lnc FCC had a higher mean number of nucleoli per cross-section of nucleus and more eccentrically located nucleoli. Moreover, the measurements show that the differences in number and location of nucleoli between large noncleaved follicle center cells and B-immunoblasts are smaller than generally described in the literature. Our results show that it is possible to differentiate by morphometry between lnc FCC, B-immunoblastic, and true histiocytic lymphomas.

Analysis of Variance↗