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Biomedical subjects

H Rappaport

Publications and source records attributed to H Rappaport.

At least 91 records · Page 5Linked to original sources

The clinical significance of the morphological subdivision of diffuse "histiocytic" lymphoma: a study of 162 patients treated by the Southwest Oncology Group.

We grouped 162 patients wtih advanced, diffuse histiocytic lymphoma (DHL) into various morphological subtypes to ascertain whether there were any significant differences in survival among them. These patients were staged and treated from 1972 to 1977 according to the protocols of the Southwest Oncology Group. Of the 159 patients on whom a consensus on the diagnosis was reached, 115 were classified morphologically as having large non-cleaved, 26 as B-immunoblastic, 9 as large cleaved, and 6 as T-immunoblastic. The 3 remaining patients did not fit any of these subtypes, but each had a single prominent nucleolus in most tumor cells ("prominent nucleolus" type). Morphological subdivision of DHL did not identify any subgroup of patients with a significantly longer survival, but clinical parameters such as stage, symptoms, and type of treatment significantly influenced survival times.

Adolescent↗

Ultrastructural identification of neoplastic histiocytes--monocytes: an application of a newly developed cytochemical technique.

We applied a newly developed ultrastructural cytochemical technique utilizing 2-naphthyl thiol acetate (NTA) as a substrate in 3 cases of true histiocytic-monocytic malignancy and 3 controls. The enzyme NTA esterase was identified in both neoplastic and benign histiocytes-monocytes in the form of electron-dense material within the cytoplasm. The NTA esterase varied in size and shape and showed no clear relationship with cytoplasmic organelles. The distribution and pattern of staining were very similar to those of the light-microscopically demonstrated alpha-naphthyl acetate esterase reaction. The main advantages of this method are: 1) histiocytes-monocytes can be identified in the absence of lysosomes or phagocytosis; 2) unequivocal, simultaneous documentation of both histiocytic esterase and subcellular structure is possible; and 3) both blood and solid tissue specimens can be utilized. Our findings demonstrate the usefulness and applicability of ultrastructurally demonstrated NTA esterase in the study of histiocytic-monocytic malignancies.

Cell Line↗

Reversal of acute ("malignant") myelosclerosis by allogeneic bone marrow transplantation.

A 28-yr-old woman with acute malignant myelosclerosis received, as primary treatment, ablative chemotherapy and total body radiation therapy followed by bone marrow transplantation from her histocompatible brother. The patient is now well more than 15 mo after bone marrow transplantation, with normal peripheral blood counts, a normal bone marrow, no evidence of graft-versus-host disease, and is on no therapy. In light of the poor results obtained with conventional chemotherapy in this disease, bone marrow transplantation may represent the treatment of choice for patients who have an appropriate donor.

Acute Disease↗

Lymphoblastic lymphoma: a clinicopathologic study of 95 patients.

A retrospective clinicopathologic study of lymphoblastic lymphoma was based on 95 patients from the files of the Repository Center for Lymphoma Clinical Studies. All patients were treated according to different protocols of Cooperative Oncology groups sponsored by the National Cancer Institute. The patients ranged in age from 4 to 84 years, with a median of 30 years. Sixty-eight patients were male and 27 female, with respective median ages of 27 and 50 years. The male-to-female ratio was 2.5:1. Forty patients had mediastinal masses; 30 (75%) of whom were male. The median survival of all patients was 17 months (range 1-100 months). To ascertain the influence of various clinical and morphologic parameters of survival, univariate and multivariate statistical analyses were performed. Patients older than 30 years of age had significantly lower incidences of mediastinal involvement (P = 0.01), number of mitotic figures (P = 0.04), and development of leukemia (P = 0.02) than patients younger than 30. Whereas lymphoblastic lymphoma is generally considered to be a disease of children and young adults, this study indicates that lymphoblastic lymphoma occurs in all age groups. These findings further suggest that lymphoblastic lymphoma may have a different biologic behavior in older patients.

Adolescent↗

Follicular (nodular) lymphoma during the first two decades of life: a clinicopathologic study of 12 patients.

Twelve patients who developed non-Hodgkin's lymphoma with a follicular pattern during the first two decades of life were studied. Eight had the poorly differentiated lymphocytic type; the remaining four had the "histiocytic" type. Eleven of the 12 patients were male. Nine were asymptomatic, and eight had lymphadenopathy in the head and neck region. Comparison of ages revealed the extent of disease tended to be localized (Stages I and II) in the pediatric (less than 16 years old) patients (83%) and generalized in the adolescent-young adult (16-19 years old) patients (83%). Of ten patients treated with chemotherapy and/or radiotherapy, eight achieved complete remissions that lasted 3-58 months (median, 17.5 months). Five are still in remission; three have relapsed. Seven are alive 12-120 months from diagnosis (median, 48 months); six have no clinical evidence of disease. The remaining five patients died two to 164 months after diagnosis (median, 13 months). Three of the four patients who died with lymphoma had diffuse "histiocytic" lymphoma demonstrated at autopsy examination. Poor prognostic factors included 1) failure to achieve a complete remission following initial therapy; 2) extranodal disease (with the exception of the poorly differentiated lymphocytic type involving the spleen and liver); 3) development of diffuse "histiocytic" lymphoma. Follicular lymphoma occurring in the second decade of life has a biologic behavior similar to follicular lymphoma in adults.

Adolescent↗

Chronic monocytic leukemia in adults.

Clinical, hematologic, and histologic material from five patients with chronic monocytic leukemia is analyzed, and the literature is reviewed on 28 patients either reported as having this disease or referenced as such in subsequent publications. Patients with chronic monocytic leukemia have a characteristic clinical course. All have splenomegaly of uncertain etiology, and initial hematologic evaluation usually shows anemia with normal leukocyte and differential counts. One of the authors' patients had slight monocytosis at presentation. In the four patients for whom presplenectomy bone marrow smears were available for review, there was no detectable increase in the number of monocytes. The patients developed monocytosis, usually with accompanying leukocytosis, at intervals ranging from 3.5 to 24 months after splenectomy. In all patients, there was a corresponding increase in the numbers of mature monocytes in the bone marrow. Survival times from the detection of monocytosis ranged from five to eight months. Of the 28 cases reported in the literature, only two were considered by the authors of this study to have the characteristics of chronic monocytic leukemia, and of these, only one had features identical to those reported in the present series. The remainder represent a variety of hematologic disorders including chronic myelomonocytic leukemia, acute leukemia, histiomonocytic proliferations that cannot be sub-classified, and cases in which the data are insufficient for analysis. The differential diagnosis includes chronic myelomonocytic leukemia, chronic malignant histiocytosis, and hairy cell leukemia. In chronic monocytic leukemia, in contrast to hairy cell leukemia, splenectomy does not appear to be beneficial. Although chronic monocytic leukemia is an extremely rare disease, it is a distinct hematologic entity that appears to have a characteristic clinical course.

Adult↗

Malignant lymphoma, intermediate lymphocytic type: a clinicopathologic study of 42 cases.

A clinicopathologic analysis of 42 cases of non-Hodgkin's lymphoma of the intermediate lymphocytic type (ILL) having morphologic features between those of well-differentiated (WDLL) and poorly differentiated lymphocytic lymphoma (PDLL) is presented. In lymph node sections, ILL was characterized by a diffuse proliferation consisting predominantly of small lymphoid cells with slightly irregular or indented nuclei. A mixture of lymphoid cells with entirely round nuclei and lymphoid cells with angulated and cleaved nuclei was also present, but each of these two cell populations did not comprise more than 30% of the total. The median age of the patients was 65 years, and the male-to-female ratio was 5:1. Generalized lymphadenopathy was evident in 74% of the patients, and B symptoms were presented in 36%. Peripheral blood involvement was present at the onset of disease in 21% of the patients, and the bone marrow was involved by lymphoma in 76% of those examined. Five percent of the patients had Stage I disease, 24% had Stage III disease, and 71% had Stage IV disease. Ninety-three percent of the patients received multiagent chemotherapy and 41% achieved a complete remission. The overall median survival was 31 months. Clinical features which appeared to influence survival adversely included the presence of B symptoms (P = 0.007), age greater than 70 years (P = 0.09), an absolute lymphocyte count above 5000/mm3 (P = 0.05), and anemia (P = 0.09). Achievement of a complete remission influenced survival favorably (P = 0.02). Pathologic features which appeared to influence survival included sinus obliteration, which had an adverse effect (P = 0.05), and the presence of residual germinal centers which had a favorable effect (P = 0.06). Patients with 0-5 mitoses/10 high power fields (HPF) had a significantly longer survival than those with more than 20 mitoses/10 HPF (P = 0.02), while those with 6-20 mitoses/10 HPF had an intermediate survival. The clinical and pathological features of patients with ILL suggest that this entity is closely related to PDLL and should be distinguished from WDLL.

Adult↗

An immunocytochemical study of non-Hodgkin's lymphomas.

Lymph node specimens obtained intraoperatively and/or at autopsy from 89 patients with non-Hodgkin's lymphoma were studied immunohistochemically. The peroxidase anti-peroxidase (PAP) technique was used for detecting monoclonal cytoplasmic immunoglobulin (CIg) and for determining the classes and types of immunoglobulins in the tumors. Following rigid criteria, monoclonal CIg was demonstrated in four (16%) of 25 cases of nodular, poorly differentiated lymphocytic lymphoma (NPDL); in three (14%) of 21 cases of diffuse, poorly differentiated lymphocytic lymphoma (DPDL); and in 13 (30%) of 43 cases of diffuse histiocytic lymphoma (DH). Of the four NPDL patients, two had the M kappa, one the A kappa, and one the lambda chain type. Of the three DPDL patients, one had the M kappa, one the G kappa, and one the lambda chain type. Of the 13 DH patients, five had the M kappa, four the A kappa, one the GM kappa, one the A kappa, one the G kappa, and one the kappa chain type. In two DH patients negative for cytoplasmic immunoglobulins, cytoplasmic lysozyme was present, indicating the histiomonocytic nature of the tumor cells. There was no significant difference between the overall survival rates for the DH patients with or without monoclonal CIg. In all three types of lymphoma studied, we encountered many patients (67%) who had tumor cell populations without demonstrable CIg and few patients (11%) with polyclonal CIg. There are several possible reasons why many of the patients were PAP-negative and why some had polyclonal cell populations. The PAP method may be useful in establishing the monoclonal nature of neoplastic lymphoid cell populations.

Antibodies, Monoclonal↗

The relationship between lymphocyte nuclear morphology and cell cycle stage in lymphoid neoplasia.

A significant percentage of lymphoid cells isolated from three lymphoid neoplasms (nodular lymphoma mixed cell type, mycosis fungoides, and Sézary syndrome) had tetraploid or near-tetraploid DNA content, as determined by flow cytometric analysis. In each case, a morphologically distinct population of cells with large, irregular nuclei was present, the percentage of which corresponded to the percentage of tetraploid cells. In a fourth case (diffuse "histiocytic" lymphoma), cells were sorted on the basis of DNA content from the G0-G1 compartment and compared morphologically to cells sorted from the S-G2(M) compartment. The G0-G1 cells has clumped nuclear chromatin, lacked prominent nucleoli, and had a mean nuclear diameter of 10.18 +/- 1.22 micrometer. The sorted cells with S-G2 (M) DNA content had one to several prominent nucleoli and less clumped nuclear chromatin, and they were significantly larger, with a mean nuclear diameter of 13.76 +/- 1.59 micrometer (p less than 0.00001). These preliminary results suggest that, in lymphoid malignancies, certain morphologic characteristics of individual lymphoid cells are related to their DNA content (level of ploidy) and/or the stage of the cell within its division cycle.

Cell Cycle↗

Cor pulmonale in cystic fibrosis.

A VCG and an orthogonal ECG were done on 66 ambulatory patients with cystic fibrosis. Arteriolized pO2, FEV1/VC and MBC were related to electrocardiographic measurements. In this group of adolescent and young adult patients the most helpful electrocardiographic sign of cor pulmonale is a low voltage representing the left ventricle. The four best indicators from the cardiogram are (1) Rx less than .8 mv; (2) Rx/Sx less than 4.0; (3) Tx less than .4 mv; and (4) MLVF + MLVH less than 2.5 mv. If more than one indicator is found cor pulmonale is likely present. Increased voltage over the right ventricle does not identify patients with cor pulmonale.

Adolescent↗

Terminal deoxynucleotidyl transferase activity in neoplastic and nonneoplastic hematopoietic cells.

Terminal deoxynucleotidyl transferase activity was investigated by enzyme assay and (or) an indirect immunofluorescence method with specimens from 151 patients who had a variety of neoplastic and nonneoplastic conditions: leukemia, 62; non-Hodgkin's lymphoma, 36; Hodgkin's disease, seven; lymph nodes without neoplasms, 21; normal peripheral blood, 15; normal bone marrow, ten. Immunologic studies were done on samples from 82 of these patients. Increased terminal deoxynucleotidyl transferase activity was found by both methods in patients who had acute lymphoblastic leukemia and the lymphoid blast crisis of chronic myelocytic leukemia and by the immunofluorescence method in patients who had lymphoblastic lymphoma. A single patient with acute monoblastic leukemia was found by both technics to have increased enzyme activity. Three B-cell proliferations were positive by the enzyme assay; none was positive with the immunofluorescence method. In the remaining 42 B-cell proliferations, the levels of terminal deoxynucleotidyl transferase activity were found to be normal by both the enzyme assay and the immunofluorescence method. Cytoplasmic positivity was observed in as much as 10% of the cells in 13 specimens that were otherwise negative and in eight samples in association with nuclear positivity. A comparison of terminal deoxynucleotidyl transferase activity in microunits/mg protein (enzyme assay) with the percentage of positive cells (immunofluorescence method) yielded a correlation coefficient of 0.62 (P less than 0.01).

Adult↗

Prevention of spontaneous tumors of aged mice by immunopharmacologic manipulation: study of immune antitumor mechanisms.

Effects produced by long-term application of three immune modifiers (azimexon, retinoic acid, and tuftsin) on the depressed immune systems of 18-month-old inbred C57BL/6 female mice were investigated. The effect of each agent was examined on four cell types (cytotoxic T-cells, K-cells, NK cells, and macrophages) possibly involved in antitumor defenses and on the spontaneous tumor development that accompanied advancing age. Three substances chosen for this study appeared able to alter immune parameters, and each one displayed its own pattern of activity. Common to all three agents were an increase of age-depressed tumoricidal activity of peritoneal macrophages and no effect on the depressed NK activity of spleen cells. Retinoic acid increased splenic K-cell activity, already elevated in aged mice and unaffected by the other two agents. Cytotoxic T-cell activity, diminished by age, was stimulated considerably by retinoic acid and by tuftsin but only slightly by azimexon. Histopathologic studies revealed a decrease in the incidence of spontaneous tumors in the 3 treated groups. This decrease was statistically significant in the retinoic acid- and tuftsin-treated groups when compared with the incidence in untreated mice of the same age. Correlation of drug-induced modifications of the immune system with tumor incidence in aged mice was attempted.

Adjuvants, Immunologic↗

Histopathology of the thymus of patients with acute lymphoblastic leukemia and lymphoblastic lymphoma in complete clinical remission.

The histologic features of thymuses from three patients who underwent thymectomy for acute lymphoblastic leukemia or lymphoblastic lymphoma in complete clinical remission are described. The thymuses from all three patients were fibrotic with a variability in the appearance of the lobules. Some of the lobules consisted predominantly of epithelial cells with small numbers of mature appearing lymphocytes, while other lobules were expanded and composed predominantly of cells having morphological features of immature lymphoid cells consistent with residual or recurrent disease.

Cell Transformation, Neoplastic↗