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R K Brynes

Publications and source records attributed to R K Brynes.

At least 55 records · Page 3Linked to original sources
PubMed1994

Detection of the Philadelphia chromosome in paraffin-embedded tissue by fluorescence in situ hybridization.

The bcr-abl fusion gene situated on the Philadelphia chromosome is a tumor-specific marker for chronic myelogenous leukemia. We evaluated the usefulness of two color fluorescence in situ hybridization with bcr and abl probes as a means of detecting the Philadelphia chromosome in formalin-fixed, paraffin-embedded sections of spleen and lymph node specimens from eight patients with myeloproliferative diseases showing clinical and morphological features of chronic myelogenous leukemia in accelerated phase. Our analysis showed co-localized hybridization signals corresponding to the bcr-abl fusion product in tissue sections from six patients previously found to have the Philadelphia chromosome by conventional cytogenetics and polymerase chain reaction. The two remaining specimens lacked bcr-abl fusion signals and were obtained from patients who were negative for the Philadelphia chromosome by cytogenetic and polymerase chain reaction analysis. We conclude that fluorescence in situ hybridization is a sensitive method for the detection of the bcr-abl fusion gene in histological specimens from patients with chronic myelogenous leukemia. The technique may become a useful tool in the evaluation of tissue specimens from patients with chronic myelogenous leukemia and related Philadelphia chromosome-positive hematologic malignancies.

Fusion Proteins, bcr-abl↗
PubMed1994

Detection of trisomy 8 by fluorescence in situ hybridization on bone marrow smears from patients with subtle myelodysplastic changes.

Trisomy 8 is the most common hyperdiploid numerical chromosomal abnormality that is found in myelodysplastic syndromes (MDSs). We explored the utility of combining fluorescence in situ hybridization interphase cytogenetics with routine morphologic analysis to characterize cases for which signs and symptoms were suggestive of MDS in which dysplastic changes were insufficient for a definitive diagnosis. Hybridization with a chromosome 8-specific centromeric probe was performed on bone marrow smears that were obtained from four patients with cytogenetically documented trisomy 8 and hematopoietic cell atypia that was suggestive but not diagnostic of MDS. Signals that corresponded to trisomy 8 were detected in 14.6% to 32.2% of the cells (detection threshold of trisomic clone, 5.0%). The conditions of two patients have remained hematologically stable with no disease progression, and these two patients are now considered to have refractory anemia. The conditions of the other two patients rapidly progressed to morphologically recognizable MDSs. This study demonstrates that the detection of trisomy 8 by fluorescence in situ hybridization can provide useful supplemental information in bone marrow specimens with morphologic changes that are suggestive of but not sufficient for a diagnosis of MDS. It should prove to be useful when standard cytogenetic analysis has not been performed or when it is not readily available.

Adult↗
PubMed1993

Terminal acute myelogenous leukemia in a patient with congenital agranulocytosis.

Congenital agranulocytosis terminating in acute myelogenous leukemia has been previously reported in only two cases of adolescent males. We describe the clinical and laboratory features of a 13-year-old male with congenital agranulocytosis, treated with G-CSF with initial good neutrophil response, who subsequently developed acute myeloid leukemia. This rare complication may define a preleukemic subset of patients for whom G-CSF therapy is ineffective. The diagnostic challenges of this case are presented.

Adolescent↗
PubMed1993

Osteitis fibrosa cystica simulating metastatic tumor. An almost-forgotten relationship.

The diagnosis of primary hyperparathyroidism most often results from the incidental finding of hypercalcemia. In two recent cases of osteitis fibrosa cystica (OFC), however, patients without adequate access to health care served as graphic reminders that the clinical spectrum of the disease includes bone disease, and that OFC can be the presenting manifestation of long-standing primary hyperparathyroidism. Both patients complained of bone pain and had widespread osteolytic bone lesions in addition to hypercalcemia on a multitest biochemical panel. The presumptive diagnosis of malignancy with bone involvement (metastatic cancer or multiple myeloma) led to random bone marrow trephine biopsies. Examination of the bone marrow biopsy material revealed the characteristic pathology of OFC, leading to appropriate diagnosis and surgical management of large parathyroid adenomas in both patients.

Adult↗
PubMed1993

Extramedullary myeloid cell tumors. An immunohistochemical and morphologic study of 28 cases.

In an attempt to correlate the morphologic and immunophenotypic findings in extramedullary myeloid cell tumors (EMT), we studied 28 cases with a large panel of antibodies using paraffin section immunohistochemistry. A previous or concurrent diagnosis of acute myelogenous leukemia or chronic myelogenous leukemia was made in 25 cases. Six EMT were morphologically classified as well differentiated (WD-EMT), 17 as poorly differentiated (PD-EMT), and five as blastic EMT. The WD-EMT were easily recognized morphologically and displayed a relatively mature myeloid phenotype, with elastase, CD15, and CD68 positivity in all cases. On the other hand, the five blastic-EMT displayed no morphologic evidence of myeloid derivation, were completely negative for CD15, and were weakly positive for elastase in only one case. The PD-EMT, with a morphologic appearance that resembles large cell non-Hodgkin's lymphoma, variably expressed CD15 and elastase. CD68 and lysozyme were present in the majority of PD-EMT, with some variability, but were negative in most blastic-EMT. CD45 (LCA) was detected in 75% of all EMT and CD34 was positive in 36%; neither antigen was significantly associated with a specific morphology. CD30 reactivity was not evident in any case, but slight positive staining was seen with CD20 (L26) in one WD-EMT. CD43 (Leu 22) was the only antibody that was positive in 100% of cases; staining was always intense and widespread. Antimyeloperoxidase (MPO) was positive in all cases but two, both with a blastic morphology. We conclude that (a) an immunohistochemical panel including CD20, CD43, CD68, and MPO can successfully identify the vast majority (96%) of EMT in paraffin sections, and (b) there is an association between morphology and phenotype in these lesions.

Antigens, Differentiation↗
PubMed1993

Graft versus leukemia effect after transplantation with interleukin-2-activated bone marrow. Correlation with eradication of residual disease.

IL-2 has been used after autologous BMT (ABMT) with the aim of inducing graft versus leukemia (GVL) effect. Our studies in mice have shown that IL-2 therapy induces GVL effect when employed after BMT with bone marrow (BM) that has been activated with IL-2 in vitro (ABM). The present study was carried out to define the time of optimal GVL effect after BMT so that the immunomodulatory approaches could be concentrated at the time of maximum GVL effect. Our data show that GVL effect was induced if IL-2 was instituted immediately after BMT with ABM in mice with acute myeloid leukemia; institution of IL-2 1 week after BMT with ABM did not induce GVL effect. IL-2 therapy instituted immediately or 1 week after BMT with fresh bone marrow (FBM) did not induce any GVL effect. A significant increase in the NK activity was noticed whether IL-2 was instituted immediately or 1 week after BMT, either with FBM or with ABM. To evaluate the ability of IL-2 in the eradication of residual disease from the autograft and the host, BM with variable infiltration with leukemia was activated with IL-2 and used for BMT in leukemic mice. The GVL effect of BM with minimal leukemic infiltration (absence of morphologically demonstrable disease) was comparable to the GVL effect of normal BM. These findings suggest that: (a) maximum GVL effect after BMT with ABM is concentrated in the early post-transplant period possibly because of minimal residual disease during this time; (b) an increase in the NK activity induced by IL-2 therapy may not predict for an improved GVL effect; and (c) for optimum GVL effect, BM with minimal leukemic infiltration should be activated with IL-2 before BMT.

Animals↗
PubMed1992

Monocytoid B-cell lymphomas: an assessment of diagnostic criteria and a perspective on histogenesis.

To determine which morphologic criteria are most useful in distinguishing reactive from malignant monocytoid B cells (MBCs), we compared 16 monoclonal cases (11 nodal, five extranodal) of monocytoid B-cell lymphoma (MBCL) with 12 cases of various reactive diseases in which MBCs were polyclonal. The results of our study showed that in MBCL the MBC component was the predominant architectural finding and that there was confluence of MBCs in all but one case. In contrast, the MBC component did not predominate in the reactive group (P less than .000001) and focal confluence was seen in only one case. A cytologic comparison showed that in MBCL areas there were more large transformed (prominent nucleolated) MBCs (P = .003), a higher mitotic rate (P = .03), and more nuclear irregularities (P = .007) than were present in the reactive group. In addition, evolution to an aggressive histologic type was found in four cases of MBCL. Our results also revealed concomitant multiple, monoclonal, morphologically distinct populations in other compartments (follicular center cells in seven, mantle cells in five, small lymphocytes in five, and plasma cells in 11). These unique findings can be reconciled by postulating (1) that the simultaneous presence of these diverse cytologic types represents morphologic expressions of a B cell whose population is in different phases of its cell cycle and/or its evolution or (2) that the histogenesis of MBCL is possibly from a nodal pluripotent B-stem cell that can differentiate directly into these various cytologic types.

Adult↗
PubMed1992

Lymphokine-activated killer cells in autologous bone marrow transplantation. Evidence against inhibition of engraftment in vivo.

Lymphokine activated killer cells have potent antitumor effect both in vitro and in vivo. They have been reported to suppress bone marrow (BM) progenitor cell activity (PCA) in vitro, thus raising concern about the feasibility of their use after autologous bone marrow transplantation. The present study was carried out to evaluate the effect of LAK cells on BM engraftment in a syngeneic BMT setting in mice. LAK cells supplemented with or without exogenous interleukin-2 therapy did not impair the hematopoietic reconstitution or survival of mice undergoing BMT. LAK cells also did not reduce the PCA of the engrafted BM. LAK cell therapy did not cause graft-versus-host disease. Finally, LAK cells supplemented with IL-2 therapy improved the graft-versus-leukemia effect. These findings suggest that LAK cells plus IL-2 therapy after BMT does not impede hematopoiesis and should be evaluated as an adjuvant therapy with the aim of eradication of minimal residual disease after autologous BMT.

Animals↗
PubMed1992

Interleukin-2 (IL-2) and IL-2-activated bone marrow in transplantation: evaluation from a clinical perspective.

Incubation of bone marrow (BM) with interleukin-2 (IL-2) in vitro results in generation of killer cells providing a tool for enhancing the graft-versus-tumor effect in transplantation. We have evaluated the influence of IL-2 on the progenitor cell activity (PCA), homing pattern of BM and hemopoiesis in a syngeneic bone marrow transplantation (BMT) model in mice. The PCA index and homing pattern of BM activated with IL-2 in vitro for 24 h (ABM) were similar to those of fresh bone marrow (FBM). In vitro culture of BM for more than 1 day resulted in progressive decline in its PCA index; this was not related to the presence or absence of IL-2 in the culture medium. Toxicity of IL-2 was related to the dose and not the time of institution of IL-2 therapy after BMT. Maximum tolerated dose of IL-2 instituted immediately after BMT was 10 times higher than the dose in a non-BMT setting. The pattern of marrow reconstitution following BMT with ABM was comparable to that with FBM. This study shows that BMT with BM activated with IL-2 for 24 h results in normal hemopoiesis, and IL-2 therapy instituted immediately after BMT with ABM does not cause additional toxicity.

Animals↗
PubMed1991

Induction of graft versus leukemia effect in bone marrow transplantation: dosage and time schedule dependency of interleukin 2 therapy.

The present work is a continuation of our studies to improve the graft versus leukemia (GVL) effect in autologous bone marrow transplantation. We have recently shown that the GVL effect of bone marrow transplantation (BMT) with interleukin 2 (IL-2)-activated bone marrow (ABM) followed by IL-2 therapy immediately after BMT is superior to the GVL effect of BMT with fresh, syngeneic bone marrow, with or without IL-2 therapy, in mice with acute myeloid leukemia. The present studies show that institution of IL-2 treatment 1, 2, or 3 weeks after BMT with ABM resulted in shortening of survival and fall in cure rate as compared to IL-2 therapy instituted immediately after BMT with ABM. Increasing the dose of IL-2 did not improve results. However, reducing the frequency of IL-2 administration to once a day instead of twice a day affected the results adversely. Commencing IL-2 therapy 1, 2, or 3 weeks after BMT with fresh, syngeneic bone marrow did not improve the GVL effect as compared to IL-2 therapy started immediately after BMT with fresh, syngeneic bone marrow. Cryopreserved bone marrow was effectively activated with IL-2 and used successfully for BMT after thawing. The animals cured of leukemia by BMT with ABM and and IL-2 therapy were not resistant to leukemia and died when reinfused with leukemic cells. Our findings suggest that for optimum GVL effect, activation of bone marrow is necessary and IL-2 therapy should be started immediately after BMT with ABM.

Acute Disease↗
PubMed1991

Epstein-Barr virus in benign lymph node biopsies from individuals infected with the human immunodeficiency virus is associated with concurrent or subsequent development of non-Hodgkin's lymphoma.

Individuals infected with the human immunodeficiency virus (HIV) have an increased incidence of high-grade B-cell lymphoma. In many instances, these lymphomas contain Epstein-Barr viral (EBV) genomes. To investigate the role of EBV in development of HIV-related lymphoma, benign fixed lymph node biopsies from normal individuals and HIV-infected individuals with persistent generalized lymphadenopathy (PGL) were analyzed for EBV sequences by polymerase chain reaction and in situ DNA hybridization techniques. EBV DNA was not detected in any of 16 benign lymph node biopsies from normal individuals, but could be detected from 13 of 35 PGL biopsies. The EBV-infected cells were present in both follicular and interfollicular areas and in both small and large lymphoid cells. The presence of detectable amounts of EBV DNA in the 13 PGL biopsies was associated with an increased incidence of concurrent lymphoma at another site (n = 3) or development of lymphoma in time (n = 2). In contrast, only 1 of 22 individuals with EBV-negative PGL biopsies developed lymphoma in time (P less than .05). EBV was detected in all five lymphomas in which tissue was available for subsequent analysis, including the lymphoma that developed in the individual without EBV in his previous PGL biopsy. These findings support the hypothesis that EBV plays a role in development of some HIV-related lymphomas. Detectable EBV lymphoproliferations occur in a few PGL biopsies and are associated with a significant risk of EBV DNA-positive non-Hodgkin's lymphoma.

Antigens, Viral↗
PubMed1991

Kaposi's sarcoma in the bone marrow of a patient with AIDS.

The authors report a case of Kaposi's sarcoma (KS) involving the bone marrow of a patient with acquired immune deficiency syndrome (AIDS). The morphologic features, differential diagnosis, immunostaining pattern, and unusually low frequency of marrow involvement by AIDS-related KS are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Hodgkin's disease occurring in monocytoid B-cell clusters.

The authors report three cases of Hodgkin's disease (HD) occurring in monocytoid B-cell (MBC) clusters within lymph nodes, a finding heretofore not published. MBC clusters were found mainly in a perisinusoidal and perifollicular distribution in all three cases. Within some of the MBC clusters of each case, small foci of overt necrosis were evident. Sternberg-Reed cells or their variants were found adjacent to all of these foci, as well as within some MBC clusters that were free of necrosis. These findings suggest that the presence of necrosis within MBC clusters has diagnostic utility. In two cases, evidence of HD was detected only within MBC clusters and nowhere else. In the third case, HD was found primarily within MBC clusters. These observations imply that HD arose within MBC clusters. Minimal involvement of lymph node by HD can occur within MBC clusters and should be recognized as such on the basis of morphologic features. The earlier a diagnosis of HD can be made, the better is the patient's outlook for survival.

Aged↗
PubMed1991

Auer rod-like inclusions in circulating lymphoma cells.

Circulating malignant lymphocytes from a 55-year-old woman with small cleaved follicular center cell lymphoma contained azurophilic splinter-shaped cytoplasmic inclusions. By light microscopic and ultrastructural criteria, these structures closely resembled Auer rods found in acute myeloid leukemia; however, the authors could not find cytochemical evidence of lysosomal origin (results were negative for myeloperoxidase, Sudan black B, acid phosphatase, and periodic acid-Schiff). Immunostaining and flow cytometric analysis confirmed a monoclonal IgM-kappa immunophenotype of the circulating malignant lymphoid cells. The inclusions did not show specific immunoglobulin staining by light microscopic or electron microscopic immunostaining techniques. The authors conclude that these membrane-bound inclusions probably represent aberrant lysosomes in the malignant cells.

Female↗
PubMed1991

Bone marrow examination for the diagnosis of mycobacterial and fungal infections in the acquired immunodeficiency syndrome.

In a series of 342 bone marrow examinations from 314 patients with human immunodeficiency virus infection, 70 examinations (20%) detected opportunistic mycobacterial or fungal infections. One hundred eleven of the 314 patients had such infections, and, hence, 63% (70/111) were detected by bone marrow examination. Special stains for microorganisms detected 16 (32%) of 50 Mycobacterium avium complex infections, 10 (22%) of 45 Mycobacterium tuberculosis infections, eight (73%) of 11 Histoplasma capsulatum infections, and five (83%) of six Cryptococcus neoformans infections. Bone marrow cultures detected 36 (72%) of the 50 M avium complex infections, 13 (29%) of the 45 M tuberculosis infections, and 63% of the fungal infections. Marrow examination revealed infection in only one of the 70 specimens (1%) collected to evaluate thrombocytopenia alone or hematologic malignancy, but in 69 (25%) of 274 with fever, neutropenia, anemia, or miscellaneous other indications for marrow examination. Granulomas were detected in 102 (30%) of the biopsy specimens, including 71 (64%) of those in cases with mycobacterial or fungal infection. The granulomas showed caseous necrosis in nine cases, all in patients with tuberculosis, and the 27 cases with tuberculosis-associated granulomas tended to show large, tightly cohesive granulomas. The presence of granulomas correlated with opportunistic infection in 82 (80%) of 102 cases. Without granulomas, special stains were positive in only eight (3%) of 240 specimens. These results suggest that (1) bone marrow granulomas are a common and valuable histologic clue to opportunistic infection; (2) without them, special stains may not be a cost-efficient way to diagnose such infection; and (3) bone marrow examination can be a useful method of diagnosing opportunistic mycobacterial and fungal infections in patients with fever, anemia or neutropenia, and underlying human immunodeficiency virus infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Bone marrow transplantation with interleukin-2-activated bone marrow followed by interleukin-2 therapy for acute myeloid leukemia in mice.

We have investigated approaches to induce graft-versus-leukemia (GVL) effect in autologous bone marrow transplantation (ABMT) without graft-versus-host disease to improve survival and cure in leukemia. The present study shows that bone marrow transplantation (BMT) using syngeneic bone marrow activated with interleukin-2 (ABM) for 24 hours in vitro, followed by interleukin-2 (IL-2) therapy, was superior to BMT with fresh, syngeneic bone marrow (FBM) in terms of survival and cure in mice with acute myeloid leukemia (P less than .001) and led to normal hematopoietic reconstitution. Addition of IL-2 therapy after BMT with FBM did not improve the results over BMT with FBM alone (P = .98). These results suggest that the GVL effect of ABMT can be enhanced by using ABM for BMT followed by IL-2 therapy without compromising engraftment.

Animals↗
PubMed1990

Detection of specific t(14;18) chromosomal translocations in fixed tissues.

The present study was undertaken to establish the incidence of t(14;18) (q32:q21) chromosomal translocations detectable by a polymerase chain reaction (PCR) assay on fixed lymphoma biopsies. DNA samples from 113 formalin-fixed, paraffin-embedded tissue biopsies (non-Hodgkin's lymphomas, 96 cases; Hodgkin's disease, six cases; reactive, 11 cases) were amplified by the PCR. Of the 96 non-Hodgkin's lymphoma cases, 56 had a follicular pattern and 40 had a diffuse pattern. Polymerase chain reaction-amplifiable t(14;18) chromosomal translocations were detected in 23 of 43 follicular low-grade lymphomas, one of eight follicular intermediate grade lymphomas, one of five follicular high-grade lymphomas, and one of 10 diffuse large-cell lymphomas. The remaining 30 diffuse lymphomas represented the spectrum of the Working Formulation classification. There were six biopsy specimens of Hodgkin's disease and 11 biopsy specimens of follicular hyperplasia; all were negative. The translocation was not detected in 16 biopsies (non-Hodgkin's lymphomas, seven cases; follicular hyperplasia, nine cases) from patients infected with the human immunodeficiency virus. Since this procedure uses the widely available fixed paraffin-embedded material, correlative studies between histology and genetic aberrations can be readily undertaken.

Chromosomes, Human, Pair 14↗