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R S Neiman

Publications and source records attributed to R S Neiman.

At least 19 recordsLinked to original sources
PubMed1995

Splenic marginal zone cell lymphoma: report of an indolent variant without massive splenomegaly presumably representing an early phase of the disease.

Splenic marginal zone (MRZ) cell lymphoma is a recently described neoplasm arising in a unique compartment of splenic white pulp, producing massive splenomegaly and spreading to bone marrow and distant lymph nodes. We report three cases of splenic lymphoma that morphologically and immunohistochemically appear to originate from MRZ cells that presented as indolent neoplasms involving the spleen but with no or only moderate enlargement of the organ, presumably representing an early clinical stage of this disorder. Despite the evidence of involvement of the liver in one case, lymph nodes and bone marrow proved to be uninvolved. Histologically, the three spleens showed similar features, being characterized by the involvement of white pulp follicles and periarteriolar lymphoid sheaths by medium-sized lymphoid cells with slightly irregular nuclei and ample cytoplasm. Immunohistochemically, all the specimens expressed a series of B-lineage markers that, in contrast to specimens of monocytoid B cell lymphoma (MBCL) and hairy cell leukemia (HCL) studied for comparison, did not react with KiB3, LN1, and DBA.44 monoclonal antibodies.

Aged↗
PubMed1995

In vivo effects of recombinant human stem cell factor treatment. A morphologic and immunohistochemical study of bone marrow biopsies.

Bone marrow (BM) aspirate and biopsy specimens from seven female patients with advanced or metastatic breast cancer and preserved marrow function treated on a phase I trial of recombinant methionyl human stem cell factor (r-metHuSCF; SCF) were evaluated by immunohistochemical staining before and after treatment with SCF. Doses of SCF included 10 g/kg/day in 2 patients, 25 micrograms/kg/day in 2 patients, and 50 micrograms/kg/day in 3 patients administered as subcutaneous bolus injections for 14 days. Following treatment, bone marrow cellularity increased up to 1.6-fold (P = NS), with an increased frequency of promyelocytes (P < .002), but an unchanged relative frequency of other marrow hematopoietic cells. The mean relative frequency of BM CD34+ progenitor cells increased from 0.9% to 1.8% (P < .001). The mean proportion of BM cells stained by Ki-67/MIB 1 and PCNA/PC10, monoclonal antibodies (MoAb) recognizing proliferation-associated nuclear proteins, increased from 18.6% to 35.4% (P < .003) and from 32.4% to 49.4% (P < .01), respectively. Most of the Ki-67 and PCNA positive cells were represented by promyelocytes, proerythroblasts, and myeloblasts. SCF therapy was not associated with marrow fibrosis or increases in the number of macrophages. Peripheral white blood cell counts increased 1.3- to 3.6-fold following SCF. The mean absolute neutrophil counts increased from 3.9 x 10(9)/L (range 2.6-5.3) to 7.2 x 10(9)/L (range 4.7-12.3), and reticulocyte counts increased by a mean of 1.5 fold (range 1.2-fold to 2.0-fold). No consistent difference in platelet counts was seen. These results suggest that SCF given in vivo is effective in increasing the frequency of CD34+ BM progenitor cells, and has the capacity to increase the proliferation and differentiation rate of hematopoietic precursor cells. These effects indicate that SCF may represent a cytokine capable of affecting multiple hematopoietic lineages.

Adult↗
PubMed1995

Correlation between presence of clonal rearrangements of immunoglobulin heavy chain genes and B-cell antigen expression in Hodgkin's disease.

Southern blot analysis of Hodgkin's disease (HD), although often compromised by the small number of abnormal cells present in the tissue, have tended to favor a B-cell derivation of the Hodgkin's and Reed-Sternberg (HRS) cells in cases of nodular sclerosis (NS) and mixed cellularity (MC) Hodgkin's disease. Eighteen frozen and 29 paraffin-embedded sections of lymph node specimens from 29 patients with pretreatment HD (22 NSHD and 7 MCHD) were studied by molecular analysis and immunohistochemistry to determine the phenotype of HRS cells. All cases were reviewed and showed typical morphology and CD45-, CD30+, CD15+, BLA.36+ HRS cells. In 11 of 29 (38%) cases, HRS cells were reactive with at least one B-cell marker (CD20, CD79a, MB2), 7 of 29 (24%) cases showed reactivity with the T-cell marker CD3, and 11 of 29 (38%) cases displayed a "null" phenotype. By using a polymerase chain reaction (PCR) and consensus primers for the V and J regions of the immunoglobulin heavy chain (IgH) gene, the authors were able to detect B-cell clonality in 9 of 18 (50%) frozen samples of HD analyzed. IgH gene rearrangement was present in 8 of 15 (53%) NSHD and in 1 of 3 (33%) MCHD. In five of nine (56%) of these cases, HRS cells were reactive with at least one B-cell marker, whereas one case expressed the T-cell marker CD3. The other three cases with IgH gene rearrangement showed a "null" immunophenotype. IgH gene analysis was negative in all remaining CD3+ cases and in two other cases that expressed B-cell markers by immunohistology. Southern blotting failed to detect rearrangement of the T-cell receptor beta-chain gene and immunoglobulin heavy and light genes in any of these cases. The results show that PCR represents a specific and sensitive technique for the detection of IgH gene rearrangements in cases of Hodgkin's disease. The results also suggest a lymphoid B-cell derivation of HRS cells in a high proportion of the cases.

Antigens, Neoplasm↗
PubMed1994

Benign hematologic neoplasm associated with mediastinal mature teratoma in a patient with Klinefelter's syndrome: a case report.

An 18-year-old male with Klinefelter's syndrome presented with a mature teratoma of the mediastinum. He was treated with debulking surgery and brief cisplatin-based chemotherapy. Ten years later, he presented with paraplegia and was found to have an isolated epidural mass. The mass was composed of mature histiocytoid cells reminiscent of those seen in malignant histiocytosis. There was no evidence of medullary dissemination and there was no evidence of recurrence of the germ cell tumor. He received local radiation therapy and a single course of leukemic induction. He remains well 4 years later. This case represents a localized variant of the diffuse histiocytic malignancies associated with malignant mediastinal germ cell tumors.

Adolescent↗
PubMed1994

CD34 immunostaining of bone marrow biopsy specimens is a reliable way to classify the phases of chronic myeloid leukemia.

Flow cytometry studies have shown that high expression of CD34 antigen in patients with chronic myeloid leukemia (CML) is indicative of accelerated or blastic phases. It has also been suggested that similar information can be obtained by CD34 immunostaining of bone marrow biopsy specimens. To test this hypothesis, the authors studied 59 conventionally fixed, paraffin-embedded bone marrow trephine biopsy specimens, representing the three phases of the disease (stable, accelerated, and blast crisis). Immunohistochemical staining for CD34 was performed using QBEnd10, a monoclonal antibody reactive in routine paraffin-embedded tissue. The differences in CD34 positivity among chronic, accelerated, and blastic phases of CML were highly significant (P = .0001). This study demonstrated that CD34 immunohistochemical staining of bone marrow biopsy specimens represents a reliable method for classifying patients with CML and may provide essential diagnostic and prognostic information when a marrow aspirate is unavailable.

Antigens, CD↗
PubMed1994

Terminal deoxynucleotidyl transferase staining in acute leukemia and normal bone marrow in routinely processed paraffin sections.

Terminal deoxynucleotidyl transferase (TdT) is a nuclear protein widely used as a marker for the diagnosis and classification of acute leukemia. The usual methods for detecting TdT require smears, imprints, or cryostat sections of unfixed tissue. A polyclonal rabbit anti-TdT serum was used to immunostain 54 routinely processed bone marrow sections from patients with acute leukemic disorders, using a recently described antigen-unmasking technique based on microwave oven heating. The specificity of this method of TdT analysis was confirmed by comparing the results obtained with conventional TdT analysis by indirect immunofluorescence. Terminal deoxynucleotidyl transferase reactivity was also evaluated in 44 nonmalignant and normal bone marrow specimens. All cases that were TdT-positive by immunofluorescence (41 of 42 "pre-B" and T-cell acute lymphoblastic leukemia, 2 of 5 acute myeloid leukemia, and 1 of 5 chronic myeloid leukemia in blast crisis) were also positive in paraffin sections. The percentage fluorescence positivity correlated with the percentage of immunoperoxidase stained cells in 44 of 45 cases. The remaining nonneoplastic and normal bone marrow biopsy specimens were TdT-negative. These results show that TdT immunoperoxidase staining of conventionally processed bone marrow specimens can be readily achieved by the use of a simple antigen-unmasking technique and may provide useful diagnostic information particularly in cases in which fresh tissue samples are unavailable.

Acute Disease↗
PubMed1994

Long-term follow-up of a CHOP-based regimen with maintenance therapy and central nervous system prophylaxis in lymphoblastic non-Hodgkin's lymphoma.

The Eastern Cooperative Oncology Group (ECOG) conducted a phase II trial in adult patients with lymphoblastic non-Hodgkin's lymphoma. Thirty-nine patients with no central nervous system (CNS) involvement were treated with an induction cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)/L-asparaginase regimen and CNS prophylaxis that included intrathecally administered methotrexate given 6 times and 24 Gy midplane cranial radiation in 12 fractions. Thirty-one patients (79%) achieved a complete remission (CR). Of the 31 patients with CRs, 12 relapsed (39%). CNS relapse occurred in three patients. All patients who entered a CR were treated with maintenance CHOP, cytosine arabinoside (AraC), and methotrexate and subsequently with Ara-C and methotrexate. Life-threatening leukopenia or thrombocytopenia was experienced in 69% of patients in the induction phase and in 70% in the maintenance phase. Nineteen of 39 patients (49%) remain in CR with a followup to 9 years. Bone marrow involvement was associated with a significantly worse survival (P = 0.03).

Adolescent↗
PubMed1994

Assessment of cell proliferation in paraffin sections of normal bone marrow by the monoclonal antibodies Ki-67 and PCNA.

Assessment of the proliferative index of human bone marrow using immunohistology in tissue sections offers practical advantages over other techniques. It is simpler to perform and can be applied to archival material. Progress in this area has been hampered by technical problems. Ki-67 studies, limited to fresh or frozen tissues, have been contradictory, and the labeling indices have been criticized for being unrealistically low. Proliferating cell nuclear antigen (PCNA) studies have also been considered unreliable because labeling indices include nondividing cells. We stained 82 routinely processed nonneoplastic bone marrow biopsies for Ki-67 equivalent MIB 1 antibody and PCNA/PC10 using a microwave oven antigen retrieval technique. 44.7% +/- 12.0 SD of the bone marrow cells stained with Ki-67/MIB 1. PCNA/PC10 staining gave similar results (50.7% +/- 12.3 SD). Pro- and basophilic erythroblasts, myeloblasts, promyelocytes, myelocytes, and megakaryocytes stained with both monoclonal antibodies in a manner consistent with known morphologic and cytokinetic data. Patients in different clinical groups showed similar mean values, the only exception being a group of cytokine-treated patients, which showed higher values than the other cases. Immunoperoxidase staining of bone marrow sections with Ki-67/MIB 1 and PCNA/PC10 monoclonal antibodies is a reliable method for assessing proliferation of hematopoietic cells.

Adult↗
PubMed1994

Terminal deoxynucleotidyl transferase staining of malignant lymphomas in paraffin sections.

Terminal deoxynucleotidyl transferase (TdT) represents a useful marker for the diagnosis of acute lymphoblastic leukemia and lymphoblastic lymphoma. It is usually assayed in fresh tissue or cell suspensions by enzyme analysis, immunofluorescence, or immunoperoxidase. We have obtained satisfactory staining for TdT in routinely processed paraffin sections using a recently described antigen retrieval pretreatment based on microwave oven heating of the sections and a polyclonal rabbit anti-TdT serum. With this technique, we assayed paraffin sections from lymph nodes of 91 patients with a variety of malignant lymphomas, including 35 cases of lymphoblastic lymphoma. The specificity of this immunoperoxidase method of TdT analysis was confirmed by comparing the results obtained with conventional TdT analysis by indirect immunofluorescence. Neoplastic cells from 33 of the 35 (94%) patients with lymphoblastic lymphoma were TdT positive with both techniques. All remaining 50 cases of other subtypes of malignant lymphoma were TdT negative. Specificity was further confirmed by demonstrating TdT-positive blasts in paraffin sections of bone marrow biopsies from 44 patients with TdT-positive (by indirect immunofluorescence) acute leukemias and in paraffin sections of extramedullary leukemic infiltrates from eight patients with relapsed acute lymphoblastic leukemia. Other control material studied included eight lymph nodes with Hodgkin's disease, four normal spleen, seven reactive lymph nodes, and 25 nonneoplastic bone marrow samples, all of which gave the expected results, i.e., rare scattered TdT-positive cells in bone marrow and lymph nodes, absence of staining in Hodgkin's disease malignant cells and spleen. Our results confirm that TdT is a specific marker for the diagnosis and classification of lymphoblastic lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA Nucleotidylexotransferase↗
PubMed1994

Hodgkin's disease with coexistent Castleman-like histologic features. A report of three cases.

We report three cases of Hodgkin's disease with coexistent histologic features reminiscent of Castleman's disease. In each case, reactive follicular hyperplasia was prominent and lymphoid follicles contained normal- or small-sized germinal centers. In two lesions, sheets of mature plasma cells and vascular proliferation were present in the interfollicular region, and some of the follicle centers were small, relatively depleted of lymphoid cells, and surrounded by concentric layers of small lymphocytes (so-called onionskin layers). However, unequivocal hyaline-vascular lesions were absent. Both cases were referred with the diagnosis of Castleman's disease, most consistent with the plasma cell variant. Subsequent review demonstrated scattered Reed-Sternberg and Hodgkin cells in the interfollicular region, highlighted by immunohistochemical studies, and the diagnosis of interfollicular Hodgkin's disease was made. In the third lesion, the majority of the lymph node was replaced by Hodgkin's disease, nodular lymphocyte predominance subtype. In the regions not involved by tumor, reactive lymphoid follicles with hyaline-vascular lesions were numerous. This case was also referred with the diagnosis of Castleman's disease, of the hyaline-vascular type. We report these lesions to emphasize that histologic features reminiscent of Castleman's disease may occur in lymph nodes involved by Hodgkin's disease, resulting in diagnostic confusion. Castleman-like histologic features may represent a nonspecific immune response to a variety of immunologic stimuli including, as in these cases, the presence of Hodgkin's disease. The possibility of Hodgkin's disease needs to be considered and excluded before the diagnosis of Castleman's disease is made.

Aged↗
PubMed1993

Hematopoietic lineage- and stage-restricted expression of the ETS oncogene family member PU.1.

The ETS oncogene family member PU.1 is a transcriptional activator that is dysregulated by Friend erythroleukemia virus insertion. Northern analysis found that PU.1 is highly expressed in cells of myeloid and B-lymphoid origin, but not expressed at all in a number of nonhematopoietic tissues. Interferon-gamma and retinoic acid downregulated PU.1 expression in marrow macrophages. In situ immunohistochemistry found that PU.1 is expressed only in early granulocytic and erythroid cells and megakaryocytes, but not in mature erythroid cells, mature granulocytes, endothelial cells, or osteocytes. Thus, its expression pattern makes PU.1 a candidate for a genetic determinant of lineage commitment and stage progression in blood cell development. It also lends insight into how PU.1 might play a role in Friend virus erythroleukemia.

Animals↗
PubMed1993

Primary hepatic B-cell lymphoma in a child.

Lymphoma arising in the liver is uncommon in adults and rare in children. A 12-year-old boy with hepatomegaly and jaundice had a calcified intrahepatic large-cell lymphoma of B-cell origin that expressed bcl-2 protein and had near-tetraploid chromosome number with a t(8;14) (q24;q32) and a homogeneously staining region (HSR). This tumor, only the fourth example of primary hepatic lymphoma in a child, has the rare finding of an HSR before treatment and is the first human lymphoma with t(8;14) that expresses bcl-2 protein. In addition, the demonstration of extensive calcification in the tumor by computed tomography scan is highly unusual for lymphoma. Lymphoma must be considered in the differential diagnosis of primary liver tumors in children and adults, especially if the serum alpha-fetoprotein level is normal.

Child↗
PubMed1993

Frequent p53 overexpression in therapy related myelodysplastic syndromes and acute myeloid leukemias: an immunohistochemical study of bone marrow biopsies.

p53 overexpression was studied immunohistochemically in paraffin-embedded bone marrow biopsies using a recently described technique for antigen retrieval based on microwave oven heating of paraffin sections. Using a monoclonal antibody (PAb1801) that reacts with human cellular p53, nuclear staining was detected in 7/11 (63%) therapy-related myelodysplastic syndromes and in 3/4 (75%) therapy-related acute myeloid leukemias. Conversely, staining for p53 was seen only in 9/40 (22%) cases of "primary" hematologic conditions (P < 0.007); these included myelodysplastic syndromes [#2], acute myeloid leukemia [#4], and chronic granulocytic leukemia in accelerated phase or blast crisis [#3]. Biopsies of normal controls and of chronic granulocytic leukemia in stable phase were consistently p53(-). Nine of the 10 karyotyped p53(+) acute myeloid leukemia/myelodysplastic syndrome cases showed complex cytogenetic findings with frequent involvement of chromosome 5 and/or 7. Only four of the 33 karyotyped p53(-) cases showed similar cytogenetic changes. Chromosome 17 involvement was present in four of 13 (31%) cytogenetically assessed p53+ cases, but in none of the p53(-). In univariate analysis, p53 expression in both MDS and AML was significantly associated with shorter survival. The frequent overexpression of p53 in therapy-related myelodysplastic syndromes, therapy-related acute myeloid leukemias and in accelerated phase/blast crisis, chronic granulocytic leukemia and its strong association with complex karyotypes suggests an important role of this gene in the pathogenesis of these leukemic conditions.

Acute Disease↗
PubMed1992

Non-Hodgkin's lymphoma and occupational exposure.

A case-control study was conducted to assess the effect of occupational exposures on the risk of non-Hodgkin's lymphoma. Interviews were conducted with 303 persons with non-Hodgkin's lymphoma newly diagnosed from January 1, 1980, to May 31, 1982, among residents of the Boston, MA, metropolitan area and 303 age and gender matched controls. The study found an increased risk of disease among persons employed in the agriculture, forestry, and fishing industry [relative risk (RR) = 3.0]; the construction industry [RR = 2.1]; and the leather industry [RR = 2.1]. The particular job groupings at increased risk were plant farmers and gardeners (RR unbounded); painters and plasterers (RR = 6.0); and carpenters, brick and stone masons, plumbers, and roofers (RR = 12.0). Although other exposures may have led to these increased risks, the findings in this study are consistent with an increased risk of non-Hodgkin's lymphoma for workers who may be exposed to chlorophenols or phenoxyacetic acids.

Adolescent↗
PubMed1992

The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study.

One hundred and forty one patients were treated in a combined Eastern Cooperative Oncology Group and Southwest Oncology Group phase-III study evaluating low-dose cytarabine (LDAC) versus supportive therapy for the treatment of myelodysplastic syndrome (MDS). Patients were randomized to either cytarabine 10 mg/m2 subcutaneously BID or supportive therapy. Central pathology review was required. All patients were classified according to the FAB criteria for MDS. The overall concordance rate for the MDS subtype was 52%, and 25 patients were pathology exclusions, including 20 with AML. The overall response rate to a single cycle of LDAC was 32%, with 11% complete and 21% partial responses. The median duration of response was 5.9 months, with a range of 1.4-33.5 months. Responses were seen in all subtypes. Infections were more common in the LDAC arm. There was no difference in the time to progression or the overall survival for patients treated with LDAC or supportive therapy. The incidence of leukemic transformation was similar in both arms at 15%, but it differed according to the MDS subtype. Patients receiving LDAC had a decreased transfusion requirement after 3 months. There was a significant correlation between the degree of cytoreduction after receiving a single cycle of LDAC and survival. This survival difference was most marked in patients with the RAEB and RAEB-T subtypes. Although LDAC produced responses in all subtypes of the MDS, there was no effect on overall survival or transformation to AML. However, selected patients benefited from a single cycle of LDAC with durable responses. A cytoreductive effect appears to be required for a durable response. Future studies should include pathology review and must address the clinical and biological heterogeneity of MDS.

Adult↗