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Biomedical subjects

R B Mann

Publications and source records attributed to R B Mann.

At least 37 records · Page 2Linked to original sources
PubMed1995

Localization of Epstein-Barr virus in Castleman's disease by in situ hybridization and immunohistochemistry.

Paraffin wax sections of lymph node biopsies from a total of thirteen patients with the morphologic and clinical features of Castleman's disease were analyzed for the presence of the Epstein-Barr virus (EBV) by in situ hybridization for the noncoding EBV early RNAs (EBERs) and by immunohistochemistry for the EBV-encoded latent membrane protein-1 (LMP-1). Of twelve cases of localized Castleman's disease EBER-positive cells were identified in five, and in these cases were only rarely found and were always confined to the interfollicular regions. LMP-1 was not detected in any of these cases, either alone or after dual staining for EBERs and LMP-1. (A similar pattern of EBER expression is seen in nonneoplastic lymphoid tissue from EBV-positive individuals.) No EBER-positive or LMP-1 positive cells were identified in a single case of multicentric Castleman's disease. In two additional patients initially diagnosed with Castleman's disease of localized plasma cell type, repeat biopsy showed Hodgkin's disease. In both cases Reed-Sternberg cells and their variants were identified in the original biopsy on which the diagnosis of Castleman's disease was made. In one of these cases these cells showed expression of EBERs and LMP-1, indicating latent infection with EBV. The results suggest that EBV is not generally associated with Castleman's disease. Further analysis of a series of cases of multicentric Castleman's disease is indicated.

Adult↗
PubMed1995

Epstein-Bar virus and progression of non-Hodgkin's lymphoma to Ki-1-positive, anaplastic large cell phenotype.

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a variety of lymphoproliferative disorders (LPDs) including endemic Burkitt's lymphoma, Hodgkin's disease (HD), HIV-associated non-Hodgkin's lymphomas (NHLs), and LPDs arising in immunosuppressed transplant patients. More recently, EBV has been associated with Ki-1-positive anaplastic large cell lymphoma (ALCL), a recently described NHL that shares with HD expression of the CD30 antigen Ki-1. Because EBV has been shown to induce Ki-1 expression in vitro, and ALCL has been diagnosed in patients with prior or concurrent HD or NHL, it has been proposed that EBV may mediate progression of a "primary" lymphoma to a "secondary" ALCL. We report a case in which an AIDS-associated, Ki-1-negative, large-cell immunoblastic lymphoma progressed to a Ki-1 positive ALCL. Analysis of the immunoglobulin heavy chain locus revealed a clonal relationship between these morphologically and immunophenotypically distinct tumors. Although EBV was absent from the original large-cell immunoblastic lymphoma as assessed by in situ hybridization for EBV-encoded small RNA1 (EBER1), polymerase chain reaction for EBNA-1, immunocytochemistry for latent membrane protein 1, and Southern blot hybridization for EBV terminal repeat sequences, all for techniques confirmed the presence of EBV in the secondary ALCL. Moreover, analysis of EBV terminal repeat sequences indicated that the ALCL resulted from expansion of a single EBV-infected clone. These data suggest that EBV may mediate progression of NHL to Ki-1-positive ALCL, and that in some instances, EBV may be involved in the later stages of clonal progression of NHL.

AIDS-Related Opportunistic Infections↗
PubMed1994

Epstein-Barr-encoded RNA in situ hybridization: diagnostic applications.

Latent Epstein-Barr virus (EBV) infection is associated with a variety of malignancies and other diseases. Highly restricted viral antigen expression and low viral genome copy number in infected tissues impede conventional immunohistochemical or in situ hybridization approaches to the detection of virus in these tissues. In situ hybridization detection of two small but very abundant nuclear RNAs known as the EBERs serves as an alternative approach. The EBERs are stable over time and can be detected in all common fixatives. This technique facilitates characterization of the cellular locus of latent EBV infection in histologically complex tissues, such as Hodgkin's disease and angioimmunoblastic lymphadenopathy with dysproteinemia.

Herpesviridae Infections↗
PubMed1994

Epstein-Barr virus is infrequently identified in non-Hodgkin's lymphomas associated with Hodgkin's disease.

Epstein-Barr virus (EBV) was identified in a subset of cases of Hodgkin's disease (HD) and in some non-Hodgkin's lymphomas (NHLs), particularly those associated with immunodeficiency. Because patients with HD have associated immune system defects, we hypothesized that EBV might be involved in NHLs associated with HD. Using fixed paraffin sections and in situ hybridization for EBV EBER1 RNA, we studied 12 cases of composite NHL + HD, two patients with NHL who simultaneously also had HD involving a different site (simultaneous HD and NHL), 14 NHLs arising in patients who previously had HD, and seven NHLs from patients who subsequently developed HD. Epstein-Barr virus was identified most frequently in composite NHL + HD. Five (42%) cases of composite NHL + HD contained EBV in Reed-Sternberg and Hodgkin cells, four of which also had EBV-positive NHLs, diffuse mixed or large-cell type, with 10 to more than 50 EBV-positive cells per x400 microscopic field. These results suggest that in this subset of four cases, both the NHL and HD components may have arisen from the same EBV-infected progenitor cell. We did not find EBV in two cases of simultaneous NHL and HD or in seven NHLs preceding development of HD. We identified EBV in only two of 14 NHLs following HD, one small noncleaved cell lymphoma and one plasmacytoma, both containing more than 50 EBV-positive cells per x400 microscopic field. These results suggest that EBV plays a minimal role in NHLs associated with HD, with the exception of composite NHL + HD. Hodgkin's disease-associated immune defects may be involved in the pathogenesis of a subset of NHLs following HD, but the exact pathogenesis of most NHLs associated with HD remains uncertain. Parallels with the high-grade Burkitt-like lymphomas associated with human immunodeficiency virus infection are noted.

Adult↗
PubMed1994

Intravascular lymphomatosis: a clinicopathologic study of 10 cases and assessment of response to chemotherapy.

PURPOSE: We report a clinicopathologic study of 10 cases of intravascular lymphomatosis (IVL) seen at a single institution, and assess the response to chemotherapy in these patients, as well as those collected from a literature review. PATIENTS AND METHODS: The clinical, pathologic, and immunophenotypic features of 10 cases of IVL diagnosed at the Johns Hopkins Hospital since 1977 were studied. Follow-up information was obtained in each case by consultation with the treating physician. In addition, cases of IVL reported previously in which patients were treated with chemotherapy and for which follow-up data were available at the time of publication were reviewed. RESULTS: In the present series of 10 cases, the most common clinical features were fever of unknown origin (FUO), mental status changes, and rash. Diagnostic specimens were obtained from a variety of sources, including brain, skin, prostate, liver, kidney, and gallbladder. All of the four patients treated with combination chemotherapy are alive and two have achieved long-term survival (48 and 45 months, respectively); the remaining two are alive and in complete remission (CR) after short follow-up duration of 6 months. Among 35 patients reported in the literature who received chemotherapy (including four from this series), 43% attained a CR and were free of disease at the time of publication. None of the three patients in our series who received localized therapy (surgery with or without radiation therapy) is alive (mean survival duration, 9 months). For the three patients diagnosed at postmortem examination, the mean interval between onset of symptoms and death was 3 months, and disease was widespread. CONCLUSION: These findings suggest that IVL represents a high-grade non-Hodgkin's lymphoma (NHL) with a propensity for systemic dissemination, and that CR and long-term survival may result in patients treated with aggressive combination chemotherapy.

Aged↗
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

Detection and characterization of Epstein-Barr virus in clinical specimens.

Epstein-Barr virus (EBV) is associated with a wide spectrum of benign and malignant diseases. Recent additions to the list include oral hairy leukoplakia; a subset of Hodgkin's lymphomas, particularly those with mixed cellularity histology or those occurring in underdeveloped countries; a subset of diffuse large cell/immunoblastic lymphoma in the immunocompromised, particularly primary central nervous system lymphoma; a subset of peripheral T cell lymphomas; and a subset of gastric carcinomas, particularly undifferentiated carcinomas. There are several distinctive aspects of the biology of the virus that are important in investigations of virus in clinical specimens. The presence of repeated elements in the genome facilitates detection of viral nucleic acids by a variety of hybridization techniques as well as the characterization of the clonality of virus-infected tissues. Latent viral infection is associated with several different patterns of viral gene expression in infected cells. Latent gene products are important because of their growth-regulating and -transforming properties as well as the potent cytotoxic T cell response they elicit. The abundant expression of the EBER RNA transcripts makes possible the sensitive detection of latent infection in EBV-associated tumors. Lytic infection can be inhibited by antiviral nucleoside analogues. Two lytic gene products are of special interest because of their homology to the cellular proteins BCL-2 and interleukin-10. Two viral biotypes or strains with different properties in terms of lymphocyte immortalization and transformation have recently been characterized. Current evidence suggests a differential biotype association with particular malignancies. Characterization of the association of EBV with various disease processes promises to be important for diagnosis and treatment as well as for a better understanding of the epidemiology and pathogenesis of these diabetes.

Herpesvirus 4, Human↗
PubMed1993

Epstein-Barr virus and childhood Hodgkin's disease in Honduras and the United States.

In industrialized populations, Hodgkin's disease (HD) has an initial peak in young adulthood, whereas in economically developing populations the initial peak occurs in childhood. This pattern resembles that of infection with poliovirus and suggests an infectious cofactor in the etiology. Serologic studies have linked Epstein-Barr virus (EBV) to young adult and adult HD, and viral nucleic acids and antigens have been detected in a subset of Hodgkin's tumor specimens. To investigate the association of childhood HD with EBV we studied tumor specimens from 11 children treated in Honduras and 25 children treated in the United States using in situ hybridization and antigen detection techniques. Among the patients from Honduras, tumor specimens from all cases were EBV positive. Among the patients from the United States, tumor specimens from six of seven patients with mixed cellularity histology, 2 of 15 with nodular sclerosis histology, and neither of two patients with lymphocyte-predominant histologies were EBV positive. These findings support the hypothesis that EBV contributes to the pathogenesis of HD in children, particularly in mixed cellularity HD, and raises the possibility that there are important geographic, racial, or ethnic factors in the EBV association with HD.

Adolescent↗
PubMed1993

Rapid in situ hybridization for the diagnosis of latent Epstein-Barr virus infection.

Latent Epstein-Barr virus (EBV) infection is associated with a variety of malignancies. Rapid in situ hybridization techniques have been described for various lytic viral infections because of limited gene expression. However, EBERS (Epstein Barr early RNAs) are expressed in abundance in tumour cells which are latently infected with EBV. We have targeted these transcripts in a rapid (3 h) in situ hybridization assay fo the detection of latent EBV in clinical specimens, including formalin-fixed paraffin-embedded material. EBER RNA was detected in control cell lines which have two copies of the EBV genome and in paraffin-embedded biopsy specimens from patients with nasopharyngeal carcinoma, EBV-associated Hodgkin's disease, Burkitt's lymphoma and post-transplant lymphoma. The technique did not detect EBER RNA in oral hairy leukoplakia, a pathologic process previously characterized as associated with lytic EBV infection. The sensitivity, specificity and rapidity of this technique make it ideal for the diagnostic detection of EBV in latently infected clinical specimens.

Burkitt Lymphoma↗
PubMed1993

Uveal involvement in systemic angiotropic large cell lymphoma. Microscopic and immunohistochemical studies.

BACKGROUND: Angiotropic large cell lymphoma is a rare, generally fatal disease characterized by multifocal proliferation of neoplastic mononuclear cells within the lumens of blood vessels. METHODS: The authors report the clinical and immunohistochemical features of four patients with angiotropic large cell lymphoma. RESULTS: All patients presented with central nervous system symptoms, and three of the four had fever of unknown origin and anemia. The diagnosis was established by postmortem examination of the eyes in four patients and additionally by autopsy in three of the four patients. Two of the three autopsied patients had rare foci of extravascular involvement. One patient had erythrophagocytosis. Immunohistochemical stains on paraffin-embedded sections confirmed the diagnosis of lymphoma in all four patients. CONCLUSION: The results of this study support the B-cell lymphocyte origin of angiotropic large cell lymphoma.

Aged↗
PubMed1993

In situ detection of lytic Epstein-Barr virus infection: expression of the NotI early gene and viral interleukin-10 late gene in clinical specimens.

Riboprobes that detect two genes expressed only during productive infection were developed to characterize the clinical spectrum of Epstein-Barr virus (EBV) lytic infection and identify diseases that may be responsive to antiviral drug therapy. The NotI antisense probe hybridizes to tandem repeats in the abundant early lytic cycle BHLF1 mRNA. Transcripts were detected in lytically infected cell lines, AIDS-associated oral hairy leukoplakia, bone marrow of a patient with virus-associated hemophagocytic syndrome, and spleen of an AIDS patient but not in EBV-positive primary central nervous system lymphomas or in circulating EBV-infected B cells from a patient with acute infectious mononucleosis. The viral (v) interleukin-10 (IL-10) probe hybridizes to the unique 5' end of the late lytic cycle BCRF1 mRNA, which encodes a protein homologous to the human cytokine IL-10. The vIL-10 probe detected transcripts in lytically infected cell lines and within the differentiated layers of oral hairy leukoplakia.

Adolescent↗
PubMed1992

Activity of fludarabine in previously treated non-Hodgkin's low-grade lymphoma: results of an Eastern Cooperative Oncology Group study.

PURPOSE: Fludarabine (2-fluoro-arabanoside-monophosphate) is a new antimetabolite chemotherapeutic agent. We performed a multicenter, phase II study of this drug in previously treated patients with refractory or relapsed non-Hodgkin's lymphoma (NHL) to determine its response rate by histologic classification. PATIENTS AND METHODS: Sixty-two assessable patients were given 18 mg/m2 by intravenous (IV) bolus injection daily for 5 days, every 28 days. Forty-eight percent had previously had one chemotherapy regimen, and the remainder had had two regimens; 42% had had radiation. RESULTS: Patients received 273 cycles of fludarabine chemotherapy, with a median of two cycles and ranging up to 25 cycles. Sixty patients were assessable for response, including nine complete responses (CRs; 15%) and nine partial responses (PRs; 15%). The response rate for patients with lower-grade histology was 52% (13 of 25); the greatest response rate was seen in those with follicular small cleaved-cell lymphoma, including seven of 11 treated. Five responders remain in unmaintained remission; the median survival of responders is greater than 30 months. Toxicity included mild neutropenia and a 10% incidence of grade 3 neurologic toxicity with occasional reversible visual and auditory changes. CONCLUSION: Fludarabine is active in patients with previously treated NHL (particularly low-grade histologies). Future studies will examine its activity in combination with other chemotherapeutic agents in previously untreated patients.

Adolescent↗
PubMed1992

In situ localization of Epstein-Barr virus in thymic carcinoma.

Epstein-Barr virus (EBV) genome is associated with a variety of lymphoid and epithelial malignancies. EBV DNA has been detected in some cases of thymic carcinoma, but the cellular locus of the virus has never been defined. Detection of EBV has also been reported in normal thymus, thymic lymphoid hyperplasia, and thymoma by some investigators but not by others. In order to better define the association of the virus with benign and malignant thymic tissues and to characterize its cellular locus, we applied a recently developed in situ hybridization technique using a very abundant EBV transcript (EBER1) as target to a variety of thymic tissues. We detected expression of this transcript only in the malignant epithelial cells in one case of thymic lymphoepithelioma-like carcinoma. EBV expression was not detected in six other cases of thymic carcinoma, nor in tissue from 16 normal thymuses, 14 thymomas, and 10 thymic lymphoid hyperplasias.

Adult↗
PubMed1992

A comparison between the Rappaport Classification and Working Formulation in cooperative group trials: the ECOG experience.

The Working Formulation (WF) for the classification of non-Hodgkin's lymphomas was shown to be reproducible and clinically relevant in the original study. However, it has not yet been tested by an NCI-supported cooperative clinical oncology group. As a result, the Hematopathology Subcommittee of the Eastern Cooperative Oncology Group (ECOG) undertook a retrospective study to compare concordance and practical utility between the WF and the Rappaport Classification (RC). Data indicate that with appropriate modifications to minimize unclassifiable lymphomas, the WF can be effectively utilized in cooperative clinical oncology groups.

Humans↗
PubMed1991

Epstein-Barr virus in AIDS-related primary central nervous system lymphoma.

Primary central nervous system lymphoma occurs more often in patients with AIDS. Epstein-Barr virus (EBV) has been detected in these tumours, but the degree of association has not been defined because of both the highly restricted expression of EBV in malignant tissue and the lack of a technique that is reliable in formalin-fixed paraffin-embedded specimens. EBV-transformed lymphocytes contain short non-protein coding EBV transcripts (EBERs), which are expressed in much higher quantity than other EBV-latency transcripts. We describe a new strategy for detection of latent EBV with these transcripts as targets for in-situ hybridisation. 18 cases of AIDS-related primary CNS lymphoma from a consecutive necropsy series together with specimens from 3 further cases were studied. In each case, a strong positive signal over tumour cells indicated abundant expression of the EBV-EBER1 transcript. This 100% association suggests that the pathogenesis of these AIDS-associated lymphomas may differ from the systemic disease in which only 30-50% of tumours are associated with EBV. A pathogenetic role for EBV was further supported by showing expression of a viral protein (the latent membrane protein) that is implicated as an effector for EBV-associated lymphomagenesis. EBV might have a role as a tumour marker in the diagnosis and management of AIDS-related primary CNS lymphoma.

Central Nervous System Neoplasms↗
PubMed1991

Solitary, isolated metastasis from Ewing's sarcoma to the brain: case report.

We report a case of a 30-year-old woman who developed an intraparenchymal cerebral metastasis from a Ewing's sarcoma of the chest wall diagnosed and treated 3 years earlier and in apparent remission at the time of the neurological presentation (seizures). The case was complicated by a spontaneous preoperative intratumoral hemorrhage that occurred the morning of the scheduled surgical resection and caused a left dense hemiparesis. The tumor and the hematoma were removed. The patient improved after surgical intervention and a postoperative course of cranial irradiation followed by systemic chemotherapy was given. Nineteen months after treatment the patient remains disease-free from the clinical and radiological standpoint.

Adult↗