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N C Sun

Publications and source records attributed to N C Sun.

At least 19 recordsLinked to original sources
PubMed1998

Clinically silent primary adrenal lymphoma: a case report and review of the literature.

Primary adrenal lymphoma (PAL) is extremely uncommon. We describe a case of clinically silent non-Hodgkin's B-cell lymphoma of diffuse large cell type with exclusive left adrenal localization. The tumor was discovered by computed tomography (CT) as a 2.5-cm dense mass and diagnosed at autopsy. Literature concerning this unusual neoplasm is reviewed. During the early stage, particularly when the lesion is small, PAL is likely to be missed. This unusual entity should be included in the differential diagnosis of adrenal masses so that early diagnosis may be made and intervention might dramatically affect the clinical outcome.

Adrenal Gland Neoplasms↗
PubMed1998

Expression of the cell-cycle-related proteins E2F-1, p53, mdm-2, p21waf-1, and Ki-67 in multiple myeloma: correlation with cyclin-D1 immunoreactivity.

Approximately 30% of multiple myelomas (MMs) express cyclin D1 when assessed using immunohistochemical techniques. Cyclin D1 expression correlates with greater tumor burden in MM, because cyclin D1-positive cases are more frequently associated with extensive bone marrow involvement, i.e., high pathologic stage, than are cyclin D1-negative cases. The mechanisms that explain this association are unknown. To explore other differences between cyclin D1-positive and cyclin D1-negative MMs, we assessed 59 MMs immunohistochemically for several G1 cell-cycle regulatory proteins, including cyclin D1, E2F-1, p53, mdm-2, and p21waf-1, using routinely fixed and processed, paraffin-embedded bone marrow specimens. Twenty MMs (34%) were cyclin D1 positive, and 39 (66%) were cyclin D1 negative. Eighteen (90%) of 20 cyclin D1-positive MMs were Stage III, in contrast to 19 (49%) of 39 cyclin D1-negative MMs (P = .003). Cyclin D1-positive MMs were more likely to express E2F-1 (16/20 vs. 4/39, P < .001), p53 (11/20 vs. 10/39, P = .041), and p21waf-1 (12/20 vs. 7/39, P = .003). There was no significant difference in mdm-2 expression between these groups. We also assessed proliferation rate using an antibody specific for the Ki-67 antigen. A relatively high percentage (> 20%) of Ki-67-positive cells was found in cyclin D1-positive MMs compared with cyclin D1-negative MMs (13/20 vs. 3/39, P < 0.001). These results suggest that cyclin D1-positive MMs are more likely to possess additional derangements involving other G1 cell-cycle regulatory proteins. We speculate that these abnormalities might result in increased proliferation, thereby explaining the correlation between cyclin D1 expression and greater tumor burden.

Bone Marrow Cells↗
PubMed1997

Cyclin D1 protein in multiple myeloma and plasmacytoma: an immunohistochemical study using fixed, paraffin-embedded tissue sections.

In this study, we analyzed 69 plasma cell neoplasms, including 54 multiple myelomas (MMs), 3 cases of plasma cell leukemia, and 12 plasmacytomas, for expression of cyclin D1 protein using an immuno-histochemical method applied to routinely fixed, paraffin-embedded tissue sections. Cyclin D1 was expressed in 18 (26%) of 69 plasma cell neoplasms, including 16 (30%) of 54 MMs and 2 (17%) of 12 plasmacytomas. Three cases of plasma cell leukemia were negative. Cyclin D1 expression correlated with the cytologic differentiation and histologic stage of MM. Twelve (75%) of 16 MMs had intermediate or immature cytologic features and were histologic Stage III. With use of a polymerase chain reaction assay, we also analyzed six cases (three cyclin D1 positive, three cyclin D1 negative) for the t(11;14); one MM carried the t(11;14) and expressed cyclin D1 protein. We conclude that cyclin D1 expression occurs in approximately one-quarter of plasma cell neoplasms and correlates with the degree of cytologic differentiation and histologic stage. The relatively high frequency of cyclin D1 expression, compared with the less than 5% incidence of the t(11;14) detected by conventional cytogenetics reported in the literature, suggests that upregulation of cyclin D1 protein might be the result of mechanisms other than the t(11;14).

Adult↗
PubMed1996

Concurrent thrombotic thrombocytopenic purpura and immune thrombocytopenic purpura in an HIV-positive patient: case report and review of the literature.

Immune thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP) have each been associated with HIV infection. Sequential occurrence of these two diseases with a disease-free interval has been occasionally reported in the literature, whereas simultaneous manifestations of these two diseases have not been described. Here, we report an AIDS patient who was initially diagnosed as having TTP and showed an apparent partial response to plasmapheresis but was found to have a clinical course similar to ITP. Although precise mechanisms for the development of TTP and ITP in these patients are unclear, we offer several hypotheses. It is important to recognize that these two processes may be seen concurrently.

AIDS-Related Opportunistic Infections↗
PubMed1995

HIV-1 heterogeneity and cytokines. Neuropathogenesis.

Mild manifestations (HIV-1 associated minor cognitive/motor disorder), severe manifestations (HIV-1 associated dementia complex and HIV-1 associated myelopathy), and sensory neuropathy are consequences of HIV-1 infection. Our goal is to elucidate the role of HIV-1 in the complications of AIDS including cytokine immunopathology and HIV-1 DNA sequence variants. We have examined the brain and sensory ganglia from 60 AIDS patients and 20 seronegative controls using PCR, DNA sequencing of the HIV-1 envelope protein (env), in situ hybridization (ISH), and immunohistochemistry (IHC). Using our combined ISH-IHC technique, we could identify different types of cells and HIV-1 simultaneously in cryostat and paraffin sections. We found HIV-1 predominantly in macrophage/microglia in brain. In dorsal root ganglia (DRG) we found rare macrophages infected with HIV-1 and neurons and interstitial cells (including macrophages) which were apoptotic. Cytokines were detected in mononuclear and endothelial cells near neurons. We achieved single copy sensitivity detecting HIV-1 in nervous tissue using nested PCR. We sequenced HIV-1, DNA from 3 intravenous drug users (IDUs): from brain, CSF, and blood. PCR amplification was followed by cloning and then sequencing the HIV-1 insert: V1-V5 regions of the envelope (env) gene. We found that the env genes had increased sequence variation compared to the literature, cDNA sequences derived from RNA were less heterogeneous than clones derived from DNA from the same specimens, clones derived from brain are more closely related (show restricted heterogeneity) compared to clones from blood and CSF from the same patients. Patient 149 clones we examined to date did not correspond to any of the designated subtypes (A-F) of HIV-1 based on the DNA sequences of the C2-V3 regions. Finally, the HIV-1 RNA produced in these tissues is derived from a minority of DNA clones. Although HIV-1 infected macrophages are not entirely responsible for pathology in the brain and less so in sensory ganglia, some of the products of infection, cytokines, are more widespread in these tissues. Furthermore, HIV-1 strains infecting the brain appear to exhibit restricted heterogeneity compared to autologous CSF and blood and these strains may be associated with cytokines and pathology. HIV-1 strains that infect nervous tissue and cytokines produced in this tissue may effect neuropathogenesis, in vivo, in spite of low levels of local HIV-1 infection. We attempt to delineate, here, common sequence variations in HIV-1 isolates in the hope of developing future therapeutic strategies.

AIDS Dementia Complex↗
PubMed1995

T-cell-rich B-cell lymphoma. A clinicopathologic study of eight cases.

Although T-cell-rich B-cell lymphoma (TCRBCL) is a recently recognized form of non-Hodgkin's lymphoma (NHL), limited information regarding its incidence, cellular origin, morphologic spectrum, and biologic behavior is currently available. In this study, the clinicopathologic features of eight patients with TCRBCL are presented. This neoplasm comprised about 1% of all NHLs seen at Emory University Hospital over 2 years. The male-to-female ratio was 1.6, and the mean age at diagnosis was 60 years. At presentation, TCRBCL was nodal in 88% of the patients and widely disseminated in 50% of the patients. A complete remission was seen in three of the five patients treated with combination chemotherapy that was directed at intermediate grade NHL. Three patients received inadequate or incomplete chemotherapy. One of these patients later achieved a complete remission with more intensive therapy. Two of the patients were not evaluable for response to therapy. The actuarial and disease-free survival rates of the group at 5 years were 72% and 21%, respectively. Morphologically, the lymph nodes in seven of eight cases were diffusely obliterated, whereas one had markedly expanded interfollicular zones that lead to an initial diagnosis of T-zone lymphoma. All tumors were characterized by no more than 25% large lymphoid cells, which were scattered in a background of small lymphocytes with round or irregular nuclei. The presence of numerous histiocytes imparted a lymphoepithelioid appearance in two cases. Although immunoperoxidase stains of frozen tissue were initially suggestive of a peripheral T-cell lymphoma in some cases, paraffin immunoperoxidase stains clearly established the B-cell nature of the large cells, whereas most of the small cells were T lymphocytes. The clonal nature of the large cells was confirmed in seven cases by monotypic immunoglobulin (Ig) light chain restriction or Ig gene rearrangements. Epstein-Barr virus genomic DNA was detected in two of the six cases tested by polymerase chain reaction or Southern blot analysis, but no evidence of a bcl-2 rearrangement was found in any of the five cases examined. These findings indicate that TCRBCL is an uncommon form of NHL with a therapeutic response and overall survival consistent with intermediate grade lymphoma. Paraffin immunoperoxidase stains and occasionally genotypic analysis are required to exclude the diagnosis of PTCL or diffuse lymphocyte predominant Hodgkin's disease. The authors found no morphologic or molecular evidence to support a follicular center cell origin in these cases of TCRBCL.

Adult↗
PubMed1995

Trisomy 12 in Richter's transformation of chronic lymphocytic leukemia.

Conventional cytogenetic data and fluorescence in situ hybridization (FISH) interphase cytogenetic studies have shown that trisomy 12 is found in many cases of B-cell chronic lymphocytic leukemia (B-CLL). Several reports indicate that +12 is an acquired numerical cytogenetic abnormality, and may be associated with a worse prognosis or more extensive disease. Wright-Giemsa-stained blood or bone marrow smears obtained after initial diagnosis, and subsequent lymph node cells, bone marrow aspirate smears, or effusions were retrospectively studied from five patients whose disease underwent morphologic transformation from typical B-CLL to a high grade lymphoproliferative disease (Richter's syndrome). Using an alpha-satellite DNA probe to the centromere of chromosome 12, trisomy 12 was found in a proportion of cells from all five specimens with high grade lymphoproliferative disease, but in only one of five samples collected before transformation. These data suggest that +12 is an acquired cytogenetic abnormality in CLL and has a high frequency in Richter's syndrome. Because only a subpopulation of the neoplastic cells contain an extra copy of chromosome 12, it is unlikely that this numerical abnormality plays a direct role in transformation to high grade lymphoproliferative disease.

Bone Marrow↗
PubMed1995

Dendritic cell tumors associated with low-grade B-cell malignancies. Report of three cases.

Indeterminate and interdigitating cell tumors are rare proliferations of immunoregulatory cells that demonstrate morphologic, immunologic, and ultrastructural features similar to their cells of origin. Although an association of lymphoproliferative disease with Langerhans' cell histiocytosis is well described, only sporadic cases of non-Langerhans' dendritic cell proliferations have been published. The authors describe three patients with low grade B-cell lymphoproliferative disease who developed subsequent indeterminate cell or interdigitating cell tumors. When the two cases of indeterminate cell tumor are added to those previously described in the literature, it appears that 4 of 13 cases (31%) are associated with a history of low grade B-cell malignancy. Possible explanations for the relationship between these two disorders are discussed.

Dendritic Cells↗
PubMed1994

Expression of HIV-1 and interleukin-6 in lumbosacral dorsal root ganglia of patients with AIDS.

We examined the immunopathology and the expression of human immunodeficiency virus type 1 (HIV-1) in lumbosacral dorsal root ganglia (DRGs) from 16 patients with acquired immunodeficiency syndrome (AIDS) and 10 HIV-1-seronegative controls. Using in situ hybridization, we detected HIV-1 RNA in a few perivascular cells in DRGs from five of 16 AIDS patients (31%). In addition, using polymerase chain reaction, we detected HIV-1 DNA more frequently in DRGs from four of five AIDS patients (80%) examined. We detected interleukin-6 (IL-6) immunoreactivity in endothelial cells in DRGs from seven of 16 AIDS patients (44%) but from none of 10 HIV-1-seronegative controls (0%). We found more nodules of Nageotte, CD8+ T lymphocytes, and intercellular adhesion molecule-1 (ICAM-1)-positive endothelial cells and mononuclear cells in DRGs from AIDS patients than in DRGs from controls. Increased numbers of nodules of Nageotte in DRGs of AIDS patients were associated with detection of HIV-1 RNA by in situ hybridization and detection of IL-6 by immunohistochemistry. We conclude that low levels of replication of HIV-1, through cytotoxic T lymphocytes or expression of cytokines, may play a role in the subclinical degeneration of sensory neurons frequently observed in DRGs of AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The white IRIS leukocyte differential analyzer for rapid high-precision differentials based on images of cytoprobe-reacted cells.

Combining unique cytoprobe, rapid hemacyte fractionation, and novel color image analysis, The White IRIS (TWI) extends automated intelligent microscopy to leukocyte differentiation. TWI provides flow cytometry precision and microscopical resolution to review specimens flagged by hematology analyzers with differential capabilities or to complement other analyzers without these capabilities. The system includes compartments for closed sampling, rapid leukocyte-rich plasma preparation, cytoprobe-induced metachromasia, and collection and color analysis of leukocyte images, and presents the results as a single-view 500-cell differential on a 20-in. (50-cm) touch-screen monitor. Method correlations for the five mature cell types averaging r > 0.90 were obtained with a prototype system. Classification of normal and abnormal specimens showed 95% agreement with a reference method without any undetected significant morphologic abnormality. False-positive and false-negative rates of 7.27% and 3.53%, respectively, exceeded performance of current commercial systems. Case studies demonstrate the ease and speed with which unusual pathologies and leukemias can be observed and interpreted.

Cell Differentiation↗
PubMed1993

Application of Leu M5 (CD 11c) antibody in the cytodiagnosis of body fluids: preliminary results.

Identification of metastatic malignant cells in body fluids and their distinction from reactive mesothelial cells is a common diagnostic problem. Application of the immunoalkaline phosphatase method using epithelial membrane antigen, cytokeratin, vimentin, carcinoembryonic antigen, lysozyme, and leukocyte common antigen (CD 45) is routinely performed in our Hematology Laboratory in conjunction with morphological examination of body fluids. Recently, we found that anti-Leu M5 (CD 11c), a monoclonal antibody to human monocyte/macrophage, is frequently reactive to mesothelial cells. We then undertook a prospective study, adding anti-CD 11c to the above-listed antibody panel and applying to cytocentrifuge preparations of body fluid. The neoplastic cells in only 2 out of 34 cases (5.9%) with the diagnosis of metastatic carcinomas reacted positively for CD 11c. The neoplastic cells in four cases of malignant lymphoma were non-reactive for CD 11c. In addition, malignant cells on touch preparations of 25 carcinomas were also negative. Mesothelial cells in all 15 cases of reactive effusions and those mesothelial cells present in malignant effusions were positively stained with CD 11c, although the intensity of staining varied in different mesothelial cells of the same cases. We conclude that anti-CD 11c can be considered as a useful adjunct to the differential diagnosis of malignant effusions.

Adolescent↗
PubMed1992

Simultaneous detection of ferritin and HIV-1 in reactive microglia.

Using ferritin as a marker of reactive microglia, we demonstrated a close association between proliferation of reactive microglia and expression of human immunodeficiency virus type 1 (HIV-1) in brain tissue from autopsied cases of acquired immunodeficiency syndrome (AIDS). An increased number of ferritin-positive reactive microglia was observed in formalin-fixed paraffin-embedded brain sections from all 13 AIDS cases examined. Similar findings were observed in brain tissue from other neurological diseases (subacute sclerosing panencephalitis, herpes simplex encephalitis and multiple sclerosis). Multinucleated giant cells were found in 7 of the AIDS cases which were also intensely labeled for ferritin. Dual-label immunohistochemistry using anti-ferritin and cell-specific markers showed that ferritin-positive cells were distinct from astrocytes, neurons and endothelia using anti-glial fibrillary acidic protein (anti-GFAP), anti-neurofilament protein and Ulex europaeus agglutinin 1, respectively. In 5 AIDS brains, only ferritin-positive cells were shown to contain HIV-1 gp41 antigen using dual-label immunohistochemistry. In addition, HIV-1 RNA was localized in ferritin-positive reactive microglia but not in GFAP-positive astrocytes using immunohistochemistry combined with in situ hybridization. Ferritin-positive reactive microglia and multinucleated giant cells were co-labeled with the microglial marker, Ricinus communis agglutinin 1 (RCA-1). However, RCA-1 also extensively stained resting microglia only a few of which were co-labeled for ferritin. The density of ferritin-positive cells was correlated with the presence of HIV-1 RNA-positive cells in AIDS brain. Thus, ferritin immunoreactivity can be used as an activation marker of microglia in archival paraffin sections and reflects the extent of inflammation in HIV-1-infected brain.

Acquired Immunodeficiency Syndrome↗
PubMed1992

HIV-1 in postmortem brain tissue from patients with AIDS: a comparison of different detection techniques.

OBJECTIVE: The presence of HIV-1 in postmortem brain tissue from 31 patients with AIDS and 12 HIV-1-negative controls was investigated. DESIGN: Most laboratories have access to the methods used. We readily applied in situ hybridization and immunohistochemistry to archival formalin-fixed paraffin-embedded (FFPE) brain specimens. METHODS: The techniques used to detect HIV-1 were explant culture, in situ hybridization with 35S-labeled polymerase (pol) gene riboprobes and immunohistochemistry with monoclonal antibody to gp41. RESULTS: HIV-1 was isolated from explant cultures in 13 out of 20 (65%) patients, whereas HIV-1-infected cells were detected in FFPE brain tissue from nine out of 26 (35%) patients examined by in situ hybridization and in seven out of 26 (27%) patients examined by immunohistochemistry. CONCLUSIONS: Although the isolation technique was the most sensitive of the three techniques tested, infected cells may be identified with in situ hybridization in conjunction with immunohistochemistry.

AIDS-Related Opportunistic Infections↗
PubMed1992

A clinicopathologic study on the diffuse malignant lymphoma--a morphologic and immunophenotypic analysis in 62 patients at Harbor-UCLA Medical Center.

In order to compare the prognoses of patients with diffuse malignant lymphomas on the basis of histology and immunophenotypes, we retrospectively studied 62 cases of diffuse lymphoma arising in lymph nodes. We also evaluated the reactivity patterns of monoclonal antibodies (MoAb) LN1, LN2 and LN3 to determine the criteria for making a differential diagnosis in B cell lymphomas. The immunologic phenotypes were determined by the avidin biotin peroxidase complex method, using frozen or paraffin fixed tissues. The majority (66.3%) were B cell with the remaining 20.9% being T cell and 12.9% were non-B, non-T cell lineage. Immunological heterogeneity was found especially in the mixed small and large cell and the immunoblastic lymphomas. There was no significant difference between B- and T-cell lymphomas with respect to survival and death (P > 0.05). Histologically 79% (49/62) of the lymphoma was large cell and 21% (13/62), small cell lymphoma. There was a difference in prognosis between low, intermediate and high-grade of lymphomas. However there were no significant differences among the subtypes of the diffuse aggressive lymphomas. Factors associated with poor prognosis were advanced stages (P < 0.025) and histology of the malignant lymphomas. MoAb LN1, LN2 and LN3 gave positive staining in 83.3%, 91.7% and 60% of B cell lymphomas, respectively. The most common phenotypic pattern in B cell lymphomas was LN1+, LN2+, LN3+/-, suggestive of follicular center cell origin. As a panel, phenotypic patterns of MoAb LN1, LN2 and LN3 may be useful in differentiation of follicular center cell lymphoma from others.

Adolescent↗
PubMed1992

The use of combined in situ hybridization and immunocytochemistry to identify HIV-infected cells in brain tissue.

It is frequently important to identify the types of cells that are infected with human immunodeficiency virus type-1 (HIV-1) in sections of formalin-fixed paraffin-embedded (FFPE) brain tissue. Currently, both immunocytochemical and in situ hybridization methods are used for this purpose. Combined in situ hybridization and immunocytochemistry results in simultaneous detection of HIV-1 nucleic acids and proteins and allow comparison of transcriptional and translational events of cells infected with HIV-1 in the same section. In addition, this technique allows morphologic and immunologic identification of the cells within which in situ hybridization occurs and confirmation of the identity of the cells that are not hybridized. Procedures are described for use with FFPE brain tissue.

Brain↗