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S Alkan

Publications and source records attributed to S Alkan.

At least 19 recordsLinked to original sources
PubMed2000

Mucosa-associated lymphoid tissue-type lymphomas occurring in post-transplantation patients.

Post-transplantation lymphoproliferative disorders (PTLDs) are usually Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders that vary in their morphologic spectrum. Extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue-type (MALT-type) have not been considered to be part of this spectrum. The authors encountered five such cases recently. The clinical, histopathologic, and immunophenotypic features are reported. There were three men and two women with a mean age of 51.2 years (range, 48-63 years). Two patients were cardiac transplant recipients, two patients were liver transplant recipients, and the remaining patient was a renal transplant patient. Sites of lymphoma were the stomach in three patients and the parotid gland in two patients. Mean time to the lymphoma was 84 months after transplantation. All patients had morphologic features of low-grade extranodal marginal zone lymphomas of the MALT-type, and Helicobacter pylori was present in all three gastric cases. All patients exhibited the B-cell immunophenotype and were negative for EBV by in situ hybridization. These lymphomas were treated with a variety of modalities, including reduction of immunosuppression, antibiotics, surgical resection, radiation therapy, and chemotherapy. At last follow-up, one patient had developed signet ring adenocarcinoma at 27 months but had no evidence of PTLD, one patient relapsed at 17 months but is alive with stable disease at 24 months, and the remaining patients were alive without disease at 11, 12, and 14 months. Extranodal low-grade MALT-type lymphomas can occur in the post-transplantation setting and generally develop years after transplant. As seen in immunocompetent patients, EBV appears to play no role in the pathogenesis of these lymphomas. These lymphomas appear to have more in common with MALT-type lymphomas in nonimmunocompromised patients than conventional PTLDs, although they occur in "at-risk" patients due to their immunosuppressive therapy. These lymphomas do not appear to be clinically aggressive. Recognition of MALT-type lymphomas in the post-transplantation setting as an indolent disease avoids unnecessary treatment.

Combined Modality Therapy↗
PubMed1999

Characterization of the interleukin-1beta-converting enzyme/ced-3-family protease, caspase-3/CPP32, in Hodgkin's disease: lack of caspase-3 expression in nodular lymphocyte predominance Hodgkin's disease.

Apoptosis (programmed cell death) serves an important role in the normal morphogenesis, immunoregulation, and homeostatic mechanisms in both normal and neoplastic cells. Caspase-3/CPP32, a member of the ICE/Ced-3-family of cysteine proteases, is an important downstream mediator of several complex proteolytic cascades that result in apoptosis in both hematopoietic and nonhematopoietic cells. Previous studies have demonstrated that caspase-3 is commonly expressed in classical Hodgkin's disease (CHD); however, the biological significance of its expression in Hodgkin's disease is unknown. In this report, the expression of caspase-3 in nodular lymphocyte predominance Hodgkin's disease (NLPHD) was evaluated by immunohistochemistry; in addition, we investigated the role of caspase-3 in CD95 (Fas)-mediated apoptosis in three CHD cell lines. Formalin-fixed, paraffin-embedded tissue sections from 11 cases of NLPHD were immunostained for caspase-3 using a polyclonal rabbit antibody that detects both the 32-kd zymogen and the 20-kd active subunit of the caspase-3 protease. Only 1/11 cases of NLPHD demonstrated caspase-3 immunopositivity in lymphocytic/histiocytic cells. Caspase-3 expression was also evaluated in three CHD cell lines, HS445, L428, and KMH2. Whereas caspase-3 expression was detected in HS445 and L428 cell lines, no expression was found in KMH2 cells by immunohistochemical staining. Treatment of HS445 and L428 cell lines for 72 hours with agonistic CD95 monoclonal antibody induced marked apoptosis that was significantly inhibited by pretreatment with the caspase-3 inhibitor, DEVD-FMK, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and flow cytometric analysis of 7-amino-actinomycin D staining. In addition, a significant increase in caspase-3 activity as determined by an enzyme colorimetric assay was detected in HS445 and L428 cells after 48 hours of CD95 stimulation. In marked contrast, treatment of caspase-3-deficient KMH2 cells with anti-CD95 mAb did not demonstrate an increase in caspase-3 activity or induce apoptosis. These data demonstrate caspase-3 is important for CD95-mediated apoptosis in CHD cell lines. In addition, the majority of NLPHD cases examined in this study failed to express detectable levels of caspase-3, suggesting these tumor cells may be resistant to apoptotic stimuli dependent on caspase-3 activity. Furthermore, these data suggest the differential expression of caspase-3 noted between NLPHD and CHD may provide additional evidence that each is a unique disease entity.

Caspase 1↗
PubMed1999

Usefulness of molecular detection of human herpesvirus-8 in the diagnosis of Kaposi sarcoma by fine-needle aspiration.

Kaposi sarcoma (KS), a multifocal angioproliferative disorder, occurs most commonly in patients with AIDS, in whom it remains an important cause of morbidity and mortality. KS is often in the differential diagnosis in HIV-infected patients undergoing fine-needle aspiration (FNA). FNA diagnosis of KS is usually made by morphologic observation of scant tissue fragments composed of bland spindle cells and crush artifact. Human herpesvirus-8 (HHV-8) has been identified by polymerase chain reaction (PCR) amplification of DNA samples isolated from various epidemiologic forms of KS. In an attempt to improve the accuracy of KS diagnosis by FNA, we analyzed for the presence of HHV-8 DNA in 13 spindle-cell lesions evaluated by FNA: KS, 8 cases; granulomatous inflammation due to Mycobacterium avium-intracellulare, 1; nodular fasciitis, 1; dermatofibrosarcoma protuberans, 1; dermatofibroma, 1; benign spindle-cell lesion of nerve sheath origin, 1; and 2 lesions with lymphoid hyperplasia. DNA isolated from archival Wright-Giemsa-stained glass slides was used for the PCR amplification of the HHV-8 DNA sequences. All of the cases diagnosed as KS and 1 of the lymphoid hyperplasia cases were PCR-positive for HHV-8 DNA, while all other cases of spindle-cell lesions were negative. The molecular demonstration of HHV-8 DNA may be a useful adjunct in the diagnosis of KS by FNA.

Adult↗
PubMed1999

Bcl-6 protein expression by follicle center lymphomas. A marker for differentiating follicle center lymphomas from other low-grade lymphoproliferative disorders.

Low-grade lymphoproliferative disorders are a heterogeneous group of lymphoid neoplasms with wide variation in histologic features, immunologic phenotype, and molecular abnormalities. Subclassification of these disorders with small lymphocytic proliferation may be difficult on the basis of morphologic findings alone. The bcl-6 gene, originally cloned from a tumor with 3q27 translocation, is commonly expressed in large cell lymphomas. In humans, bcl-6 encodes for a Krüppel-type zinc finger protein and is believed to be important in germinal center formation. Bcl-6 protein is expressed mainly by follicle center cells and a few interfollicular T lymphocytes. We analyzed Bcl-6 expression with immunologic methods in common low-grade lymphoproliferative disorders as an aid to differentiation of tumors with follicle center origin. We analyzed Bcl-6 staining of formalin-fixed paraffin-embedded tissue from 72 indolent lymphomas including 31 grade I and II follicle center lymphomas (FCL). 13 small lymphocytic lymphomas (SLL), 12 mantle cell lymphomas (MCL), and 16 marginal zone lymphomas (MZL) including lymphomas of mucosa-associated lymphoid tissue and spleen. All of 31 FCL were positive for Bcl-6 expression. One of 13 SLL and 1 of 12 MCL were positive, whereas none of 16 MZL were positive. Bcl-6 was also detected in 5 of 5 FCL and 1 of 3 MZL but in no SLL or MCL by Western blot analysis in 14 cases with lymphoid disorders. Our study demonstrates that Bcl-6 expression is common in low-grade FCL but is rare in other indolent B-cell lymphoid disorders, and may be a useful adjunct in classification of indolent lymphomas.

Adult↗
PubMed1999

High-level variability in the ORF-K1 membrane protein gene at the left end of the Kaposi's sarcoma-associated herpesvirus genome defines four major virus subtypes and multiple variants or clades in different human populations.

Infection with Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) is common in certain parts of Africa, the Middle East, and the Mediterranean, but is rare elsewhere, except in AIDS patients. Nevertheless, HHV8 DNA is found consistently in nearly all classical, endemic, transplant and AIDS-associated KS lesions as well as in some rare AIDS-associated lymphomas. The concept that HHV8 genomes fall into several distinct subgroups has been confirmed and refined by PCR DNA sequence analysis of the ORF-K1 gene encoding a highly variable glycoprotein related to the immunoglobulin receptor family that maps at the extreme left-hand end of the HHV-8 genome. Among more than 60 different tumor samples from the United States, central Africa, Saudi Arabia, Taiwan, and New Zealand, amino acid substitutions were found at a total of 62% of the 289 amino acid positions. These variations defined four major subtypes and 13 distinct variants or clades similar to those found for the HIV ENV protein. The B and D subtype ORF-K1 proteins differ from the A and C subtypes by 30 and 24%, respectively, whereas A and C differ from each other by 15%. In all cases tested, multiple samples from the same patient were identical. Examples of the B subtype were found almost exclusively in KS patients from Africa or of African heritage, whereas the rare D subtypes were found only in KS patients of Pacific Island heritage. In contrast, C subtypes were found predominantly in classic KS and in iatrogenic and AIDS KS in the Middle East and Asia, whereas U.S. AIDS KS samples were primarily A1, A4, and C3 variants. We conclude that this unusually high diversity, in which 85% of the nucleotide changes lead to amino acid changes, reflects some unknown powerful biological selection process that has been acting preferentially on this early lytic cycle membrane signalling protein. Two distinct levels of ORF-K1 variability are recognizable. Subtype-specific variability indicative of long-term evolutionary divergence is both spread throughout the protein as well as concentrated within two 40-amino-acid extracellular domain variable regions (VR1 and VR2), whereas intratypic variability localizes predominantly within a single 25-amino-acid hypervariable Cys bridge loop and apparently represents much more recent changes that have occurred even within specific clades. In contrast, numerous extracellular domain glycosylation sites and Cys bridge residues as well as the ITAM motif in the cytoplasmic domain are fully conserved. Overall, we suggest that rather than being a newly acquired human pathogen, HHV8 is an ancient human virus that is preferentially transmitted in a familial fashion and is difficult to transmit horizontally in the absence of immunosuppression. The division into the four major HHV8 subgroups is probably the result of isolation and founder effects associated with the history of migration of modern human populations out of Africa over the past 35,000 to 60,000 years.

Africa↗
PubMed1999

Immobilization of invertase in conducting thiophene-capped poly(methylmethacrylate)/polypyrrole matrices.

Immobilization of invertase in thiophene-capped poly(methylmethacrylate)/polypyrrole matrices was achieved by constant potential electrolysis using different supporting electrolytes. Optimum reaction conditions such as substrate concentration, temperature, and pH for the enzyme electrodes were determined. The temperature and pH were found to be 60 degrees C and 4.8, respectively. The effect of supporting electrolyte on the enzyme activity revealed that SDS was the best in the immobilization procedure. Michaelis-Menten constant and the maximum reaction rate in PMMA/PPy matrices were of the order of that of pristine polypyrrole. However, in terms of repeated use, the copolymer matrices were superior to polypyrrole.

Electric Conductivity↗
PubMed1999

Simian virus 40 is present in most United States human mesotheliomas, but it is rarely present in non-Hodgkin's lymphoma.

Simian virus 40 (SV40) causes mesotheliomas, osteosarcomas, ependymomas, choroid plexus tumors, and lymphomas in hamsters. In humans, SV40 has been detected in tumors of the first four types. Using the polymerase chain reaction (PCR), we tested 29 non-Hodgkin's lymphomas (intermediate and high-grade), 25 posttransplant lymphoproliferative disorders, and 5 AIDS lymphomas for SV40 DNA. PCR analysis revealed that 3 of 29 lymphomas, 6 of 25 posttransplant lymphoproliferative disorders, and 2 of 5 AIDS lymphomas contained SV40 sequences corresponding to the retinoblastoma (RB)-pocket binding domain of SV40 tumor antigen (Tag). However, among positive samples, only one posttransplant lymphoproliferative disorder and one AIDS lymphoma contained the SV40 regulatory region, which suggest a higher viral load in these patients. In parallel experiments, 8 of 12 mesotheliomas tested positive for SV40 for both the RB-pocket binding domain of Tag and the SV40 regulatory region. These data confirm the presence of SV40 in most United States mesotheliomas and indicate that in human non-Hodgkin's lymphomas, the prevalence of SV40 is low.

Animals↗
PubMed1998

Geographically distinct HHV-8 DNA sequences in Saudi Arabian Iatrogenic Kaposi's sarcoma lesions.

A new member of the gamma-herpesvirus family, HHV-8 (also known as Kaposi's sarcoma (KS)-associated herpesvirus), has been linked to KS and body cavity-based lymphoma. Other members of this family, eg, Epstein-Barr virus, were originally thought to have only one strain, but subsequent analysis revealed different strains correlating to cellular patterns of infectivity and geographical location. To determine whether multiple strains of HHV-8 exist, we compared DNA sequences among KS and body cavity-based lymphoma-derived HHV-8 and examined differences in HHV-8 subgroups between American and Saudi Arabian iatrogenic KS patients. Samples were analyzed by polymerase chain reaction using multiple primer sets to five different open reading frames from HHV-8, and DNA sequencing was performed. HHV-8 DNA was present in all of our KS and body cavity-based lymphoma samples by polymerase chain reaction. HHV-8 DNA was detected in each body cavity-based lymphoma sample using a majority of the primers, whereas only two primer sets consistently amplified HHV-8 DNA derived from KS lesions. DNA sequencing within open reading frames 26 and 27 indicate the existence of at least three variants of HHV-8, with the majority of iatrogenic KS patients in Saudi Arabia containing unique nucleotide changes that may define a distinct, previously unidentified subgroup we term SA, whereas those from America were of Group A or B. Thus, although the sequencing data within open reading frames 26 and 27 did not permit discrimination between patients with lymphoma versus KS disease processes, HHV-8 derived from Saudi Arabian KS lesions were shown to have a distinct nucleotide sequence not seen in any of the other clinical samples examined.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Monoclonal IgH gene rearrangement in microdissected nodules from nodular sclerosis Hodgkin disease.

Recently, single-cell PCR studies have demonstrated that Hodgkin and Reed-Sternberg (HRS) cells are clonally related in many cases of Hodgkin disease. To investigate the lineage and clonality of neoplastic cells in local environments in nodular sclerosis Hodgkin disease (NSHD), we microdissected multiple distinct nodules from patients with NSHD and analyzed them for IgH gene rearrangement by PCR. These results were correlated with immunophenotype, Epstein-Barr-encoded RNA (EBER) expression, and clinical outcome. Forty individual nodules from 10 patients with NSHD (11 specimens) were microdissected from formalin-fixed paraffin-embedded tissue. DNA extracts were analyzed for IgH gene rearrangement by using PCR with FRIIIa and JHa primers. Cases were immunophenotyped in paraffin sections with antibodies to CD20(L26), CD79a(HM57), CD45RO(A6), CD15 (Leu-M1), and CD30(Ber-H2). Infection of HRS cells by Epstein-Barr virus was evaluated by using EBER in situ hybridization (EBER-ISH). DNA extracts from 12 of 40 microdissected nodules from 8 of 10 patients demonstrated a monoclonal pattern by IgH-PCR. Three patients demonstrated 2 individual nodules with different monoclonal patterns. One patient demonstrated 2 nodules with bands that appeared similar in size but were found to be different from one another upon further testing. All 28 remaining nodules demonstrated a polyclonal pattern. Six of 10 patients were positive for the Epstein-Barr virus genome by EBER-ISH. No correlation was found between IgH monoclonality, immunophenotypic features, Epstein-Barr virus infection, or clinical outcome. It was concluded that a subset of NSHD cases contain detectable monoclonality within individual nodules by IgH-PCR, suggesting that HRS cells are clonally related within local microenvironments.

Adolescent↗
PubMed1998

Molecular and pathologic characterization of an AIDS-related body cavity-based lymphoma, including ultrastructural demonstration of human herpesvirus-8: a case report.

Body cavity-based lymphoma, also known as primary effusion lymphoma, is a newly recognized acquired immunodeficiency syndrome (AIDS)-related lymphoma that has been linked to the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). To date, direct visualization of the virus in a clinical sample has not been demonstrated. We have performed an extensive clinical, histologic, immunophenotypic, ultrastructural, and molecular genetic correlative study on multiple tissue samples obtained premortem and at autopsy from an patient with AIDS with Kaposi's sarcoma and body cavity-based lymphomas. We demonstrate the presence of human herpesvirus-8 in a primary clinical sample at the ultrastructural and molecular level, as well as document multiple lymphomatous tumor masses at autopsy.

Adult↗
PubMed1998

Post-transplantation lymphoproliferative disorder of the NK-cell type: a case report and review of the literature.

Post-transplantation lymphoproliferative disorders (PTLDs) are primarily B-cell disorders that are thought to be Epstein-Barr virus (EBV) driven and that can occur months to years after solid organ or bone marrow transplantation. A small percentage of cases have also been shown to be T-cell phenotype, but a PTLD of NK-cell type has not been previously described. We report here the case of a renal transplant recipient in whom a clinically aggressive, histologically monomorphic PTLD developed that was documented to be of an NK-cell phenotype according to paraffin section and flow cytometric immunophenotyping. Molecular-genetic analysis showed the PTLD to contain germline immunoglobulin heavy, kappa light chain, and T-cell receptor beta and gamma genes. Studies for EBV failed to demonstrate the presence of viral infection in tumor cells. Clinical follow-up showed a rapidly fatal course. To our knowledge, this is the first reported case of an EBV-negative PTLD of true NK-cell type.

Adult↗
PubMed1998

Immunohistochemical analysis of mycosis fungoides on paraffin-embedded tissue sections.

Mycosis fungoides (MF) is typically characterized by dermal and epidermal infiltration of T lymphocytes with a helper/inducer phenotype. Immunophenotypic analysis of such cases was traditionally performed by flow cytometry or immunohistochemistry on cryostat sections. With the advent of new monoclonal antibodies developed against T-cell antigens, including CD3, CD4, CD5, and CD8, it is now possible to immunophenotype T-cell subpopulations in paraffin-embedded tissues. To investigate the potential use of these antibodies for the evaluation of cutaneous lesions, 35 specimens (34 skin and 1 lymph node) from 29 patients with MF were retrospectively reviewed and immunophenotyped in paraffin sections with antibodies to CD3 (T-cell CD3), CD4 (NCL-CD4-1F6), CD5 (NCL-CD5-4C7), CD8 (CD8/144B), and CD20 (L26). Epidermal and dermal distribution of T and B cells were analyzed, and we assessed the ratios of CD4+ to CD8+ T cells. All of our 35 cases demonstrated a predominant CD3+ T-cell population. In 32 cases, the neoplastic cells expressed CD3, CD4, and CD5 consistent with a T-helper/inducer phenotype. In three cutaneous cases, the neoplastic CD4+ T cells showed minimal or absent expression of CD5, indicating an aberrant phenotype. In the majority of cases, minimal CD8+ T cells were present in the background, but in four cases, the CD4:CD8 ratios were 2:1 or less. Thirty-two cutaneous cases demonstrated epidermotropism exclusively by CD4+ T cells; one case showed both CD4+ and CD8+ T cells. In 17 cutaneous cases, scattered dermal CD20+ B cells were found individually or in small clusters within the background surrounding the neoplastic infiltrates. We concluded, therefore, that the immunophenotypic analysis of T-cell subpopulations using monoclonal antibodies of CD3, CD4, CD5, and CD8 was useful for histologic evaluation and confirmation of MF lesions in paraffin-embedded tissue. These antibodies might also provide an effective method of immunophenotyping other neoplastic and non-neoplastic T-cell populations in paraffin-embedded tissues.

Adult↗
PubMed1998

Usefulness of an immunohistochemical panel in paraffin-embedded tissues for the differentiation of B-cell non-Hodgkin's lymphomas of small lymphocytes.

Diagnosis of small B-cell lymphomas is sometimes difficult without fresh tissue for flow cytometry (FC) or immunohistochemistry (IHC). Therefore, we examined the usefulness of a paraffin section IHC panel consisting of antibodies to CD5, CD10, CD20, CD23, CD43, and cyclin D1. We tested 55 formalin-fixed small B-cell lymphomas, including 16 small lymphocytic lymphomas (SLLs), 10 mantle cell lymphomas (MCLs), 25 follicle center lymphomas (FCLs), and 4 mantle zone lymphomas (MZLs). Seventeen cases had B5-fixed sections that were stained in the same manner. The findings were correlated with FC immunophenotyping when available. All of the SLLs and 90% of the MCLs expressed CD5 by IHC, with occasional weak expression in some MCLs. All of the FCLs and MZLs lacked CD5 expression. These results were comparable to those obtained by FC. CD43 expression was seen in 100% of the SLLs, 90% of the MCLs, and 75% of the MZLs. CD23 expression was seen in 94% of the SLL; of these, 100% also showed expression of CD23 by FC. Cyclin D1 was detected in all of the MCLs by IHC but also in 3 of the 16 SLLs. CD23 was absent in all of the MCLs. CD10 expression was present in 21 (95%) of 22 FCLs. All of the 17 cases fixed in B5 showed a decreased immunoreactivity for CD5 in the neoplastic cells. In contrast, CD10 immunoreactivity was judged better in B5-fixed sections. We concluded, therefore, that anti-CD5 and -CD10 were useful tools in the differential diagnosis of B-cell lymphomas of small lymphocytes and that a paraffin-section IHC panel consisting of antibodies to CD5, CD10, CD20, CD23, CD43, and cyclin D1 was a useful ancillary technique that compared favorably with FC.

Antigens, CD↗
PubMed1997

Human herpesvirus-8-associated body cavity-based lymphoma in human immunodeficiency virus-infected patients: a unique B-cell neoplasm.

Human immunodeficiency virus (HIV)-related body cavity-based lymphomas (BCBLs) are known to exhibit unusual clinical, immunophenotypic, and genotypic features, and have recently been found to harbor DNA sequences of a new human herpesvirus, designated Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8). The authors have encountered eight cases of HHV-8-associated BCBL in HIV-infected patients. A literature search revealed an additional 50 reported cases of HIV-related BCBL, as well as reports of several other disorders associated with HHV-8 DNA. Comprehensive analysis of the clinical and pathobiological features of all 58 known cases of HIV-related BCBL shows it to be a unique B-cell neoplasm with a strong propensity for body-cavity involvement without mass lesions and with little or no dissemination, poor prognosis, high grade usually immunoblastic morphology, late B-cell phenotype and genotype, no associated c-myc gene rearrangement, frequent presence of Epstein-Barr virus (EBV) genome, and uniform association with HHV-8 DNA. Considering these features in the context of other disorders associated with HHV-8 DNA, HHV-8 appears to play a causal role in BCBL, possibly in concert with EBV, and may induce this lymphoma through dysregulation of cytokines, particularly interleukin-6, or infection of an unusual B-cell subset. The characteristics of HHV-8-associated BCBL suggest a possible role for antiherpes or anticytokine agents in the treatment of this lymphoma.

DNA, Viral↗
PubMed1997

Human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus in organ transplant patients with immunosuppression.

Several recent studies have demonstrated Kaposi's sarcoma-associated herpes virus (KSHV), also known as putative human herpes virus-8 (HHV-8), DNA in various epidemiologic forms of Kaposi's sarcoma (KS), including AIDS-associated, classic, and endemic types. Risk of developing KS in non-HIV-infected immunosuppressed hosts, such as patients following solid organ transplantation, is also significantly higher compared to normal individuals. We have retrospectively evaluated 28 organ transplant patients with KS (23 cutaneous and five visceral) for the presence of KSHV genome by polymerase chain reaction (PCR) amplification of DNA isolated from formalin-fixed, paraffin-embedded archival tissue samples. 27/28 KS patients were positive for the presence of KSHV. In four KS patients, tissue samples with no histologic evidence of KS were also analysed for KSHV. No evidence of positivity in three samples was noted, but one patient had weak positive amplification products on DNA samples isolated from a gastric biopsy with chronic gastritis and lymph node with sinus histiocytosis. These data support the association of KSHV with KS developing in non-HIV-infected immunosuppressed patients, similar to other forms of KS, and suggest that KSHV may play a significant role in the development of all forms of KS.

Blotting, Southern↗
PubMed1997

Visualization of human herpesvirus type 8 in Kaposi's sarcoma by light and transmission electron microscopy.

BACKGROUND: Human herpesvirus type 8 (HHV-8) has been associated with Kaposi's sarcoma, body cavity-based lymphoma (BCBL), and multicentric Castleman's disease through DNA, in situ hybridization, and serologic studies. HHV-8 has been visualized only in HHV-8-positive/Epstein-Barr virus (EBV)-negative/ cytomegalovirus (CMV)-negative BCBL cell lines, but not in HHV-8-positive/EBV-negative/ CMV-negative Kaposi's sarcoma lesions. DESIGN: Kaposi's sarcoma of the skin, lymph node, and spleen from three patients with AIDS were analysed for HHV-8, EBV and CMV DNA by polymerase chain reaction (PCR), for HHV-8 RNA (Tl.1 riboprobe) by in situ hybridization (ISH), for viral inclusions by light microscopy, and for herpesviruses by transmission electron microscopy (TEM). Sections were also labeled with Tl.1 counterstained with CD34, an endothelial cell marker. RESULTS: The skin lesion was DNA PCR-positive for HHV-8 and CMV (nested, but not single PCR), the lymph node was positive for HHV-8 and EBV, and the spleen was positive for only HHV-8. TEM revealed infection by a virus displaying the typical morphology and cytopathicity of herpesviruses. Hexagonal nucleocapsids and mature enveloped virions were present in vasoformative spindle cells and mononuclear cells, often resembling lymphocytes. Extrapolating from TEM to standard light microscopy on hematoxylin and eosin-stained paraffin sections, eosinophilic, targetoid intranuclear inclusions were identified within spindle cells which often lined vascular lumina. The Tl.1-riboprobe labeled CD34+ spindle cells containing intranuclear inclusions, as well as mononuclear cells within Kaposi's sarcoma and residual lymphoid tissue. CONCLUSION: The herpesvirus visualized in Kaposi's sarcoma lesions has morphologic and cytopathic features typical of human herpesviruses, productively infects vasoformative spindle cells and mononuclear cells, and is consistent with HHV-8. It can also form intranuclear inclusions that are identifiable by light microscopy in hematoxylin and eosin sections and by ISH.

Herpesvirus 8, Human↗
PubMed1996

Follicular lymphoma with involvement of the splenic marginal zone: a pitfall in the differential diagnosis of splenic marginal zone cell lymphoma.

Follicular lymphomas (FL) involving the spleen arise in and expand the germinal centers of the white pulp, whereas mantle cell lymphomas arise in the mantle zone and surround the benign germinal center. The recently described marginal zone cell lymphoma (MZCL) is a B-cell neoplasm characterized by concentric expansion of cells around the follicle, with or without infiltration of the mantle zone or germinal center. In addition, the immunoglobulin heavy chain gene is rearranged although none of the MZCL reported have been shown to be positive for the bcl-2 gene translocation by molecular studies. We report a patient with FL showing preferential involvement of the marginal zone of spleen morphologically mimicking a primary splenic MZCL. The patient reported here had a well-documented previous lymph node diagnosis of FL. The immunoglobulin heavy chain gene and bcl-2 gene rearrangement analysis confirmed the clonal origin of both the original FL, as well as the lymphoma, with a marginal zone pattern in the spleen.

Base Sequence↗