Cases reported "Lymphoma, AIDS-Related"

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1/24. Epstein-Barr virus-associated intravascular lymphomatosis within Kaposi's sarcoma in an AIDS patient.

    Intravascular lymphomatosis (IL) is an unusual neoplasm characterized by multifocal proliferation of lymphoma cells exclusively within the blood vessels. We report here a patient with acquired immunodeficiency syndrome (AIDS) and disseminated Kaposi's sarcoma. A 233-bp amplification product of HHV-8 was detected in the dna extracted from specimens of Kaposi's sarcoma at different sites by polymerase chain reaction (PCR). At autopsy, the vessels within the Kaposi's sarcoma were dilated and filled with atypical large mononuclear cells. No such feature was seen in the vessels of non-Kaposi's sarcomatous regions. Immunohistochemically, the spindle cells of Kaposi's sarcoma were positive for CD31 (endothelial cell marker). The intravascular tumor cells were positive for CD45 (leukocyte common antigen) but negative for others, including chloroacetate esterase, CD45-RO (UCHL-1, Pan-T), CD3, CD43, CD20 (L26, Pan-B), CD30 (Ki-1), immunoglobulin heavy chains and light chains, CD56 (natural killer cell antigen), and CD31. Monoclonal rearrangement of immunoglobulin heavy chain gene was detected in the dna extracts from fresh tissue of Kaposi's sarcoma by PCR, which indicated that the lymphoma cells within the Kaposi's sarcoma were of monoclonal B cell origin. in situ hybridization revealed that EBER-1 transcripts were present in the lymphoma cells of IL but not in the spindle cells of Kaposi's sarcoma. To the authors' best knowledge, this is the first instance of IL in an AIDS patient with direct evidence of EBV association.
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2/24. Peripheral T-cell lymphoma with Toutonlike tumor giant cells associated with HIV infection: report of two cases.

    T-cell lymphoma in patients infected with HIV is much less common than B-cell lymphoma. We describe two cases of HIV-associated extranodal lymphoma that showed Toutonlike tumor giant cells and mononuclear large lymphoma cells. Both cell types expressed T-cell-associated antigens, including CD3, CD5, CD43, and CD45RO, and were CD4- and CD30-positive and negative for all B-lineage-associated antigens. Both cases showed T-cell receptor gamma chain gene rearrangements using the polymerase chain reaction and were negative for the Epstein-Barr virus by in situ hybridization. Despite the expression of CD30 by the multinucleated cells, both cases were negative for ALK1 by immunohistochemistry and failed to show evidence of the nucleophosmin-anaplastic lymphoma kinase fusion product characteristic of t(2;5) using the reverse-transcriptase polymerase chain reaction. Although rare, CD4-positive, T-cell lymphoma with Toutonlike giant cells may be a distinct type of HIV-associated malignant lymphoma.
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3/24. Virological and molecular characterisation of a new B lymphoid cell line, established from an AIDS patient with primary effusion lymphoma, harbouring both KSHV/HHV8 and EBV viruses.

    We report here a new case of primary effusion lymphoma (PEL), occurring in a French homosexual hiv-1 infected male with a pericardial, pleural and mesenteric tumour dissemination, and the establishment from his pleural effusion of a new cell line, Cra-BCBL, dually infected by EBV and KSHV/HHV8. Cra-BCBL cells are of B-cell origin as judged by their clonal immunoglobulin heavy chain (IgH) gene rearrangement, identical to that of the parental tumour. Both the cell line and the lymphoma cells expressed CD38 and CD45 antigens but no classical B-cell or T-cell lineage-restricted antigens. Cra-BCBL harbours a type I EBV virus, expressing a latency type II. Expression of KSHV/HHV8 ORF72 and ORF75 was detected by RT/PCR. In addition, KSHV lytic replication could be induced by treatment by n-butyrate. An equivalent and high copy number of KSHV genomes (20 to 200 copies by cell) was detected both in the primary tumour cells and in the cell line. Southern blot (SB) analysis of EBV terminal repeats (TR) displayed the same unique band in the cell line dna and in the original tumour cells, consistent with a monoclonal infection of EBV. Furthermore, SB analysis of KSHV/HHV8 TR revealed the same hybridisation pattern between Cra-BCBL and the effusion cells, with a common band at around 30-40 kb corresponding to the fused termini of the viral episomes and a 5 Kb rearranged fragment. The new cell line characterised here could be a useful model to study interactions between two human herpes viruses and their contribution to lymphomagenesis.
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4/24. Ongoing hypermutation in the Ig V(D)J gene segments and c-myc proto-oncogene of an AIDS lymphoma segregates with neoplastic B cells at different sites: implications for clonal evolution.

    To investigate the role of somatic Ig hypermutation in the evolution of AIDS-associated B cell lymphomas, we analyzed the Ig V(D)J and c-myc genes expressed by neoplastic B cells in two extranodal sites, testis and orbit, and clonally related cells in the bone marrow. testis and orbit B cells expressed differentially mutated but collinear V(H)DJ(H), V kappa J kappa and c-myc gene sequences. Shared mutations accounted for 10.2%, 8.4%, and 4.3% of the overall V(H)DJ(H), V kappa J kappa, and c-myc gene sequences. Tumor-site specific V(H)DJ(H), V kappa J kappa, and c-myc mutations were comparable in frequency, and a single point-mutation gave rise to an EcoRI site in the testis c-myc dna. Both shared and tumor site-specific V(H)DJ(H), V kappa J kappa, and c-myc mutations displayed predominance of transitions over transversions. The "neoplastic" V(H)DJ(H) sequence was expressed by about 10(-5) cells in the bone marrow, and contained two of the three orbital, but none of the testicular V(H)DJ(H) mutations. The nature and distribution of the Ig V(D)J mutations found in the kappa chain suggested a selection by antigen in testis and orbit. Our data suggest that, in AIDS-associated B cell lymphomas, the Ig hypermutation machinery targets V(H)DJ(H), V kappa J kappa, and c-myc genes with comparable efficiency and modalities.
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5/24. Primary hepatic anaplastic large-cell lymphoma of T-cell phenotype in acquired immunodeficiency syndrome: a report of an autopsy case and review of the literature.

    Anaplastic large-cell lymphomas (ALCL) were first described by Stein et al. in 1985 as large-cell neoplasms with a pleomorphic appearance, subtotal effacement of the lymph node structure, and expression of the lymphoid activation antigen CD-30 (Ki-l). Since their first description, these tumors have been documented in a variety of extranodal sites. We report a primary hepatic anaplastic large-cell lymphoma in a patient with advanced AIDS, who presented with hepatic failure and multiple nodules in the liver. A complete autopsy showed discrete tumor nodules throughout the entire liver without gross or microscopic involvement of lymph nodes or any other organs by the neoplastic process. The tumor cells showed typical histological and immunohistochemical features of ALCL and were strongly immunoreactive with the T-cell markers CD-3 and UCHL-1. Only one previous case of primary hepatic ALCL has been reported in the literature, and this tumor occurred in an immunocompetent patient and was not immunoreactive for B- or T-cell markers. To our knowledge, this study represents the first reported case of primary hepatic anaplastic large-cell lymphoma of T-cell phenotype. Additionally, this is the first case of primary hepatic ALCL reported in an AIDS patient.
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6/24. Primary effusion lymphoma with herpesvirus 8 dna in patients coinfected with HIV and hepatitis c virus: a report of 2 cases.

    The primary effusion lymphoma (PEL), commonly described in patients with AIDS, is a unique subset of diffuse large cell lymphoma in which the malignant lymphocytes proliferate exclusively in serous cavities. The cytologic, immunophenotypic, and molecular features of PEL are presented from findings of 2 patients coinfected with HIV and hepatitis c virus who presented with abdominal pain. Abdominal radiography in both patients displayed marked peritoneal effusions. Cytomorphologic examination of peritoneal fluid revealed a malignant lymphoma in both. Their immunophenotypic expression was CD30 (Ki-1) and epithelial membrane antigen. Molecular analysis demonstrated human herpesvirus 8 dna in both patients and bcl-2 oncogene rearrangement within the major breakpoint region of t(14;18) chromosome translocation in Case B only. Clinical correlation supports the current concept that PEL represents a primary HIV/AIDS-related lymphoma in effusion. Cytomorphologic examination of body cavity fluid serves as a tool for the initial diagnosis of PEL.
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7/24. Concomitant progressive multifocal leucoencephalopathy and primary central nervous system lymphoma expressing jc virus oncogenic protein, large T antigen.

    This report describes the concomitant occurrence of the jc virus (JCV) induced demyelinating disease progressive multifocal leucoencephalopathy (PML) and a primary central nervous system lymphoma (PCNS-L) in a patient with AIDS. Postmortem neuropathological examination revealed characteristic features of PML including multiple lesions of demyelination, enlarged oligodendrocytes with hyperchromatic nuclei (many containing eosinophilic intranuclear inclusions), and enlarged astrocytes with bizarre hyperchromatic nuclei. Immunohistochemical analysis demonstrated the expression of the JCV capsid protein VP-1 in the nuclei of infected oligodendrocytes and astrocytes. The PCNS-L lesion located in the basal ganglia was highly cellular, distributed perivascularly, and consisted of large atypical plasmacytoid lymphocytes. Immunohistochemical examination of this neoplasm identified it to be of B cell origin. Moreover, expression of the JCV oncogenic protein, T antigen, was detected in the nuclei of the neoplastic lymphocytes. This study provides the first evidence for a possible association between JCV and PCNS-L.
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8/24. New insights into transmission, diagnosis, and drug treatment of pneumocystis carinii pneumonia.

    pneumocystis carinii has been recognized as a human pathogen for nearly 50 years. We present a case of P carinii infection that typifies clinical presentation in the era of the acquired immunodeficiency syndrome epidemic. The high incidence of P carinii pneumonia in persons infected with human immunodeficiency virus (HIV) has served to focus laboratory and clinical research efforts on better understanding the biology of the organism and on improving diagnosis, treatment, and prevention of this disease. Although inability to culture P carinii has hampered research efforts, molecular and immunologic approaches have led to the recognition that the organism represents a family of fungi with a very restricted host range and have allowed characterization of clinically relevant antigens and enzymes. Molecular epidemiologic studies have identified more than 50 strains of human-derived P carinii and have suggested that recently acquired infection, as opposed to reactivation of latent infection, may account for many cases of clinical disease. diagnosis has been improved by the development of organism-specific monoclonal antibodies and, more recently, by polymerase chain reaction using multicopy gene targets, together with induced sputum or oral wash samples. Chemotherapeutic prophylaxis is very effective in preventing P carinii pneumonia; the combination of trimethoprim-sulfamethoxazole remains the first-line agent for both therapy and prophylaxis. Prophylaxis needs to be administered only during periods of high risk; in HIV-infected patients responding to effective antiretroviral therapies, prophylaxis no longer needs to be lifelong. Molecular studies have identified mutations in the target of sulfa drugs that appear to represent emerging resistance in P carinii. Resistance to atovaquone, a second-line agent, may also be developing.
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9/24. Regression of a plasmablastic lymphoma in a patient with HIV on highly active antiretroviral therapy.

    We describe an HIV-infected 44-year-old man who presented 1 month after discontinuation of HAART therapy with a large mass extending from the mediastinum, enclosing the heart and extending through the diaphragm to the epigastric region. Biopsies subsequently revealed a highly aggressive non-Hodgkin's lymphoma (NHL) producing sheets of cells with an organoid distribution. The cells had abundant basophilic cytoplasm and a plasmacytic appearance. Although immunohistochemistry failed to show either B- or T-cell markers, antigens consistent with plasma cells were found. An immunoglobulin heavy chain clonal rearrangement was identified by PCR analysis. These studies were supportive of a diagnosis of a plasmablastic lymphoma. While awaiting the results of these tests, the patient was reinitiated on his HAART regimen. He was found on follow-up a month later to have complete resolution of his bulky mediastinal mass. He remained free of disease for 3 months with subsequent rectal and abdominal recurrence. Treatment with CHOP chemotherapy with filgrastim support was begun which resulted in another remission. Plasmablastic lymphoma is now reported in some studies to account for 2.6% of all HIV-related NHL. Originally described in 1997 in a series of 16 patients, this entity is highly associated with HIV infection in its later stages. Often, patients present with oral or jaw lesions with a rapidly progressive course. The tumors have the morphologic appearance of a plasmacytoid tumor with high proliferative index. Markers are positive mainly for LCA, CD79a, VS38C, and CD138. Co-infection with HHV-8 and EBV has not been consistently reported. Therapy with standard regimens has variable response. One case has been reported with a 3.5 year disease free survival. The regression of disease after resumption of HAART therapy alone in this patient suggests that HAART has an important role in the treatment of lymphoma in the HIV infected patient.
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10/24. Natural killer-like T-cell lymphoma of the parotid in a patient infected with human immunodeficiency virus.

    A 42-year-old man with acquired immunodeficiency syndrome developed a mass of the right parotid gland and multiple hepatic masses. hematoxylin-eosin-stained sections of the parotid lesion showed a diffuse infiltrate of large mononuclear cells with vesicular nuclei and prominent nucleoli, consistent with a non-Hodgkin lymphoma. Immunohistochemical stains demonstrated expression of the T-cell markers CD3 and UCHL-1, as well as latent membrane protein 1 and T-cell intracellular antigen 1. flow cytometry showed surface expression of CD2, CD3, CD7 (dim), CD8, and CD56. CD5 was not expressed. Molecular evaluation by polymerase chain reaction demonstrated monoclonal rearrangement of the T-cell receptor gamma gene. Epstein-Barr virus early rna and human immunodeficiency virus rna were demonstrated by in situ hybridization. To our knowledge, this is the first reported case of T-cell lymphoma of the parotid in a patient infected with human immunodeficiency virus. After 2 separate chemotherapy regimens, the patient achieved clinical remission for 1(1/2) years; he then developed progressive pulmonary lesions and died.
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