Nora C. J. Sun

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‐Hodgkins 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. Am. J. Hematol. 58:130–136, 1998.

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.

Histological and immunohistochemical characterization of extranodal diffuse large-cell lymphomas with prominent spindle cell features.

Histological and immunohistochemical characterization of extranodal diffuse large‐cell lymphomas with prominent spindle cell features

Simultaneous detection of ferritin and HIV-1 in reactive microglia

SummaryUsing 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 penencephalitis, 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 territin-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 colabeled with the microglial marker, Ricinus communis agglutinin 1 (RCA-1). Howerver, RCA-1 also extensively stained resting microglia only a few of which were colabeled 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.

Herpes Simplex Virus Lymphadenitis: Case Report and Review of the Literature

Localized or regional necrotizing lymphadenitis is an extremely uncommon manifestation of herpes simplex virus (HSV) infection. We report a case of necrotizing HSV lymphadenitis in a patient with both common variable immunodeficiency and natural killer cell deficiency and review the literature on this unusual complication of HSV infection.

HIV-1 Heterogeneity and Cytokines

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.

Simultaneous occurrence of hodgkin's disease and kaposi's sarcoma in a patient with the acquired immune deficiency syndrome

Kaposis sarcoma and Hodgkins disease have each been associated with abnormalities in T lymphocyte function and occur with increased frequency in the immunosuppressed host. Although the association of Kaposis sarcoma with lymphoreticular disorders has long been recognized, only sporadic cases of Hodgkins disease have been described in patients with the acquired immune deficiency syndrome (AIDS) in contrast to the frequent occurrence of non-Hodgkins lymphoma in these patients. The simultaneous occurrence of Kaposis sarcoma and Hodgkins disease in the same lymph node is described in a patient with AIDS. This case suggests an association of AIDS with both Kaposis sarcoma and malignant lymphomas and raises the question of a common pathogenetic mechanism.

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.

Plasmablastic lymphoma may occur as a high-grade transformation from plasmacytoma

Plasmablastic lymphoma (PBL) is an uncommon aggressive lymphoma arising most frequently in the oral cavity of HIV-infected patients. Rare cases of PBL have been reported in extraoral sites, particularly extranodal sites, as well as in immunocompetent patients. We report an unusual case of PBL in a 69-year-old, HIV-negative non-immunocompromised man presenting with generalized lymphadenopathy. To our knowledge, this is the first case of PBL presented as primarily generalized lymphadenopathy in HIV-negative patients. Histologic examinations of cervical, inguinal and axillary lymph nodes demonstrated a neoplastic proliferation of large cells with extensive necrosis. The neoplastic cells formed sheets with a relatively cohesive growth pattern interspersed by small lymphocytes and plasma cells. The large tumor cells expressed MUM1, OCT-2 and BOB.1, and were negative for CD138, CD38, AE1/AE3, melan A, PLAP, S100, vimentin, CD117, CD30, ALK-1, leukocyte common antigen (CD45), T-cell, B-cell and histolytic markers, CD56, CD10 and BCL-6. The proliferation index by Ki-67 immunohistochemistry was approaching 100%. In situ hybridization for Epstein-Barr Virus-encoded RNA (EBER) was positive in large malignant cells. A diagnosis of PBL was made. These findings indicate that PBL should be included in the differential diagnosis of an HIV-negative, immunocompetent patient with generalized lymphadenopathy. The adjacent plasma cells were positive for CD138 and CD38 and show kappa-light chain restriction, but without EBER expression, raising the possibility of a preexisting or concurrent plasmacytoma and that the PBL may be a high-grade transformation from a preexisting plasma cell neoplasm following Epstein-Barr virus infection. Electron microscopy showed numerous circumferential long slender peripheral cytoplasmic projections in the large tumor cells, suggesting that some of the previously reported large B-cell lymphoma with cytoplasmic projections may actually be PBL.

Changing pattern of AIDS: a bone marrow study.

We compared bone marrow findings in 2 groups of patients with AIDS during 2 different periods: group 1, n = 20; male/female ratio, 19/1; and group 2, n = 120; male/female ratio, 6/1. Bone marrow iron stores were decreased significantly in group 2 (P < .01), and the incidence of AIDS-related lymphomas was higher, with frequent bone marrow involvement. Two group 1 patients had Kaposi sarcoma, and a 21-month-old girl with transfusion-transmitted AIDS had Burkitt-like lymphoma. In group 2, 44 patients had a history of malignant neoplasms, including Kaposi sarcoma (10 cases), hematologic neoplasms (33 cases), and metastatic leiomyosarcoma (1 case). Of the 120 patients, 15 (12.5%) had bone marrow involvement by malignant neoplasms. The majority of the non-Hodgkin lymphomas were high-grade lymphomas. Patients with AIDS-related malignant neoplasms had higher CD4+ cell counts and viral loads than patients without malignant neoplasms (P < .01, P < .05, respectively). The finding of decreased iron stores in patients with AIDS might aid clinical management of their anemia. The increased incidence of malignant neoplasms, especially lymphomas, in recent years might be related to prolonged survival but with incomplete reconstitution of immune function after antiretroviral therapy.