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1/65. Case of the month: March 1999--A 26 year old HIV positive male with dura based masses.

    A 26-year-old male with AIDS presented with a chief complaint of headaches and neck pain. An MRI revealed two enhancing extra-axial dura based masses, one in the area of the left sphenoid wing and one at the level of C2-3. In both cases, microscopic sections showed actin positive spindle cell neoplasms with long slender nuclei, consistent with leiomyomas. Both tumors were positive for Epstein Barr virus by in situ hybridization. This case report serves to emphasize the importance of considering soft tissue tumors such as leiomyoma in the differential diagnosis of mass lesions that occur in the central nervous system in AIDS and discusses the role of EBV in tumorigenesis.
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2/65. Epstein-Barr virus-associated adult respiratory distress syndrome in a patient with AIDS: a case report and review.

    BACKGROUND: Epstein-Barr virus (EBV) infection has been associated with fatal pneumonitis in immunocompetent patients. We present a case of fatal adult respiratory distress syndrome caused by EBV infection in a patient with acquired immunodeficiency syndrome (AIDS), to our knowledge the first such reported case, along with a survey of archival autopsy cases to assess baseline expression of EBV in AIDS patients. DESIGN: The case patient's autopsy material was studied exhaustively for infectious agents by culture, histochemistry, and immunohistochemistry, with negative results. Formalin-fixed paraffin-embedded lung, spleen, lymph node, and liver tissue were further studied by in situ hybridization using a probe for EBV early rna (EBER, Kreatech). The same method was applied to lymphoid tissues from eight other archival AIDS autopsy cases. Case patient tissues were also examined by electron microscopy. RESULTS: Strikingly numerous lymphocytes were positive for EBV early rna in the case patient's spleen, lymph nodes, and hepatic portal areas. In addition to positive lymphocytes in the lung, EBV-infected pneumocytes were also present. Electron microscopy also demonstrated viral material in lymphocytes and pneumocytes. Of the archival cases studied, only one spleen was found to have rare positive lymphocytes. CONCLUSION: Primary or reactivation EBV infection may represent a previously underreported cause of morbidity and mortality in AIDS patients. autopsy tissues from AIDS patients do not routinely show overexpression of EBV early rna by in situ hybridization, making this technique ideal for assessing the contribution of EBV to terminal events in these patients.
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3/65. Extensive enteric leiomyolysis due to cytomegalovirus enterocolitis in vertically acquired human immunodeficiency virus infection in infants.

    We report two infants with the acquired immunodeficiency syndrome (AIDS) and rectal bleeding due to cytomegalovirus (CMV) ileitis and colitis with minimal focal mucosal ulceration but with extensive leiomyolysis of the muscularis propria. Immunostaining and in situ hybridization for CMV showed numerous viral inclusions in the myocytes of the muscularis propria and vascular endothelium/smooth muscle with only occasional inclusions present in the muscularis mucosae. colectomy was curative in one patient; in the other the bowel was only examined at postmortem.
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4/65. Condyloma acuminatum presenting as a dorsal tongue lesion in a patient with AIDS.

    Oral lesions have been recognized as a prominent feature of HIV infection and AIDS since the beginning of the epidemic. This report describes the case of a man with advanced AIDS and a nonpainful but enlarging dorsal tongue soft tissue growth of 6 months' duration. Incisional biopsy showed a red, papillary lesion with koilocytosis consistent with condyloma acuminatum. in situ hybridization and molecular techniques were used to identify human papillomavirus (HPV)-31 sequences in warty tissue. Eighteen months later, the lesion recurred and was reexcised without complication. This case is reported to illustrate that venereal transmission may not be as important in warts of the oral cavity as in HIV-associated anogenital warts, because warts of the oral cavity are rarely associated with HPV types 6, 11, 16, and 18. Instead, they may be present as a result of activation of latent HPV infection or perhaps autoinfection from skin and facial lesions. The carcinogenic potential of oral warts in HIV disease is undefined, as is the role of antiretroviral therapy in controlling HPV-associated oral lesions.
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5/65. Multiple Epstein-Barr virus-associated subcutaneous angioleiomyomas in a patient with acquired immunodeficiency syndrome.

    Tumours of smooth muscle origin, either solitary or multiple, are occasionally found in immunocompromised patients, particularly in children with acquired immunodeficiency syndrome (AIDS). Most of the reported AIDS-associated leiomyomatous neoplasms have been found in the visceral organs, and the tumour cells all possessed the Epstein-Barr virus (EBV) genome. Here we present a 32-year-old-man with AIDS who developed three skin nodules on his lower left extremity. No other tumorous lesions were found using computed tomography scans. Two of the three nodules were resected for pathological examination. Histologically, both tumours were well circumscribed and located in the subcutis. The tumours were composed of interlacing fascicles of spindle-shaped cells with prominent vasculature and lymphocytic infiltration. No pleomorphism, mitosis or necrosis was seen. Immunohistochemically, the tumour cells were reactive to smooth muscle actin and desmin. Angioleiomyoma was diagnosed. EBV-encoded small RNAs were also demonstrated in the nucleus of the tumour cells by in situ hybridization but no EBV receptor (CD21) or latent membrane protein (LMP)-1 was found in the tumour cells. No human herpesvirus (HHV)-8 genome was detected in the lesion using polymerase chain reaction analysis. The results of this study indicated that EBV containing subcutaneous angioleiomyoma was another neoplasm that must be considered in patients with human immunodeficiency virus infection who develop skin nodules. The role of EBV in the pathogenesis of this unique neoplasm is still unknown.
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6/65. Vacuolar myelopathy and vacuolar cerebellar leukoencephalopathy: a late complication of AIDS after highly active antiretroviral therapy-induced immune reconstitution.

    Controversy exists as to whether vacuolar myelopathy (VM) responds to highly active antiretroviral therapy (HAART) in a salutary fashion similar to other primary human immunodeficiency virus (HIV)-related neurologic complications such as acquired immune deficiency syndrome (AIDS) dementia complex and progressive multifocal leukoencephalopathy. Herein, we describe the case of a patient with AIDS, non-Hodgkin's lymphoma, and cytomegalovirus colitis, who began HAART and cytotoxic chemotherapy. After 6 months of therapy, restaging studies showed no residual lymphoma or active opportunistic infection. For 2 years he was maintained on HAART, during which time his HIV viral load remained nondetectable and his CD4 count improved from 20 to 300 cells per microliter. Shortly after developing the acute onset of cerebellar ataxia, he aspirated, developed adult respiratory distress syndrome, and died. At autopsy the spinal cord demonstrated a characteristic vacuolated appearance that extended into the cerebellum. No relation between HIV and the development of VM was discerned by in situ hybridization studies. Experience with this one patient suggests that HAART may not alter the natural history of VM. Whether this case represents yet another variant of the recently described inflammatory immune response syndrome whereby progression of previously quiescent disorders evolve to symptomatic disease after initiation of HAART is uncertain.
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7/65. Productive infection of cerebellar granule cell neurons by jc virus in an HIV individual.

    BACKGROUND: In the setting of severe immunosuppression, the polyomavirus JC (JCV) can cause a lytic infection of oligodendrocytes. This demyelinating disease of the CNS white matter (WM) is called progressive multifocal leukoencephalopathy (PML). JCV has a very narrow host-cell range and productive infection of neurons has never been demonstrated. Patient, methods, and results: An hiv-1-infected patient presented with signs of pyramidal tract and cerebellar dysfunction. brain MRI revealed T2 hyperintensities in the WM of both frontal lobes and cerebellar atrophy. His disease progressed despite therapy and he died 6 months later. In addition to classic PML findings in the frontal lobe WM, autopsy revealed scattered foci of tissue destruction in the internal granule cell layer (IGCL) of the cerebellum. In these foci, enlarged granule cell neurons identified by the neuronal markers MAP-2 and NeuN reacted with antibodies specific for the polyomavirus VP1 capsid protein. Electron microscopy showed 40 nm viral particles, consistent with polyomaviruses, in these granule cell neurons. In addition, JCV dna was detected by PCR after laser capture microdissection of cells from the areas of focal cell loss. Finally, in situ hybridization studies demonstrated that many granule cell neurons were infected with JCV but did not contain viral proteins. sequence analysis of the JCV regulatory region from cerebellar virions showed a tandem repeat pattern also found in PML lesions of the frontal lobe WM. CONCLUSION: JCV can productively infect granule cell neurons of the IGCL of the cerebellum. This suggests a role for JCV infection of neurons in cerebellar atrophy occurring in HIV-infected individuals.
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8/65. Primary anaplastic lymphoma kinase-negative anaplastic large cell lymphoma of the brain in a patient with acquired immunodeficiency syndrome.

    Anaplastic large cell lymphoma is a unique diagnostic subcategory of the T-cell lymphomas in the current world health organization classification. Representing approximately 3% of adult and 10% to 30% of childhood non-Hodgkin lymphomas, anaplastic large cell lymphoma classically consists of CD30 large lymphoid cells with abundant cytoplasm and pleomorphic, often horseshoe-shaped or kidney-shaped nuclei. Among the reported nodal and extranodal sites of occurrence, the gastrointestinal tract and central nervous system have rarely been noted. We report a case of primary anaplastic lymphoma kinase-negative anaplastic large cell lymphoma in the brain of a 46-year-old patient with acquired immunodeficiency syndrome. T-cell lineage was confirmed by T-cell receptor gamma chain gene rearrangements using polymerase chain reaction, and extra copies of the anaplastic lymphoma kinase gene of chromosome 2 were demonstrated by fluorescence in situ hybridization analysis. To our knowledge, primary anaplastic large cell lymphoma of the brain has not previously been reported in acquired immunodeficiency syndrome.
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9/65. A case of multifocal lupus vulgaris that preceded pulmonary tuberculosis in an immune compromised patient.

    We describe the rare case of a Japanese male with multifocal lupus vulgaris that preceded asymptomatic pulmonary tuberculosis and adult T-cell leukemia/lymphoma (ATL). He visited our hospital with multiple reddish plaques and erythema of 4-12 months duration. A skin biopsy revealed non-caseating epithelioid granulomas. mycobacterium tuberculosis was detected by polymerase chain reaction (PCR)-hybridization from a skin biopsy specimen and was also isolated from a culture of the skin biopsy sample. The result of chest roentogenography was compatible with pulmonary tuberculosis. In addition, the diagnosis of ATL was based upon the presence of atypical lymphocytes with convoluted nuclei in his peripheral blood and a positive anti-ATL antibody reaction. Cases of cutaneous tuberculosis presenting with unusual clinical features may be on the increase, accompanying the spread of tuberculosis in immunosuppressed patients, including those with ATL and acquired immunodeficiency syndrome (AIDS).
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10/65. Unusual oral presentation of non-Hodgkin's lymphoma in association with HIV infection.

    In 4.4% of human immunodeficiency virus-associated non-Hodgkin's lymphoma the presenting lesion is seen in the mouth. Often the lesion may clinically resemble a less sinister process, and a definitive diagnosis of lymphoma may be delayed. We describe three unusual cases of non-Hodgkin's lymphoma, appearing intraorally in association with other oral lesions, in HIV-positive homosexual men. The three patients reported here were all diagnosed as having diffuse, large-cell malignant non-Hodgkin's lymphoma. We performed Epstein-Barr virus dna in-situ hybridization on our cases and Epstein-Barr virus dna sequences were not seen. We review the pertinent literature and stress the importance of including non-Hodgkin's lymphoma in the differential diagnosis of oral lesions in patients at risk of HIV infection.
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