AIDS-related primary brain lymphomas: histopathologic and immunohistochemical study of 51 cases. The French Study Group for HIV-Associated Tumors.

Fifty-one cases of acquired immunodeficiency syndrome (AIDS)-related primary brain lymphomas (AR-PBL) were investigated for clinical characteristics; human immunodeficiency virus (HIV)-associated disorders; histopathologic features; immunophenotype; Epstein-Barr virus (EBV) infection; and, when frozen tissue was available, oncogene rearrangements. AR-PBL occurred late in the course of AIDS and were usually associated with other systemic or cerebral disorders and with a low level of CD4 lymphocytes. All cases were high grade lymphomas according to the Working Formulation or updated Kiel classification, and often displayed a multifocal pattern. Thirty cases were classified as immunoblastic with plasmacytic differentiation, 18 cases were large cell lymphomas with an immunoblastic component or centroblastic polymorphic lymphomas, and 2 were small noncleaved non-Burkitt lymphomas (Working Formulation). This latter category is classified as Burkitt's-like lymphoma in the REAL nomenclature. One case could not be classified because of necrosis. AR-PBL showed a high level expression of activation and adhesion molecules. The presence of EBV was detected in most cases, and, when PCR was used, this was a constant finding. bcl-2 oncoprotein and latent membrane protein-1 (LMP-1) were strongly expressed. None of the tested cases expressed p53, or were rearranged for bcl-2 or c-myc oncogenes. This study confirms the immunophenotypic specificity of AR-PBL, which may reflect the special immune status of the brain.

Expression of the bcl-2 protein in B cell lymphomas arising from mucosa associated lymphoid tissue.

AIM: To determine whether lymphomas arising from mucosa associated lymphoid tissue (MALT) express the bcl-2 protein. METHODS: Forty two cases of MALT B cell lymphomas, 20 low grade neoplasms and 22 high grade tumours, were studied. Immunohistological staining was performed on paraffin wax embedded tissue using a monoclonal antibody specific for the bcl-2 protein. RESULTS: All of the low grade lymphomas gave positive results on staining, with clear cytoplasmic labelling for bcl-2 protein in the small neoplastic cells, some of which formed characteristic lympho-epithelial lesions. A striking feature was that larger bcl-2 negative cells were observed in nine of these tumours. They were either scattered singly among the small neoplastic cells or formed small clusters, suggesting that they could represent early areas of transformation to high grade neoplasia. Germinal centres in the vicinity of the tumours lacked bcl-2 protein and hence contrasted clearly with the neoplastic cells. In some cases this permitted germinal centres, which were not obvious on conventional histological staining, to be recognised. In 20 of the 22 cases of high grade B cell lymphoma the large neoplastic cells were bcl-2 negative; the remaining two cases, however, contained a proportion of large neoplastic bcl-2 positive cells. In four of the 22 cases of high grade tumours a low grade component was found which expressed bcl-2 in all cases. CONCLUSION: Bcl-2 protein is expressed in low grade, but not in most high grade, MALT lymphomas. In view of recent data indicating that most high grade nodal lymphomas express bcl-2, these findings suggest that MALT lymphomas may regulate bcl-2 gene expression differently to nodal lymphomas.

In vivo expression of IL-1 beta and IL-6 genes during viral infections in human.

Macrophage infiltration is a constant feature of human virus-infected tissues. However, the in situ functional status of these cells remains undetermined. In order to document an activation of macrophages in virus-infected tissues, the expression of IL-1 beta and IL-6 genes was analyzed using in situ hybridization. Several tissues were studied, as well as infections induced by different viruses: lymph nodes infected by HIV-1 (9 cases) or EBV (one case), lungs infected by CMV (5 cases) or adenovirus (1 case), livers infected by HBV, either chronically (2 cases) or acutely (7 cases presenting a fulminant hepatitis). With the exception of fulminant HBV hepatitis, IL-1 beta and IL-6 genes were expressed in all cases. IL-1 beta and IL-6 genes were usually coordinately regulated, as cells containing IL-1 beta or IL-6 mRNA were present in identical amounts and displayed a similar distribution. Analysis of the location and the morphology of monokine gene-expressing cells indicated that both small macrophages and endothelial cells expressed IL-1 beta and IL-6 genes. However, neither tingible body macrophages present in lymph node follicles nor Kupffer cells expressed these genes at a detectable level. Infected cells themselves were also negative for monokine gene expression. These findings indicate that expression of IL-1 beta and IL-6 genes by reactive cells may play a role in viral spreading limitation as well as virus-induced tissue damage.

Primary Epstein-Barr virus-related non-Hodgkin's lymphoma of the pleural cavity following long-standing tuberculous empyema.

Primary non-Hodgkin's lymphomas of the pleural cavity have been described mostly in Japan. We report a case of high-grade non-Hodgkin's lymphoma (immunoblastic type) of the pleural cavity occurring in a nonimmunocompromised patient 55 years after an artificial pneumothorax was performed for the treatment of pulmonary tuberculosis. Immunohistochemical study revealed a B phenotype (CD20), and an in situ hybridization detected small nuclear RNAs encoded by Epstein-Barr virus in most lymphomatous cells. A link between primary pleural lymphoma and the local long-standing chronic inflammation, inducing a clonal transformation of Epstein-Barr virus-infected immortalized B lymphocytes, is suspected.

Assessment of dysplasia, mucosal mucins, p53 protein expression, and DNA content in ulcerative colitis patients with colectomy and ileorectal anastomosis.

BACKGROUND: Patients with ileorectal anastomosis after colectomy for ulcerative colitis remain at risk of developing rectal malignancy. Detection of mucosal dysplasia has been used for regular screening but is difficult in inflammatory mucosa, prompting the search for complementary markers. METHODS: This prospective study aimed to assess the prevalence of dysplasia, the predominance of sialomucin, DNA aneuploidy, and p53 overexpression as possible predictors of colorectal tumourigenesis, in the rectal mucosa of an unselected group of 27 patients with ileorectal anastomosis performed for ulcerative colitis. Patients had neither neoplastic nor dysplastic lesions on the colectomy specimen and the retained rectum at the time of surgery. One biopsy specimen of each lateral rectal wall was studied, using routine histology, mucin histochemistry, DNA flow cytometry, and the streptavidin-biotin complex method with D07 monoclonal antibodies directed towards the p53 protein. RESULTS: Seventeen, seven, and three patients showed inflammatory lesions of inactive, moderate, and severe active colitis, respectively. Dysplasia, sialomucin predominance, DNA aneuploidy, and p53 overexpression were not detected. CONCLUSIONS: The risk of malignant transformation of the rectal mucosa after ileorectal anastomosis seemed to be low in this ulcerative colitis group without high-grade dysplasia or carcinoma in the previous colectomy specimen, carefully followed up endoscopically and histologically. It remains to be evaluated which of the methods studied above will optimize the histopathologic surveillance of the rectal mucosa of ulcerative colitis patients with ileorectal anastomosis.

Expression of cell adhesion molecules by microvascular endothelial cells in the cortical and subcortical regions of the normal human brain: an immunohistochemical analysis.

We studied the repertoire of junctional, cell-matrix and leucocyte-endothelial adhesion molecules normally expressed by cortical and subcortical brain microvessels, as compared with large intracranial vessels. An indirect immunoperoxidase method was applied to acetone-fixed cryostat sections of normal brain tissue obtained from 10 adult patients during surgical resections for intracranial aneurysms or at autopsy. Like large intracranial vessels, brain microvessels expressed the two endothelial-specific junctional cell adhesion molecules VE-cadherin and platelet-cell adhesion molecule-1. We verified that they also expressed the molecular components of adherens-type junctions, including catenins, plakoglobin, vinculin and alpha-actinin. Brain microvessels expressed a large repertoire of integrin molecules of the beta 1, beta 3 and beta 4 subfamilies. However, they displayed apparently lower levels of alpha 2, alpha 5, alpha V and beta 3 integrin chains than large intracranial vessels. Brain microvessels constitutively expressed large amounts of the leucocyte-endothelial adhesion molecules, intercellular adhesion molecule (ICAM)-2 and CD34 and very low amounts of ICAM-1 and lymphocyte function-associated antigen-3. In contrast to large intracranial vessels, brain microvessels presented no constitutive expression of P-selectin. Our study shows that, in contrast to their highly specific structural and functional characteristics, brain microvascular endothelial cells present a repertoire of cell adhesion molecules very similar to that of most other capillary vessels in the body.

Monokine gene expression in normal human liver: selective involvement of the portal compartment.

Monokines play a major role in the regulation of hepatocyte functions. To document a possible in situ production of these mediators under physiological conditions, expression of IL-1 beta and of IL-6 genes was analyzed by in situ hybridization in four histologically normal human livers. We detected cells containing IL-1 beta mRNA or IL-6 mRNA in all cases. Cells expressing either the IL-1 beta gene or the IL-6 gene were found with equal frequency and were similarly distributed. Although present in all liver compartments, they were selectively enriched in portal areas, in which they were detected both in endothelial positions and in perivascular connective tissues. Few positive cells were observed in hepatic lobules, most of them being located in the walls of centrolobular veins, in an endothelial position. Subcapsular cells were also shown to express monokine genes. The location of positive cells and their pattern of labelling suggested that macrophages, fibroblasts and endothelial cells were the main cell populations expressing monokine genes. In contrast, Kupffer cells, biliary epithelial cells and hepatocytes did not express monokine genes. No marker of immune activation other than monokine gene expression was detected in these histologically normal livers. The expression of the IL-1 beta gene and of the IL-6 gene may be induced by gut-derived LPS, and could play a role in the modulation of hepatocyte function in normal liver.

Regression of rectal stenosis secondary to neoplasm in an HIV1-positive patient with gancyclovir antiviral therapy: report of a case.

PURPOSE: The case of a human immunodeficiency virus-positive patient with rectal stenosis caused by a tumor that completely regressed in response to gancyclovir is presented. METHODS: Several biopsies from the tumoral mass failed to show any stigmata of non-Hodgkin's lymphoma, adenocarcinoma, or Kaposi sarcoma. No parasites could be detected in rectal biopsies. Viral inclusions showing both Epstein-Barr virus and cytomegalovirus on immunostained sections suggested an unusual form of viral infection. RESULTS: Antiviral therapy (gancyclovir 10 mg/kg/day) had a dramatic effect on pain and discharge of blood, and suppressed rectal difficulties within three days of therapy. The antiviral treatment was stopped at Day 10 because of leukopenia. Endoscopic and histologic examinations revealed normal rectal mucosa after 3, 6, 9, 12, and 18 months of follow-up. CONCLUSION: This is the first case of complete and long-term regression of a rectal stenosis secondary to a tumoral mass in response to antiviral therapy in patients with human immunodeficiency virus.

Human herpesvirus 6 infection associated with anticonvulsant hypersensitivity syndrome and reactive haemophagocytic syndrome.

Viral infections are thought to play a part in some cutaneous drug reactions. Human herpesvirus 6 (HHV6), which is the agent of exanthema subitum (sixth disease), has never been implicated in a drug reaction. We report a patient with severe phenobarbital-induced anticonvulsant hypersensitivity syndrome in whom a fulminant haemophagocytic syndrome was associated with HHV6 infection. We discuss the possible role of HHV6 in this reactive condition.