Infectious exposure in the first year of life and risk of central nervous system tumors in children: analysis of day care, social contact, and overcrowding.

Little is known regarding the aetiology of central nervous system tumors in children. Recent studies have speculated on a potential infectious aetiology, but no clear associations have been found. This article uses parent reported questionnaire data from the UK Childhood Cancer Study (UKCCS), a population-based case-control study, to examine the relationship between the infectious exposure in the first year of life and the likelihood of developing a CNS tumor. The variables representing infectious exposure were social contact (including social contact with other infants and attendance at informal and formal day care), sharing a bedroom with another child, birth order, and exposure to a school-age child within the home. Children reported to have had no social contact with other infants in the first year of life displayed an increased risk of developing a CNS tumor when compared to those who had (OR 1.37, 95% CI 1.08-1.75). This effect was most prominent in the primitive neuroectodermal tumor/medulloblastoma subgroup (OR 1.78, 95% CI 1.12-2.83). Those who had attended informal (OR 0.86, 95% CI 0.68-1.09) or formal day care (OR 0.93, 95% CI 0.68-1.26) showed slightly non-statistically significant reduced risks when compared to those reporting social contact only. No association with any of the other variables was observed. Overall, the inconsistent findings by variable and tumor subtype suggest that an early exposure to infections is not strongly implicated in the aetiology of CNS tumors. However, the effect for social contact outside the home, particularly for PNET/medulloblastomas warrants further investigation.

Infections in patients with lymphoma: An analysis of incidence, relationship and risk factors.

INTRODUCTION: Bacterial infections and febrile neutropenia (FN) are major causes of morbidity and mortality in patients with hematological malignancy. The aim of this study was to investigate the incidence and risk factors of infections in lymphoma patients. METHODOLOGY: This retrospective study was conducted on 200 lymphoma patients diagnosed and treated between January 2009 and December 2017 in Diskapi Yildirim Beyazit Training and Research Hospital, a tertiary referral hospital in Ankara, Turkey. RESULTS: The mean follow-up period was 20.09 ± 19.81 months. The incidence of infection episode (IE) was 32.5% (65/200) and FN was 18.5% (37/200). Analysis of the data revealed that patients with IE had significantly higher rates of diagnosis of primary central nervous system lymphoma (PCNSL), lower baseline hemoglobin, lower baseline hematocrit, higher baseline lactate dehydrogenase levels, higher usage of central cathater, and a higher number of chemotherapy lines compared to patients with no IE. In logistic regression analysis, disease subtype of PCNSL, usage of central catheter and lactate deyhydrogenase (LDH) were found to increase the risk of infection. The odds ratio for PCNSL was 37.866 (p = 0.003), 2.679 for central catheter (p = 0.008) and 1.001 for LDH (p = 0.011). CONCLUSIONS: The risk of infection in patients with lymphoma was associated with central catheter usage, higher LDH levels and a diagnosis of PCNSL. Baseline hematological parameters were not determined to have any impact on the occurrence of infection. Patients with these risk factors should be monitored more carefully and the maximum level of infection prevention should be taken.

Population mixing, childhood leukaemia, CNS tumours and other childhood cancers in Yorkshire.

We tested the hypothesis that variation in population mixing attributable to the diversity of migrants moving to an area is associated with the incidence of childhood leukaemia and other childhood cancers. An ecological analysis was performed on 954 children (<15 years) diagnosed with a malignancy between 1986 and 1996 in 532 electoral wards in Yorkshire, UK. Incidence rate ratios (IRR) were calculated for all childhood leukaemias (n=325), acute lymphoblastic leukaemia (ALL) (n=248), central nervous system (CNS) tumours (n=236) and other solid tumours (n=393) Incidence of all childhood leukaemias was significantly lower in areas of high (top decile) population mixing (IRR 0.72, 95% Confidence Interval (CI) 0.54-0.97) and higher in areas of low (bottom decile) population mixing (IRR 1.56, 95% CI 0.73-3.34), but similar patterns of incidence were not observed for central nervous system or other solid tumours. Population mixing may be a proxy for the range of infections circulating in a community and these results are consistent with the hypothesis that greater exposure to infections reduces the risk of developing childhood leukaemia by conferring efficient modulation of the immune system.

Primary central nervous system lymphomas in 72 immunocompetent patients: pathologic findings and clinical correlations. Groupe Ouest Est d'étude des Leucénies et Autres Maladies du Sang (GOELAMS)

We reviewed 72 primary central nervous system lymphomas occurring in immunocompetent patients. The cases were reviewed for clinical data, histology, immunophenotype, bcl-2 and p53 expression, and Epstein-Barr virus association. Follow-up was available for 40 patients included in the Groupe Ouest Est d'étude des Leucénies et Autres Maladies du Sang (GOELAMS) lymphomes cérébraux primitifs (LCP 88) trial. Each diagnosis, requiring a consensus among at least 3 pathologists, was performed according to the recent Revised European-American Lymphoma classification and equivalents in the updated Kiel classification. Tumors were predominantly classified as diffuse large B-cell lymphomas. There were 3 T-cell lymphomas and 1 Hodgkin lymphoma. The proteins bcl-2 and p53 were expressed in 35% and 16% of the tested cases, respectively. Epstein-Barr virus was not found by in situ hybridization except in the case classfied as a cerebral localization of Hodgkin disease. No significant association was found between subtypes, bcl-2 or p53 expression, and patient survival. From the standpoint of their biologic characteristics, primary central nervous system lymphomas are very similar to systemic diffuse large B-cell lymphomas. In contrast to AIDS-related primary central nervous system lymphomas, primary central nervous system lymphomas are rarely associated with Epstein-Barr virus and in immunocompetent patients they express bcl-2 at a relatively low rate.

Intra-cranial lesions in a patient with Hodgkin lymphoma.

Central nervous system (CNS) lesions in newly diagnosed, advanced Hodgkin's disease (HD) commonly suggest intracranial involvement with HD. However, occasionally this could be the result of a CNS infection. We report a case of concurrent CNS tuberculosis in a patient with stage III E HD the first reported in the English literature. Management of this case and the literature pertaining to infectious complications of HD are reviewed.

Investigations of the bacteriological factors in clean neurosurgical wounds.

A number of questions remained unanswered by the empirical success of antimicrobial prophylaxis for neurosurgical patients at The Mount Sinai Hospital during a 15-year period. Vancomycin (1 g intravenously) and tobramycin (80 mg intramuscularly) were administered in the induction room. Streptomycin (50 mg) was mixed into each liter of saline used to irrigate the surgical incision. A series of 45 consecutive clean neurosurgical operations were investigated. The potential sources of random contamination of the surgical wound that were studied included the following: 1) the patient's skin; 2) the flora of the skin and nares of the operating team; 3) the surgical apparel; 4) the surgeons' gloves; and 5) the airborne organisms in the operating theater. No wound infections were documented during a 4-month period between June and September of 1991. A remarkable 98% of the intraoperative cultures of the surgical wounds were free of bacteria. Positive cultures of glove imprints were found in 29% of the operations, and the bacterial source was traced to four different surgeons in four operations (9%). The surgeons' gloves were also a source of potential pathogens (Staphylococcus aureus) in two instances, but the bacterial species were also recovered from cultures of the environment. Based on individual biotyping of bacteria and antibiotic susceptibility testing, no consistent source or pattern could be uncovered for the bacteria in the surgical wound or the operating room air.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuropathology of the acquired immune deficiency syndrome (AIDS): report of 39 autopsies from Vancouver, British Columbia.

Neuropathological findings from 39 acquired immune deficiency syndrome (AIDS) autopsies of primarily neurologically symptomatic patients and 7 brain biopsies from AIDS patients performed at St. Paul's Hospital, Vancouver, British Columbia are reported. Autopsy findings included human immunodeficiency virus-1 (HIV)-type multinucleated giant cell (MNGC)-associated encephalitis seen in 17 patients, toxoplasmosis in 7 patients, and cytomegalovirus encephalitis and/or microglial nodule-associated nuclear inclusions in brain parenchyma in 9 patients. Central nervous system lymphoma was identified in 11 autopsy patients and in 4 of 7 brain biopsies. Infectious processes including HIV encephalitis were seen in 10 of 11 autopsied patients with lymphoproliferative lesions in the brain parenchyma, while 40% of patients without lymphoma had HIV-type MNGC or opportunistic infections. CNS lymphoma was not significantly increased in incidence in patients with a clinical history of zidovudine treatment, but increased duration of survival after the diagnosis of AIDS was associated with increased incidence of lymphoma in both untreated and zidovudine-treated patients. Patients displaying HIV MNGC within microglial nodules had a shorter mean duration of survival after diagnosis of AIDS than those patients with HIV encephalitis with dispersed MNGC, white matter vacuolation, and gliosis.

Epstein-Barr and human immunodeficiency viruses in acquired immunodeficiency syndrome-related primary central nervous system lymphoma.

The prevalence of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in acquired immunodeficiency syndrome (AIDS)-related primary central nervous system (CNS) lymphoma was examined. Deoxyribonucleic acid (DNA) extracted from 12 formalin-fixed, paraffin-embedded tumors was used as substrate for the polymerase chain reaction (PCR). Targets for amplification were the EBNA-1 region of EBV, the gag region of HIV, and a single copy cellular sequence as a control. The cases studied were autopsy and surgical specimens collected between the years 1985 and 1989. By the working formulation for non-Hodgkin's lymphomas, five had large cell, four had mixed large and small cleaved cell, two had small cleaved cell, and one had an unclassified histology. Epstein-Barr virus was detected in 6 of 12 tumors studied. Human immunodeficiency virus was not detected in any of the tumors. The presence of EBV was not correlated with any particular histologic tumor type. It is concluded that EBV, not HIV, can be detected in a large percentage (50%) of AIDS-related primary central nervous system (CNS) lymphomas. This viral association may be significant in light of the demonstrated ability of EBV to induce lymphoid tumors in experimental mammalian systems.

Epstein-Barr virus in AIDS-related primary central nervous system lymphoma.

Primary central nervous system lymphoma occurs more often in patients with AIDS. Epstein-Barr virus (EBV) has been detected in these tumours, but the degree of association has not been defined because of both the highly restricted expression of EBV in malignant tissue and the lack of a technique that is reliable in formalin-fixed paraffin-embedded specimens. EBV-transformed lymphocytes contain short non-protein coding EBV transcripts (EBERs), which are expressed in much higher quantity than other EBV-latency transcripts. We describe a new strategy for detection of latent EBV with these transcripts as targets for in-situ hybridisation. 18 cases of AIDS-related primary CNS lymphoma from a consecutive necropsy series together with specimens from 3 further cases were studied. In each case, a strong positive signal over tumour cells indicated abundant expression of the EBV-EBER1 transcript. This 100% association suggests that the pathogenesis of these AIDS-associated lymphomas may differ from the systemic disease in which only 30-50% of tumours are associated with EBV. A pathogenetic role for EBV was further supported by showing expression of a viral protein (the latent membrane protein) that is implicated as an effector for EBV-associated lymphomagenesis. EBV might have a role as a tumour marker in the diagnosis and management of AIDS-related primary CNS lymphoma.

Epstein-Barr virus in acquired immune deficiency syndrome (AIDS) and non-AIDS primary central nervous system lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) still occurs mainly in patients who are immunosuppressed, but its incidence is rising dramatically among immunocompetent individuals. The Epstein-Barr virus (EBV) has been detected by in situ hybridization in PCNSL tumor tissue from patients who are immunodeficient, but not from patients who are immunocompetent. Using the more sensitive polymerase chain reaction (PCR) technique, the authors analyzed PCNSL tissue from 13 patients with acquired immune deficiency syndrome (AIDS) and 13 patients who were immunocompetent for the presence of EBV genome. METHODS: DNA was extracted from paraffin-embedded biopsy or autopsy specimens. PCR was run using primers for EBV (from the first internal repeat segment of the EBV genome), and identical samples were run simultaneously with primers against actin or the p53 gene as controls to establish the presence of DNA in the sample. Reaction products were also Southern blotted to confirm EBV specificity. RESULTS: EBV was detected in the tumor tissue of 11 of 13 patients (85%) with AIDS and of 7 of 13 patients (54%) who did not have AIDS. There was a history of illness that might suggest or predispose to immune compromise in 5 of 13 patients without AIDS; however, prior illness did not predict EBV-positive tumors. CONCLUSIONS: Although mechanisms remain to be clarified, EBV was present in a high percentage of patients with AIDS-related PCNSL and non-AIDS-related PCNSL:

In situ demonstration of Epstein-Barr virus small RNAs (EBER 1) in acquired immunodeficiency syndrome-related lymphomas: correlation with tumor morphology and primary site.

Some acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARLs) are infected with Epstein-Barr virus (EBV), although the frequency and importance of this association is disputed. Using paraffin section RNA in situ hybridization (ISH) with digoxigenin-labeled riboprobes, we screened 16 central nervous system (CNS) non-Hodgkin's lymphomas (NHLs), 101 systemic NHLs, and 11 Hodgkin's disease cases arising in human immunodeficiency virus-seropositive individuals for EBV-encoded small RNA (EBER 1) expression, an EBV gene product transcribed in abundance during latent infection. Tumor cells contained EBV in 85 of 128 ARLs (66%), but infection rates differed with lymphoma type. EBER 1 was expressed in tumor cells in 11 of 11 Hodgkin's disease cases (100%), 15 of 16 CNS NHLs (94%), and 46 of 60 systemic immunoblast-rich/large-cell lymphomas (77%), but in only 12 of 35 Burkitt-type (small noncleaved cell) (34%) and 1 of 6 monomorphic centroblastic (diffuse large noncleaved cell) (17%) lymphomas. In most EBV-positive ARLs, all recognizable viable tumor cells expressed EBER 1. We conclude that (1) EBV infects tumor cells in all AIDS-related Hodgkin's disease cases, in virtually all primary CNS ARLs, and in most systemic immunoblast-rich/large-cell ARLs; (2) only a minority of Burkitt-type and monomorphic centroblastic lymphomas are associated with EBV; and (3) EBER-ISH is ideal for the histopathologic detection of latent EBV in routine tissue specimens.