Oral Burkitt's lymphoma in children: the Moroccan experience.

Thirty-seven children with Burkitt's lymphoma of the oral region diagnosed between 1998 and 2005 were reviewed. There were 31 boys and 6 girls. The mean age at diagnosis was 6.64 years (range 2-15 years) with a mean delay to diagnosis of 41 days (range 10 days-2 months). There was a predominance of maxillary over mandibular involvement: 1.44:1. Complaints included exophytic mass with dental displacement (100%), abdominal pain (68%), nerve palsy (28%) and orbital swelling (21%). Toothache as initial complaint led to dental extraction in 12 cases. According to the Murphy classification, there were 4 stage II, 11 stage III and 22 stage IV tumours; 43% and 41% had bone marrow and central nervous system involvement, respectively. After chemotherapy, complete remission was seen in 59% of cases. Remission in two children was relatively brief, lasting no more than 3 months. After a median follow-up of 45 months (range 9-99 months), the disease-free survival rate was 54%. In conclusion, in this series, oral presentation of Burkitt's lymphoma was a component of more widely disseminated disease. The pattern seemed to fall between that of the endemic and the sporadic types. Even with intensive chemotherapy, patients with advanced disease maintained a poor prognosis.

Burkitt's lymphoma in Turkish children: clinical, viral [EBV] and molecular studies.

Eighty-one Turkish children with Burkitt's lymphoma (BL) were observed during a period of 24 years (1968-1992). The diagnosis was established histologically according to WHO criteria. BL represented 48.5% of NHL in this series. The median age of patients was 5 years with a sex (M/F) ratio of 2.3/1. The most common primary site of tumor involvement at initial presentation was the abdomen (70.4%), which was followed by facial tumors, in particular the jaw and orbit (45.7%). The majority of the patients (84.0%) were in advanced stages (C and D) at initial diagnosis. Facial tumors observed in Turkish children with BL were more similar to African Burkitt's lymphoma than American or European cases. High titers of antibodies against VCA and EA of EBV were also observed in 32 recent cases of BL. Preliminary molecular and immunologic studies revealed EBV-DNA (type I) and T cell deficiency. The clinical presentation, median age, and association with EBV revealed that BL appears to be inbetween African and non-African types in Turkish children. This will be further elucidated in the future by direct examination of tumor cells for EBV and investigation of the molecular characteristics in these cases.

Association of Burkitt's lymphoma with the Epstein-Barr virus in two developing countries.

The clinical presentation of Burkitt's lymphoma (BL) and it's association with the Epstein-Barr virus (EBV) varies in different geographic areas, BL in developing countries being "intermediate" between the sporadic and endemic types, both in it's clinical presentation and it's association with EBV, which varies from 25-80%. In this study we have analysed the clinical features, EBV association, subtype and prevalence of the deleted variant of the Latent Membrane Protein-1 (LMP-1) of EBV in forty-two cases from two developing countries- India (n = 25) and Argentina (n = 17). In both countries the abdomen was the site most commonly involved while jaw involvement was rare. EBV was detected by in-situ hybridization using the EBER-1 RNA probe. 47% of cases from Argentina and 80% of cases from India were EBER positive. EBV typing using EBNA-3C primers showed a predominance of Type A in both countries (India-13/16 and Argentina-(7/8)). The 30bp deletion of the LMP-1 gene was detected in all evaluated cases from Argentina while the wild type of the gene was seen in all the evaluable Indian cases. Our study highlights the similarities and differences in the clinical presentation and EBV association of BL in two developing countries and also indicates that the subtype of EBV and prevalence of the LMP-1 deletion may reflect the predominant subtype in a particular population.

Expression of EBV encoded nuclear small non-polyadenylated RNA (EBER) molecules in 32 cases of childhood Burkitt's lymphoma from Israel.

We have analyzed paraffin sections from 32 children with histologically confirmed Burkitt's Lymphoma (BL) for the presence of EBV using in situ hybridization to detect expression of the EBV-encoded early RNAs (EBERs). EBV was present in the tumors of 11 patients (34%). Sixty nine percent of the children presented with abdominal disease, 19% had bone marrow infiltration and only one child had jaw involvement. There was no statistically significant difference between EBV positive and EBV negative children with regard to age, gender, origin, primary site at presentation, or clinical stage of disease. However, there was a trend for younger age in the children with EBV positive BL with a median age of 4, compared to 7 years in children with EBV negative BL. None of the 7 children of Ashkenazi Jewish origin had EBER positive disease. There was no difference in the treatment outcome between the EBV positive patients (estimated survival at 24 months of 82%) and EBV negative children (estimated survival rate of 71% (p=0.58)). In conclusion, although this is only a small series it seems that childhood BL in Israel has the clinical characteristics of sporadic, non-African type with 34% EBV association and a low incidence of jaw tumors. Our data suggest that Ashkenazi Jewish children with BL are less likely to have EBV positive tumors than other ethnic groups. However, more patients will need to be studied in order to assess the validity of this observation.

[Association of Epstein-Barr virus with primary malignant lymphomas of the digestive tract].

The association of Epstein-Barr virus (EBV) with 85 non-Hodgkin lymphomas of the digestive tract in nonimmunocompromised cases was investigated, using in situ hybridization technique to detect EBV encoded small RNAs in paraffin sections. 85 cases (83 B-cell type and 2 T-cell type) included 3 gingivas, 1 tongue, 3 palates, 10 tonsils, 43 stomachs, 2 jejunums, 12 ileums, 3 ileo-cecal regions, 5 colons and 3 rectums. Out of 85 cases, 4 (4.7%) were EBV-positive, comprising 1 B-cell lymphoma of the tonsil, 2 B-cell lymphomas of the stomach, and 1 T-cell lymphoma of the rectum. On the other hand, EBV-positive rate in nasal/nasopharyngeal lymphomas examined for comparison was very high, 81.8% (9 out of 11). These results show that EBV is associated with only a small proportion of lymphomas of the digestive tract in nonimmunocompromised case, suggesting the existence of the other oncogenetic factors in the pathogenesis of this group of lymphomas.

Viral response to chemotherapy in endemic burkitt lymphoma.

PURPOSE: Some EBV-directed therapies are predicted to be effective only when lytic viral replication occurs. We studied whether cyclophosphamide chemotherapy induces EBV to switch from latent to lytic phases of infection in a series of EBV-associated Burkitt lymphomas. EXPERIMENTAL DESIGN: Children with first presentation of an expanding, solid maxillary or mandibular mass consistent with Burkitt lymphoma underwent fine-needle aspiration just prior to the initiation of cyclophosphamide therapy and again 1 to 5 days later. Aspirated cells were examined for latent and lytic EBV infection using in situ hybridization to EBV-encoded RNA (EBER), immunohistochemical analysis of the lytic EBV proteins BZLF1 and BMRF1, reverse transcription PCR targeting BZLF1 transcripts, and EBV viral load measurement by quantitative PCR. RESULTS: Among 21 lymphomas expressing EBER prior to chemotherapy, 9 of 10 still expressed EBER on day 1 after therapy whereas only 2 of 11 (18%) specimens still expressed EBER at days 3 to 5, implying that chemotherapy was fairly effective at eliminating latently infected cells. Neither of the lytic products, BZLF1 or BMRF1, were significantly upregulated at the posttherapy time points examined. However, EBV genomic copy number increased in 5 of 10 samples 1 day after treatment began, suggesting that viral replication occurs within the first 24 hours. CONCLUSION: Cyclophosphamide may induce the lytic phase of EBV infection and is fairly effective in diminishing EBER-expressing tumor cells within 5 days. These findings provide the rationale for a trial testing synergistic tumor cell killing using cyclophosphamide with a drug like ganciclovir targeting lytically infected cells.

Clearance of circulating Epstein-Barr virus DNA in children with acute malaria after antimalaria treatment.

Children living in malaria-endemic regions have a high incidence of Burkitt lymphoma (BL), the etiology of which involves Plasmodium falciparum malaria and Epstein-Barr virus (EBV) infections. In the present study, we compared EBV DNA loads in plasma and saliva samples from Ugandan children with acute malaria (M+) at the time of diagnosis and 14 days after antimalaria treatment, children without malaria (M-), and children with BL. EBV DNA was detected, by real-time polymerase chain reaction, in 31% of the plasma and in 79% of the saliva samples from children in the M+ group. Antimalaria treatment led to clearance of plasma viral load in 85% of the cases but did not affect the levels in saliva. There was a significant difference in plasma EBV loads across the groups. The lowest levels were detected in samples from the M- group, increased levels were detected in samples from the M+ group, and levels reached the highest values in samples from children with BL. The same trend was evident in the frequency and levels of anti-BZLF1 antibodies, which is indicative of viral reactivation. In the M+ group, the positive plasma samples clustered around 7-9 years of age, the peak incidence of BL. The clearance of circulating EBV after antimalaria treatment suggests a direct relationship between active malaria infection and viral reactivation.

Activation of the Epstein-Barr virus lytic cycle by the latex of the plant Euphorbia tirucalli.

Exposure to the plant Euphorbia tirucalli has been proposed to be a cofactor in the genesis of endemic Burkitt's lymphoma (eBL). The purpose of this study was to examine the effects of unpurified E. tirucalli latex on Epstein-Barr virus (EBV) gene expression. A Burkitt lymphoma cell line was treated with varying dilutions of the latex and the effects on EBV gene expression were measured. We observed that the latex was capable of reactivating the EBV lytic cycle in a dose-dependent manner and at dilutions as low as 10(-6). Simultaneous treatment of cells with E. tirucalli latex and the protein kinase C inhibitor 1-(5-isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride blocked lytic cycle activation. These data suggest that environmental exposure to the latex of E. tirucalli could directly activate the EBV lytic cycle and provide further evidence of a role for E. tirucalli in the aetiology of eBL.

Burkitt's lymphoma of the scapula.

Burkitt's lymphoma may involve the maxilla or mandible, but to date, there has been no reference in the literature to scapular involvement by this tumor. This article describes the case of a 9-year-old child who presented with a huge tumor involving the right shoulder with osteolytic and sclerotic lesions in the scapula. The histopathological findings were suggestive of Burkitt's lymphoma, and the immunohistochemical findings discard a lymphoblastic lymphoma or plasmablastic lymphoma. In addition, in situ hybridization for Epstein-Barr virus encoded small nuclear RNA (EBER) was positive. Although the child also presented a cervical lymphadenopathy, the fact that Burkitt's lymphoma is generally extranodal, the marked swelling of the shoulder, and the extensive involvement of the bone strongly argue that this tumor had its origin in the scapula. This case demonstrates the importance of including Burkitt's lymphoma in the differential diagnosis of lymphoma involving bones in children.