An aggressive case of Burkitt's lymphoma with t(8;14) and c-myc rearrangement transformed from CD5+ B-cell lymphoma

We experienced a case of Burkitt's lymphoma showing an unusual surface phenotype, CD5 expression, at an early stage of the disease. Initially, this patient showed massive abdominal para-aortic lymph node swelling which rapidly developed into leukemic change. Based on the clinical course and cytogenetic features of lymphoblasts in the bone marrow, which showed t(8;14) and c-myc gene rearrangement, the patient was diagnosed with Burkitt's lymphoma. Combination chemotherapy induced short-term remission, but central nervous system (CNS) involvement developed, followed by a regrowth of lymphoma cells in the bone marrow. The bone marrow at the end stage showed monotonous expansion of large cells with conspicuous vacuolation in the basophilic cytoplasm. The initial lymphoma cells showed pan-B markers and were CD5 positive but weakly CD10 positive; however, the lymphoma cells obtained from the bone marrow at the terminal stage did not express CD5. The chromosomal t(8;14) was seen, and identical rearrangement of immunoglobulin heavy chain joining gene and c-myc gene were detected by Southern blot analysis in the bone marrow lymphoblasts throughout the clinical course. This case is evidence that remarkable transformation of CD5-positive lymphoblasts to CD5-negative lymphoblasts occurred in an identical clone of Burkitt's lymphoma.     

The so-called white Burkitt's lymphoma

A case of histopathologically proven Burkitt's lymphoma is described with special reference to clinical, serological and immunological features. This case report is followed by a review of the literature on the problem of American and African Burkitt's lymphoma. We can state that there is good correspondence between the white and black Burkitt's lymphomas with regard to epidemiology, histopathology, therapy and some immunological aspects. The two groups differ from each other in age, primary tumor manifestation, involvement of the bone marrow at time of diagnosis and quantitatively in the positive EBNA-test. It is therefore suggested that black and white Burkitt's lymphoma are not different diseases but different patterns of one disease.     

In vitro suppression of programmed cell death of B cells by tissue inhibitor of metalloproteinases-1

Cellular pathways for induction of programmed cell death (PCD) have been identified, but little is known about specific extracellular matrix processes that may affect apoptosis along those pathways. In this study, a series of Burkitt's lymphoma (BL) cell lines were assayed for their expression of tissue inhibitor of metalloproteinases (TIMP)-1. Results indicate that TIMP-1-positive BL lines show resistance to cold-shock-induced apoptosis. Furthermore, recombinant TIMP-1, but not TIMP-2 or a synthetic metalloproteinase inhibitor (BB-94), confers resistance to apoptosis induced by both CD95-dependent and -independent (cold shock, serum deprivation, and gamma-radiation) pathways in TIMP-1-negative BL lines. TIMP-1 suppression of PCD is not due to metalloproteinase inhibition, as reduction and alkylation of the TIMP-1 did not abolish this activity. Retroviral induction of TIMP-1 not only resulted in cell survival but also in continued DNA synthesis for up to 5 d in the absence of serum, while controls underwent apoptosis. This resistance to apoptosis is reversed by anti-TIMP-1 antibodies, demonstrating that secreted TIMP-1 is active in blocking apoptosis. Furthermore, TIMP-1 upregulation induced expression of Bcl-XL but not Bcl-2 as well as decreased NF-kappaB activity as compared with controls. These results demonstrate that TIMP-1 suppresses apoptosis in B cells and suggests a novel activity for TIMP-1 in tissue homeostasis.     

Structure and polymorphism of horse MHC class II DRB genes: convergent evolution in the antigen binding site

Burkitt's tumor is a undifferentiated lymphoma of lymphocytes B with a characteristic histologic pattern often called as "starry sky". It is classified in two groups: endemic Burkitt's lymphoma (African form), and non-endemic Burkitt's lymphoma (American form). The extranodal involvement of the head and neck in the American type is uncommon, so the diagnosis can be delayed. The authors present in this paper a case of American Burkitt's lymphoma in a patient with gingival hyperplasia, and compare the epidemiological, clinical, radiographic, therapeutic and prognostic characteristics of the endemic and non-endemic forms of Burkitt's lymphoma.     

Age and sex as factors influencing remission duration in African Burkitt's lymphoma

The frequency of Burkitt's lymphoma peaks in children six to nine years of age and is twice as high in males as in females. To determine if age or sex had any relationship to outcome of therapy, the authors examined the experience of 387 patients treated for Burkitt's lymphoma at the Burkitt Tumor Project, Accra, Ghana, between 1966 and 1978. No age or sex relationship could be demonstrated with overall survival. However, among children without central nervous system disease who achieved an initial remission, the relapse rates were higher for those diagnosed initially in the age interval 6-9 years than for those diagnosed at younger or older ages. This pattern was seen for each stage of the disease as well as overall. Sex did not influence relapse rate. The relationship of these findings to the Epstein-Barr virus and malaria, both suspected factors in the etiology of this disease, is discussed, but neither appears to explain our results.     

Burkitt's lymphoma mimicking an acute dentoalveolar abscess

Burkitt's lymphoma is a monoclonal proliferation of B lymphocytes classified histologically as a poorly differentiated lymphocytic lymphoma. The jaw and retroperitoneal structures are the most commonly involved sites. Prognosis is highly dependent on the stage of the disease. In some cases, the first manifestation of Burkitt's lymphoma is in the jaws, and symptoms may be misdiagnosed as infection. Dental radiographs can play an important role in the diagnosis. A case of a peculiar Burkitt's lymphoma involving the mandible that was misdiagnosed as an acute dentoalveolar abscess is presented.     

Soft tissue Burkitt's lymphoma: radiological findings

An unusual case is reported of a soft tissue mass in the lower extremity, without bone involvement, in an 85-year-old woman; the histopathological diagnosis was Burkitt's lymphoma. Pertinent clinical history, histological examination, and imaging procedures allowed early diagnosis. To our knowledge, the radiological findings in Burkitt's lymphoma with this unusual clinical presentation have not been described previously.     

Apoptotic death of tumor cells correlates with chemosensitivity, independent of p53 or bcl-2

p53 has been implicated as a determinant of chemosensitivity and radiosensitivity. We measured chemosensitivity of human tumor cell lines (n = 11), with or without wild-type p53, following exposure to clinically useful chemotherapeutic drugs (n = 4). Chemosensitivity and apoptosis induction were correlated independently of p53 status or Bcl-2 protein levels in vitro. Wild-type p53 correlated with chemosensitivity in ovarian carcinoma and some Burkitt's lymphoma cells, but not in leukemia or lung cancer. Bcl-2 levels correlated with chemoresistance only in Burkitt's lymphoma. p53-dependent p21(WAF1/CIP1) induction and cell cycle arrest occurred at sublethal doses of chemotherapy, whereas at lethal doses of chemotherapy apoptotic death was observed, consistent with models proposing a relationship between the level of DNA damage versus survival or death. Loss of apoptosis induction was observed in drug-resistant ML-1 and HL-60 leukemia cells, without changes in p53 or Bcl-2. Targeted loss of p53 protein in H460 lung cancer cells using HPV-16 E6 inhibited the etoposide-induced G1 checkpoint but did not decrease chemosensitivity. Our studies suggest that the simple measurement of apoptosis induction may be a useful predictor of chemosensitivity, at least in vitro, and confirm that p53 status and Bcl-2 expression may be useful predictors of chemosensitivity in certain cell types.     

Epstein-Barr virus and associated diseases. Course of Medical Virology, Institut Pasteur, 1995/1996

The Epstein-Barr virus (EBV) is an ubiquitous virus infecting nearly the entire adult human population. The EBV is closely associated with rhinopharyngeal cancer in Southern China and Northern Africa. Three geographic subtypes of EBV have been identified to date. They differ by their nuclear antigene EBNA2. The EBNA2 AC strains predominate in Asia; EBNA2 AD strains predominate in the United States; EBNA2 B strains have all been identified in black Africa. Burkitt's lymphoma is the most frequent tumor in children aged 5 to 9 years in equatorial Africa. A prospective study in 42,000 children in Ouganda demonstrated that children who develop Burkitt's lymphoma have severe EBV infection during the first months of life. Very early EBV infection observed in North or equatorial Africa increases the risk of Burkitt's lymphoma by 20-times that in Europe. Hyperendemic malaria observed in the equatorial zone increases the incidence of tumors by a factor of 20. An association between EBV and rhinopharyngeal cancer is a constant feature only in South China, in North and East Africa, as well as in arctic regions as cases of carcinoma not associated with EBV infection have been reported in Greece. Surveys in the Democratic Republic of China concerning several hundred thousand persons have shown that serum IgA/VCA allows early diagnosis of cancer. It is estimated that the risk of rhinopharyngeal cancer is 20% in Chinese with high levels of IgA/VCA.     

Cranial cystic epidermoid: report of two cases and review of the literature

Among non-Hodgkin's lymphomas occurring in childhood two major histologic subgroups can be identified: (1) Burkitt's lymphoma and (2) T-cell lymphoblastic lymphoma, an uncommon high-grade malignant non-Hodgkin's lymphoma. Although Burkitt's lymphoma with maxillofacial involvement is a well-documented disease, T-cell lymphoblastic lymphoma in the perioral region is rare. An unusual case of T-cell lymphoblastic lymphoma with initial oral manifestation in an 18-month-old child is presented.     

Burkitt's lymphoma in Australia

An Australian case of Burkitt's lymphoma is reported. The clinical features of large ovarian masses and subsequent bone marrow invasion, as well as the results of investigations related to the Epstein-Barr virus, were more consistent with the American than the African type of Burkitt's lymphoma. After a good initial response to cyclophosphamide and vincristine, the tumour rapidly became resistant to these and other therapeutic measures and the patient died 10 months after diagnosis.     

The gray zone between malignant and reactive processes in lymphoproliferative diseases

The differences between reactive and malignant processes are sometimes blurred. Homogeneity is no longer a requisite for the diagnosis of lymphoma, as witnessed in mucosa-associated lymphatic tissue lymphoma and T-cell-rich B cell lymphoma, which are composed of an admixture of neoplastic clonal B cells and reactive T cells which occasionally are very prominent in the histological picture. Infectious mononucleosis, anaplastic large cell lymphoma, composite lymphoma and Hodgkin's disease, all share many similarities and may actually represent a continuous spectrum of pathological conditions. Immunodeficiency states, whether primary or acquired, are commonly associated with clonal lymphatic malignancies preceded by a polyclonal lymphoproliferative stage, which is usually reversible by reducing immunosuppression. The distinction between these stages is sometimes difficult to assess. Immunologists have so far failed to find a lymphatic tumor-specific antigen, hence, monoclonality is usually based on a constellation of factors, namely homogeneity of the phenotypic expression of few antigens, aberrant expression of antigens and restricted expression of kappa- or lambda-chains in malignancies expressing surface immunoglobulins. Nonrandom chromosomal translocations as well as other aberrations, usually important in the diagnosis of malignancy, are sometimes of limited value. This is mainly due to the existence of translocations [like t(14;18) and t(2;5)] in nonmalignant states, and their non-specificity [the existence of t(8;14) in Burkitt's lymphoma and large cell lymphoma, t(2;5) in Hodgkin's disease and anaplastic large cell lymphoma, and t(14;18) in large cell lymphoma evolving from follicular lymphoma and Burkitt's lymphoma]. The diagnostic tools available in 1995, although usually sufficient, are sometimes unable to distinguish between malignancy and reactivity. Some problematic cases will be more accurately defined as lying in the gray zone, or as belonging to a spectrum ranging between reactivity and malignancy.     

Prospective study of tardive dyskinesia in the elderly: rates and risk factors

Estimated incidence rates are presented for three human immunodeficiency virus (HIV)-associated cancers [Kaposi's sarcoma (KS), Burkitt's lymphoma (BL) and other non-Hodgkin's lymphomas (NHLs)] from across the African continent, based on data collected before the HIV epidemic. Mapping of the rates and comparisons with a range of geographical variables indicate completely different distributions for KS and BL but a degree of similarity in the occurrence of Burkitt's lymphoma and other NHLs. Comparisons with rates elsewhere in the world suggest, most notably, that KS was as common in some regions of sub-Saharan Africa as was cancer of the colon in much of Western Europe. Comparison with data from the era of AIDS indicates 20-fold increases in the occurrence of Kaposi's sarcoma in Uganda and Zimbabwe. The highest rates for BL were three to four times the rates for leukaemia at young ages in Western populations, but the general incidence of other NHL was no higher than in the West and very low rates were indicated for much of southern Africa.     

Chromosome 8-14 translocation in a non-African Burkitt's lymphoma with leukemic conversion

A specific chromosome translocation, t(8q-; 14q+), was observed in a 43-year-old female with non-African Burkitt's lymphoma in which leukemic conversion had occurred. The chromosome studies used cells from ascites. The ascites was apparently the result of a primary tumor involving the ovaries and contained 68% of lymphoma cells. The frequent occurrence of abnormalities related to chromosomes 1, 8 and 14 in African and non-African Burkitt's lymphomas was emphasized.     

Selective expression of one c-myc allele in two human myeloma cell lines

Chromosomal translocations or DNA rearrangements affecting c-myc occur in almost all murine plasmacytoma and human Burkitt's lymphoma tumors and are associated with a high incidence of exon 2 missense mutations and selective expression of the affected allele. Screening nine multiple myeloma cell lines, we identified no exon 2 missense mutations but did identify two lines with single, silent mutations in exon 1 and exon 2, respectively. Each of these informative multiple myeloma cell lines selectively expresses only one c-myc allele despite the apparent absence of chromosomal translocations or DNA rearrangements affecting c-myc.     

EBV-associated lymphoma

Several subtypes of human malignant lymphomas are known to be highly associated with the Epstein-Barr virus. These include the Burkitt's lymphoma, opportunistic (immune deficiency-associated) lymphoma, nasal T/NK lymphoma, Hodgkin's disease pyothorax-associated lymphoma, cutaneous panniculitis-type lymphoma, and mediastinal large B-cell lymphoma. Improvement of histopathological technology, the demonstration of EBV-encoded small RNAs(EBERs), as well as the molecular virological methods, contributed much in the progression of such EBV-associated lymphomas.     

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in reactive and neoplastic lymphoid cells

We have studied the expression of gelatinase A, gelatinase B, interstitial collagenase, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in reactive lymphoid cells, as well as in a series of cell lines derived from neoplasms of B- and T-cell lineage. Using both Northern blot analysis and zymography, gelatinase B activity was detected by zymography in two Burkitt cell lines and in a tonsillar cell suspension, while gelatinase A and interstitial collagenase activities were not detected by either method. TIMP-1 expression was demonstrated by Northern blot analysis in the multipotential neoplastic K-562 cell line, the high grade Burkitt's B-cell lymphoma lines, isolated tonsillar B cells and at low levels in peripheral blood T cells, but was not expressed in any of the neoplastic T-cell lines or isolated peripheral blood B cells. In contrast, TIMP-2 expression was restricted to tissues containing cells of T-cell lineage with high levels being observed in the neoplastic T-cell lines and lower levels in normal peripheral blood T cells and hyperplastic tonsil. Expression of TIMP-1 and TIMP-2 was confirmed at the protein level by reverse zymography and immunofluorescence assays using antihuman TIMP polyclonal antibodies. Expression of gelatinase B by the high grade B-cell Burkitt's lymphoma cell lines is consistent with previous findings in large cell immunoblastic lymphomas and indicates that this enzyme may play an important role in high grade non-Hodgkin's lymphomas. TIMP expression correlated with cell lineage in that TIMP-1 was primarily observed in B cells and TIMP-2 was restricted to T cells.     

Toward a final design for the Birmingham boron neutron capture therapy neutron beam

CD10 (CALLA) antigen is expressed in a wide variety of epithelial and nonepithelial tissues, but its most significant application is in the diagnosis and classification of certain types of malignant lymphoma and leukemia. CD10 is expressed in a high percentage of cases of acute lymphoblastic leukemia (ALL), follicular lymphoma, Burkitt's lymphoma, and some hematopoietic tumors. Although the antigen is not lineage specific, CD10 expression is widely used to define subgroups within B-ALL and is a useful tool for detecting the presence of leukemic blasts in the bloodstream. Currently available monoclonal antibodies to CD10 have been found to be effective only in fresh-frozen tissue and for techniques such as flow cytometry. We have used a recombinant protein corresponding to the whole of CD10 to generate a monoclonal antibody that is effective in paraffin-embedded tissue sections. We have used this antibody to assay for the presence of CD10 on a range of normal and pathological tissues. Strong staining was seen in lymphoid germinal centers, renal tubules, glomeruli, syncytiotrophoblast, hepatic parenchymal canaliculi, B-lineage ALL, follicle center cell lymphoma, and a proportion of cases of large-B-cell lymphoma. We believe that this antibody will be of value in the characterization of malignant lymphoma, in particular the differential diagnosis of small-B-cell lymphoma and subtyping of lymphoblastic leukemia, as well as the investigation of the significance of expression of CD10 in other normal and pathological tissues.