Publisher Summary This chapter discusses the evidence that deregulation of c-myc is a critical component of the pathogenesis of Burkitt's lymphoma, and consideration is given to the potential pathogenetic role of Epstein–Barr virus (EBV). The clinical and epidemiological observations pertinent to the pathogenesis of this tumor are also presented. A consideration of the structural changes in c-myc provides strong, though indirect evidence that a major element in the pathogenesis of Burkitt's lymphoma is the deregulation of c-myc. The possibility of the structural changes in c-myc can be considered, if the c-myc allele involved in the translocation is the expressed allele in Burkitt's lymphoma. Evidence for this comes from two sources. First, in tumor cell lines in which there is a truncated c-myc gene that is, one in which the breakpoint on chromosome 8 is within the first intron, the first exon sequences cannot be detected by Northern blot in the messenger RNA. Second, somatic cell hybrid experiments have been performed in which the Burkitt's lymphoma cell lines were fused to mouse plasmacytoma cells and clones which contained either the derivative chromosomes or their normal alleles were isolated. In the case of hybrids in which one of the parents was a cell line bearing an 8;14 translocation four types of clone, each containing only one of the chromosomes 8, 14, derivative 8, or derivative 14, were isolated. Human c-myc expression was detectable only in clones bearing the derivative chromosome 14.

The Pathogenesis of Burkitt's Lymphoma

Acquired immunodeficiency syndrome-related lymphoma.

Cytohistological and immunological classification of canine malignant lymphomas: comparison with human non-Hodgkin's lymphomas.

Histologic slides were reviewed from 192 autopsies of patients with non-Hodgkin's lymphomas admitted to the National Cancer Institute (NCI) from 1953 to 1975. Each autopsy was classified according to the systems of Rappaport and Lukes-Collins. Comparisons with the initial diagnosis were made. The initial histologic diagnoses of the autopsied population were similar in distribution to other published series of non-Hodgkin's lymphomas. Of the 56 cases which initially demonstrated nodular patterns of growth, the following distribution was found at autopsy: 25%, no lymphoma; 6%, nodular lymphoma; 32%, diffuse histiocytic (large cell) lymphoma (DHL); 21%, diffuse undifferentiated (non-Burkitt's) lymphoma (DUL); and 16%, the remaining diffuse morphologies. Of the 136 patients with initial diagnosis of diffuse lymphoma, the following distributions were observed at autopsy: 20%, no lymphoma; 0%, nodular lymphoma; 31%, diffuse histiocytic (large cell) lymphoma; 12%, diffuse undifferentiated (non-Burkitt's) lymphoma; 9%, Burkitt's tumor; 14%, diffuse poorly differentiated lymphocytic lymphoma; and 14%, the remaining diffuse morphologic types. One hundred and thirty-four cases which were initially diagnosed as follicular center cell type within the Lukes-Collins classification gave the following distribution at autopsy: 21%, no lymphoma; 25%, small noncleaved type; 17%, large non-cleaved type; 23%, non-follicular center cell lymphomas (17% immunoblastic B); and the remaining 13% were distributed among the other follicular center cell types. This autopsy review demonstrates the rarity of nodular (follicular) lymphomas at autopsy, and the predominance of the diffuse histiocytic or “transformed” type. This study provides a comparison of the rate of histologic progression of lymphomas in the same patient population at autopsy with a previously published study of progression during life.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819830801%2952%3A3%3C393%3A%3AAID-CNCR2820520302%3E3.0.CO%3B2-M

An autopsy study of histologic progression in non‐Hodgkin's lymphomas 192 cases from the national cancer institute

Adult, de novo B-cell lymphomas meeting the WHO morphologic criteria for atypical Burkitt/Burkitt-like lymphoma cause diagnostic difficulty for pathologists because the genetic and clinical characteristics of this group of lymphomas have not been clearly defined. Thirty-one such lymphomas, designated as Burkitt-like lymphomas (BLL), were selected based on morphologic features and evaluated for immunophenotype, MYC and BCL2 status, and clinical features. Nine childhood Burkitt lymphomas (BL) and 87 adult, de novo diffuse large B-cell lymphomas (DLBL) were similarly evaluated for comparison. The BL group demonstrated uniform characteristics: all had Burkitt lymphoma morphology, an identical immunophenotype (positive for CD20, CD10, bcl-6, CD43, and p53; negative for CD138, CD23, bcl-2), high MIB-1 positivity, IGH/MYC translocation, no IGH/BCL2 translocation, and all patients were alive at the last follow-up. The BLL and DLBL groups were heterogeneous. Burkitt-like morphology alone correlated with decreased survival. IGH/MYC or IGL/MYC fusion was identified in 11 of 27 (41%) BLL and 4 of 76 (5%) DLBL and was associated with decreased survival in both groups. MIB-1 positivity did not correlate with morphology, MYC abnormalities, or survival. We propose that adult B-cell lymphomas with BLL morphology are a phenotypically and genetically heterogeneous group of aggressive lymphomas, biologically distinct from childhood BL. Until biologically accurate subgroups within this morphologically defined group are identified, it is appears that both recognition of BLL morphology and direct evaluation for the presence of MYC fusion to immunoglobulin genes are important for identification of adult patients with poorer prognosis than those with DLBL.

Adult B-cell lymphomas with burkitt-like morphology are phenotypically and genotypically heterogeneous with aggressive clinical behavior.

A retrospective study of 66 cases of undifferentiated non-Hodgkin'S lymphomas at the National Cancer Institute over a 22-year period suggests that the histologic distinction between Burkitt'S and non-Burkitt'S types is clinicopathologically meaningful. Thirty-nine patients with Burkitt'S lymphoma had a median age at presentation of ten years. The primary site of disease in these patients was more commonly extranodal; at the time of diagnosis 26 (66%) of these cases revealed intra-abdominal involvement; 25 (64%) of the cases were Stage IV. The 27 patients with non-Burkitt'S lymphomas had a median age at presentation of 34 years; the primary site of disease was more commonly nodal (peripheral adenopathy was often present at the time of diagnosis); only nine (33%) of the cases were Stage IV. Median survival was essentially equivalent in the two groups, 9.5 months for Burkitt'S lymphoma and 10.0 months for the non-Burkitt'S lymphoma. Overall, survival was not significantly different among the two patient populations; however, patients with Burkitt'S lymphoma had a longer survival than those with non-Burkitt'S lymphoma. Estimates of five-year survival (with 95% confidence) are 42% for Burkitt'S lymphoma and 11% for non-Burkitt'S lymphoma, respectively, which are significantly different (P = 0.01)).

John A. Miliauskas

Papers

Undifferentiated non-Hodgkin's lymphomas (Burkitt's and non-Burkitt's types). The relevance of making this histologic distinction.