title: Double-hit lymphoma demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-hit translocations, MYC/BCL-2 and IRF4/BCL-2.
abstract: Here, we report a rare case of double-hit lymphoma, demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2. The present case had a rare abnormal chromosome, t(6;14;18)(p25;q32;q21), independently, in addition to known dual-hit chromosomal abnormalities, t(14;18)(q32;q21) and t(8;22)(q24;q11.2). Lymph node was characterized by a follicular and diffuse growth pattern with variously sized neoplastic follicles. The intrafollicular area was composed of centrocytes with a few centroblasts and the interfollicular area was occupied by uniformly spread medium- to large-sized lymphocytes. CD23 immunostaining demonstrated a disrupted follicular dendritic cell meshwork. The intrafollicular tumor cells had a germinal center phenotype with the expression of surface IgM, CD10, Bcl-2, Bcl-6, and MUM1/IRF4. However, the interfollicular larger cells showed plasmacytic differentiation with diminished CD20, Bcl-2, Bcl-6, and positive intracytoplasmic IgM, and co-expression of MUM1/IRF4 and CD138 with increased Ki-67-positive cells (> 90%). MUM1/IRF4 has been found to induce c-MYC expression, and in turn, MYC transactivates MUM1/IRF4, creating a positive autoregulatory feedback loop. On the other hand, MUM1/IRF4 functions as a tumor suppressor in c-MYC-induced B-cell leukemia. The present rare case arouses interest in view of the possible "dual" activation of both c-MYC and MUM1/IRF4 through two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2.
authors.affiliation: Department of Internal Medicine, Hyogo Prefectural Tsukaguchi Hospital, Hyogo, Japan. rtabata@hp.pref.hyogo.jp
authors.forename: Rie
authors.initials: R
authors.lastname: Tabata
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yasumizu
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tabata
authors.forename: Masaru
authors.initials: M
authors.lastname: Kojima
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D002896:Chromosomes, Human, Pair 6; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008198:Lymph Nodes / Q000473:pathology; D008223:Lymphoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D014178:Translocation, Genetic; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D000099218:Interferon Regulatory Factor-4