Double-hit lymphoma demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-hit translocations, MYC/BCL-2 and IRF4/BCL-2

J Clin Exp Hematop. 2013;53(2):141-50. doi: 10.3960/jslrt.53.141.

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.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Bone Marrow / pathology
  • Cell Transformation, Neoplastic / genetics*
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 18
  • Chromosomes, Human, Pair 6
  • Humans
  • In Situ Hybridization, Fluorescence
  • Interferon Regulatory Factors / genetics*
  • Lymph Nodes / pathology
  • Lymphoma / diagnosis
  • Lymphoma / drug therapy
  • Lymphoma / genetics*
  • Male
  • Neoplasm Staging
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-myc / genetics*
  • Translocation, Genetic*

Substances

  • Interferon Regulatory Factors
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • interferon regulatory factor-4