Molecular characterization of a rare case of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 rearrangements

J Hematop. 2024 Sep;17(3):155-161. doi: 10.1007/s12308-024-00593-8. Epub 2024 Jun 24.

Abstract

Quadruple-hit lymphomas are extremely rare non-Hodgkin lymphomas with a reported dismal prognosis in the few reported cases. A "quadruple hit" has been defined by the presence of concurrent MYC, BCL2, BCL6, and CCND1 chromosomal rearrangements. We report a new case of a quadruple hit lymphoma in a 73-year-old Hispanic man who presented with an enlarging left-sided neck mass. Computed tomography showed a 1.9-cm mass in left the tonsil with bulky cervical lymphadenopathy. The presence of all four chromosomal rearrangements can reportedly occur with disease progression in both diffuse large B-cell lymphomas and mantle cell lymphomas. Further characterization of the tumor by next-generation sequencing may be of benefit to delineate between these two possibilities. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing were used to confirm and classify the diagnosis. Histologic sections of the cervical lymph node demonstrated an atypical lymphoid infiltrate with large and pleomorphic cells, which were positive for CD20, CD10, BCL1 (Cyclin D1), BCL2, BCL6, and cMYC and negative for CD5 and SOX11 on immunohistochemistry with a Ki-67 proliferative index of 70%. FISH demonstrated MYC, BCL2, BCL6, and CCND1 rearrangements and the diagnosis of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 was rendered. Our patient was treated with dose adjusted etoposide, doxorubicin, cyclophosphamide, prednisone, and rituximab chemotherapy and has been in remission for 20 months.

Keywords: KMT2D; MYC-BCL2 rearrangements; MYC-BCL6 rearrangements; Lymphadenopathy; Quadruple hit lymphoma.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cyclin D1* / genetics
  • Cyclin D1* / metabolism
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Etoposide / administration & dosage
  • Etoposide / therapeutic use
  • Gene Rearrangement
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lymphoma, B-Cell / diagnosis
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / pathology
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / diagnostic imaging
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Neoplasm Grading
  • Prednisone / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2* / genetics
  • Proto-Oncogene Proteins c-bcl-6* / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Rituximab / therapeutic use

Substances

  • Proto-Oncogene Proteins c-bcl-6
  • Cyclin D1
  • Proto-Oncogene Proteins c-bcl-2
  • BCL6 protein, human
  • CCND1 protein, human
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-myc
  • MYC protein, human
  • Cyclophosphamide
  • Doxorubicin
  • Prednisone
  • Rituximab
  • Etoposide