Cytopathology of "double-hit" non-Hodgkin lymphoma

Cancer Cytopathol. 2011 Aug 25;119(4):263-71. doi: 10.1002/cncy.20160. Epub 2011 May 10.

Abstract

Background: B-cell lymphomas with concurrent IGH-BCL2 and c-MYC rearrangements (so-called "double-hit lymphomas" [DHL]) are a relatively rare, recently described category in the 2008 World Health Organization classification of hematopoietic neoplasms. Response to chemotherapy and survival are poor.

Methods: The authors reviewed files of cytogenetically documented DHL to identify cytologic features that would allow its possible recognition.

Results: Twelve fine-needle aspirates (FNAs), 2 pleural fluids, and 1 touch imprint of cytogenetically proven DHL were uncovered. Primary DHL was correctly recognized in 3 of 12 FNA cases using Ki-67 staining coupled with a positive bcl-2 result as the basis for performing fluorescence in situ hybridization (FISH) analysis of c-MYC and IGH-BCL2 rearrangements. Remaining FNAs and non-FNA cases were diagnosed as non-Hodgkin lymphoma, B-cell lymphoma, or atypical lymphocytosis. Ten cases had cell block material available. All cases had high cellularity with a dissociated smear pattern and background lymphoglandular bodies. Cell size ranged from intermediate to large. Nuclei were predominantly rounded or slightly irregular in contour; 4 FNAs had markedly cleaved nuclei. Some nuclei harbored discrete but small nucleoli, whereas in others coarse chromatin and indistinct or multiple small nucleoli existed. A variable number of mitotic figures, tingible body macrophages, and background apoptotic cells were also present.

Conclusions: No specific cytomorphologic feature(s) were found to reliably identify DHL using FNA or exfoliative cytology. A high Ki-67 proliferation index and positive bcl-2 staining (on cytospin slides or cell block material) of cases not conforming to typical Burkitt lymphoma morphology should prompt FISH analysis for c-MYC and/or IGH-BCL2 rearrangements to identify DHL, particularly if tissue biopsy is not expected.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy, Fine-Needle
  • Female
  • Follow-Up Studies
  • Gene Rearrangement*
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Ki-67 Antigen
  • Lymphoma, Non-Hodgkin / genetics*
  • Lymphoma, Non-Hodgkin / pathology*
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Translocation, Genetic*

Substances

  • Immunoglobulin Heavy Chains
  • Ki-67 Antigen
  • MYC protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc