Cytopathology of "double-hit" non-Hodgkin lymphoma

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.

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

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.

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.