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7 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
An aggressive B-cell lymphoma defined not by how it looks but by two genetic faults in the same cell: a rearrangement of MYC, which drives growth, and one of BCL2, which blocks the cell from dying. It behaves worse than ordinary diffuse large B-cell lymphoma, so finding the rearrangements changes the treatment.
What it is. Two genes have to be broken for this diagnosis. MYC is a master switch for cell growth; BCL2 is the brake on programmed cell death. A cell that is told to grow and is also prevented from dying becomes a lymphoma that behaves worse than either fault alone would predict. The rearrangements are found by fluorescence in situ hybridisation, a test done on the biopsy, and they are the diagnosis. Nothing about the way the cells look under a microscope reliably identifies them, which is why every aggressive B-cell lymphoma is now tested.
How it differs from its family. It is a separate entity from diffuse large B-cell lymphoma, although it was carved out of it. WHO-HAEM5 named it diffuse large B-cell lymphoma / high-grade B-cell lymphoma with MYC and BCL2 rearrangements, so that a tumour made of large cells and one made of smaller blastoid cells can carry the same name once the genetics are known; the two books describe it as a homogeneous group with a germinal-centre gene expression profile and a close relationship to follicular lymphoma. Its gene expression overlaps that of Burkitt lymphoma, which is the other aggressive germinal-centre disease driven by MYC.
| Setting | Approach | Guideline |
|---|---|---|
| Making the diagnosis | Every aggressive B-cell lymphoma biopsy is tested by fluorescence in situ hybridisation for MYC, and if MYC is rearranged, for BCL2 and BCL6. A lymphoma cannot be identified as double-hit by appearance, by immunohistochemistry for MYC and BCL2 protein, or by the cell-of-origin assay; dual protein expression is a separate and much commoner finding with its own, lesser, prognostic weight. Follicular lymphoma is excluded from the entity by both classifications even when it carries both rearrangements. | not mapped |
| Treatment, and what is known about it | Treated more intensively than diffuse large B-cell lymphoma, and with prophylaxis against disease in the brain and spinal cord, which is more frequent here. There has never been a randomised trial confined to this entity: the intensified regimens in use were adopted from retrospective comparisons after the group was shown to do less well with standard immunochemotherapy. The regimens, the doses and the evidence behind each are on the diffuse large B-cell lymphoma page and in the treatment layer of this family. | not mapped |