t(11;14), cyclin D1 and SOX11

What is measured: the IGH::CCND1 translocation and the proteins that go with it. How: cyclin D1 immunohistochemistry (nuclear staining in over 95 percent of mantle cell lymphomas; the rare negatives carry CCND2 or CCND3 rearrangements and are caught by SOX11 positivity), FISH for CCND1::IGH on tissue, blood or marrow, karyotype, and SOX11 immunohistochemistry, which is positive in classic nodal mantle cell lymphoma and negative in the indolent leukaemic non-nodal form (IGHV-mutated, often CD5-negative). In myeloma, FISH panels find t(11;14) in 15 to 20 percent, a standard-risk lesion whose cells depend on BCL2, and more often in AL amyloidosis and plasma cell leukaemia. What a result changes: it separates mantle cell lymphoma from CLL and small lymphocytic lymphoma (cyclin D1-negative, LEF1-positive) and follicular lymphoma; SOX11-negative leukaemic non-nodal disease can often be observed; in myeloma, t(11;14) selects patients for venetoclax-based regimens (a BELLINI subgroup, CANOVA, and NCCN listing off label) and predicts BCL2-inhibitor response in AL amyloidosis. Where it matters: mantle cell lymphoma, plasma cell leukaemia and relapsed myeloma.