Fluorescence in situ Hybridization (FISH)
- Test is useful in identifying ALK-negative anaplastic large cell lymphomas and large B-cell lymphoma with IRF4 rearrangement
- The rearrangement is associated with an improved prognosis
The IRF4/DUSP22 locus is rearranged in a newly recognized subtype of non-Hodgkin lymphoma, large B-cell lymphoma with IRF4 rearrangement. These lymphomas are uncommon, but are clinically distinct from morphologically similar lymphomas, including diffuse large B-cell lymphoma, high-grade follicular lymphoma, and pediatric-type follicular lymphoma. The IRF4/DUSP22 locus is also rearranged in a subset of ALK-negative anaplastic large cell lymphomas (ALCL), where this rearrangement is associated with a significantly better prognosis.
- Large B-cell lymphoma with IRF4 rearrangement accounts for <1% of all non-Hodgkin B-cell lymphomas overall
- More common in younger patients, with an incidence of 5-6% under age 18
- IRF4/DUSP22 rearrangement is found in 30% of ALK-negative ALCLs
Large B-cell lymphoma with IRF4 rearrangement typically presents with limited stage disease in the head and neck, while the presentation of ALK-negative ALCLs is variable.
Patients with large B-cell lymphoma with IRF4 rearrangement typically have a favorable outcome after treatment. Rearrangement of the IRF4/DUSP22 locus in ALK-negative ALCL is associated with a better prognosis than ALK-negative ALCL without this rearrangement.
The limit of detection (LOD) for the IRF4/DUSP22 probe was established by calculating the upper limit of the abnormal signal pattern in normal cells using the Microsoft Excel BETAINV function. The LOD of IRF4/DUSP22 fluorescence in situ hybridization (FISH) is 11% when 100 cells are enumerated. Using the LOD of 11% the analytical sensitivity was found to be 100% when testing two 6p25 rearranged samples.
- Depending on the context of the case, the presence of the 6p25 gene rearrangement supports a diagnosis of large B-cell lymphoma with IRF4 rearrangement or ALK-negative ALCL with IRF4/DUSP22 rearrangement.
- Absence of the 6p25 gene rearrangement
- IRF4/DUSP22 FISH testing has not been validated for
- Tissue fixed in alcohol-based or non-formalin fixatives
- Decalcified tissue
- Results should be analyzed in conjunction with morphology, immunohistochemistry, and immunophenotyping results.
Castellar ERParrilla, Jaffe ES, Said JW, et al. ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood. 2014;124(9):1473-1480.
Salaverria I, Philipp C, Oschlies I, et al. Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults. Blood. 2011;118(1):139-147.
Swerdlow S, Campo E, Jaffe E, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th ed. Lyon, France: International Agency for Research on Cancer, 2017.