Flow cytometry study:
Approximately 73% lymphoid cells are positive for CD19, CD20 and CD22 and exhibit Kappa restriction. All the other markers including CD10, Tdt and T-lymphocyte markers are negative. This finding is consistent with a mature B-cell lymphoma.
Approximately 73% lymphoid cells are positive for CD19, CD20 and CD22 and exhibit Kappa restriction. All the other markers including CD10, Tdt and T-lymphocyte markers are negative. This finding is consistent with a mature B-cell lymphoma.
IHC stains:
Cytogenetic results:
46,XX,t(6;17)(p25;q24),inv(14)(q31q32),der(22)t(11;22)(q12.3;p11.2)[19]
46,XX[1]
FISH: IRF4 rearranged, partner gene not identified.
46,XX,t(6;17)(p25;q24),inv(14)(q31q32),der(22)t(11;22)(q12.3;p11.2)[19]
46,XX[1]
FISH: IRF4 rearranged, partner gene not identified.
Microarray analysis showing segmental gains within 11q. Solid blue bars representing areas of gain (blue arrows), the red bracket in the smooth signal indicates a relative loss (=2 copies) of a 2Mb region within 11q24.3
Diagnosis: large‐B‐cell lymphoma with IRF4 rearrangement
LBL-IRF4, another newly recognized provisional entity by the 2016 WHO classification, most commonly affects children and young adults. It mainly involves the Waldeyer's ring and cervical lymph nodes and usually presents as low stage disease. Microscopically, the tumor cells are medium to large in size with finely clumped chromatin and small basophilic nucleoli. Mitotic figures are usually infrequent, and a starry sky pattern is absent, though proliferation rate is usually high by Ki67 stain. These lymphomas may have a diffuse growth pattern consistent with DLBCL, follicular growth pattern consistent with grade 3 follicular lymphoma (FL), or follicular/diffuse pattern (composite FL grade 3/DLBCL). The tumor cells are positive for B-cell specific markers (CD20, CD79a, PAX5), and characteristically show strong expression of IRF4/MUM1 and BCL6. Over 50% of the cases are also positive for BCL2 and CD10. Despite the strong expression of IRF4/MUM1, these cases have a germinal center signature by gene expression profiling. Most cases have a cytogenetically cryptic rearrangement of IRF4 with an IGH locus. BCL6 alterations may be detected in some cases, but essentially all cases lack MYC and BCL2 rearrangement. Most cases have shown good response to chemotherapy [16, 17]. The diagnosis of this entity should be suspected in high-grade FL or DLBCL cases with strong and diffuse expression of MUM1 and BCL6, especially in Waldeyer's ring and cervical regions, and should be confirmed by FISH analysis for IRF4 rearrangement.
Ref:
- Zhang L, Brown LE, Bowen LM, Application of 2016 WHO classification in the diagnosis of pediatric high grade MYC-negative mature B-cell lymphoma with Burkitt-like morphological features. J Clin Pathol 2020. doi:10.1136/jclinpath-2019-206267