Emerging entities: high-grade/large B-cell lymphoma with 11q aberration, large B-cell lymphoma with IRF4 rearrangement, and new molecular subgroups in large B-cell lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop

Abstract

Emerging entities and molecular subgroups in large B-cell lymphomas (LBCLs) were discussed during the 2022 European Association for Haematopathology/Society for Hematopathology workshop in Florence, Italy. This session focused on newly recognized diseases and their diagnostic challenges. High-grade/large B-cell lymphoma with 11q aberration (HG/LBCL-11q) is defined by chromosome 11q-gains and telomeric loss. FISH analysis is recommended for the diagnosis. HG/LBCL-11q can occur in the setting of immunodeficiency, including ataxia-telangiectasia, and predominates in children. The morphological spectrum of these cases is broader than previously thought with often Burkitt-like morphology and coarse apoptotic bodies. It has a Burkitt-like immunophenotype (CD10+, BCL6+, BCL2−) but MYC expression is weak or negative, lacks MYC rearrangement, and is in contrast to Burkitt lymphoma 50% of the cases express LMO2. LBCL with IRF4 rearrangement (LBCL-IRF4) occurs mainly in the pediatric population but also in adults. LBCL-IRF4 has an excellent prognosis, with distinguishing molecular findings. IRF4 rearrangements, although characteristic of this entity, are not specific and can be found in association with other chromosomal translocations in other large B-cell lymphomas. Other molecular subgroups discussed included primary bone diffuse large B-cell lymphoma (PB-DLBCL), which has distinctive clinical presentation and molecular findings, and B-acute lymphoblastic leukemia (B-ALL) with IGH::MYC translocation recently segregated from Burkitt lymphoma with TdT expression. This latter disorder has molecular features of precursor B-cells, often tetrasomy 1q and recurrent NRAS and KRAS mutations. In this report, novel findings, recommendations for diagnosis, open questions, and diagnostic challenges raised by the cases submitted to the workshop will be discussed.

The fifth edition of the WHO classification of mature B‐cell neoplasms: open questions for research

“…This phenomenon has served as an argument for the present classification to exclude cases with MYC rearrangement from the definition of HGBL‐11q. However, such cases have been reported more recently, suggesting that MYC rearrangement can occur as secondary alteration in HGBL‐11q [107,108]. Therefore, this issue should be treated as an open question to be resolved in further research.…”

“…Therefore, this issue should be treated as an open question to be resolved in further research. The number of such cases may be underestimated, as screening for 11q aberrations is recommended for MYC ‐R‐negative B‐cell lymphomas that are morphologically and immunophenotypically similar to BL, but not for MYC ‐R‐positive cases [108].…”

“…HGBL‐11q has been described as being particularly frequent in post‐transplant patients, who develop B‐cell lymphomas with Burkitt‐like morphology. It has also been described in the setting of HIV infection and, more recently, in primary immunodeficiency syndromes (inborn errors of immunity), such as ataxia‐telangiectasia [108]. Whether there is indeed a direct mechanistic association to immune deficiency/dysregulation needs to be further established.…”

“…In a recent study, coarse apoptotic bodies were reported as characteristic of HGBL‐11q and to represent an important morphological feature to suspect the diagnosis and prompt FISH analysis [109]. This is a helpful feature, but its absence does not exclude the diagnosis [108].…”

“…MYC expression may vary from case to case, always displaying weak staining. A recent study demonstrated that 46% of HGBL‐11q expressed LMO2, a GC marker, and this may represent a useful marker to support HGBL‐11q over BL in difficult cases [108]. In contrast to BL, mutations in the ID3‐TCF3 pathway, recognised as the biological hallmark of BL, are not detected in HGBL‐11q.…”