Application of 2016 WHO classification in the diagnosis of paediatric high-gradeMYC-negative mature B-cell lymphoma with Burkitt-like morphological features

Abstract

AimsHistorically, there has been no consensus on the diagnostic classification of high-grade B-cell lymphoma (HGBCL) with morphological features of Burkitt lymphoma (BL) but no MYC gene rearrangement (MYC-negative). The 2016 WHO classification of tumours of haematopoietic and lymphoid tissues has shed some light on this field with the modification of the grey-zone lymphoma with features intermediate between BL and diffuse large B-cell lymphoma, and the creation of several new entities. The aim of this study was to investigate how the revised WHO classification affects our practice in diagnosing these lymphomas in children.MethodsWe retrospectively reviewed cases of mature HGBCL diagnosed at our hospital between 2015 and 2018.ResultsAmong 14 mature HGBCL cases with BL morphological features, 11 showed MYC rearrangement consistent with BL and 3 were MYC-negative. Two MYC-negative cases showed regions of 11q gain and loss by microarray consistent with Burkitt-like lymphoma with 11q aberration (BLL-11q). The third MYC-negative case showed diffuse and strong MUM1 expression, translocation involving 6p25 by chromosome analysis and IRF4 rearrangement by fluorescence in situ hybridisation analysis consistent with large B-cell lymphoma with IRF4 rearrangement (LBL-IRF4). All patients were treated according to applicable chemotherapeutic protocols and achieved remission.ConclusionsBLL-11q and LBL-IRF4, two newly defined entities, should be considered in paediatric MYC-negative mature HGBCL cases. Accurate diagnosis needs careful histopathological examination and proper cytogenetic testing. Since they have unique cytogenetic features, specific treatments for them may emerge in the future. Therefore, accurate diagnosis based on the 2016 WHO classification is clinically significant.

Burkitt-like lymphoma with 11q aberration confirmed by needle biopsy of the liver: A case report

“…Some authors suggest that all MYC rearrangement negative HGBCLs with BL/BL-11q morphology should be detected by microarray or FISH detection with 11q aberration, while others support a step-by-step method, starting with FISH detection. If FISH detection is difficult or negative, then microarray detection is performed[ 18 ].…”

“…The abdominal and pelvic masses and liver nodules disappeared, and the patient is now in a good condition. Therefore, we can consider that BLL-11q is a separate lymphoma subtype[ 1 , 18 ], and the chemotherapy dose can be reduced, or specific treatment methods can be formulated to prevent overtreatment[ 2 , 18 ]. However, more case-cohort studies and clinical comparisons at the same stage and risk are needed to determine the best treatment regimen.…”

Pathogenesis and Pathology of Pediatric Lymphoma

“…It is controversial to make a diagnosis of BL when MYC rearrangement is not detectable. In practice, without MYC rearrangement, the diagnosis of BL should always be questioned, and a new WHO entity, BLL-11q, should be considered (4,43). BLL-11q (Figure 4B) comprises cases with morphologic, phenotypic, and gene expression resemblance to BL, but lacking MYC translocation (MYC-) and harboring characteristic proximal 11q gains and distal 11q loss.…”

“…BLL-11q cases occur over a wide age range but are more common in children and young adults. The actual incidence of this entity in children is not known, but it seems not uncommon (43,44). BLL-11q cases are more frequently nodal than BL and tend to present as a single dominant mass or conglomerate mass at low stage.…”

“…The most sensitive modality for detecting this characteristic cytogenetic finding is DNA microarray. FISH and chromosome analysis can detect 11q aberration in some cases, but both methods show lower sensitivity (43). DNA microarray or FISH analysis should be performed on all MYC-high grade mature B-cell lymphomas with BL/BL-like morphology.…”