Diagnosis of Burkitt lymphoma in due time: a practical approach

Abstract

Summary The quick diagnosis of Burkitt lymphoma (BL) and its clear‐cut differentiation from diffuse large B‐cell lymphoma (DLBCL) is of great clinical importance because treatment strategies for these two disease entities differ markedly. As these two lymphomas are difficult to distinguish using the current World Health Organization classification, we studied 39 cases of highly proliferative peripheral blastic B‐cell lymphoma (HPBCL) to establish a practical differential‐diagnostic algorithm. Characteristics set for BL were a typical morphology, a mature B‐cell phenotype of CD10+, Bcl‐6+ and Bcl‐2− tumour cells, a proliferation rate of >95%, and the presence of C‐MYC rearrangements in the absence of t(14;18)(q32;q21). Altogether, these characteristics were found in only five of 39 cases, whereas the majority of tumours revealed mosaic features. We then followed a pragmatic stepwise approach for a classification algorithm that included the assessment of C‐MYC status to stratify HPBCL into four predefined diagnostic categories (DC), namely DC I (5/39, 12.8%): ‘classical BL’, DC II (11/39, 28.2%): ‘atypical BL’, DC III (9/39, 23.1%): ‘C‐MYC+ DLBCL’ and DC IV (14/39, 35.9%): ‘C‐MYC− HPBCL’. This proposal may serve as a robust and objective operational basis for therapeutic decisions for HPBCL within 1 week and is applicable to be evaluated for its prognostic relevance in clinical trials with uniformly treated patients.

Simple karyotype and bcl-6 expression predict a diagnosis of Burkitt lymphoma and better survival in IG-MYC rearranged high-grade B-cell lymphomas

“…Previous studies have suggested that high proliferation fraction (Ki-67490%), typical Burkitt lymphoma immunophenotype (CD10 þ /bcl-6 þ /bcl-2 À ), and a CD38 þ / CD44 À /TCL-1 þ pattern may predict the presence of MYC rearrangement. [2][3][4][5] In this study, 87% of cases had a high Ki-67 (495%), and 83% of cases expressed TCL-1 and lacked CD44, which is in general consistent with these published results. However, the immunophenotype of CD10 þ /bcl-6 þ / bcl-2 À is mainly present in group I cases (89%) and at very low rate in group II cases (21%), implying that such immunophenotype may not be a reliable predictor in MYC-complex lymphomas.…”

“…28 Recognition of MYC rearrangement is important because it portends a more aggressive disease and may prompt more timely and intensive therapy. 2,12 However, MYC-rearranged lymphomas may be underrecognized because karyotype and/or FISH analysis are not performed in all cases. Therefore, recognition of the features suggestive of MYC rearrangement may be important to prompt additional testing.…”

“…This study design is different from recent studies that targeted high-proliferative gray-zone lymphomas with variable features similar to those of Burkitt lymphoma, in which there was no karyotypic analysis and many cases lacked MYC rearrangement. [2][3][4] Although the 2008 criteria include up to 10% of molecularly defined Burkitt lymphoma without demonstrable MYC rearrangement, it is unknown how this would affect our daily practice. It is probably prudent to assess for a MYC rearrangement in all cases having a high index of suspicion for such abnormalities.…”

“…1 However, these rearrangements are not entirely specific as they are also seen occasionally in other high-grade B-cell lymphomas, [2][3][4][5][6][7] including those in the newly proposed entity 'B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma' (hereafter referred to as unclassifiable B-cell lymphoma) in the 2008 World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissue. 8 Furthermore, MYC rearrangements are often accompanied by varying numbers of additional cytogenetic abnormalities.…”

“…Although prompt diagnosis of Burkitt lymphoma and other high-grade B-cell lymphomas carrying MYC rearrangements is clinically important because they are aggressive and may require more intensive therapy, 12 the diagnosis sometimes can be challenging. [2][3][4] Two major gene expression profiling studies recently sharpened the molecular distinction between Burkitt lymphoma and diffuse large B-cell lymphoma. Despite this, there remain borderline cases with a molecular signature intermediate between these entities.…”