Double-hit lymphomas: clinical, morphological, immunohistochemical and cytogenetic study in a series of Brazilian patients with high-grade non-Hodgkin lymphoma

Abstract

BackgroundDouble-hit lymphomas (DHL) are rare high-grade neoplasms characterized by two translocations: one involving the gene MYC and another involving genes BCL2 or BCL6, whose diagnosis depends on cytogenetic examination. This research studied DHL and morphological and/or immunophenotypic factors associated with the detection of these translocations in a group of high-grade non-Hodgkin lymphoma cases.MethodClinical and morphological reviews of 120 cases diagnosed with diffuse large B-cell lymphoma and Burkitt lymphoma were conducted. Immunohistochemistry (CD20, CD79a, PAX5, CD10, Bcl6, Bcl2, MUM1, TDT and Myc) and fluorescence in situ hybridization for detection of MYC, BCL2 and BCL6 gene translocations were performed in a tissue microarray platform.ResultsThree cases of DHL were detected: two with translocations of MYC and BCL2 and one with translocations of MYC and BCL6, all leading to death in less than six months. Among 90 cytogenetically evaluable biopsies, associations were determined between immunohistochemistry and fluorescence in situ hybridization for MYC (p = 0.036) and BCL2 (p = 0.001). However, these showed only regular agreement, indicated by Kappa values of 0.23 [0.0;0.49] and 0.35 [0.13;0.56], respectively. “Starry sky” morphology was strongly associated with MYC positivity (p = 0.01). The detection of three cases of DHL, all resulting in death, confirms the rarity and aggressiveness of this neoplasm.ConclusionsThe “starry sky” morphological pattern and immunohistochemical expression of Myc and Bcl2 represent possible selection factors for additional cytogenetic diagnostic testing.

C-MYC and BCL2: Correlation between Protein Over-Expression and Gene Translocation and Impact on Outcome in Diffuse Large B Cell Lymphoma

“…Most of our patients with DEL or DHL had a high stage (III, IV), intermediate to high IPI, and higher extra-node involvement (P <0.001). These results matched with many previous studies (Oliveira et al, 2017;Snuderl et al, 2010;Riedell et al, 2018;Friedberg, 2017, Reagan et al, 2017.…”

“…In our study and among DEL patients, the morphological pattern of diffuse growth was the commonest (99%) with a "starry sky" pattern of 20% of the cases, which represented the main features of BL. In the DHL group, the typical morphology was a diffuse monomorphic pattern of numerous apoptotic bodies (Oliveira et al, 2017).…”

Disseminated Double-Hit Lymphoma in a Young Adult

“…Most of the reported cases appear to exhibit a DLBCL morphology with a diffuse growth pattern, variable nuclear size, prominence of nucleoli, variable mitotic figures and variable proliferation rate. 1,3,8 Our case also reports similar high-grade, diffuse large B-cell lymphomalike morphologic features with that of previously reported cases.…”

c‐MYC and p53 expression highlight starry‐sky pattern as a favourable prognostic feature in R‐CHOP‐treated diffuse large B‐cell lymphoma

“…In our work, to counterbalance the potential interpretation bias in evaluating the presence of SSP, we took four DLBCL samples per case to maximise tumour representativeness on the TMAs. In the literature, a correlation of c‐MYC /SSP was once described but this was only between SSP and c‐MYC gene rearrangement [ 47 ]. Moreover, a statistical analysis confirmed that these two factors could stratify DLBCL patients into prognostically relevant subgroups.…”