Diagnostic and predictive biomarkers for lymphoma diagnosis and treatment in the era of precision medicine

Abstract

Lymphomas are a group of hematological malignancies derived from lymphocytes. Lymphomas are clinically and biologically heterogeneous and have overlapping diagnostic features. With the advance of new technologies and the application of efficient and feasible detection platforms, an unprecedented number of novel biomarkers have been discovered or are under investigation at the genetic, epigenetic, and protein level as well as the tumor microenvironment. These biomarkers have enabled new clinical and pathological insights into the mechanisms underlying lymphomagenesis and also have facilitated improvements in the diagnostic workup, sub-classification, outcome stratification, and personalized therapy for lymphoma patients. However, integrating these biomarkers into clinical practice effectively and precisely in daily practice is challenging. More in-depth studies are required to further validate these novel biomarkers and to assess other parameters that can affect the reproducibility of these biomarkers such as the selection of detection methods, biological reagents, interpretation of data, and cost efficiency. Despite these challenges, there are many reasons to be optimistic that novel biomarkers will facilitate better algorithms and strategies as we enter a new era of precision medicine to better refine diagnosis, prognostication, and rational treatment design for patients with lymphomas.

EMT‐ and MET‐related processes in nonepithelial tumors: importance for disease progression, prognosis, and therapeutic opportunities

“…Lymphomas occur mostly in lymph nodes and can be subdivided in to two major groups, Hodgkin's (HL) and non‐Hodgkin's lymphoma (NHL). NHLs include many different types such as B cell‐derived Burkitt lymphoma, diffuse large B‐cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and T‐cell lymphomas (Sun et al ., ).…”

“Triple hit” lymphomas: A retrospective cytology case series of an uncommon high grade B‐cell malignancy with C‐MYC, BCL‐2 and BCL‐6 rearrangements

“…lymphomas. [13][14][15][16][17][18] Novel treatment strategies with small molecule inhibitors may hold hope for newly diagnosed individuals, and combination therapy with pembrolizumab and lenalidomide has been reported to induce remission in refractory disease. 19,20 It is our hope that this manuscript will raise awareness of this uncommon type of B-cell lymphoma within the cytodiagnostic community.…”

“…Whether features such as morphologic classification, BCL2 expression, or type of MYC translocation partner may mitigate the adverse prognosis in “double‐hit” and “triple‐hit” lymphomas is controversial . An expanding literature exists regarding predictive biomarkers, therapeutic regimen recommendations, and precision tailored approaches to “double‐hit” and “triple‐hit” lymphomas . Novel treatment strategies with small molecule inhibitors may hold hope for newly diagnosed individuals, and combination therapy with pembrolizumab and lenalidomide has been reported to induce remission in refractory disease .…”

Cytologic perspectives on neoteric B‐cell lymphoproliferative disorders

“…MYC-mutated DLBCLs are known to be associated with more aggressive clinical courses following standard therapy. [9][10][11][12][13][14][15][16][17][18][19][20][21] The authors of the limited papers on cytomorphologic evaluations of "double-hit" lymphomas suggest that MYC/BCL2/BCL6 in situ hybridization testing should be considered in patients with cytologically HGBCLs with clinically aggressive presentations and when high proliferation indices are noted. 5 The 2016 WHO classification includes the new entity of HGBCL with MYC and BCL2 and/or BCL6 rearrangements.…”