Routine next generation sequencing of lymphoid malignancies: clinical utility and challenges from a 3-Year practical experience

Pillonel, Vincent; Juškevičius, Darius; Bihl, Michel; Stenner, Frank; Dirnhofer, Stefan; Tzankov, Alexandar

doi:10.1080/10428194.2020.1786560

Cited by 10 publications

(7 citation statements)

References 67 publications

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“…However, 11 cases were reclassification of low‐grade B‐NHL: MZL to FL ( n = 2) and vice versa ( n = 2) and from MZL to LPL ( n = 6) and from FL to AITL ( n = 1). Pillonel et al 31 reported 80 cases and a diagnostic aid in 63 cases (79%) using a 68 custom‐made gene panel. Fifty cases were without a final diagnosis and NGS had a diagnostic impact in 35 cases (70%), but this patient group was very heterogenous and also included TCL and atypical lymphoproliferations and LBCL.…”

Section: Discussionmentioning

confidence: 99%

Next generation sequencing in routine diagnostics of maturenon‐Hodgkin's B‐cell lymphomas

Breinholt

Schejbel

Gang

et al. 2023

European J of Haematology

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IntroductionIntegration of molecular characterization of lymphomas in clinical diagnostics may improve subclassification and risk‐stratification, and we implemented a next generation sequencing (NGS) analysis as part of routine diagnostic work‐up of all mature B‐cell non‐Hodgkin's lymphoma (B‐NHL). Here, we present data of mutational profiles with potential complementary diagnostic, prognostic, and predictive value detected in our consecutive non‐selected cohort of B‐NHL patients.MethodsNGS results from 298 patients with both newly diagnosed and relapsed/refractory disease were included as a single center study. NGS was performed as routine analysis together with standard diagnostic work‐up using a custom‐made amplicon PCR‐based multiplex NGS panel covering all coding exons and consensus splice sites in 59 genes.ResultsMutations were detected in 94% of the 298 samples. Most lymphomas could be classified definitively, but 24 cases were classified as small B‐cell lymphomas without defining characteristics. Of these, 50% (12/24 cases) could retrospectively be assigned a likely diagnostic subtype according to mutational findings.ConclusionImplementation of a 59 gene exome sequencing panel added diagnostic value to 50% of unclassified cases and provided in 94% of the cases possible biomarkers for disease monitoring as well as potential diagnostic, prognostic, and predictive markers for future studies.

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Section: Discussionmentioning

confidence: 99%

Next generation sequencing in routine diagnostics of maturenon‐Hodgkin's B‐cell lymphomas

Breinholt

Schejbel

Gang

et al. 2023

European J of Haematology

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“…Selected cases of FL (14/148) and FH (3/42) underwent molecular work-up with our customized lymphoma panel as described elsewhere [ 24 ]. Only somatic mutations described as pathogenic or possible/probable pathogenic were considered in further analysis.…”

Section: Methodsmentioning

confidence: 99%

H3K27m3 overexpression as a new, BCL2 independent diagnostic tool in follicular and cutaneous follicle center lymphomas

et al. 2022

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Approximately 15% of follicular lymphomas (FL) lack overexpression of BCL2 and the underlying translocation t(14;18). These cases can be diagnostically challenging, especially regarding follicular hyperplasia (FH). In a subset of FL, mutations in genes encoding for epigenetic modifiers, such as the histone-lysine N-methyltransferase EZH2 (enhancer of zeste homolog 2), were found, which might be used diagnostically. These molecular alterations can lead to an increased tri-methylation of histone H3 at position lysine 27 (H3K27m3) that, in turn, can be visualized immunohistochemically. The aim of this study was to analyze the expression of H3K27m3 in FL, primary cutaneous follicle center lymphomas (PCFCL), and pediatric-type FL (PTFL) in order to investigate its value in the differential diagnosis to FH and other B cell lymphomas and to correlate it to BCL2 expression and the presence of t(14;18). Additionally, the mutational profile of selected cases was considered to address H3K27m3’s potential use as a surrogate parameter for mutations in genes encoding for epigenetic modifiers. Eighty-nine percent of FL and 100% of PCFCL cases overexpressed H3K27m3, independently of BCL2, EZH2, and the presence of mutations. In contrast, 95% of FH and 100% of PTFL cases lacked H3K27m3 overexpression. Other B cell lymphomas considered for differential diagnosis also showed overexpression of H3K27m3 in the majority of cases. In summary, overexpression of H3K27m3 can serve as a new, BCL2 independent marker in the differential diagnosis of FL and PCFCL, but not PTFL, to FH, while being not of help in the differential diagnosis of FL to other B cell lymphomas.

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“…Clinical utility of NGS-based assay on LPDs has been suggested by recent studies, both in diagnostic and prognostic perspectives [82][83][84][85]. One example is a report of angioimmunoblastic T-cell lymphoma [86], of which the primary diagnosis was made on pleural effusion fluid by detecting pathognomic RHOA G17V mutation by targeted NGS as well as immunophenotyping on CB.…”

Section: Mutational Analysis and Next-generation Sequencingmentioning

confidence: 99%

Lymphoproliferative disorder involving body fluid: diagnostic approaches and roles of ancillary studies

Koh

Shin

Lee

et al. 2022

J Pathol Transl Med

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Lymphocyte-rich effusions represent benign reactive process or neoplastic condition. Involvement of lymphoproliferative disease in body cavity is not uncommon, and it often causes diagnostic challenge. In this review, we suggest a practical diagnostic approach toward lymphocyte-rich effusions, share representative cases, and discuss the utility of ancillary tests. Cytomorphologic features favoring neoplastic condition include high cellularity, cellular atypia/pleomorphism, monomorphic cell population, and frequent apoptosis, whereas lack of atypia, polymorphic cell population, and predominance of small T cells usually represent benign reactive process. Involvement of non-hematolymphoid malignant cells in body fluid should be ruled out first, followed by categorization of the samples into either small/medium-sized cell dominant or large-sized cell dominant fluid. Small/medium-sized cell dominant effusions require ancillary tests when either cellular atypia or history/clinical suspicion of lymphoproliferative disease is present. Large-sized cell dominant effusions usually suggest neoplastic condition, however, in the settings of initial presentation or low overall cellularity, ancillary studies are helpful for more clarification. Ancillary tests including immunocytochemistry, in situ hybridization, clonality test, and next-generation sequencing can be performed using cytologic preparations. Throughout the diagnostic process, proper review of clinical history, cytomorphologic examination, and application of adequate ancillary tests are key elements for successful diagnosis.

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Routine next generation sequencing of lymphoid malignancies: clinical utility and challenges from a 3-Year practical experience

Cited by 10 publications

References 67 publications

Next generation sequencing in routine diagnostics of maturenon‐Hodgkin's B‐cell lymphomas

Next generation sequencing in routine diagnostics of maturenon‐Hodgkin's B‐cell lymphomas

H3K27m3 overexpression as a new, BCL2 independent diagnostic tool in follicular and cutaneous follicle center lymphomas

Lymphoproliferative disorder involving body fluid: diagnostic approaches and roles of ancillary studies

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