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

Abstract

Since 2016, a next-generation sequencing (NGS) panel targeting 68 genes frequently mutated in lymphoid malignancies is an accredited part of routine diagnostics at the Institute of Pathology in Basel, Switzerland. Here, we retrospectively evaluate the feasibility and utility of integrating this NGS platform into routine practice on 80 diagnostic cases of lymphoid proliferations. NGS analysis was useful in most instances, yielding a diagnostically, predictively and/or prognostically meaningful result. In 35 out of the 50 cases, in which conventional histopathological evaluation remained indecisive, molecular subtyping with the NGS panel was helpful to either confirm or support the favored diagnosis, enable a differential diagnosis, or seriously question a suspected diagnosis. A total of 61 actionable or potentially actionable mutations in 34 out of 80 cases that might have enabled patient selection for targeted therapies was detected. NGS panel analysis had implications for prognosis in all 15 cases interrogated for risk assessment.

Keywords:

• Gene panel testing
• diagnostic molecular pathology
• lymphoma
• next generation sequencing

Author contributions

VP performed research, collected, analyzed and interpreted the histopathological, genetic and clinical data and wrote the manuscript; DJ designed the lymphoma panel and reviewed the manuscript; MB performed NGS sequencing; FS and JH identified patients, contributed samples, provided clinical context and reviewed the manuscript; SD identified patients, executed histopathological evaluation, interpreted data and reviewed the manuscript; AT conceived, designed and coordinated the study, identified patients, provided genetic and histopathological evaluations, interpreted data and revised the manuscript; all authors have read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).