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Diffuse large B cell lymphoma (DLBCL): epidemiology, pathophysiology, risk stratification, advancement in diagnostic approaches and prospects: narrative review

202533 citationsOpen accessDebre Tabor University

In plain language

Diffuse large B-cell lymphoma is an aggressive form of non-Hodgkin lymphoma that originates in the germinal centre. Representing approximately 40 per cent of all non-Hodgkin lymphoma cases globally, its incidence typically rises with age. The condition is clinically and molecularly heterogeneous, with gene expression profiling distinguishing subtypes such as germinal centre and activated B-cell-like forms. Although the International Prognostic Index remains the primary instrument for stratifying patient risk, definitive diagnosis relies on excisional biopsy of suspicious lymph nodes. Recent diagnostic advancements incorporate techniques like immunohistochemistry, next-generation sequencing, and array-based comparative genomic hybridisation to uncover diverse genetic alterations. While these modern molecular tools show promise for refining diagnoses and predicting patient outcomes, they require further validation before widespread implementation in routine clinical practice.

Key takeaways

  • Diffuse large B-cell lymphoma accounts for around 40 per cent of non-Hodgkin lymphomas worldwide, with incidence rising alongside patient age.
  • The disease is biologically diverse, featuring distinct transcriptional subtypes differentiated by gene expression profiling.
  • Excisional lymph node biopsy remains the preferred diagnostic route, while the International Prognostic Index serves as the primary risk stratification tool.
  • Techniques such as next-generation sequencing and comparative hybridisation help identify genetic alterations but require further clinical validation.

Why it matters

Diffuse large B-cell lymphoma represents a substantial proportion of aggressive blood cancers globally. Understanding the distinct genetic variations behind different disease subtypes allows clinicians to better categorise tumours and assess patient risk. Validating advanced molecular diagnostic methods is essential for moving towards more precise disease characterisation, which helps healthcare teams predict outcomes more reliably and plan appropriate management strategies.

Commercialisation angle

Diagnostic developers and clinical pathology laboratories are the primary target users of the discussed methods, such as next-generation sequencing and array-based comparative hybridisation. These technologies could form the basis of advanced diagnostic and prognostic testing kits. However, the commercialisation pathway remains at an early applied stage, as these advanced tools require extensive clinical validation before they can be incorporated into routine diagnostic workflows.

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Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin's lymphoma that arises from the germinal center. It represents a heterogeneous disease characterized by different pathological, clinical, and molecular entities. Gene expression profiling based on the alleged cell of origin differentiates transcriptional subtypes such as germinal center and activated B cell-like. DLBCL accounts for around 40% of all non-Hodgkin's lymphomas worldwide. Its incidence generally increases with age. The international prognostic index remains the most important tool for disease stratification.The diagnosis of DLBCL is best made through an excisional biopsy of a suspicious lymph node. Nowadays, advanced techniques are employed to accurately diagnose and determine the clinical outcomes of patients. Immunohistochemistry, next-generation sequencing, and array-based comparative hybridization facilitate the global identification of diverse and numerous genetic alterations. However, further validation should be necessary to apply advanced techniques in clinical practice. In this review, we summarize the current literature and discuss the pathophysiology, epidemiology, and diagnostic advancements of DLBCL.

Research topics

  • Lymphoma Diagnosis and Treatment
  • Cancer Genomics and Diagnostics
  • Chronic Lymphocytic Leukemia Research

Sustainable Development Goals

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DOI: 10.1007/s12672-025-01958-w

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