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Oncogenesis of Lymphoma (2nd Edition)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 15 November 2026 | Viewed by 705

Editors


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Guest Editor
Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
Interests: immunohistochemistry; in situ molecular techniques; brightfield in situ hybridization; virologic characterization; EBV; HHV8/KSHV; HPV; tumor microenvironment; Hodgkin’s lymphoma; HIV-associated lymphomas
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
Interests: molecular pathology; lymphoma pathology; breast cancer; molecular tumor; genomic research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of "Oncogenesis of Lymphoma".

Advances in the fields of molecular genetics, immunology, and virology have clarified the mechanisms involved in lymphomagenesis. Human lymphomas have been found to be heterogeneous, not only pathologically, but also in terms of pathogenetic pathways, cellular derivation, and tumor microenvironment. Traditionally, some types of lymphomas, such as follicular lymphomas and mantle cell lymphomas, are consistently correlated with genetic abnormalities involving BCL2 and BCL1, respectively. It is well known that the molecular pathway in Burkitt lymphoma involves activation of MYC, inactivation of p53, and infection by EBV. Furthermore, in diffuse large B-cell lymphomas (DLBCL), molecular studies have shown rearrangements in BCL2, BCL6, and MYC genes. Recent studies with NGS and mutational profiling have identified clinically significant genetic subgroups. Four major genetic subgroups have been demonstrated in DLBCL. They are based on (1) mutations in MYD88 and CD79B, (2) BCL6 fusions and NOTCH2 mutations, (3) NOTCH1 mutations, and (4) EZH2 mutations/BCL2 rearrangement. A new concept, viral cooperation, has been revealed in lymphomagenesis by molecular virologic studies on primary effusion lymphomas (PELs). In immune-deficient/dysregulated patients, PEL tumor cells, in addition to consistent infection by KSHV/HHV8, are also commonly infected by EBV. Finally, recent insights in genetics, epigenetics, and knowledge of the cellular microenvironment have led to the refinement of diagnostic definition and appropriate therapy.

Dr. Annunziata Gloghini
Prof. Dr. Giancarlo Pruneri
Guest Editors

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Keywords

  • lymphomagenesis
  • molecular genetics
  • immunology
  • molecular virology
  • KSHV/HHV8
  • EBV
  • HIV
  • pathogenetic pathways
  • genotypic subgroups
  • tumor microenvironment
  • follicular lymphoma
  • mantle cell lymphoma
  • diffuse large B-cell lymphoma
  • targeted therapy
  • drug target

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Published Papers (1 paper)

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Review

17 pages, 1129 KB  
Review
Classic Hodgkin Lymphoma Beyond the Lymph Node: A Systemic Immunobiological Paradigm
by Antonino Carbone and Annunziata Gloghini
Cancers 2026, 18(11), 1813; https://doi.org/10.3390/cancers18111813 - 1 Jun 2026
Viewed by 466
Abstract
Classic Hodgkin lymphoma (cHL) has traditionally been conceptualized as a malignancy confined to lymphoid tissues, with disease extent defined primarily by anatomical staging systems. While this framework has guided clinical management for decades, it incompletely captures the biological complexity of cHL. Emerging evidence [...] Read more.
Classic Hodgkin lymphoma (cHL) has traditionally been conceptualized as a malignancy confined to lymphoid tissues, with disease extent defined primarily by anatomical staging systems. While this framework has guided clinical management for decades, it incompletely captures the biological complexity of cHL. Emerging evidence from molecular, immunological, and translational studies supports a reinterpretation of cHL as a systemic immunobiological disease rather than a purely nodal malignancy. A defining feature of cHL is the rarity of malignant Hodgkin and Reed–Sternberg (HRS) cells, which orchestrate a highly structured tumor microenvironment through constitutive activation of signaling pathways, including NF-κB and JAK/STAT, and through expression of immune checkpoint ligands. Beyond local effects, HRS cells secrete cytokines, chemokines, and extracellular vesicles that enter the systemic circulation, promoting widespread immune reprogramming. This includes T-cell exhaustion, expansion of regulatory T cells, and activation of immunosuppressive myeloid populations, which collectively shape host immunity beyond the lymph node. Circulating tumor DNA (ctDNA) and soluble mediators such as thymus and activation-regulated chemokine (TARC/CCL17) provide measurable evidence of systemic disease activity and enable dynamic monitoring of tumor burden. These biological insights help explain key clinical features of cHL, including constitutional (“B”) symptoms, extranodal involvement, and heterogeneous patterns of treatment response and resistance. Importantly, integration of ctDNA kinetics, peripheral immune profiling, and functional imaging offers a multidimensional framework for disease assessment that overcomes the limitations of conventional staging systems. Therapeutically, the efficacy of immune checkpoint inhibitors underscores the central role of systemic immune dysregulation, while emerging biomarker-driven strategies support adaptive and personalized approaches to treatment. Collectively, these findings support a paradigm shift toward understanding cHL as a systemic immunobiological disease. This framework has important implications for disease monitoring, therapeutic decision-making, and future research, paving the way for biology-driven, precision medicine approaches in cHL. Full article
(This article belongs to the Special Issue Oncogenesis of Lymphoma (2nd Edition))
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