B-cell lymphomas
2025-08-04 Paola Dal Cin, PhD , Judith Ann Ferry, MD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
2.Massachusetts General Hospital/ Harvard Medical School
Keywords
primary extranodal lymphomas, B-cell lineageClassification
Definition
Most extranodal lymphomas primary in the head and neck are non-Hodgkin lymphomas of B-cell lineage. While diffuse large B-cell lymphoma is the most common type overall,1 there are important variations in frequency of different types of B-cell lymphomas in different sites. For example, diffuse large B-cell lymphoma is the most common type of lymphoma in the sinonasal tract and thyroid, while the majority of primary ocular adnexal and salivary gland lymphomas are extranodal marginal zone lymphomas of mucosa associated lymphoid tissue (MALT lymphoma).2,3 Plasmablastic lymphoma has a strong predilection for the oral cavity.4
| B-cell lymphomas | Genetic events |
|---|---|
| Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL) | The most common head and neck site for extranodal marginal zone Lymphoma (EMZL) is the ocular adnexa followed by the salivary glands. Rare sites include the Waldeyer ring , oral cavity, sinonasal tract and larynx. 5-8 Trisomy 3 and trisomy 18 are common .9 IGH::MALT1 is reported in a subset but BIRC3::MALT1 is rare in head and neck EMZLs. 10 Heterozygous loss-of-function mutation in TNFAIP3 has been associated with TNFAIP3 heterozygous deletion at 6q23.3, mainly in translocation-negative ocular adnexal EMZL. 11,12 Mutated TBL1XR1 and GPR34 are common in salivary EMZLs. 13,14 Thyroid EMZLs show frequent TET2, TNFRSF14 and PIK3CD mutations.13 Information on genetic changes in rare sites is limited. |
| Pediatric nodal MZL (pnMZL) predominantly affects male adolescents and usually presents with localized lymphadenopathy in the head and neck region.15 This indolent lymphoma has distinct characteristics that differ from those of conventional nodal marginal zone lymphoma (NMZL). Few cases of pnMZL have been analyzed genetically. The most frequent cytogenetic aberration is trisomy 18. Trisomy 3 and translocations involving IGH are rare. 16 | |
| Mantle cell lymphoma (MCL) | In the head and neck, MCL most often involves lymph nodes and Waldeyer's ring. Few cases of MCL affecting the oral cavity have been reported. 17,18 Diagnosis can be established by immunohistochemistry: identifying the appropriate immunophenotype including cyclin D1 and/or SOX11 expression. The cytogenetic hallmark of MCL is t(11;14)(q13;q32)/ IGH::CCND1 which can be demonstrated by karyotype or FISH analysis. |
| Follicular lymphoma (FL) | Head and neck FL, including rare FL with marginal zone differentiation, can develop in both lymph nodes and extranodal sites, such as the ocular adnexa and salivary glands.2,19 The cytogenetic hallmark of classic FL is t(14;18)(q32;q21)/IGH::BCL2.20 |
| Pediatric-type follicular lymphoma (PTFL) presents with localized lymphadenopathy, mainly in children and young adults, with a male preponderance. It lacks BCL2, BCL6, MYC and IRF4 rearrangements. 21 Mutations and deletions of TNFRSF14 and mutations of MAP2K1 are common; alterations of TNFRSF14 and MAP2K1 mostly occur independently. Mutated IRF8 occurs in a minority of cases and is often associated with TNFRSF14 mutations.15,22 | |
| Recent data indicate that PTFL and pnMZL may represent a single disease with some variation in histologic features. They have overlapping clinical, morphologic, and molecular findings, e.g., low genetic complexity; recurrent alterations in MAP2K1, TNFRSF14, and IRF8 , and similar methylation profiles. 23,24 | |
| Large B-cell lymphoma with IRF4 rearrangement (LBCL-IRF4) | LBCL-IRF4 typically affects children and young adults and presents with cervical lymphadenopathy or involvement of Waldeyer's ring. Strong expression of IRF4/MUM1 is characteristic. Demonstration of IRF4 rearrangement in the appropriate context confirms the diagnosis. The prognosis is favorable. 15,25 LBCL-IRF4 has occasionally been identified in older patients and at localizations other than the head and neck region.26 |
| Diffuse large B-cell lymphoma (DLBCL) | DLBCL occurs in multiple sites in the head and neck and is the most common type of lymphoma in the sinonasal tract and the oral cavity. Molecular studies focused on DLBCL of the head and neck are few, however.27-29 DLBCL can be classified in ABC and GCB subtypes based on their mutational and cytogenetic profiles, as well as clinical behavior. ABC lymphomas show constitutive activation of BCR signaling and NFkB pathways with frequent MYD88, CD79B, PIM1 and PRDM1 mutations. 30 GCB DLBCL in contrast harbors frequent mutations of EZH2, GNA13, MEF2B, KMT2A, THFRSF14 ,CREBBP and others; IGH::BCL2 is also common. 30 MYC and BCL2 protein coexpression and HLA-II loss are more common in ABC DLBCL than GCB DLBCL.28 |
| DLBCL, NOS is by definition Epstein-Barr Virus-(EBV)-negative. Certain other types of DLBCL are often EBV+, e.g., plasmablastic lymphoma.31 EBV+ DLBCL (formerly EBV+ DLBCL, NOS) is by definition EBV+.32 | |
| Burkitt lymphoma (BL) | Sporadic BL most often involves the abdomen, but its presentation in the head and neck region is relatively rare, while endemic BL commonly presents with head and neck involvement. The primary genetic event in BL is an IGH::MYC fusion.33,34 Of note, high grade B-cell lymphoma with 11q aberration (BLL-11q) is a rare lymphoma that resembles Burkitt lymphoma morphologically and phenotypically, but lacks MYC rearrangement. It has also been observed in the head and neck region and is characterized by an 11q23.3 gain/11q24.3 loss pattern.35,36 |
| Plasmacytoma | Extramedullary plasmacytoma and multiple myeloma are closely related entities, 37 but genetic features have not been extensively studied in head and neck sites. |
| Plasmablastic lymphoma (PBL) | Plasmablastic lymphoma (PBL) is a rare and aggressive form of mature B cell neoplasm typically associated with immunosuppression, often related to human immunodeficiency virus (HIV). It presents most commonly in the oral cavity, and less often in the sinonasal area and other sites.38 Complex karyotypes are common. MYC rearrangements are found in the majority of cases. The mutational profiles of EBV+ and EBV-negative PBL differ. 31,39,40 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 38604163 | 2024 | Clinical characteristics and prognostic analysis of primary extranodal non-Hodgkin lymphoma of the head and neck. | Lv J et al |
| 2 | 17255761 | 2007 | Lymphoma of the ocular adnexa: A study of 353 cases. | Ferry JA et al |
| 3 | 18156143 | 2008 | Low-grade mucosa-associated lymphoid tissue lymphoma: a retrospective analysis of 97 patients by the Hellenic Cooperative Oncology Group (HeCOG). | Papaxoinis G et al |
| 4 | 9028965 | 1997 | Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection. | Delecluse HJ et al |
| 5 | 18158571 | 2007 | Histopathological variation of primary mucosa-associated lymphoid tissue lymphoma of the oral cavity. | Kojima M et al |
| 6 | 26094364 | 2015 | Oral Cavity Lymphoid Neoplasms. A Fifteen-Year Single Institution Review. | Philipone E et al |
| 7 | 31757436 | 2020 | Marginal zone B-cell lymphoma: lessons from Western and Eastern diagnostic approaches. | Nakamura S et al |
| 8 | 33198051 | 2020 | Two cases of rare subglottic MALT lymphoma of the larynx. | Johnson AO et al |
| 9 | 17052360 | 2006 | Fluorescence in situ hybridization (FISH) analysis of primary ocular adnexal MALT lymphoma. | Tanimoto K et al |
| 10 | 18158751 | 2007 | Suitable conditions for sealing of open dentinal tubules using a pulsed Nd:YAG laser. | Zapletalová Z et al |
| 11 | 19006194 | 2009 | A20 deletion is associated with copy number gain at the TNFA/B/C locus and occurs preferentially in translocation-negative MALT lymphoma of the ocular adnexa and salivary glands. | Chanudet E et al |
| 12 | 22207688 | 2012 | A20 inactivation in ocular adnexal MALT lymphoma. | Bi Y et al |
| 13 | 29674500 | 2018 | Novel GPR34 and CCR6 mutation and distinct genetic profiles in MALT lymphomas of different sites. | Moody S et al |
| 14 | 30065018 | 2018 | G-protein coupled receptor (GPCR) mutations in lymphoid malignancies: linking immune signaling activation and genetic abnormalities. | Martinez-Climent JA et al |
| 15 | 31187530 | 2019 | Rare mature B-cell lymphomas in children and adolescents. | Woessmann W et al |
| 16 | 20305621 | 2010 | Marginal zone lymphomas in children and the young adult population; characterization of genetic aberrations by FISH and RT-PCR. | Rizzo KA et al |
| 17 | 32014402 | 2020 | Mantle cell lymphoma of the oral cavity: An uncommon site for an uncommon lesion, two new cases and literature review. | Lukach L et al |
| 18 | 34716903 | 2022 | Blastoid Mantle Cell Lymphoma of the Palate: Report of a Rare Aggressive Entity and Review of the Literature. | Georgaki M et al |
| 19 | 29972093 | 2019 | Immunohistochemical Reappraisal Regarding the Frequency of Primary Salivary Gland Follicular Lymphoma. | Itami H et al |
| 20 | 37516620 | 2023 | Head and neck follicular lymphoma with marginal zone differentiation and BCL2 translocation t(14;18) in both nodular and extranodular sites: a case report with mini-review. | Vageli DP et al |
| 21 | 35312979 | 2022 | Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Hematolymphoid Proliferations and Neoplasia. | Ferry JA et al |
| 22 | 28533310 | 2017 | Mutations of MAP2K1 are frequent in pediatric-type follicular lymphoma and result in ERK pathway activation. | Schmidt J et al |
| 23 | 35609565 | 2022 | A unifying hypothesis for PNMZL and PTFL: morphological variants with a common molecular profile. | Salmeron-Villalobos J et al |
| 24 | 39379519 | 2024 | Pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma: additional evidence to support they are a single disease with variation in the histologic spectrum. | Li HG et al |
| 25 | 37081786 | 2023 | IRF4 rearrangement may predict favorable prognosis in children and young adults with primary head and neck large B-cell lymphoma. | Jiang XN et al |
| 26 | 36779226 | 2023 | Reclassification of diffuse large B cell lymphoma to large B cell lymphoma with IRF4 rearrangement in an adult population. | Hesius EAM et al |
| 27 | 34706861 | 2023 | Prevalence and prognostic value of MYD88 and CD79B mutations in ocular adnexal large B-cell lymphoma: a reclassification of ocular adnexal large B-cell lymphoma. | Kirkegaard MK et al |
| 28 | 38324724 | 2024 | Sinonasal DLBCL: molecular profiling identifies subtypes with distinctive prognosis and targetable genetic features. | Eriksen PRG et al |
| 29 | 38542066 | 2024 | The Genetic Profile of Large B-Cell Lymphomas Presenting in the Ocular Adnexa. | Vest SD et al |
| 30 | 25805586 | 2015 | The genetic landscape of diffuse large B-cell lymphoma. | Pasqualucci L et al |
| 31 | 34465776 | 2021 | Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma. | Frontzek F et al |
| 32 | 34039950 | 2021 | Genomic insights into the pathogenesis of Epstein-Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing. | Gebauer N et al |
| 33 | 12560151 | 2003 | Sporadic Burkitt's lymphoma of the head and neck in the pediatric population. | Banthia V et al |
| 34 | 3458257 | 1986 | Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma. | Pelicci PG et al |
| 35 | 30733272 | 2019 | Burkitt-like lymphoma with 11q aberration: a germinal center-derived lymphoma genetically unrelated to Burkitt lymphoma. | Gonzalez-Farre B et al |
| 36 | 34078047 | 2021 | [Clinicopathological and molecular genetic features of Burkitt-like lymphoma with 11q aberration]. | Zhang YP et al |
| 37 | 23368088 | 2013 | Cytogenetics of extramedullary manifestations in multiple myeloma. | Billecke L et al |
| 38 | 40026453 | 2024 | Sinonasal Plasmablastic Lymphoma: A Systematic Review. | Chen S et al |
| 39 | 20962620 | 2010 | IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas. | Valera A et al |
| 40 | 33951889 | 2021 | MAPK and JAK-STAT pathways dysregulation in plasmablastic lymphoma. | Ramis-Zaldivar JE et al |
Citation
Paola Dal Cin, PhD ; Judith Ann Ferry, MD
B-cell lymphomas
Atlas Genet Cytogenet Oncol Haematol. 2025-08-04
Online version: http://atlasgeneticsoncology.org/solid-tumor/209332/b-cell-lymphomas
