B Cell Lymphoma

B cell lymphoma refers to a group of cancers that develop from the abnormal production of B cells, also known as B lymphocytes. It is the most prevalent of all lymphomas, comprising 90% of non-Hodgkin lymphoma (B-NHL) cases.1 NHL as a whole account is responsible for 260,000 deaths globally each year and is most common in men aged 65 and above.2 These lymphomas typically begin in the lymph nodes, although some – known as primary extranodal lymphomas – can develop in other parts of the body.3

Types of B cell lymphomas:

  • Diffuse large B cell lymphoma (DLBCL)
  • Follicular lymphoma
  • Chronic lymphocytic leukemia/small lymphocytic lymphoma
  • Mantle cell lymphoma (MCL)
  • Marginal zone lymphoma (including nodal, extranodal and splenic marginal zone lymphoma)
  • Burkitt’s lymphoma
  • Lymphoplasmacytic lymphoma (Waldenström macroglobulinemia)
  • Primary mediastinal large B cell lymphoma

Formation

The driving genetic mutations and risk factors for B cell lymphoma vary between each subset of disease. For example, 11:14 translocation is found in MCL, but 8:14 translocation is significant in Burkitt’s lymphoma.4 However, tumor cells across subtypes do share characteristics that promote the growth and survival of malignant B cells in the tumor microenvironment. Most B cell lymphoma types develop from a reciprocal chromosomal translocation of an immunoglobulin loci and proto-oncogene, causing deregulated expression of the translocated gene.5 Survival of B cell lymphoma tumors is aided by the dysregulation of B cell receptor signaling pathways by means of antigen-driven activation,6 and modifications to the Bcl-2 protein family can help cells avoid apoptosis.7 Complex communication with heterotypic signaling between the neoplastic B cells and cellular elements of the surrounding tumor microenvironment – such as the stroma cells that modulate the release of cytokines, chemokines and growth factors – helps promote malignant progression.8

Diagnosis and treatment assessment

Expression levels of C-MYC, BCL2 and BCL6 can be indicative of B cell lymphoma and disease aggression,9 although diagnosis varies between each disease subset as they have distinctive biomarkers and cell-of-origin signatures.

Cell markers

The National Comprehensive Cancer Network recommends the following markers in the initial evaluation of B cell lymphomas: CD45, CD3, CD5, CD19, CD10, CD20, CD30, CD4, CD8, CD7, CD2, CD23, CD43, CD103, TdT, CD13, CD33, CD1a, cytoplasmic CD3, CD22, and myeloperoxidase.10

CD5 and CD10 can be used to help distinguish B cell lymphoma types:11

  • CD5+/CD10- include small lymphocytic lymphoma and MCL
  • CD5-/CD10+ include follicular lymphoma and Burkitt’s lymphoma. MCL can occasionally be positive for CD10+, while DLBCL can be CD10- positive.
  • CD5-/CD10- include mature B cell lymphomas such as marginal zone lymphomas and Waldenström macroglobulinemia.

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References

  1. NHL Subtypes. Leukemia and Lymphoma Society. Retrieved 2 November 2021, from https://www.lls.org/lymphoma/non-hodgkin-lymphoma/nhl-subtypes
  2. Thandra, K.C,. Barsouk, A,. et al. (2021). Epidemiology of Non-Hodgkin’s Lymphoma. Medical Sciences. 9(5). doi: 10.3390/medsci9010005
  3. Vannata B, Zucca E. Primary extranodal B-cell lymphoma: current concepts and treatment strategies. Chinese Clinical Oncology. 2015 Mar;4(1):10. doi: 10.3978/j.issn.2304-3865.2014.12.01. PMID: 25841717.
  4. Küppers, R. Mechanisms of B-cell lymphoma pathogenesis. (2005). Nature Reviews Cancer. 5, 251–262. doi: 10.1038/nrc1589
  5. Singh, R., Shaik, S., et al. (2020). Non-Hodgkin’s Lymphoma: a review. Journal of Family Medicine and Primary Care. 9(4): 1834–1840. doi: 10.4103/jfmpc.jfmpc_1037_19
  6. Valla, K., Flowers, R, C., et al. (2018). Expert Opinion on Investigational Drugs. 27 (6): 513-522. doi: 10.1080/13543784.2018.1482273
  7. Adams, C., Clark-Garvey, S., et al. (2018). Targeting the Bcl-2 Family in B Cell Lymphoma. Frontiers in Oncology. 8: 636. doi: 10.3389/fonc.2018.00636.
  8. Shain, KH., Dalton, WS., and Tao, J. (2015) The Tumor Microenvironment Shapes Hallmarks of Mature B-cell Malignancies. Oncogene. 34(36): 4673-4682.
  9. Salam, D, S, D, A., Thit, E, E., et al. (2020). C-MYC, BCL2, and BLC6 Translocation in B-Cell Non-Hodgkin Lymphoma Cases. Journal of Cancer. 11(1): 190-198. doi: 10.7150/jca.36954.
  10. National Comprehensive Cancer Network. (2021) Clinical Practice Guidelines in Oncology: B-cell lymphomas. Retrieved 2 November 2021 from https://www.nccn.org/guidelines/category_1.
  11. Huan-You Wang and Youli Zu. (2017). Diagnostic Algorithm of Common Mature B-Cell Lymphomas by Immunohistochemistry. Archives of Pathology and Laboratory Medicine. 141 (9): 1236–1246. doi: https://doi.org/10.5858/arpa.2016-0521-RA

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