Non-Hodgkin’s lymphoma

Non-Hodgkin’s lymphoma (NHL) is a heterogeneous group of cancers that originate in the lymphoid system and that spread in a disorderly manner, often to extranodal sites.1,4 This group of cancers has overlapping diagnostic features. There are several novel biomarkers that are being investigated at the genetic, epigenetic, protein level, and tumor microenvironment that can potentially provide insights into the processes underlying lymphomagenesis and aid in the diagnosis, classification, outcome stratification, and personalizing non-Hodgkin’s patient treatment.2


There are over 40 major subtypes of NHL, with follicular lymphoma (FL) as the most common indolent type of NHL and diffuse large B-cell lymphoma (DLBCL) as the most common aggressive type of NHL. There is no ‘gold standard’ when it comes to the basis of classification of the various types of NHL; however, cancers are generally grouped by using a combination of morphology, immunophenotype, and clinical and genetic features (Table 1).1 The focus of this website is on B-cell neoplasms.

Table 1: WHO classification of B-cell lymphomas1

Mature (peripheral) B-cell lymphomas
B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma
Extranodal marginal zone B-cell lymphoma of MALT type
B-cell prolymphocytic leukemia
Nodal marginal zone B-cell lymphoma
Lymphoplasmacytic lymphoma
Follicular lymphoma
Splenic marginal zone B-cell lymphoma
Mantle cell lymphoma
Hairy cell lymphoma
Diffuse large B-cell lymphoma
Plasma cell lymphoma
Primary effusion lymphoma
Mediastinal large B-cell lymphoma
Burkitt lymphoma
Precursor B-cell lymphomas
Precursor B-lymphoblastic leukemia/lymphoma (B-cell acute lymphoblastic leukemia)

The International Lymphoma Epidemiology Consortium (InterLymph) was established in 2001 to address the heterogeneity of NHL and determine specific mechanisms and risk factors for various subtypes.3 Risk factors for non-Hodgkin’s lymphomas like diffuse large B-cell lymphoma and follicular lymphoma, both non-modifiable and modifiable, are outlined in Table 2.

Table 2: Risk factors for NHL3

Non-modifiable Risk Factors Modifiable Risk Factors
Age (>60 years)
Gender (Male sex)
Chemical Exposure (Pesticides, chemotherapy drugs)
Race/Ethnicity (Caucasians have higher risk)
Family History (Parent, child, sibling of a person with NHL at higher risk)
Tobacco Smoking and Alcohol
Autoimmune Diseases (eg, Crohn disease, lupus, etc.)
Breast Implants
Immunosuppression or a weakened immune system
Vitamin D Deficiency
Infections such as HCV or H. pylori

NHL is the most common type of hematological cancer worldwide; this includes both T-cell and B-cell proliferations.3 Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive form of NHL in Western countries (30%) followed by mantle cell lymphoma (6%) and Burkitt’s lymphoma (2%), and follicular lymphoma (FL) which is the most common indolent form of NHL (25%), followed by marginal zone lymphoma (7.5%), chronic lymphocytic leukemia/small-cell lymphocytic leukemia (CLL/SLL; 6%), and lymphoplasmacytic lymphoma (LPL; 1%) (Figure 1). In 2020, approximately 78,000 new cases were diagnosed in the US. NHL accounted for up to 2.6% of all cancer-related mortality, with approximately 20,000 mortality numbers in the US in 2020. The 5-year survival rates (2010-2016) reported showed a 158% improvement over rates reported in 1975. Newly available treatments including targeted therapies like venetoclax and pembrolizumab and anti-CD20 antibodies such as rituximab have contributed to these improved outcomes.5

Figure 1: Common subtypes of non-Hodgkin’s lymphoma6


  1. Singh R, Shaik S, Negi BS, et al. Non-Hodgkin’s lymphoma: A review. J Family Med Prim Care. 2020;9:1834-1840.
  2. Sun R, Medeiros LJ, Young KH. Diagnostic and predictive markers for lymphoma diagnosis and treatment in the era of precision medicine. Mod Pathol. 2016;29:1118-1142.
  3. Thandra KC, Barsouk A, Saginala K, Padala SA, Barsouk A, Rawla P. Epidemiology of non-Hodgkin’s lymphoma. Med Sci (Basel). 2021;9:5.
  4. Nogai H, Dörken B, and Lenz G. Pathogenesis of non-Hodgkin’s lymphoma. J Clin Oncol. 2011;29:1803-1811.
  5. Howlander N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review (CSR) 1975-2016. Natl Cancer Institute. Updated April 9, 2020. Accessed October 27, 2022.
  6. Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: Clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol. 1998;16:2780-2795.
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