What is Non-Hodgkin’s Lymphoma (NHL)

If you or a loved one has been recently diagnosed with NHL, you may be wondering what non-Hodgkin’s lymphoma cancer is and want to know the difference between non-Hodgkin’s versus Hodgkin’s lymphoma. Cancer occurs when the body’s normal cells begin to grow uncontrollably. When this process happens to white blood cells or lymphocytes, the cancer is called Non-Hodgkin’s Lymphoma or NHL. NHL refers to a group of closely related cancers or lymphoma types that have some common characteristics.

Sites of lymph tissue in our body³
Cancers of the lymphatic system are termed lymphomas. The lymphatic system, as part of the body’s immune system, helps in fighting off infections and certain diseases.³

Lymph nodes: These are sites that contain the body’s immune cells including lymphocytes. They can be found inside the chest, abdomen, and pelvis. Various sites are connected via a system of lymphatic vessels (the network of green vessels in the figure) making up the lymphatic system.³

Spleen: Production of various immune system cells such as lymphocytes occurs inside the spleen. It is also a store for healthy blood cells and helps to filter our damaged blood cells as well as foreign and bodily waste. The spleen lies under the lower ribs on the left side of the body.³

Bone marrow: New blood cells are produced in the bone marrow, a spongy tissue contained inside certain bones.³

Thymus: This is an organ located behind the upper part of the breastbone and in front of the heart. It is essential in the development of one type of lymphocyte called T-lymphocytes.³

Digestive tract: Various parts of the digestive tract have lymph tissue including the stomach and intestine.³
Classification of lymphomas

Non-Hodgkin’s vs Hodgkin’s lymphoma
A defining characteristic of Non-Hodgkin’s versus Hodgkin’s Lymphoma is its ability to spread through the lymphatic system in a non-orderly manner. Hodgkin’s lymphoma, on the other hand, spreads from one group of lymph nodes to another in an orderly manner (it is not discussed here).⁴

Lymphoma based on cell type
The immune system contains different types of lymphocytes including T-cells, B-cells, and NK-cells. NHL can occur in any of these cell types. This site will focus only on B-cell lymphomas which comprise about 85% of NHLs. B-cells fight infections by producing antibodies.⁵

Indolent vs aggressive
NHLs are also classified as indolent/slow-growing or aggressive/fast-growing. While both types are equally common among adults, children are more prone to aggressive NHL. Some non-Hodgkin’s lymphoma types have both indolent and aggressive characteristics, for eg, mantle cell lymphoma.⁶

Indolent lymphomas, while typically not curable, are treatable and patients with these types of NHL can live long lives while in remission. Some indolent lymphomas can develop into aggressive lymphomas over time.⁷

Aggressive lymphomas are often curable.⁷

Indolent B-cell Lymphomas	Aggressive B-cell Lymphomas
Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL)	Burkitt Lymphoma
Follicular Lymphoma (FL)	Diffuse Large B-cell Lymphoma (DLBCL)
Lymphoplasmacytic Lymphoma (LPL)/ Waldenström Macroglobulinemia (WM)	Primary Mediastinal B-cell Lymphoma (PMBCL)
Marginal Zone Lymphoma (MZL)	Double-hit/triple-hit Lymphoma
	Mantle Cell Lymphoma (MCL)

NHL Subtypes
The World Health Organization (WHO) has classified more than 80 types of non-Hodgkin’s lymphoma based on unique characteristics including appearance under a microscope, genetic/molecular characteristics (ie, features of the chromosome in the cancerous cells), location, and pattern of growth in the body, treatment options, outcome of disease, presence of certain proteins on the cancer cell surface, and so on.^3,7

Frequencies of B-cell lymphomas in the United States

DLBCL is the most common type of NHL in the United States, with 29% frequency, followed by FL, with 20% frequency. FL may turn into DLBCL over time in a process called transformation. A genetic abnormality in the FL cells leads to a change in the function of a protein called BCL2.⁶ MCL occurs in 5%-7% of people and is more commonly seen in older people (>60 years) and in men. It is characterized by a change in the function of a protein called cyclin D1. A highly aggressive form of DLBCL is double-hit lymphoma, which is characterized by changes in two genes: the MYC gene and the BCL2 or BCL6 gene. When all three genes show changes, the lymphoma is classified as triple-hit lymphoma.⁶