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Updated on October 20, 2023
Diffuse Large B-Cell Lymphoma (DLBCL) is a type of non-Hodgkin’s lymphoma (NHL). Lymphomas are a type of cancer than occurs when white blood cells called lymphocytes become cancerous. DLBCL is the most common form of lymphoma in the United States.
DLBCL begins in a type of lymphocyte called B cells. B cells are part of the body’s adaptive immune system—the part of the immune system that responds when the body encounters disease-causing pathogens and other harmful substances. B cells move around the body through the lymph system, which includes lymph vessels, lymph nodes, the spleen, and the thymus gland.
Cancerous B cells grow and multiply at a much faster rate than normal, and do not expire like normal B cells. These cancerous cells can crowd out healthy white blood cells, weakening the immune system and leaving a person vulnerable to infections. Because the lymph system extends throughout many parts of the body, DLBCL can affect many different organs and systems, depending on where the cancer begins and if it spreads.
Non-Hodgkin’s lymphomas are complex conditions, with numerous subtypes, and subtypes within those subtypes. If you or a loved one has received a diagnosis of DLBCL, the information below can help you understand the different subtypes and other key terms.
Nodal and extra-nodal
DLBCL can be described as nodal or extra-nodal, depending on the site where the cancer originated:
- Nodal. This refers to lymphoma that originates in the lymph nodes. Lymph nodes are bean-shaped structures that contain white blood cells and act as filters for the lymph system.
- Extra-nodal. This refers to lymphoma that originates in lymphatic tissue outside the lymph nodes. The stomach, intestines, nose and sinuses, testicles, skin, and thyroid are among the many locations extra-nodal DLBCL can occur.
Staging
Like many other types of cancer, DLBCL is assigned a stage at diagnosis. The stage is determined based on how many lymph nodes or extra-nodal sites are involved, where those primary sites are located, and if the cancer has spread beyond the primary sites.
“Not otherwise specified”
Most cases of DLBCL are categorized as diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). There are two main subtypes within the DLBCL, NOS category. There are also less common subtypes and subtypes that cannot be classified.
ABC and GBC
While the lifecycle of a B-cell is complex and involves many stages, it can be broken down into three main stages—development, activation, and differentiation. The two main subtypes of DLBCL, NOS are categorized based on where in this lifecycle the cancerous mutation originates.
- Activated B-cell-like (ABC). Cancer-causing mutations occur during the activation stage, when a B-cell encounters an antigen (like a disease-causing pathogen or a toxin) and begins producing antibodies.
- Germinal center B-cell-like (GBC). Mutations occur at the later differentiation stage, when B-cells fine-tune the antibodies they are producing to more effectively neutralize a specific antigen.
Rare subtypes and new categorizations
While ABC and GBC are the main subtypes of DLBCL, there are others. Examples include:
- Central nervous system diffuse large B-cell lymphoma (CNS-DLBCL), which affects the brain, spinal cord, and/or eyes.
- Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV-positive DLBCL), a subtype associated with a history of infection with the Epstein-Barr virus.
- Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is a type of extra-nodal DLBCL. Cutaneous lymphomas often manifest as hard nodules underneath the skin. This type primarily involves the lower limbs.
Subtypes can change as knowledge and understanding of the disease evolves. Primary mediastinal B-cell lymphoma—a type of lymphoma that causes tumors in the chest cavity and mostly affects younger females—was previously considered a subtype of DLBCL. It is now considered a separate type of lymphoma.
Why are subtypes important?
Diagnosing the subtype involves gene expression profile testing. This testing involves taking a biopsy (tissue sample) of the cancer. Laboratory tests take a close look at the genetics of the cancer cells from that sample. This can help a healthcare team determine what treatments the cancer is more likely to respond to, and provide a more accurate prognosis.
