Diffuse large B-cell lymphoma is the most common form of aggressive lymphoma affecting adults, developing when certain white blood cells grow abnormally and spread through the body’s infection-fighting network, often appearing as swollen lymph nodes or masses in unexpected places.
Epidemiology
Diffuse large B-cell lymphoma, commonly shortened to DLBCL, stands as the most frequently diagnosed type of non-Hodgkin lymphoma, which is a broad category of blood cancers affecting the lymphatic system. In the United States and many western countries, DLBCL accounts for roughly 22 to 30 percent of all newly diagnosed cases of B-cell non-Hodgkin lymphoma each year.[3][4] More than 18,000 people receive a DLBCL diagnosis annually in the United States alone.[3]
Despite being the most common lymphoma subtype, DLBCL remains relatively uncommon when compared to all cancer diagnoses. According to the National Cancer Institute, approximately 6 people per 100,000 received a DLBCL diagnosis in 2020. To put this in perspective, about 500 people per 100,000 received a diagnosis of cancer affecting any part of their body during the same period.[2]
This disease shows distinct patterns in who it affects. DLBCL occurs more frequently in men than in women.[7] The occurrence of the disease generally increases with age, and most patients are over 60 years old at the time of diagnosis.[3] The median age at first diagnosis sits at around 70 years.[8] While DLBCL primarily affects older adults, it can occur in young adults and, in rare instances, even in children.[7][8]
Causes
The development of diffuse large B-cell lymphoma begins when B cells undergo changes at the genetic level. These cells are a type of white blood cell, also called B lymphocytes, which normally produce antibodies to help the body fight off infections like viruses and bacteria. The genetic changes that lead to DLBCL are acquired mutations, meaning people develop them during their lifetime rather than being born with them.[2]
Medical researchers have identified more than 70 different genetic mutations linked to diffuse large B-cell lymphoma.[7][13] These mutations affect genes that control cell growth and development, including changes to the BCL6 gene, which can be seen in 20 to 40 percent of patients.[4] Like other cancers, B-cell lymphomas can result from genetic alterations affecting proto-oncogenes, which are genes that help cells grow, and tumor suppressor genes, which normally help prevent cancer by controlling cell division. However, the environment within the lymph nodes themselves can also promote the development of lymphoma.[4]
In some cases, DLBCL doesn’t arise from normal B cells but instead represents a transformation of other, slower-growing types of lymphoma. For example, some people with follicular lymphoma, marginal zone lymphomas, small lymphocytic lymphoma, or chronic lymphocytic leukemia may eventually develop DLBCL as their disease changes over time.[4][7][8] This progression is sometimes called Richter’s transformation when it occurs in chronic lymphocytic leukemia.[8]
Certain infectious agents play a role in some cases of DLBCL. The Epstein-Barr virus (EBV), for instance, can directly manipulate DNA by transporting viral genetic material into B cell nuclei, altering how these cells grow and develop.[4] The bacterium Helicobacter pylori has also been associated with the development of certain subtypes of diffuse large B-cell lymphoma.[8] Other viruses linked to DLBCL development include Kaposi’s sarcoma-associated herpesvirus and human immunodeficiency virus (HIV).[8]
Risk Factors
Several factors can increase a person’s likelihood of developing diffuse large B-cell lymphoma. Understanding these risk factors can help people recognize when they might be at higher risk, though having one or more risk factors doesn’t mean someone will definitely develop the disease.
Problems with the immune system represent one of the most significant risk factors. People with underlying immunodeficiency, meaning their immune system doesn’t work properly, face a substantially higher risk of developing DLBCL.[8][9] This includes people living with HIV infection, where the virus decreases the body’s ability to regulate abnormal cells and fight off malignancies.[4] Similarly, people who take immunosuppressive medications, such as those used after organ transplants to prevent rejection, also have an elevated risk of developing B-cell lymphomas.[4]
Chronic immunodeficiency that specifically affects T cells, combined with ongoing stimulation of B cells, can create conditions that favor lymphoma development. This explains why HIV-infected patients show higher rates of non-Hodgkin lymphoma, including DLBCL.[4]
Viral infections constitute another important risk category. People who test positive for the Epstein-Barr virus may develop a specific form called EBV-positive DLBCL, which typically occurs in patients age 50 or older.[3] Those with Kaposi’s sarcoma-associated herpesvirus infection also face increased risk.[8]
A family history of lymphoma increases risk, suggesting some genetic predisposition to the disease.[7][13] People who have previously undergone chemotherapy or radiation therapy for other conditions carry a higher risk of later developing DLBCL.[7][13]
Previous diagnosis of other blood cancers or lymphomas also elevates risk. Those with a history of low-grade B-cell lymphomas, such as follicular lymphoma, marginal zone lymphomas, or small lymphocytic lymphoma, may eventually see their condition transform into DLBCL.[7] People with chronic lymphocytic leukemia face a similar risk of transformation.[7]
Chronic infections and inflammation may contribute to risk in specific cases. For instance, infection with the Helicobacter pylori bacterium, which causes stomach ulcers, has been linked to certain DLBCL subtypes that develop in the gastrointestinal system.[8]
Symptoms
The symptoms of diffuse large B-cell lymphoma can develop suddenly and worsen quickly, often over just a few weeks. Because DLBCL is classified as an aggressive or fast-growing lymphoma, the signs often appear rapidly and become more noticeable as the disease progresses.[5]
The most commonly noticed symptom involves swollen lymph nodes. People typically discover painless lumps or swellings in their neck, armpits, or groin, which are areas where lymph nodes sit close to the skin’s surface.[2][5] These swollen lymph nodes appear as lumps that don’t go away and actually seem to be getting larger over time. While these lumps usually aren’t painful, they can sometimes cause discomfort or pain.[2]
DLBCL can grow in places outside the lymph nodes, called extranodal sites. When this happens, the symptoms depend on which part of the body is affected. Lymphoma growing in the abdomen or bowel might cause pain, diarrhea, or bleeding. When it develops in the chest area, people might experience shortness of breath, difficulty breathing, or persistent coughing.[5][7] In rare cases, people might notice severe head and neck swelling, purplish discoloration of the face, or bulging neck veins if the cancer affects blood flow in major vessels.[4]
About 30 percent of people with DLBCL experience what doctors call “B symptoms,” which represent a specific group of warning signs.[2] These include high fevers above 103 degrees Fahrenheit (39.5 degrees Celsius) that last longer than two days or come and go without an obvious cause. Another B symptom is unexplained weight loss that results in losing more than 10 percent of total body weight over six months. Heavy night sweats that soak through sheets and bedclothes also count as a B symptom.[2][7] Some people also report unexplained itching all over their body.[5]
Other symptoms can include an enlarged liver or spleen, extreme fatigue that doesn’t improve with rest, and loss of appetite.[7][13] When lymphoma affects the bone marrow where blood cells are made, people might develop symptoms related to low blood cell counts, such as weakness or frequent infections.
Prevention
Currently, there are no established methods to prevent diffuse large B-cell lymphoma entirely. Because the disease results from genetic changes that occur unpredictably during a person’s lifetime, and because doctors don’t fully understand what triggers these changes in most cases, specific prevention strategies remain limited.
However, understanding risk factors can help people make informed health decisions. For those with conditions that weaken the immune system, working closely with healthcare providers to manage these underlying conditions may help reduce overall cancer risk. People living with HIV should maintain their treatment regimens and regular medical follow-up, as proper management of HIV can help reduce the risk of developing lymphomas.[4]
For people who have had previous low-grade lymphomas like follicular lymphoma or chronic lymphocytic leukemia, regular monitoring by healthcare providers is important. While this doesn’t prevent transformation to DLBCL, it allows for early detection if changes occur.[8]
Some viral infections associated with DLBCL risk can potentially be addressed. For example, treatment of Helicobacter pylori infection when detected may reduce risk of certain DLBCL subtypes that develop in the stomach, though this connection applies to specific cases rather than all DLBCL.[8]
Maintaining overall health through a balanced diet, regular exercise, and avoiding tobacco may support immune system function, though these measures haven’t been proven to specifically prevent DLBCL. People with a family history of lymphoma might benefit from discussing their elevated risk with their doctor, even though there are no specific screening tests recommended for DLBCL in people without symptoms.
Perhaps most importantly, being aware of the symptoms and seeking prompt medical attention when concerning signs develop can lead to earlier diagnosis and treatment. While this approach doesn’t prevent the disease, early detection often improves treatment outcomes. Anyone who notices persistent swollen lymph nodes, unexplained fevers, significant weight loss, or other concerning symptoms should consult a healthcare provider promptly.[5]
Pathophysiology
Understanding how diffuse large B-cell lymphoma develops and affects the body requires looking at what happens at the cellular level. The disease fundamentally disrupts the normal development and function of B lymphocytes, which are essential components of the body’s immune defense system.
Normal B cells develop through distinct stages, which can be categorized into three main phases: pre-germinal center, germinal center, and post-germinal center. Most B-cell lymphomas, including DLBCL, are derived from cells at the germinal center stage.[4] The germinal center is a specialized area within lymph nodes and other lymphoid tissues where B cells mature and learn to recognize specific threats.
When viewed under a microscope, the abnormal B cells in DLBCL appear distinctly different from healthy cells. They are notably larger than normal B lymphocytes, which is where the “large B-cell” part of the disease name comes from. These oversized cells don’t organize themselves into specific patterns but instead spread out diffusely throughout the affected tissue, explaining the “diffuse” descriptor in the disease name.[1]
The lymphatic system, which DLBCL affects, consists of a network of vessels, organs, glands, and clusters of cells called lymph nodes distributed throughout the body. This system circulates a fluid called lymph, which contains high numbers of white blood cells that fight infection.[5] In DLBCL, the cancerous B cells can build up in lymph nodes or migrate to virtually any organ in the body, including the gastrointestinal tract, central nervous system, bones, skin, thyroid, breast, bone marrow, and kidneys.[1][2]
The abnormal cells in DLBCL multiply much more rapidly than normal B cells, creating masses of cancer cells that overtake healthy tissue. Because these cells no longer function properly, they can’t fulfill their normal role of producing antibodies to fight infections. This leaves people with DLBCL more vulnerable to viruses, bacteria, and other disease-causing organisms.[2]
Different subtypes of DLBCL show variations in their cellular origins and genetic features. For example, some DLBCL cells originate from the germinal center B-cell subtype, while others come from an activated B-cell subtype. These molecular differences affect how the cancer behaves and responds to treatment.[7][13]
When DLBCL develops in specific locations, it can cause distinct physical changes. Cancerous cells growing in lymph nodes cause them to swell as the expanding cell population takes up more space. When the cancer affects bone marrow, it interferes with normal blood cell production, potentially leading to decreased counts of red blood cells, white blood cells, and platelets. Lymphoma growing in organs can disrupt their normal function by physically compressing surrounding structures or invading the tissue itself.[4]
The aggressive nature of DLBCL stems from the rapid cell division and growth characteristic of this lymphoma type. Unlike slow-growing lymphomas that may take years to cause noticeable problems, DLBCL can progress quickly, sometimes causing significant symptoms within weeks or months of its initial development.[5]
