Diffuse large B-cell lymphoma (DLBCL) stage III is an aggressive blood cancer that develops when certain white blood cells grow abnormally and spread through the lymphatic system. While this condition grows quickly and can affect multiple areas of the body, many people respond well to treatment when it is started promptly.

Understanding DLBCL Stage III

Diffuse large B-cell lymphoma is a type of blood cancer that affects B cells, which are special white blood cells that normally help your body fight infections. In DLBCL, these B cells undergo changes that turn them into fast-growing cancer cells. These abnormal cells can no longer perform their usual job of protecting you from viruses and bacteria. Instead, they multiply rapidly and crowd out healthy cells in your body.^[1]

The term “diffuse” means that the cancer cells are spread out rather than grouped together in one spot. “Large B-cell” refers to the fact that the cancerous B cells are bigger than normal, healthy B cells when examined under a microscope. Stage III indicates that the disease has spread to lymph nodes or organs on both sides of the diaphragm, which is the muscle that separates your chest from your abdomen. This means the lymphoma is present in more areas of the body compared to earlier stages.^[2]

DLBCL affects your lymphatic system, which is a network of tissues, vessels, and organs that work together to help fight infection throughout your body. The lymphatic system includes lymph nodes found in your neck, armpits, groin, and other areas. With DLBCL, cancerous B cells may appear not only in lymph nodes but also in virtually any organ, including your gastrointestinal tract, thyroid, skin, breast, bone, or brain.^[1]

How Common Is This Disease

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma, a category of blood cancers that affect the lymphatic system. DLBCL makes up more than 40 out of 100 cases of non-Hodgkin lymphoma in adults. Each year, about 5,000 people are diagnosed with DLBCL in the UK alone.^[3]

Despite being the most common lymphoma, DLBCL is still relatively uncommon compared to other types of cancer overall. According to the National Cancer Institute, in 2020, about 6 people in 100,000 received a DLBCL diagnosis. To put this in perspective, about 500 people in 100,000 received a diagnosis of cancer affecting any part of their bodies during the same time period.^[1]

DLBCL accounts for approximately 25 to 30 percent of all non-Hodgkin lymphomas. The condition is more common in males than females. The disease can occur at any age, but it is more frequently diagnosed in older adults.^[4]

What Causes DLBCL

Diffuse large B-cell lymphoma happens when B cells undergo changes or mutations in their genetic material. These are acquired genetic mutations, meaning they develop during a person’s lifetime rather than being inherited from parents. The exact reason why these mutations occur is not fully understood in most cases.^[1]

The development of B-cell lymphomas results from the abnormal growth of B cells during their various stages of development. B cells normally mature through different stages, categorized as pre-germinal center, germinal center, and post-germinal center stages. Most B-cell lymphomas, including DLBCL, are thought to arise from cells in the germinal center, which is where B cells typically mature and learn to recognize specific disease-causing invaders.^[4]

Like other cancers, B-cell lymphomas can result from genetic mutations that affect important genes. These include proto-oncogenes (genes that normally help cells grow) and tumor suppressor genes (genes that normally prevent uncontrolled cell growth). When these genes are altered, cells can start growing out of control. Genetic alterations in a gene called BCL6 can be seen in 20 to 40 percent of patients with DLBCL.^[4]

The environment within the lymph nodes themselves can also play a role in promoting the development of lymphoma. While the body’s immune system usually works to destroy abnormal cells, certain conditions can interfere with this protective mechanism, allowing cancer cells to grow unchecked.^[4]

Who Is at Risk

Several factors can increase a person’s likelihood of developing diffuse large B-cell lymphoma. Understanding these risk factors can help both patients and healthcare providers recognize who might be at higher risk for the disease.

Certain infectious agents can increase the risk of DLBCL. The Epstein-Barr virus, which causes infectious mononucleosis, can directly affect the DNA in B cells, altering their growth and development. This virus can transport its genetic material into the B cell nucleus, changing how the cells behave. Some types of DLBCL are specifically associated with Epstein-Barr virus infection.^[4]

People with HIV infection have an increased risk of developing non-Hodgkin lymphoma, including DLBCL. HIV weakens the immune system by affecting both T cells and B cells, which reduces the body’s ability to regulate the growth of abnormal cells. Additionally, chronic immune system problems and ongoing stimulation of B cells in HIV-infected patients may contribute to lymphoma development.^[4]

Individuals who take immunosuppressive medications, such as those prescribed after organ transplants to prevent rejection, face a higher risk of developing B-cell lymphomas. These medications weaken the immune system’s ability to identify and destroy abnormal cells that could become cancerous.^[4]

Some studies have found that people with certain autoimmune disorders, such as Sjögren’s syndrome, rheumatoid arthritis, and systemic lupus erythematosus, tend to have an increased risk of DLBCL. The reasons for this association are not entirely clear, but it may be related to chronic immune system activation or the medications used to treat these conditions.^[16]

DLBCL can also develop as a transformation from other types of lymphomas. For example, some people with slower-growing lymphomas may eventually develop DLBCL as their disease changes over time.^[4]

Recognizing the Symptoms

The symptoms of diffuse large B-cell lymphoma can develop or worsen quickly, sometimes in just a few weeks. Because DLBCL is an aggressive, fast-growing cancer, recognizing the signs early and seeking medical attention promptly is important.^[3]

The most common symptom that people notice with DLBCL is swelling in the lymph nodes. These swellings typically appear in the neck, armpits, or groin area. They usually feel like lumps that don’t go away and seem to be getting larger over time. Unlike swollen lymph nodes from common infections, these lumps typically are not painful, although they can be in some cases. The swellings are caused by lymph nodes that have become enlarged due to the accumulation of cancerous B cells.^[1]

About 30 percent of people with DLBCL experience what doctors call “B symptoms.” These include a fever above 103 degrees Fahrenheit (39.5 degrees Celsius) that lasts longer than two days or comes and goes without an obvious cause like an infection. Heavy night sweats are another B symptom, so intense that they drench bed sheets. Unexplained weight loss is the third B symptom, specifically losing more than 10 percent of total body weight over six months without trying to lose weight or changing diet or exercise habits.^[1]

Some people with DLBCL also experience unexplained itching of the skin. This can be bothersome and persistent, affecting quality of life. Other general symptoms may include loss of appetite and persistent fatigue that doesn’t improve with rest.^[3]

DLBCL can develop outside the lymph nodes, and when it does, symptoms depend on where the cancer is growing. For example, lymphoma growing in the abdomen or bowel might cause pain, diarrhea, or bleeding from the digestive tract. DLBCL growing in the chest might cause breathlessness or a persistent cough due to pressure on the lungs or airways.^[3]

Because DLBCL has a rapid growth rate, it often presents as masses that infiltrate tissues or obstruct organs. Pain in an enlarged lymph node or organ may be noted if the mass enlarges rapidly. Chest discomfort or shortness of breath can be caused by enlarged lymph nodes in the middle of the chest. Swelling in the legs (pedal edema) can result from extensive lymph node enlargement in the pelvis.^[6]

Prevention Strategies

Unlike some other types of cancer, there are no well-established prevention strategies specifically for diffuse large B-cell lymphoma. Because the exact causes of DLBCL are not fully understood in most cases, and because the genetic mutations that lead to the disease are acquired during a person’s lifetime rather than inherited, there are no proven lifestyle changes or screening programs that can prevent the disease from developing.

However, understanding and managing certain risk factors may help reduce the likelihood of developing DLBCL or detect it earlier. For people living with HIV, maintaining good control of the virus through antiretroviral therapy and regular medical care is important. This helps keep the immune system functioning as well as possible and may reduce the risk of developing lymphoma and other complications.^[4]

For individuals who have received organ transplants and take immunosuppressive medications, it is essential to follow the prescribed medication regimen carefully and attend all scheduled follow-up appointments. Healthcare providers can monitor for early signs of complications, including lymphoma. While these medications cannot be stopped without risking organ rejection, close medical supervision allows for early detection of any problems.^[4]

For people with autoimmune disorders, working with healthcare providers to manage these conditions effectively may be beneficial. While the relationship between autoimmune diseases and lymphoma risk is not fully understood, maintaining good overall health and following treatment plans for chronic conditions is always advisable.^[16]

Being aware of the symptoms of DLBCL and seeking prompt medical attention if they occur is crucial. While this doesn’t prevent the disease, early detection and treatment can improve outcomes. If you notice persistent swollen lymph nodes, unexplained fevers, significant unintentional weight loss, or drenching night sweats, consult a healthcare provider promptly.^[1]

How DLBCL Affects the Body

To understand how diffuse large B-cell lymphoma affects the body, it helps to first understand how the lymphatic system normally works. The lymphatic system is an important part of the immune system. It consists of tubes called lymph vessels that branch throughout all parts of the body, similar to blood vessels. These vessels carry a straw-colored liquid called lymph, which circulates around body tissues and contains a high number of white blood cells called lymphocytes that fight infection.^[3]

There are two main types of lymphocytes: T lymphocytes (T cells) and B lymphocytes (B cells). B cells are known to have functional diversity, meaning they can transform and develop in multiple ways as they mature. This diversity normally allows them to recognize and respond to many different types of infections and foreign substances. However, this same property also means there are multiple ways that B cells can become abnormal and develop into lymphoma.^[4]

In DLBCL, the body makes abnormal B lymphocytes that are larger than normal healthy B cells. These abnormal cells build up in the lymph nodes or other body organs. Unlike healthy B cells, they don’t work properly and can’t fight infection as normal white blood cells do. As more and more abnormal cells accumulate, they crowd out healthy cells and disrupt normal tissue function.^[3]

The pattern of spread in DLBCL is described as “diffuse,” meaning the cancer cells are spread out throughout affected tissues rather than being grouped together in distinct clusters. This spreading pattern is one of the key features that pathologists look for when examining tissue samples under a microscope to diagnose the disease.^[2]

As DLBCL progresses, it can affect the bone marrow, which is the soft tissue inside bones where blood cells are made. When lymphoma cells infiltrate the bone marrow, they can interfere with the production of normal blood cells. This may result in anemia (low red blood cell count, causing tiredness and weakness), thrombocytopenia (low platelet count, increasing bleeding risk), or leukopenia (low white blood cell count, reducing ability to fight infections).^[6]

In stage III DLBCL, the cancer has spread to lymph nodes or organs on both sides of the diaphragm. This means that lymphoma is present in multiple regions of the body, both above and below the large muscle that separates the chest from the abdomen. The more widespread the disease, the more areas of the body’s immune system are affected, and the greater the impact on overall health and function.^[2]

DLBCL can also cause metabolic changes in the body. The rapid growth and multiplication of cancer cells can lead to elevated levels of certain substances in the blood. For example, lactate dehydrogenase (LDH) is an enzyme that is often higher in people with lymphoma. High LDH levels correspond with the tumor burden, or amount of cancer in the body. Similarly, uric acid levels may increase as cancer cells break down.^[6]

When lymphoma grows in specific organs, it can disrupt their normal function. For example, lymphoma in the gastrointestinal tract may interfere with digestion and nutrient absorption. Lymphoma in the chest may compress the airways or blood vessels, causing breathing problems or circulation issues. The specific effects depend on which organs are involved and how much they are affected by the cancer.^[1]