What is Diffuse Large B-Cell Lymphoma?
Lymphoma is a type of cancer that affects the cells in the body’s lymph system, specifically the lymphocytes. These lymphocytes can be of three types: B cells, T cells, or natural killer (NK) cells, and can develop into lymphoma during different maturity stages. The disease is split into two categories: Hodgkin’s and Non-Hodgkin’s lymphoma, the latter making up about 80% of all lymphoma cases.
The B cells, one of the types of lymphocytes, are particularly diverse in their functions and can transform through multiple pathways. This makes them a source of a varied group of diseases that differ in clinical and pathological presentation. More than 30 subtypes of Non-Hodgkin’s lymphoma exist, but the most common ones are diffuse large B-cell lymphoma and follicular lymphoma.
What Causes Diffuse Large B-Cell Lymphoma?
B cell lymphomas are types of cancer that start from B cells at different stages of their growth. B cells can be in three different stages – pre-germinal, germinal, and post-germinal center, with most B-cell lymphomas starting from the germinal center. Like other cancers, B cell lymphomas can be caused by genetic changes that affect the genes controlling cell growth, and also by the environment within the lymph nodes.
Changes in a specific gene called BCL6 can be seen in 20% to 40% of people with B cell lymphomas. In people with HIV, which weakens the immune system, chronic issues with T cells and overactive B cells may be the reason for non-Hodgkin lymphoma. Some infections can directly change the DNA, like in Burkitt’s lymphoma where the Epstein Barr virus affects the DNA of B cells. HIV itself can also increase the risk of these cancers, since it reduces the body’s ability to control cancer cells.
Being on medications to suppress the immune system, like for people who had transplants, increases the risk of B-cell lymphomas. The same is true for other types of cancer that can transform into B cell lymphomas, along with having a personal or family history of lymphoma, having had radiation therapy or chemotherapy, and being exposed to chemical agents like dyes and pesticides. People who are obese or have a history of autoimmune diseases also have a higher chance of developing non-Hodgkin lymphoma.
Risk Factors and Frequency for Diffuse Large B-Cell Lymphoma
Non-Hodgkin lymphoma is not a rare disease in the United States, with about 7 cases per 100,000 people diagnosed each year. A specific type called DLBCL makes up 25% of all cases globally. Out of all the types of non-Hodgkin lymphoma, DLBCL is the most common, closely followed by another type called FL.
- Non-Hodgkin lymphoma sees about 7 new cases per 100,000 people each year in the United States.
- DLBCL, which stands for Diffuse Large B-Cell Lymphoma, accounts for 1/4 of global non-Hodgkin lymphoma cases.
- DLBCL is the most frequently diagnosed type of non-Hodgkin lymphoma, with Follicular Lymphoma (FL) coming next.
- The disease is most common in white people, then African Americans, then Asians.
- Men are more likely to be diagnosed than women.
- The median age of patients is 64 years old.
- The chance of getting this disease increases greatly with age.
Signs and Symptoms of Diffuse Large B-Cell Lymphoma
Most types of non-Hodgkin’s lymphoma (NHL) are known to spread through the blood. In contrast, Hodgkin lymphoma usually spreads through the lymphatic system. As a result of this blood-born spread, most people are diagnosed with advanced stages (III or IV) of NHL.
It is necessary to check the entire body for possible signs of the disease, including areas like the head, neck, elevated collar bone area (supraclavicular), underarm (axillary), near the intestines (mesenteric), thigh (femoral), and groin (inguinal). Doctors also examine the abdomen to see if the liver or spleen is enlarged—a common trait in NHL.
A particular type of NHL called diffuse large B-cell lymphoma (DLBCL) is often associated with swelling of the lymph nodes or a rapidly increasing lump along with ‘B’ symptoms. These symptoms, as noted in 30% of patients, comprise a fever, night sweats, and weight loss. Bone marrow involvement is more prevalent in more inactive diseases, affecting up to 50% of cases.
About half the patients show involvement outside the lymph nodes. The stomach or gastrointestinal tract is the most common place for this, followed by the skin. Kidney involvement may be due to extensive disease or a swollen lymph node blocking the ureter, or because of a condition caused by tumor breakdown known as tumor lysis syndrome.
DLBCL can also cause superior vena cava syndrome, a condition marked by the swelling of the face, neck, or arms due to pressure on the major vein (superior vena cava) that carries blood to the heart. It can also cause breathing difficulties. If the disease spreads beyond the lymph system to other organs, the symptoms depend on the organ involved. It can affect areas like the skin, bones, spinal cord, and testicles. Various conditions associated with B cell lymphomas can also occur.
The type of B cell lymphomas can influence the symptoms as well. Aggressive types like DLBCL and Burkitt’s lymphoma usually present with a rapidly growing lump. The spinal cord may be compressed due to NHL, mainly at the time of recurrence. More indolent (slower growing) lymphomas like follicular lymphoma (FL) and marginal zone lymphoma usually present with gradually developing swelling of the lymph nodes. FL is typically characterized by painless swelling of lymph nodes and nearly normal levels of an enzyme called LDH.
Testing for Diffuse Large B-Cell Lymphoma
To diagnose lymphoma, a thorough physical check-up, lab tests, and imaging studies are crucial. Doctors conduct a wide range of lab tests, including complete blood count (CBC), metabolic profiling, LDH level testing, HIV, and Hepatitis B and C tests, and a serum protein analysis. The complete blood count can reveal abnormal cells and deficiencies in regular cells.
If patients show symptoms or have a high risk of affecting the central nervous system, a lumbar puncture may be required. HIV testing is also essential as B cell lymphomas can be a symptom of AIDS. Since lymphoma treatment can suppress the immune system, understanding the patient’s HIV and hepatitis status is important to their care plan.
Roughly 14% of patients may experience kidney involvement, and over half of lymphoma cases show elevated LDH levels, which can indicate survival prospects.
Doctors often prefer an excisional biopsy of the lymph node over a fine-needle aspiration because it provides a comprehensive view of the node and allows for further diagnostic studies. Doctors use this method to examine the morphology and immunophenotyping and apply staining for B-cell markers to help diagnose the condition.
Imaging techniques like positron emission tomography (PET) and computed tomography (CT) scans are valuable in determining the stage of the disease. PET scans are generally useful for most B cell lymphomas. They can identify locations with high activity levels, suggesting an aggressive disease. However, PET scanning may not be as useful in CLL because it doesn’t respond as much to the FDG compound used in PET scans.
Along with determining the disease stage, imaging can also help doctors identify the least invasive site for a diagnostic biopsy. If noticeable lymph node enlargement is absent, doctors may need to sample tissue from involved organs.
Treatment Options for Diffuse Large B-Cell Lymphoma
The type of treatment for B cell lymphomas largely depends on the stage of the disease, how aggressive it is, and its molecular subtype. Diffuse Large B Cell Lymphoma (DLBCL) is an aggressive type. However, with the right chemotherapy, patients can have a long survival rate, albeit with a limited chance of complete cure.
Patients with a subtype of DLBCL known as GCB DLBCL can benefit from six cycles of a treatment regimen referred to as R-CHOP. This regimen includes rituximab along with other drugs like cyclophosphamide, doxorubicin, vincristine, and prednisone. Rituximab, in particular, is given intravenously.
Meanwhile, ABC DLBCL and double-hit and triple-hit lymphomas are not as responsive to R-CHOP. For these, research indicates that it’s beneficial for patients to participate in clinical trials. Treatments under exploration include R-CHOP combined with drugs like lenalidomide, bortezomib, or ibrutinib.
A more aggressive treatment strategy includes a regimen called R-ACVBP, followed by consolidation with methotrexate and leucovorin. Furthermore, a six to eight cycle regimen involving several drugs, referred to as R-EPOCH, has been suggested for patients with advanced double-hit DLBCL. Notably, rituximab IV therapy is an essential part of treatment for slow-growing (or indolent) lymphomas.
For indolent lymphomas such as follicular lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma, the treatment primarily depends upon the amount of the disease and the symptoms of the patients. Patients with aggressive low-grade disease have undergone treatment with allogeneic transplants intending to cure. Radiotherapy may be considered for patients with a large bulk of the disease. Another aggressive lymphoma called Mantle cell lymphoma is treated with immuno-chemotherapy and autologous stem cell transplants.
Lastly, Burkitt lymphoma and lymphoblastic lymphoma are categorized as high-grade diseases that require aggressive chemotherapy and preventative intrathecal chemotherapy (given into the space that surrounds the brain and spinal cord).
What else can Diffuse Large B-Cell Lymphoma be?
The possible conditions that could be mistaken for diffuse large B-cell lymphoma (DLBCL) include infectious mononucleosis, Hodgkin’s lymphoma, T-cell lymphomas, and other large cell diseases such as various types of cancers, skin cancer (melanoma), and Kikuchi disease.
Skin cancers like melanoma can also affect the lymph nodes, which are similar in presentation to DLBCL. However, by using specific identifying tests, like S100, HMB-45, and Melan A staining (tests used to detect proteins in cells), these can be distinguished from DLBCL.
What to expect with Diffuse Large B-Cell Lymphoma
The outlook for Non-Hodgkin’s Lymphoma, or NHL, largely depends on factors such as the stage of the disease, detailed pathology, if the disease has spread beyond the lymph nodes, patient’s age, and overall health status. Doctors keep track of how well the treatment is working through physical exams, blood tests, and imaging scans.
The International Prognostic Index (IPI) is a tool used to predict the outcome for patients with a specific type of NHL known as Diffuse Large B-Cell Lymphoma (DLBCL). If a patient is over 60 years of age, has a Eastern Cooperative Oncology Group (ECOG) health score above 2, has high levels of an enzyme called LDH, is in the final stages of the disease (stages III/IV), and has the disease spread beyond one particular lymph node region, it usually means they might have a lower chances of survival.
DLBCL is an intense type of disease, but about half of the patients who reach total remission after initial treatment can be cured. The ‘GCB’ type of DLBCL tends to have a better outlook compared to the ‘ABC’ type. However, cases referred to as ‘double hit’ and ‘triple hit’ lymphomas generally have a poor prognosis in comparison to other types of DLBCL.
Possible Complications When Diagnosed with Diffuse Large B-Cell Lymphoma
The health problems that can be caused by this condition include:
- Implication of bone marrow leading to lowered blood cell count and higher risk of infection
- Kidney failure
- Central Nervous System (brain and spinal cord) complications
Preventing Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL), a subtype of non-Hodgkin lymphoma (NHL), is quite common. It accounts for roughly 25% to 30% of all NHL cases globally. Most of the time, DLBCL is noticeable because it often presents as a fast-growing mass or swollen lymph nodes in either a nodal or non-nodal location in the body. Despite being aggressive, this type of lymphoma responds positively to chemotherapy treatments.
