Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). This cancer originates in the lymphatic system, a network of tissues and organs that helps the body fight infection. As an aggressive and fast-growing malignancy, DLBCL requires prompt diagnosis and treatment. While considered a serious disease, advancements in medical therapy have made it potentially curable for a significant number of patients.
Understanding Diffuse Large B-cell Lymphoma
DLBCL is a cancer of the B-cells, a white blood cell type that normally creates antibodies to fight pathogens. In this disease, healthy B-cells undergo malignant transformation, leading to uncontrolled proliferation within the lymph nodes or other organs. The term “large” refers to the size of the cancerous cells, which are observably bigger than normal lymphocytes when examined under a microscope.
The term “diffuse” describes the pattern of growth, meaning the malignant cells are spread throughout the tissue rather than being clustered in small, confined areas. This rapid, diffuse growth pattern classifies DLBCL as a high-grade or aggressive lymphoma, distinguishing it from slow-growing, or indolent, types. DLBCL most commonly arises in the lymph nodes, which are small, bean-shaped glands scattered throughout the body.
In approximately 40% of cases, the disease manifests in extranodal sites, meaning outside of the lymph nodes. These locations can include the gastrointestinal tract, central nervous system, skin, or bone. The aggressive nature of DLBCL means the disease progresses quickly, often necessitating immediate therapy upon diagnosis.
Recognizable Signs and Risk Factors
The most common initial sign of DLBCL is a rapidly enlarging, noticeable swelling, typically an enlarged lymph node in the neck, armpit, or groin. This lump is often painless, which can sometimes delay medical evaluation. The speed of growth is a characteristic feature distinguishing it from less aggressive conditions.
About 30% of patients also experience systemic symptoms collectively known as “B symptoms.” These include unexplained fevers, drenching night sweats severe enough to require changing bedclothes, and unexplained weight loss of more than 10% of body weight over six months.
While the exact cause of DLBCL remains unknown, several factors increase the risk. Advanced age is a primary factor, with the median age of diagnosis typically around 64 years. DLBCL is also observed slightly more frequently in men than in women.
Individuals with compromised immune systems face a higher risk, including those with HIV infection, patients taking immunosuppressive drugs after an organ transplant, or those with certain autoimmune disorders. A connection has also been established between DLBCL and chronic viral infections, such as the Epstein-Barr Virus (EBV). Exposure to specific toxic substances, like certain pesticides, is considered a potential risk factor.
How DLBCL is Identified and Classified
The definitive diagnosis of DLBCL relies on a biopsy, where a portion of the suspicious lymph node or tumor mass is removed. Pathologists examine the tissue under a microscope to confirm the proliferation of large, abnormal B-cells and the diffuse growth pattern. Specialized laboratory techniques are then employed to further characterize the cancer cells.
Immunohistochemistry (IHC) and flow cytometry confirm the B-cell origin of the lymphoma by identifying specific surface proteins, such as CD20. DLBCL is classified into molecular subtypes based on the cell-of-origin (COO), primarily Germinal Center B-cell-like (GCB) and Activated B-cell-like (ABC). This classification, often determined by genetic profiling or IHC, is important for prognosis, as the GCB subtype is generally associated with a more favorable outcome than the ABC subtype.
Once diagnosis is confirmed, the extent of the disease is determined through staging, typically using the Ann Arbor Staging System. This involves physical examination and advanced imaging, with Positron Emission Tomography (PET) and Computed Tomography (CT) scans being standard tools. Staging assesses the number of lymph node areas involved, spread across the diaphragm, and invasion of extranodal organs.
The stage is designated from I (localized to a single region) to IV (widespread dissemination). The presence of B symptoms is indicated by the letter “B” (e.g., Stage IIB). This information helps physicians determine prognosis and select the most effective treatment plan. The International Prognostic Index (IPI) is a widely used risk stratification tool that incorporates stage, age, and laboratory values to refine the patient’s outlook.
Standard Treatment Approaches
The standard first-line treatment for DLBCL is a combination regimen known as R-CHOP, which has been the cornerstone of therapy for over two decades. R-CHOP is an acronym representing five agents:
- Rituximab (a monoclonal antibody targeting the CD20 protein on B-cells)
- Cyclophosphamide (chemotherapy)
- Doxorubicin (chemotherapy)
- Vincristine (chemotherapy)
- Prednisone (a corticosteroid)
Rituximab flags the malignant B-cells for destruction by the immune system. The other four components are traditional chemotherapy drugs that kill rapidly dividing cells.
The R-CHOP regimen is typically administered in cycles, often six cycles given every 21 days for advanced-stage disease. For patients with early-stage disease, treatment may consist of fewer cycles, often followed by involved-field radiation therapy to the site of the original tumor.
Despite R-CHOP’s high success rate, some individuals experience a relapse or have refractory disease that does not respond to initial treatment. Secondary treatments involve more intensive salvage chemotherapy regimens. If the disease responds, the next step is often high-dose chemotherapy followed by an autologous stem cell transplant.
This transplant procedure uses the patient’s own previously collected stem cells to rescue the bone marrow after high-dose chemotherapy eliminates remaining cancer cells. More recently, targeted immunotherapies like Chimeric Antigen Receptor (CAR) T-cell therapy have become an option for patients with relapsed or refractory disease. This specialized therapy genetically modifies a patient’s T-cells to specifically recognize and attack the lymphoma cells.