Non-Hodgkin lymphoma

This condition is a blood cancer of the lymphocytes, the white blood cells that circulate throughout the blood and bone marrow. Lymphocytes are responsible for controlling your immune system and fighting infections. They’re often found in lymph nodes, which help the body drain fluids, though they’re also found in other parts of the lymphatic system like the spleen or tonsils.

Non-Hodgkin lymphoma has more than 60 different varieties (called subtypes) and is more common than Hodgkin lymphoma, another type of blood cancer. An accurate subtype diagnosis is critical to receiving the most effective care.

Experts in blood cancer care at Penn Medicine are international leaders in diagnosing and treating non-Hodgkin lymphoma and its subtypes. We help you access a wide variety of diagnostic tools and treatment options based on groundbreaking clinical research, like CAR T cell therapy developed right here at Penn Medicine. Our multidisciplinary team of hematologists, oncologists, and nurse navigators collaborate to provide compassionate and in-depth care, answering your questions and identifying the best options for you.

Non-Hodgkin lymphomas are classified based on the type of lymphocyte where the cancer begins. This includes B lymphocytes (B cell), T lymphocytes (T cell), and natural killer (NK) cells, among others. These cells work in different ways at the molecular level, impacting how the lymphoma evolves and spreads. 

Subtypes include:

• B cell lymphoma: This is the most common non-Hodgkin lymphoma subtype and makes up the vast majority of cases. This cancer impacts B cells that produce antibodies to target harmful cells. When B cell lymphocytes become abnormal, they multiply out of control and form tumors. This condition can be fast or slow growing and is the root cause of many types of non-Hodgkin lymphoma, like Burkitt lymphoma and cutaneous B-cell lymphoma. 
• T cell lymphoma: This type of non-Hodgkin lymphoma accounts for about 10 percent of cases. T cells attack or eliminate abnormal cells directly and support other parts of the immune system too. When cancer starts in these cells, immune cells make many copies of themselves, forming cancerous lymph nodes or tumors. It may develop slowly or more quickly and includes cutaneous T-cell lymphoma and anaplastic large cell lymphoma.  
• NK cell lymphoma: This rare type of non-Hodgkin lymphoma can arise from natural killer lymphocytes, which are exceptional at destroying abnormal cells in their early stages. Cancer found in NK cells is often grouped with T cell lymphomas and may be called nasal NK/T-cell lymphoma due to its frequent impact on the nose, sinus passages, and airways. 

Researchers continue to identify other non-Hodgkin lymphoma subtypes and develop effective therapies to treat them.  

While swollen lymph nodes are not unique to non-Hodgkin lymphoma, they are the most common sign of the condition. Depending on the subtype, non-Hodgkin lymphoma can also cause:

• Sweating during the night
• Unintentional weight loss
• Fever or chills
• Diminished or low energy levels
• Skin itchiness or rashes
• Abdominal swelling or pain
• Difficulty breathing
• Persistent coughing or chest pain

It’s not clear what causes non-Hodgkin disease, though some factors may increase your risk for developing this condition. They include: 

• Getting older: The incidence of non-Hodgkin lymphoma increases as people age. 
• Weakened immune systems: People who have diseases of the immune system or take medications that compromise the immune system may have an increased risk.
• Certain infections: Those with Epstein-Barr virus (which causes “mono”), hepatitis C virus, human T-lymphotropic virus (HTLV), and human immunodeficiency virus (HIV) may develop non-Hodgkin lymphoma at higher rates than others.

Doctors group non-Hodgkin lymphoma into four different stages to guide treatment. Staging is identified during the biopsy process by pathologists who specialize in making lymphoma diagnoses. They’ll look at the shape of lymphoma cells, the expression of protein on cells, and sometimes the DNA changes in cells, along with where the disease is in the body. 

In Stage I, the disease is found in a single lymph node region or one organ. Stage II involves two or more lymph node regions, but only on the same side of the diaphragm. Stage III means lymph node regions are affected on both sides of the diaphragm. In Stage IV, the disease has spread more widely, often involving organs outside the lymphatic system such as the liver or lungs, sometimes along with lymph node involvement.

To provide a more precise picture of the disease, each stage may be followed by a letter, for example stage IA. Letters help describe additional features that influence diagnosis and treatment. An “A” indicates that there are no concerning additional symptoms. A “B” is used when symptoms such as unexplained fevers, chills, night sweats, weight loss, or fatigue are present. An “E” shows that the disease has extended from a lymph node into a nearby organ. An “X” refers to bulky disease, meaning a larger tumor mass, often seen in the chest.

Recognized for excellence by the National Cancer Institute, specialists in Penn Medicine’s blood care program have advanced many of today’s medical approaches for diagnosing and treating all types of blood cancer, including lymphoma. Our close connection with researchers allows us to keep you updated on promising new treatments and clinical trial opportunities, with access to emerging therapies whenever possible. We offer:

• Close to 100 active clinical trials dedicated to blood cancer
• A special focus on developing treatments designed to be safer and more tolerable for older adults
• The largest bone marrow (stem cell) transplant program of its kind across Pennsylvania and New Jersey, seeing about 300 people annually 

Partnerships with organizations like the National Institutes of Health and the National Marrow Donor Program help us share best practices to deliver excellence in blood cancer care. We help people with both common and rare non-Hodgkin lymphomas, guiding them through their care journey with expertise, understanding, and support.