When a person has painless, enlarged lymph nodes that don’t shrink after a short period of time, doctors may suspect lymphoma, especially if they have had unexplained weight loss or other concerning symptoms, like fever or night sweats.  

Doctors classify lymphomas—cancers of the white blood cells known as lymphocytes—into two broad categories: Hodgkin's lymphoma and non-Hodgkin's lymphoma. The conditions have some overlapping symptoms, but doctors (i.e. hematopathologists) tell the difference between the lymphomas by reviewing a biopsy of the affected cells.  

More than 81,000 Americans are diagnosed with non-Hodgkin's lymphoma each year, including around 800 children and teenagers. It’s more common among males, older adults, and people with European ancestry.  

Non-Hodgkin's lymphoma may occur at any number of places within the body. Some types are slow-spreading—without many symptoms—while others are aggressive, spreading quickly with notable symptoms. Different types of non-Hodgkin's lymphoma respond to treatment differently, and some types have better prognoses than others.  

“Since there are more than 60 different subtypes of non-Hodgkin lymphoma, adequate tissue biopsy and review by experienced pathologists is a key first step to managing a new diagnosis of lymphoma,” says Scott Huntington, MD, an Associate Professor of Internal Medicine (Hematology) at Yale Cancer Center.

Non-Hodgkin's lymphoma is an umbrella term for several different types of cancer of the lymphocytes, which are white blood cells found within the lymphatic system, part of the immune system. These non-Hodgkin's cancers don’t contain Reed-Sternberg cells, which are the name for the abnormal cells present in people with Hodgkin's lymphoma.  

Within the immune system, different lymphocytes help to keep people healthy in different ways:

• B cells produce antibodies that help people fight infections
• T cells assist B cells, allowing them to create antibodies, which fight infection
• Natural killer (NK) cells fight viruses and cancer cells

All of these specialized white blood cells exist within the lymphatic system, a series of vessels that connect the lymph nodes throughout the body. Within the lymph nodes, these lymphocytes help to filter harmful cells out of the fluid traveling through the lymphatic system.  

Other elements of the lymphatic system include the bone marrow, spleen, tonsils, adenoids and thymus, as well as parts of the digestive system and central nervous system.  

Someone develops non-Hodgkin's lymphoma when their B-cell, T-cell or NK-cell lymphocytes mutate and multiply uncontrollably. Most commonly, the B cells are affected. (The most common type of non-Hodgkin's lymphoma is diffuse large B-cell lymphoma.)  

Non-Hodgkin's lymphoma may develop within the lymph nodes, bone marrow, or any other lymphatic tissue in the body. For example, primary central nervous system (CNS) lymphoma develops in lymph tissue within the brain or spinal cord.

Commonly diagnosed types of non-Hodgkin's lymphoma include:

• Diffuse large B-cell lymphoma
• Follicular lymphoma
• Burkitt lymphoma
• Mantle cell lymphoma
• Anaplastic large cell lymphoma
• Mucosa-associated lymphoid tissue lymphoma
• Extranodal marginal zone lymphoma
• Peripheral T-cell lymphoma
• Small lymphocytic lymphoma or chronic lymphocytic leukemia

Non-Hodgkin's lymphoma may cause a number of symptoms, including:

• Painless, enlarged lymph nodes, often in the neck, armpits, or groin
• Fever
• Night sweats
• Fatigue
• Unintentional weight loss
• Cough
• Pain in the chest or abdomen
• Bone pain
• Itchy skin
• Skin rash

Additionally, some types of non-Hodgkin's lymphoma affect organs outside of the lymphatic system, which may lead to symptoms specific to those organs. If the brain is affected (such as in Central Nervous System [CNS] lymphoma), people may experience neurological symptoms, or if the intestines are involved, people may have gastrointestinal problems.

Doctors don’t know why non-Hodgkin's lymphoma develops, but people who are at greater risk of non-Hodgkin's lymphoma include those who have, or have had:

• An inherited immune disorder
• Epstein-Barr virus (EBV), which may manifest as infectious mononucleosis (mono)
• Human immunodeficiency virus (HIV)
• HHV-8
• HTLV-1
• Hepatitis B or C
• H. pylori
• Organ transplants, because of the daily immunosuppressant medication
• Autoimmune diseases, such as Sjögren syndrome, rheumatoid arthritis, Hashimoto’s disease or celiac disease
• History of prior Hodgkin's lymphoma

Additionally, people are at greater risk if they have been exposed to:

• Agricultural chemicals, such as herbicide or insecticide
• Hair dye
• Organic solvents, which may be used in paints, glues, dyes and other products
• Radiation therapy
• A high-fat diet
• Ultraviolet radiation Smoking

Doctors confirm non-Hodgkin's lymphoma with a biopsy, but they may suspect the condition after learning about a person’s symptoms, including fever and unexplained weight loss. 

During a physical exam, doctors look for enlarged lymph nodes in the neck, chest, and/or groin area. They also ask questions about a patient’s medical history, including HIV status, hepatitis status, whether someone has an autoimmune disease and if they’ve been exposed to certain chemicals at work. Additionally, doctors ask about a family history of non-Hodgkin's lymphoma and other conditions.  

When doctors suspect non-Hodgkin's lymphoma, they may ask for additional tests, including a CT scan, a PET scan, blood tests, and a biopsy.  

To confirm a suspected diagnosis, doctors surgically remove a lymph node or a section of a lymph node, then biopsy the tissue. They may also biopsy someone’s bone marrow to check for the condition before making a diagnosis, since the bone marrow may be affected.

A variety of treatment approaches may be used for people with non-Hodgkin's lymphoma. Some are appropriate for people with low-grade or slow-spreading disease, while others are recommended for people with aggressive or advanced disease.  

Options include:

• An active surveillance approach, which may be right for people with low-grade non-Hodgkin's lymphoma that doesn’t need treatment upon diagnosis
• Chemotherapy, which combines a number of chemotherapy drugs that are designed to target different types of non-Hodgkin's lymphoma
• Targeted therapy, which attacks cancer cells in different ways than chemotherapy drugs
• Immunotherapy, such as monoclonal antibodies or chimeric antigen receptor (CAR) T-cell therapy, which may help the person’s immune system fight the cancer more aggressively
• Radiation therapy, which may be effective when non-Hodgkin's lymphoma is localized and hasn’t moved beyond the lymph nodes; or it may be given to someone after chemotherapy or another treatment regimen. Because possible long-term side effects from radiation therapy can be serious, doctors may avoid using it—or use only low-dose radiation—to treat children.
  
• Stem cell transplantation with high-dose chemotherapy, which may be given to people who don’t respond well to other treatments or those who relapse

The long-term prognosis for non-Hodgkin's lymphoma varies, depending on the type of disease and whether it’s slow-spreading or aggressive, in addition to other factors, such as a person’s age and overall health. The outlook for most kids and adolescents with non-Hodgkin's lymphoma is good, with survival rates over 90% for those with early-stage disease and between 80% and 90% for more advanced non-Hodgkin lymphoma.

“Diagnostic evaluation and treatments available for non-Hodgkin lymphoma have changed dramatically over the last decade,” says Dr. Huntington. “Yale has expertise across the non-Hodgkin lymphoma care continuum, including pathologists reviewing biopsy specimens, radiologists helping with lymphoma staging, expert clinicians in hematology/oncology, and therapeutic radiation to help optimize treatment outcomes. The multidisciplinary group of physicians, advanced practitioners, nurses, and support staff provide the highest level of care and help facilitate the delivery of several innovative treatment modalities (including stem cell transplantation, and chimeric antigen receptor T cell treatment), which are not available at other Connecticut centers.”