What is Non-Hodgkin’s Lymphoma?

The lymphatic system is the disease-fighting network spread throughout a person’s body, and non-Hodgkin’s lymphoma is cancer that originates in white blood cells called lymphocytes. Non-Hodgkin’s lymphoma is sometimes referred to as non-Hodgkin’s lymphoma or just lymphoma, but non-Hodgkin’s lymphoma has very different treatment compared to Hodgkin’s lymphoma.

The two main types of lymphocytes are B lymphocytes (B cells) that make antibodies to protect the body from bacteria and viruses and T lymphocytes (T cells), which have several types and may destroy germs or abnormal cells in the body or alter the activity of other immune system cells. Doctors differentiate between Hodgkin’s lymphoma and non-Hodgkin’s lymphoma by examining cancer cells for the presence of a specific type of abnormal cell called a Reed-Sternberg cell.

When the Reed-Sternberg cell is present, the lymphoma is classified as Hodgkin’s. If it is not present, the lymphoma is classified as non-Hodgkin’s.

Reed–Sternberg cells are distinctive, large cells resembling an “owl’s eye” appearance. Reed–Sternberg cells are named after Dorothy Reed Mendenhall and Carl Sternberg, credited with providing the first microscopic descriptions of Hodgkin’s disease.

A February 2019 research review by several former EPA scientists suggested a compelling link between glyphosate-based herbicides and non-Hodgkin’s lymphoma. On April 30, 2019, the EPA issued a press release claiming it continued to find that “there are no risks to public health when glyphosate is used in accordance with its current label and that glyphosate is not a carcinogen.”

Health Canada concluded “products containing glyphosate do not present unacceptable risks to human health or the environment when used according to the revised product label directions” and the European Food Safety Authority (EFSA) concluded “glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential.” The cancer agency for the World Health Organization’s (WHO), the International Agency for Research on Cancer (IARC), classified glyphosate as “probably carcinogenic to humans” in 2015.

The American Cancer Society notes that lymphomas may begin anywhere in the body where lymph tissue is found. Some of the most common sites of lymph tissue are:

Lymph nodes— A lymph node is a bean-shaped structure that is part of the immune system. Lymph nodes filter substances that travel through the lymphatic fluid. Lymph nodes contain lymphocytes (white blood cells) that help the body fight infection and disease and are connected by lymph vessels. Clusters of lymph nodes are found in the neck, axilla (underarm), chest, abdomen, and groin.
Spleen— The spleen is primarily a blood filter. It is purple in color and located in the upper left abdomen, under the lower ribs. The spleen makes lymphocytes and other immune system cells. It also stores healthy blood cells and filters out damaged blood cells, bacteria, and cell waste.
Bone marrow— Bone marrow is a tissue found in the spongy sections of bones. Bone marrow is the primary site of new blood cell production, or hematopoiesis, including some lymphocytes. The stem cells in bone marrow can develop into red blood cells and white blood cells.
Thymus— The thymus is located in an area of the body called the mediastinum, in the top part of the chest under the breastbone, between the lungs, and in front of the heart. The thymus is essential in the development of T cells. It is at its most significant and most active during the neonatal and pre-adolescent periods before it begins to atrophy although T lymphopoiesis continues throughout adult life.
Adenoids and tonsils— Your adenoids are glands located in the roof of the mouth, behind the soft palate where the nose connects to the throat. Tonsils are collections of lymphoid tissue located in the pharynx at the rear of the throat. Adenoids and tonsils the immune system’s first line of defense against ingested or inhaled germs.
Digestive tract— The gastrointestinal tract (or GI tract) plays a vital role in the maintenance of immune health. The stomach, intestines, and many other organs in the digestive system also have lymph tissue.

According to the Leukemia & Lymphoma Society, there are over 60 specific non-Hodgkin’s lymphoma subtypes that have been identified and assigned names by the World Health Organization (WHO). Specialists characterize the non-Hodgkin’s lymphoma subtypes based on how the disease progresses as either aggressive lymphomas or indolent lymphomas.

Aggressive lymphomas are fast-moving and make up roughly 60 percent of all non-Hodgkin’s lymphoma cases. The most common aggressive non-Hodgkin’s lymphoma subtype is diffuse large B-cell lymphoma (DLBCL), which the Lymphoma Research Foundation identifies as being the most common type of non-Hodgkin lymphoma in the United States and worldwide. It accounts for approximately 22 percent of newly diagnosed cases in the United States, and over 18,000 people are diagnosed with DLBCL each year.

Indolent lymphomas are much slower-moving and tend to grow more slowly. They have fewer signs and symptoms when first diagnosed. The most common subtype of indolent non-Hodgkin’s lymphoma is follicular lymphoma (FL), which the Lymphoma Research Foundation says accounts for 20 to 30 percent of all non-Hodgkin’s lymphoma cases.

The American Cancer Society identifies two possible causes of non-Hodgkin’s lymphoma but notes that it is connected with many different risk factors. The first cause is changes in genes, which could be the result of exposure to radiation or certain chemicals but could also occur for no discernible reason.

The other cause identified by the American Cancer Society is changes in the immune system, which includes three groups of people. This includes people with immune deficiencies, certain autoimmune diseases, or certain chronic infections.

The Mayo Clinic identifies five types of non-Hodgkin’s lymphoma:

Chronic lymphocytic leukemia progresses slowly and often affects older adults, resulting in fewer than 200,000 cases per year. It is a cancer of the blood and bone marrow that progresses more slowly, but symptoms can include fever, fatigue, night sweats, frequent infections, weight loss, pain in the upper left portion of the abdomen, and enlarged lymph nodes.
Cutaneous B-cell lymphoma begins in the B cells and attacks the skin. It is a rare form of cancer. Treatment can involve surgery to remove the cancer, radiation therapy, and chemotherapy. The Lymphoma Research Foundation states that there are four types of cutaneous B-cell lymphoma. Primary cutaneous follicle center lymphoma develops slowly over and often appear on the head, neck, or torso as a bumpy rash. Primary cutaneous marginal zone b-cell lymphoma appears as pink or red lesions on the torso or arms. Primary cutaneous diffuse large b-cell lymphoma, leg-type appears as tumor nodules on the legs, arms, and/or torso. Primary cutaneous diffuse large b-cell lymphoma, other includes a group of lymphomas that appear on the head, torso, and extremities.
Cutaneous T-cell lymphoma begins in the T cells and also attacks the skin, possibly resulting in skin redness, scaly patches, or skin tumors. According to the Lymphoma Research Foundation, subtypes of cutaneous T-cell lymphoma include mycosis fungoides which are the most common form and may appear different in every patient with skin symptoms that may appear as patches, plaques, or tumors and Sézary Syndrome that involves lymphoma cells in the blood and thin rashes on the skin.
Follicular lymphoma is a slow-growing or indolent form of non-Hodgkin lymphoma that the Lymphoma Research Foundation says accounts for 20 to 30 percent of all non-Hodgkin lymphoma cases. Symptoms may include weight loss, night sweats, shortness of breath, fatigue, and enlargement of lymph nodes in the groin, abdomen, underarms, or neck.
Waldenstrom macroglobulinemia is a rare type of cancer caused by bone marrow producing too many abnormal white blood cells that produce a protein accumulating in the blood and affecting circulation. Symptoms may include headache, easy bruising, shortness of breath, bleeding from the nose or the gums, confusion, fatigue, fever, weight loss, changes in vision, and numbness in the hands or feet.

In March 2019, Mother Jones reported that Berkeley toxicologist Luoping Zhang, Mount Sinai epidemiologist Emanuela Taioli, and University of Washington biostatistician Lianne Sheppard were three scientists who served on the EPA Scientific Advisory Panel that evaluated glyphosate in 2016. While the EPA ultimately declared glyphosate non-carcinogenic, Bloomberg Businessweek reported: “eight of the 15 experts expressed significant concerns about the EPA’s benign view of glyphosate, and three more expressed concerns about the data.”

Mother Jones reported that Sheppard, Zhang, and Taioli investigated whether glyphosate could be linked to increased risk to non-Hodgkin lymphoma. The new study was able to incorporate a compelling new set of data: the latest results of the Agricultural Health Study, which was project spanning decades from scientists at the U.S. National Cancer Institute to track health outcomes among agricultural workers in the United States and their families.

Using data from the highest-exposed, 20-year-lag subset showed a 12 percent relative risk for non-Hodgkin lymphoma that Sheppard said was a “not statistically significant” finding on it own, but contributed to a finding of a “compelling link” between glyphosate herbicides and non-Hodgkin lymphoma when averaged with data from five other studies in the meta-analysis. A statement from Bayer accused the study of cherry-picking data, and Sheppard noted that Bayer’s claims about “combining incompatible data” could apply to any meta-analysis since it, by definition, combines data from multiple studies with different structures.