What is "non-Hodgkin's lymphoma"? It is the bad guy who took Xiong Dun away

What is Non-Hodgkin's Lymphoma?

Non-Hodgkin lymphoma is cancer that starts in cells of the immune system. The immune system fights infection and other illnesses. The lymphatic system is part of the immune system. The lymphatic system includes the following:
(1) Lymphatic vessels: The lymphatic system is a network of lymphatic vessels that branch out to all tissues in the body.
(2) Lymph: The clear fluid in the lymphatic vessels is called lymph. Lymph contains white blood cells, especially lymphocytes, such as B cells and T cells.
(3) Lymph nodes: Lymphatic vessels connect to form small, round tissue masses called lymph nodes. Lymph node groups are found in the neck, armpits, chest, abdomen, and groin. Lymph nodes contain white blood cells. White blood cells can capture and remove bacteria or other harmful substances in the lymph.
(4) Other parts of the lymphatic system: Other parts of the lymphatic system include the tonsils, thymus, and spleen. Lymphatic tissue is also found in other parts of the body, including the stomach, skin, and small intestine.

Figure 1 Lymph nodes, lymphatic vessels, tonsils, thymus and spleen above and below the diaphragm (Image source: National Cancer Institute of the United States)

Since lymphatic tissue is found in many parts of the body, lymphoma can start almost anywhere. Usually, it first starts in the lymph nodes. Non-Hodgkin lymphoma begins when lymphocytes (usually B cells) become abnormal. The cells produced by abnormal cell division are identical to the original cells, that is, they replicate themselves. The new cells continue to divide, resulting in more and more abnormal cells. Abnormal cells do not die when they should. They cannot protect the body from infection or other diseases. Excess cells accumulate and often form tissue masses called tumors. The gastrointestinal tract is the most common extranodal site of non-Hodgkin lymphoma. The Waldeyer's ring (Waldeyer's ring is located at the opening of the respiratory tract and digestive tract, which includes tissues such as the nasopharynx, the base of the tongue, the bilateral tonsils, and the soft palate) is most commonly involved in southwest China. The vast majority of non-Hodgkin lymphomas occur more frequently in men.

What are the risk factors for non-Hodgkin's lymphoma?

The cause of non-Hodgkin lymphoma is unknown, but researchers have found that certain risk factors increase a person's chance of developing the disease. In general, risk factors for non-Hodgkin lymphoma include the following:
(1) Weakened immune system: A weakened immune system (such as caused by genetic diseases or certain medications used after organ transplantation) may increase the risk of lymphoma.
(2) Certain infections: Certain types of infections can increase your risk of developing lymphoma. However, lymphoma is not contagious. You cannot get lymphoma from another person. The main types of infections that increase your risk of lymphoma are:
Human immunodeficiency virus (HIV): HIV is the virus that causes AIDS. People with HIV infection have a much higher risk of developing certain types of non-Hodgkin lymphoma.
Epstein-Barr virus (EBV): EBV infection is associated with an increased risk of lymphoma. In Africa, EBV infection is associated with Burkitt lymphoma.
Helicobacter pylori: Helicobacter pylori is a bacteria that causes stomach ulcers. They also increase the risk of gastric mucosal lymphoma.
Human T-cell leukemia/lymphoma virus type 1 (HTLV-1): HTLV-1 infection increases the risk of lymphoma and leukemia.
Hepatitis C virus: Some studies have found an increased risk of lymphoma in people with hepatitis C virus infection. More research is needed to understand the role of hepatitis C virus.
(3) Age: Although non-Hodgkin's lymphoma can occur in young people, the incidence rate increases with age, and the peak incidence of non-Hodgkin's lymphoma occurs between the ages of 55 and 64.

In addition, obesity, frequent contact with herbicides or certain other chemicals, and frequent contact with hair dyes may also lead to an increased risk of non-Hodgkin's lymphoma. In a meta-analysis of epidemiological studies on dyes and non-Hodgkin's lymphoma reported by Deng Huiyang, it was shown that the risk of non-Hodgkin's lymphoma in people who use dyes increased by 14% compared to those who did not use them.

What are the symptoms of non-Hodgkin lymphoma?

Non-Hodgkin's lymphoma has inconsistent clinical manifestations due to different lesion sites and ranges, with pain and lumps as the main manifestations, and pathological fractures often occur.

(1) Enlargement of superficial lymph nodes or formation of nodules is a common initial clinical manifestation. The lumps vary in size, are often asymmetrical, firm and elastic, and are usually not tender.

(2) Lymph node masses deep within the body may cause corresponding infiltration, compression, obstruction or tissue destruction due to their occurrence in different parts of the body, resulting in corresponding symptoms. For example, mediastinal or hilar lymph node masses may cause clinical manifestations such as chest tightness, chest pain, dyspnea, and superior vena cava compression syndrome. Intra-abdominal masses may cause abdominal pain, abdominal mass, intestinal obstruction, ureteral obstruction, and hydronephrosis.

(3) Extranodal lymphoid tissue hyperplasia and masses can also cause corresponding symptoms depending on the location of the disease. Involvement of the Waldeyer's ring can manifest as enlarged palatine tonsils or pharyngeal masses, and involvement of the gastrointestinal tract can manifest as abdominal pain, abdominal mass, gastrointestinal obstruction, bleeding, perforation, etc. Involvement of the liver can manifest as hepatomegaly and jaundice.

(4) Systemic symptoms are generally seen in the late stage of the disease, including general wasting symptoms such as anemia, weight loss, weakness, etc. In addition, there may be fever, night sweats and weight loss. However, it is difficult to distinguish whether such symptoms are due to the disease itself or caused by long-term radiotherapy and chemotherapy.

In addition, non-Hodgkin's lymphoma may also cause certain complications, such as infection, fever, chest tightness, chest pain, cough, shortness of breath, difficulty swallowing, difficulty breathing, abdominal cramps, uremia, visual impairment, etc.

Types and stages of non-Hodgkin lymphoma

There are many types of non-Hodgkin lymphoma, the most common types are diffuse large B-cell lymphoma and follicular lymphoma. Depending on how fast the lymphoma grows, it can be divided into the following types:
(1) Indolent (also called low-grade) lymphomas grow slowly. They tend to cause fewer symptoms.
(2) Aggressive (also called intermediate-grade and high-grade) lymphomas grow and spread quickly. They tend to cause severe symptoms. Over time, many indolent lymphomas become aggressive lymphomas.

Doctors need to know the extent (stage) of non-Hodgkin lymphoma to plan the best treatment. Staging is carefully figuring out which parts of the body are affected. This can be done with tests such as a bone marrow biopsy, CT scan, MRI, ultrasound, spinal tap, PET scan, etc. Lymphoma usually starts in the lymph nodes but can spread through the blood to almost any other part of the body. For example, it can spread to the liver, lungs, bones, and bone marrow. The stages of non-Hodgkin lymphoma are as follows:
Stage I: The lymphoma cells are in one group of lymph nodes (such as in the neck or underarms). Or, if the abnormal cells are not in the lymph nodes but in only one part of a tissue or organ (such as the lungs but not the liver or bone marrow).
Stage II: The lymphoma cells are in at least 2 groups of lymph nodes on the same side of the diaphragm (above or below). Or, the lymphoma cells are in part of an organ and lymph nodes near that organ (on the same side of the diaphragm). Lymphoma cells may be in other groups of lymph nodes on the same side of the diaphragm.
Stage III: The lymphoma is in the lymph nodes above and below the diaphragm. It may also be in part of a tissue or organ near these lymph node groups.
Stage IV: Lymphoma cells are found in several parts of one or more organs or tissues (in addition to the lymph nodes). Or, they are in the liver, blood, or bone marrow.
Recurrent: Disease comes back after treatment.
In addition to these stage numbers, your doctor may use A or B to describe:
A: No weight loss, excessive night sweats, or fever has occurred.
B: Weight loss, severe night sweats, or fever has occurred.

Treatment of non-Hodgkin lymphoma

Treatment options for non-Hodgkin lymphoma depend mainly on its type, stage, how fast the cancer is growing, your age, and whether you have other medical conditions.

(1) If you have indolent non-Hodgkin lymphoma and are asymptomatic, you may not need immediate treatment, which is known as "watchful waiting." Sometimes the tumor may shrink temporarily without treatment, and by delaying treatment, you can try to avoid the side effects of chemotherapy and radiotherapy.

(2) If the patient has indolent lymphoma and is symptomatic, chemotherapy and biological therapy are required. For patients with stage I or stage II lymphoma, radiotherapy may be used.

Chemotherapy is a systemic treatment. While killing lymphoma cells, the drugs also damage normal human cells and cause a series of side effects, such as anemia, fatigue, hair loss, loss of appetite, nausea and vomiting, diarrhea, oral ulcers, rashes, headaches, etc. Clinically, symptomatic treatment can be taken according to the side effects of the patient. The specific chemotherapy cycle depends on the condition and the type of chemotherapy drugs.

The type of biological treatment for non-Hodgkin lymphoma is a monoclonal antibody, which can help the body's own immune system kill lymphoma cells by binding to cancer cell proteins. Biological treatments also have certain side effects, which may cause flu-like symptoms such as fever, chills, headache, weakness and nausea. A few people may have difficulty breathing, low blood pressure or severe rash.

Radiation therapy, also known as radiotherapy, is a treatment that uses high-energy rays to kill tumor cells. It can shrink tumors and help relieve pain. Radiation therapy can be divided into external radiation therapy and systemic therapy. External radiation therapy is a local treatment that uses a machine to target the lymphoma area. Systemic radiation therapy is an injection of radioactive substances that flows through the blood throughout the body and binds to monoclonal antibodies to target and destroy tumor cells. The side effects of radiation therapy mainly depend on the type of radiation therapy, the radiation dose, and the part of the body that is treated. For example, external radiation therapy to the abdomen can cause nausea, vomiting, and diarrhea. When radiation therapy is given to the chest and neck, a dry and sore throat and some difficulty swallowing may occur. In addition, the skin in the treated area may become red, dry, and tender. Hair loss in the treated area may also occur.

(3) If you have an aggressive lymphoma, treatment is usually chemotherapy and biological therapy, and radiation therapy may also be used.

(4) If non-Hodgkin lymphoma recurs, the patient is often treated with high-dose chemotherapy, radiation therapy, or both, followed by a stem cell transplant. A stem cell transplant is a procedure in which healthy blood-forming stem cells are given to the patient through a flexible tube inserted into a large vein in the neck or chest. The implanted stem cells will produce new blood cells. There are three sources of stem cells:

l Autologous stem cell transplant: This type of transplant uses your own stem cells. Your stem cells are obtained before high-dose treatment. These cells may be treated to kill any lymphoma cells that may be present. The stem cells are frozen and stored. After you receive high-dose treatment, the stored stem cells are thawed and returned to your body.

Allogeneic stem cell transplant: Sometimes healthy stem cells from a donor can be used. Your brother, sister, or parent could be the donor. Stem cells from an unrelated donor may also be used. The doctor will do a blood test to make sure the donor cells match yours.

l Syngeneic stem cell transplant: This transplant uses stem cells from the patient's healthy identical twin.

References:

[1] Deng Huiyang. Meta-analysis of epidemiological studies on hair dyes and non-Hodgkin's lymphoma[D]. Henan University of Science and Technology, 2017.

[2] National Cancer Institute. Non-Hodgkin's Lymphoma [EB/OL]. https://www.stluciabj.cn/nci/about/28/.

[3] Yang QP, Zhang WY, Yu JB, et al. Subtype distribution of lymphomas in Southwest China: analysis of 6382 cases using WHO classification in a single institution[J]. Diagnostic pathology, 2011, 6: 77.

[4] Meng Jingshu. Analysis of epidemiological characteristics of malignant lymphoma: a single center case analysis report of 2027 cases[D]. Huazhong University of Science and Technology, 2018.

[5] Ma Liangming, Zhu Qiujuan, Gong Rong. Non-surgical treatment of hematological malignancies[M]. Huazhong University of Science and Technology Press, 2015: 131-133.