Lymphoma is one of the common malignant tumors of the hematopoietic system and is a malignant heterogeneous solid tumor originating from lymphoid tissue. Since lymphoid tissue is distributed throughout the body, lymphoma can occur anywhere in the body. The most common sites of lymphoma are lymph nodes, including superficial and deep lymph nodes throughout the body; lymphatic tissues such as spleen, thymus, tonsils, and mucosa-associated lymphatic tissues distributed along the gastrointestinal tract or mucous membranes such as trachea and bronchus are also good sites for lymphoma; in addition, it can also occur from malignant appreciation of lymphatic tissues scattered in other tissues, such as heart, bone, and nervous system. Lymphomas are classified into two categories, Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL), based on the behavioral characteristics of the tumor cells, the mode of disease initiation, the rate of accumulation in tissues and organs outside the lymph nodes, the progression of the disease, and the response to treatment.
The most important feature of Hodgkin’s lymphoma is that Reed-Sternberg cells (R-S cells, also known as mirror-image cells) can be seen in its lymphoid tissue. In addition to R-S cells, the tissue also contains lymphocytes, histiocytes, plasma cells, eosinophils, neutrophils and fibrous tissue, which are usually considered to be reactive proliferations. Hodgkin’s lymphoma is subdivided into various subtypes based on histologic features.
Non-Hodgkin’s lymphoma is highly heterogeneous and has more extra-nodal invasiveness and distant spread than Hodgkin’s lymphoma. Because of its high heterogeneity, the understanding and classification and staging of non-Hodgkin’s lymphoma has been refined with the development of techniques such as cellular immunophenotyping and molecular biology. These are of great importance for the classification and staging of lymphoma as well as for determining prognosis and guiding treatment.
From the epidemiological point of view, lymphoma accounts for 3%-8% of neoplastic diseases in China, and the incidence rate ranks 11th among all malignant tumors, about 1.39/100,000 for men and 0.84/100,000 for women; the peak of the incidence age curve is about 40 years old, more men than women, and the ratio of men to women is about 2.5:1; the incidence rate is higher in central coastal areas than inland areas. The mortality rate also takes the 11th place of malignant tumors, and the mortality rate increases with age, but in the composition ratio of tumors, it decreases with age, that is, lymphoma is more common among young people than other tumors. In addition, according to the survey, the mortality rate in large cities (population above 750,000) is 1.38/100,000 population, in medium cities (population 250,000~750,000) is 1.23/100,000 population, in small cities (population below 250,000) is 1.12/100,000 population, and in rural areas is 1.17/100,000 population, which indicates that the mortality rate in large cities is slightly higher than that in small cities and rural areas.
In China, the incidence of Hodgkin’s lymphoma is less than that of non-Hodgkin’s lymphoma, 1/10 of that of non-Hodgkin’s lymphoma and less than 1/3 of that of western countries; it has two peak incidence rates, respectively, in young people aged 15-34 years and in older people older than 50 years. According to the pathological data of 12 regions in China, the lymphoma research group of the Institute of Oncology, Chinese Academy of Medical Sciences classified 3366 cases of malignant lymphoma from 1978 to 1982, Hodgkin’s lymphoma accounted for 10.9%, of which the highest was 18.4% in Changsha and the lowest was 5.9% in Beijing; non-Hodgkin’s lymphoma accounted for 89.1%, of which the highest was 94.1% in Beijing and the lowest was 81.6% in Changsha. The percentage of non-Hodgkin’s lymphoma was 89.1%, of which the highest was 94.1% in Beijing and the lowest in Changsha.
The statistics of malignant lymphoma in urban area by Beijing Cancer Institute in 1987 showed that the incidence of Hodgkin’s lymphoma was 0.16/100,000 population for men, accounting for 0.09% of malignant tumors, and 0.17/100,000 population for women, accounting for 0.12% of all tumors; non-Hodgkin’s lymphoma was 0.74/100,000 population for men, accounting for 0.42% of tumors, and 0.25/100,000 population for women, accounting for 0.25% of tumors. Non-Hodgkin’s lymphoma was 0.74/100,000 population for men, accounting for 0.42% of tumors, and 0.25/100,000 population for women, accounting for 0.18% of tumors. The statistics of Shanghai Institute of Oncology for the urban area from 1987 to 1989 showed that the incidence rate of Hodgkin’s lymphoma was 0.49/100,000 population for men, accounting for 0.2% of tumors, and 0.28/100,000 population for women, accounting for 0.1% of tumors; the incidence rate of non-Hodgkin’s lymphoma was 4.72/100,000 population for men, accounting for 1.7% of all tumors, and 3.15/100,000 population for women, accounting for 1.5% of tumors. 1.5% of the tumors. From the data, the incidence of lymphoma is significantly higher in coastal areas than inland areas.
The etiology of lymphoma has not been fully elucidated yet, and from the available information, its related etiology or risk factors are
i. Infectious factors.
①, EBV infection, EBV (a DNA herpesvirus) can cause malignant transformation of human B cells. (ii) Significantly higher EBV antibody titers in about 80% or more of patients with Burkitt’s lymphoma, compared with only 14% of non-Burkitt’s lymphoma patients in the same region.
(ii) Adult T-cell leukemia virus (HTLV-1), a C-type retrovirus prevalent mainly in Hokkaido, Japan, and the Caribbean, USA, and closely associated with T-cell lymphoma.
(iii), HIV virus, which increases the incidence of Hodgkin’s lymphoma approximately sevenfold in HIV-infected patients; the incidence of moderately to highly malignant non-Hodgkin’s lymphoma is twice that of non-AIDS patients.
④, HCV, hepatitis C virus (HCV) increases the risk of B-cell lymphoma, especially immunoblastoma and lymphoma growing in the liver and greater salivary glands.
(v) HHV-8, human herpesvirus-8, also known as Kaposi’s sarcoma-associated herpesvirus, is a new pro-lymphatic DNA virus associated with a very rare recently proposed NHL, PEL (characteristic corporal lymphoma/primary exudative lymphoma), and mostly with concomitant HIV infection.
(vi) Helicobacter pylori (HP), which can be found within the gastric mucosa in more than 90% of gastric mucosa-associated lymphomas (MALT), with a significantly higher incidence than in the normal population.
(vii) Other infectious factors. A type of Borrelia spirochetes that can cause Lyme disease (Lyme Disease) is associated with some cutaneous lymphomas, and some studies have shown that human herpesvirus-6 (HHV-6) may be involved in the development of lymphomas.
II. Immune factors.
Certain autoimmune diseases, such as Schegren’s syndrome and Hashimoto’s thyroiditis, can increase the incidence of large cell lymphoma by as much as 60-fold, and others, such as systemic lupus erythematosus, dry syndrome, and organ transplantation, can also increase the risk of lymphoma.
Third, genetic factors.
Epidemiological surveys have found that lymphoma can sometimes be seen in obvious family aggregations, and siblings can develop lymphoma sequentially or simultaneously; identical twins have a significantly higher risk of developing Hodgkin’s lymphoma than dizygotic twins. In addition, the incidence of either Hodgkin’s lymphoma or non-Hodgkin’s lymphoma is higher in white races than in other races.
IV. Environmental and occupational factors.
Agricultural workers have a higher incidence of NHL than the general population, mainly due to exposure to pesticides, herbicides, etc. In addition, nitrate pollution of surface water is to some extent associated with a high incidence of NHL in certain areas of the United States; furthermore, jobs with exposure to chemical agents such as chemists, dry cleaners, printers, carpenters, cosmetologists, etc., and hair dyeing, especially the use of permanent hair dyes, can increase the risk of developing NHL. Some data show that NHL caused by the application of hair-dyeing agents accounts for about 20% of NHL cases.
V. Nutrition and diet.
European studies have found a 2-fold increase in the risk of developing NHL with high milk intake (>2 cups/day), and this risk is limited to men. A US study of 88,410 women and 47,336 men who applied only vitamins A, C and E or multivitamins showed that the application of multivitamins increased the risk of NHL in women, but not in men, and that the application of vitamins A, C and E alone was not associated with the development of NHL. Multivitamin application followed by vitamins A, C, and E alone also increased the risk of NHL in women. In addition, long-term regular application of vitamins A, C, E or multivitamins was not associated with fatal NHL in either sex.
VI. Smoking.
It has been thought that smoking increases the risk of NHL, but epidemiological findings have not yet confirmed that smoking increases the risk of NHL. Four of the five Australian epidemiological cohort studies revealed that smoking was not associated with the development of NHL, but three of them favored nonsmoking, and another study found that heavy smoking increased the risk of developing NHL, especially under the age of 45.
VII. Ionizing radiation.
The incidence of lymphocytic and histiocytic lymphoma was significantly higher in the population affected by the atomic bombs in Hiroshima and Nagasaki, Japan, than in the control group. However, it is generally believed that radiation exposure is not a major factor in the development of NHL.
VIII. Chemotherapeutic drugs.
Exposure to certain chemical drugs is a major risk factor for NHL, such as the cumulative incidence of NHL after HL is 1% to 6%.
ix. Other.
Blood transfusion can increase the risk of developing NHL by 1.5 to 2.5 times, and this risk may be related to the transfer of infectious factors and immunosuppressive effects. The incidence of HL in children and young adults is higher in economically more backward countries and regions than in economically developed countries and regions.
The clinical presentation of lymphoma is nonspecific, and painless progressive lymph node enlargement is the most common first presentation, accounting for about 60% to 70% of all cases, with cervical lymph node enlargement in particular being the most common, followed by axillary and inguinal lymph nodes, and all other sites. These enlarged lymph nodes are characterized by painless progressive enlargement, tough texture like (hard) rubber, clear edges, smooth and mobile surface, varying in size from the size of rice grains and green beans to 10 cm or tens of centimeters, and even several lymph nodes may fuse with each other to form larger masses, fixed and adherent to the skin, with reddened skin surface and occasional rupture. Deep lymph node enlargement can only be confirmed with the help of relevant instruments and equipment. Approximately 55% of patients with lymphoma have systemic symptoms at the time of initial diagnosis, including fever, night sweats and weight loss, as well as pruritus and fatigue, which are usually indicative of a poor prognosis.
Other extra-lymph node involvement is not uncommon, such as hepatosplenic lesions accounting for about 1/3 of the cases, manifesting as hepatosplenomegaly; gastrointestinal invasion accounts for about 30% of the postmortem pathology, manifesting as abdominal pain, abdominal mass, vomiting, obstruction and gastrointestinal bleeding; chest and lung invasion accounts for about 15%-40%, manifesting as chest tightness, chest pain, cough, sputum, dyspnea, pulmonary lesions and pleural effusion; cardiac accumulation is rare and may manifest as Skin damage can be manifested as pruritus, various rashes, papules and nodular masses, skin ulcers, etc.; skeletal involvement rate is about 45%~60%, including all bones in the body can be involved, generally seen in the thoracic spine, lumbar spine, pelvis, etc., followed by ribs and skull, clinical manifestations are mainly bone pain and soft tissue swelling or even fracture, etc. Neurological involvement usually occurs in the late stage of the disease, with spinal cord compression being the most common, and parenchymal lesions are rare, about 0.25% to 0.5%; renal invasion is about 13%, mostly bilateral infiltrative lesions, or multiple small nodules, which can have hematuria, proteinuria, etc., and can lead to uremia when the kidney is extensively infiltrated, but it is rare; bone marrow involvement is about 9% to 14%, and the autopsy can be as high as 30% to 50%. The rate of bone marrow involvement is about 9%-14%, and up to 30%-50% at autopsy, which can be manifested as complete cytopenia or leukemia-like changes.
The diagnosis of lymphoma must be confirmed by pathological biopsy of lymph nodes, and with the development of immunology, cytogenetics and molecular biology techniques, the diagnosis of lymphoma will become more and more accurate. Other systemic examinations are also of great importance in determining the stage, prognosis and guiding the treatment of lymphoma.
Although lymphoma is a malignant neoplastic disease, with the continuous development and innovation of medical science and technology in recent years, the application of new drugs and new therapies has made lymphoma a curable neoplastic disease. For example, the 5-year survival rate for stage I and II Hodgkin’s lymphoma treated mainly with radiotherapy is 90%, and the cure rate for advanced stage (III and IV) Hodgkin’s lymphoma treated with a combination chemotherapy-based regimen is over 50%. However, non-Hodgkin’s lymphoma is much more complicated than Hodgkin’s lymphoma, and the clinical prognosis is also worse than that of Hodgkin’s lymphoma, and the 4-year survival rate of advanced moderately malignant non-Hodgkin’s lymphoma treated with CHOP and other regimens can reach 80%. The hematopoietic stem cell transplantation can increase the 5-year survival rate of such patients from 32% to 53%. The overall 5-year survival rate for patients with NHL treated with currently available chemotherapy regimens is 50% to 60%, and 30% to 60% of patients with moderately malignant NHL can be cured.
In recent years, with the study of chemotherapy regimens, the use of high-dose chemotherapy (HDCT) can lead to a long-term disease-free survival (DFS) of 30% to 65% and a 3-year event-free rate (EFS) of 53% from 10% in patients with relapsed refractory lymphoma. The development and application of new chemotherapeutic agents have also brought light to the pharmacological treatment of lymphoma, such as the new topoisomerase I inhibitors-Topotecan and SN-38-which have shown good efficiency in experimental studies and are gradually being used in clinical medical practice. Another new class of drugs are anti-purine metabolism drugs, such as fludarabine phosphate (FDA) and 2-cdA, both of which have broad anticancer effects and have shown good results in the treatment of low-grade malignant lymphoma, and fludarabine is now widely used as a first-line treatment for inert lymphoma for the benefit of lymphoma patients.
Low-toxicity and high-efficiency targeted antitumor drugs are also widely used in the treatment of lymphoma, such as doxorubicin hydrochloride liposome injection (Calais, Caelyx), a liposomal formulation of adriamycin. As a new antitumor drug for targeted therapy, its biotoxicity is significantly reduced. The cardiotoxicity of common adriamycin in rabbits is 67%, while Caelyx is only 16%, and the local drug concentration of tumor is at least 6 times higher than that of common adriamycin, showing extremely strong antitumor drug properties. The overall remission rate for relapsed/refractory cutaneous T-cell lymphoma was 88% for monotherapy and 85% for primary aggressive diffuse large B-cell lymphoma in combination with other chemotherapeutic agents.
Bortezomib (Velcade, Vanco), another targeted therapy, is a novel proteasome inhibitor with unique effects in inhibiting tumor cell proliferation, promoting tumor cell apoptosis, inhibiting tumor angiogenesis and attenuating tumor cell infiltration. CD20 monoclonal antibody melphalan (Rituximab) is a human-mouse chimeric monoclonal antibody with an overall remission rate of 48% in relapsed/refractory follicular non-Hodgkin’s lymphoma. The R-CHOP regimen with CHOP is now the classical treatment for diffuse large B-cell lymphoma, with an overall response rate (ORR) of 96% and a 48% reduction in the risk of “events” (death, relapse or progression, etc.) with R-CHOP compared to CHOP alone; a 49% reduction in mortality; and an approximate increase in complete remission. 49%; complete remission rate increased by about 20%; risk of disease progression decreased by 54%; and risk of relapse after complete remission decreased by 51%. Hematopoietic stem cell transplantation for malignant lymphoma is one of the important options for patients with such poor prognosis as primary drug resistance and relapsed refractory disease. Good results have been achieved with high-dose chemotherapy plus autologous hematopoietic stem cell transplantation. A group of 197 stage III high-risk aggressive NHL undergoing autologous HSCT had a median follow-up of 4 years, with 5-year EFS and overall survival (OS) rates of 55% and 74%, respectively, compared with 37% and 44% in the conventional treatment group. Thus, autologous stem cell transplantation for sensitive relapsed NHL showed an improvement in both overall survival (OS) and disease-free survival (DFS) compared to conventional treatment. Allogeneic HSCT has the following advantages over autologous HSCT: first, it avoids contamination of the returned HSCs with tumor cells; second, the graft-versus-tumor (GVHT) effect can remove residual tumor cells from the host. However, the transplantation-related mortality rate of up to 30% and the difficulty of mating are among the factors that currently limit allogeneic HSCT for lymphoma.
Other treatments including interferon, interleukin 2 (IL-2), cytotoxic T lymphocyte infusions (CTLs), biological therapies such as tumor vaccines, and radiation therapy have improved the remission, long-term survival, and cure rates of lymphoma to varying degrees. Although lymphoma is a malignant tumor disease, with the continuous improvement of people’s living standard, the gradual improvement of physical and natural environment, and the increasing investment of the Party and the government in medical care and people’s basic medical insurance in China, as long as we can pay attention to avoiding some unfavorable factors in our daily life, early detection, early diagnosis and early treatment of lymphoma, there is hope to cure this As long as we can pay attention to avoid some unfavorable factors in our daily life, early detection, early diagnosis and early treatment of lymphoma, there is hope to cure this malignant tumor.