Introduction to non-Hodgkin's lymphoma (NHL)

Introduction: Non-hodgkin's lymphoma (NHL) is a major type of malignant lymphoma. In China, non-Hodgkin's lymphoma accounts for a much higher proportion than Hodgkin's disease (HD). ). In recent years, the incidence of NHL in many countries has increased. The pathological type, clinical manifestations and treatment of NHL are far more complicated than HD. From the available data, NHL is a group of very heterogeneous diseases with different causes, pathologies, clinical manifestations and treatments. So far, the total cure rate is also lower than HD. The duration of the disease varies from no obvious symptoms and early tolerable to rapid death. In some types of NHL, 50% of children and about 20% of adult patients develop leukemia-like changes. Causes: (1) Causes of the disease The cause of non-Hodgkin's lymphoma involves viruses, bacteria, radiation, certain chemicals, and herbicides. Epstein-Barr virus is known to be associated with high-risk Burkitt lymphoma and extranodal T/NK cell lymphoma, nasal type. Adult T-cell lymphoma/leukemia is closely associated with human pro-T-cell virus type I (HTLV1) infection. Gastric mucosa-associated lymphoid tissue lymphoma is a malignant change caused by the initiation of reactive lesions infected by H. pylori. Radiation exposure, such as survivors of nuclear explosions and nuclear reactor accidents, and cancer patients receiving radiation and chemotherapy, are at increased risk of non-Hodgkin's lymphoma. AIDS, certain hereditary, acquired immunodeficiency diseases or autoimmune diseases such as ataxia - telangiectasia, combined immunodeficiency syndrome, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome (Scher Immune syndrome, Sj? gren's syndrome, low gamma globulinemia, and long-term immunosuppressive drugs (such as organ transplants) caused by immune dysfunction are high risk factors for non-Hodgkin's lymphoma. Non-Hodgkin's lymphoma is more common than Hodgkin's disease. The United States diagnoses about 50,000 cases each year. It can occur in all age groups, and the incidence increases with age. Although there are reliable experimental evidences like leukemia suggesting certain lymphomas. Caused by the virus, but the cause is still unclear. For example, HTLV-1 (reverse transcription of human T-cell leukemia-lymphoma virus) has been isolated and appears to be prevalent in southern Japan, the Caribbean, South America and the southeastern United States. Acute adult T cells Leukemia-lymphoma, clinical manifestations of acute exacerbation are skin infiltration, lymphadenopathy, hepatosplenomegaly and leukemia. Leukemia cells are malignant T lymphocytes, mostly with tortuous nucleus. Hypercalcemia often occurs due to humoral factors. Non-bone is directly caused by violations. In AIDS, the incidence of NHL, especially immune mother cells and small crack-free (Burkitt lymphoma) type has increased. Primary invasion of the central nervous system and diffuse lesions have been reported. Systemic lymphadenopathy often occurs in lymphoma in 30% of patients, suggesting that B cell polyclonal stimulation precedes lymphoma. Some AIDS-associated lymphomas may have C-myc gene rearrangement. It may be effective for chemotherapy. Toxicity common and opportunistic infections occurred in succession, this will result in a short lifetime. (B) the pathogenesis due to the different stages of differentiation of lymphocytes, which can occur at different stages of tumor cell invasion of lymph nodes or lymphatic tissue. In the same lesion, there may be poorly differentiated tumor cells or cells with more mature differentiation. As the lesion progresses, the histological type of malignant lymphoma may change, such as nodular type can be transformed into diffuse type. The proliferating tumor tissue may be a single cell component, but since the original pluripotent stem cells may differentiate in different directions, sometimes the cellular components may be more than two or more. In recent years, due to the widespread use of monoclonal antibodies and immunohistochemistry, it has been possible to distinguish T and B lymphocytes at different stages of differentiation. Tumors that occur in subcapsular cortical thymocytes are usually T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma. All other T-cell lymphomas are derived from more mature T cells, positive for CD4, including adult T-cell lymphoma (ATL), mycosis fungoides, Sezary syndrome, and most so-called peripheral T-cell lymphoma (international work) Diffuse large cells, immunoblasts, and mixed lymphoma in the classification) and more than half of T cell chronic lymphocytic leukemia. There are some peripheral T-cell lymphoma, nearly half of T-cell chronic lymphocytic leukemia and some Tγ lymphoproliferative diseases, CD8 positive. B cell lymphomas have fewer specific antibodies but surface immunoglobulin expression. The earliest B cells have the expression of CD10 and CD19 on the surface, and there are terminal transferases in the cells and recombination of the heavy bond genes. Later, the cells express CD20, the μ heavy bond is generated in the cytoplasm, the recombination of the K light bond gene, the recombination of the λ light bond gene, and the terminal transferase loss. These represent the developing pre-B cell stage. After the cell loses the expression of CD10, it becomes an immature B cell with IgM expression on its surface. IgD and IgM are produced on the surface of the cell surface expressing CD21 receptor (C3d). The developmental stage of all B cells occurs under antigenic stimulation, and the immunoglobulin genes are activated and secreted after being stimulated by the antigen. Thereafter, the cells lose CD21, CD20 and surface immunoglobulin, and the markers PC-1 and PC-2 of the plasma cells are secreted to secrete immunoglobulin. This is the development process of B cells in the cell follicle center, which becomes lymphocytic lymphoma after malignant transformation. The maturation of the B-cells in the follicular center and the initiation of the immunoglobulin genes are regulated by T helper cells, but there are also some unknown B lymphocytes. The B cells in the mantle cell area appear to be relatively less affected by T cells, which are CD5 positive, which is a full T cell marker and appears to be independent of immunoglobulin. Most acute lymphocytic leukemias are derived from pre-B cells, Burkitt lymphomas and leukemias are derived from surface IgM-positive immature B cells, and most follicular and diffuse B-cell lymphomas are derived from mature or activated B cells. Macroglobulinemia (Waldenstrom syndrome) and multiple myeloma are derived from the terminal stage of differentiation. Chronic lymphocytic leukemia expresses CD5, and diffuse moderately differentiated lymphoma expresses CD5 and CD10, suggesting that these are from the mantle cell region. B cells that are not follicular centers. The immunophenoty and clinical manifestations of some lymphomas are still very confusing. Diffuse large cell lymphoma may be the most heterogeneous, and may be derived from B cells, T cells, and tissue cells. Therefore, the prognosis of these patients does not depend entirely on clinical stage. Adult T-cell lymphoma is derived from mature T cells from an immunophenotype, but clinical manifestations are very dangerous, like lymphoblastic lymphoma from immature T cells. These are for further study, especially the role of different genes in them. Symptoms: The disease can be seen at any age. The clinical manifestations can be summarized as follows: 1. Superficial lymphadenopathy or formation of nodules and masses is the most common initial clinical manifestation, accounting for 60% to 70% of all cases, especially neck Lymph node enlargement was the most common (49.3%), followed by axillary and inguinal lymph nodes (12.9%, 12.7%). Lymph node masses vary in size, often asymmetrical, firm and elastic, and have no tenderness. In low-grade lymphoma, lymph nodes are mostly scattered, non-adhesive, multiple lymph nodes that are active, while invasive or highly aggressive lymphomas, with rapid progression, lymph nodes often fuse into clusters, sometimes adhering to the basal and skin. And may have local soft tissue infiltration, compression, edema performance. 2. Deep lymph nodes in the body may cause corresponding symptoms due to infiltration, compression, obstruction or tissue destruction due to their occurrence in different sites. For example, mediastinal, hilar lymph node mass can cause chest tightness, chest pain, dyspnea, superior vena cava compression syndrome and other clinical manifestations, intra-abdominal (mesenteric lymph nodes, retroperitoneal lymph nodes) mass, can cause abdominal pain, abdominal mass, intestinal obstruction, ureter Obstruction, renal effusion and other manifestations. 3. Hyperplasia and mass of extranodal lymphoid tissue may also cause corresponding symptoms due to different parts. At the time of initial diagnosis, only the extranodal lesions and no superficial lymph nodes were enlarged, accounting for 21.9%. Extranodal lesions are most common with the pharyngeal ring, which is characterized by a swollen tonsil or a pharyngeal mass. Submucosal lymphoid tissue in the gastrointestinal tract can be invaded to cause abdominal pain, abdominal mass, gastrointestinal obstruction, bleeding, and perforation. When the liver is invaded by lymphoma, it may have swelling and jaundice. Extranodal lymphoma can also invade the orbital eyeball, unilateral or bilateral breast mass, and can invade the bone marrow, causing anemia, bone pain, bone destruction, and even pathological fractures. When the intracranial is violated, it can cause headache, visual impairment and other symptoms of increased intracranial pressure. The lesion can also compress nerves caused by peripheral nerves, such as facial nerve spasms. It can also invade the spinal canal, causing spinal cord compression and paraplegia. Some types of non-Hodgkin's lymphoma, especially T-cell lymphoma, are prone to skin infiltration, nodules or tumors. Mycosis fungoides and Sézary syndrome are special types of cutaneous T-cell lymphoma. There is also a type of extranodal lymphoma, nasal and nasal NK/T-cell lymphoma, formerly known as "middle-line necrotizing granuloma" and "central vascular lymphoma". The most common first-time site in clinical practice is Nasal cavity, followed by ankle, nasopharynx and tonsils. Because lymphoma can occur from lymph nodes (superficial and deep) and extranodal lymphoid tissues of various organs, and can invade various tissues and organs during its development, its clinical manifestations can be very complicated and diverse. Lymphoma of different tissue types also often has its clinical features. 4. Systemic symptoms Non-Hodgkin's lymphoma may also have systemic symptoms, including general wasting symptoms such as anemia, weight loss, weakness, and may also have special "B" symptoms (with Hodgkin's lymphoma, including fever, night sweats) And weight loss). However, in general, the systemic symptoms of non-Hodgkin's lymphoma are less common than Hodgkin's lymphoma, and more common in the later stages of the disease. In fact, fever, night sweats, and weight loss, which are common in the late stages of the disease, are sometimes difficult to distinguish between clinical manifestations of the disease, long-term treatment (chemotherapy, radiotherapy), or co-infection due to impaired advanced immune function. . 1. The diagnosis of this disease depends on histological biopsy (including immunohistochemistry and molecular cytogenetics). These histological, immunological, and cytogenetic tests not only confirm NHL, but also make a type of diagnosis, which is critical to understanding the malignancy of the disease, estimating the prognosis, and choosing the right treatment. Any lymph node with no obvious infection should be considered in this disease. If the swollen lymph nodes are full, tough and so on, the disease should be considered. Sometimes swollen lymph nodes can be temporarily reduced due to anti-inflammatory measures, and then grow up again; some patients have superficial lymph nodes, but have symptoms such as fever, night sweats, and weight loss over a long period of time. Adrenal lymph nodes and other conditions. 2. The staging is the same as the HD staging. Must be associated with Hodgkin's disease, reactive follicular hyperplasia, acute and chronic leukemia, infectious mononucleosis, cat paw disease, malignant melanoma, tuberculosis (especially primary tuberculosis with hilar lymphadenopathy) And other diseases that cause lymphadenopathy include the differentiation of pseudolymphoma caused by phenytoin. The diagnosis of NHL relies on biopsy of diseased lymph nodes or related tissues. Pathological diagnosis should include at least two parts, namely histological typing and immunophenotype of tumor cells, and if necessary, immunoglobulin and T cell receptor gene rearrangement analysis, as well as cytogenetic testing. The usual diagnostic criteria for histology is that the structure of the normal lymph nodes is destroyed, and the envelope and adjacent fat are invaded by typical tumor cells. Phenotypic examination can determine the source of the cells and their subtypes, help to determine the prognosis, and The treatment regimen may also be valuable (see below). The presence of leukocyte common antigen (CD45) is determined by immunoperoxidase assay (usually used for the differential diagnosis of undifferentiated malignancies), and metastatic cancer is excluded. This method can be used on fixed tissues. Used to determine leukocyte public antigens. Most surface markers can also be examined on fixed tissues using the immunoperoxidase method. Diagnosis: It is difficult to make a definitive diagnosis based on clinical judgment alone. Many normal healthy people can also touch certain lymph nodes in the neck or groin. The enlargement of lymph nodes can also be seen in bacterial, tuberculosis or protozoal infections and certain viral infections. It also needs to be differentiated from lymph node metastasis. Specific identification is as follows: 1. Chronic lymphadenitis, general chronic lymphadenitis, more infections. In the acute phase of infection, such as foot and ankle infection, it can cause ipsilateral inguinal lymphadenopathy, or with acute manifestations such as redness, swelling, heat, pain, or only lymphadenopathy with pain. After the acute phase, the lymph nodes shrink and the pain disappears. Generally, the lymph nodes of chronic lymphadenitis are small, about 0.5-1.0 cm, the texture is soft, flat, and more active, while the lymph node enlargement of malignant lymphoma is characterized by large, full, and toughness, and biopsy is performed if necessary. 2. In addition to different degrees of fever, acute suppurative tonsillitis, the tonsils are mostly bilateral swelling, red, swollen, pain, and attached with pus moss, the texture of the sputum is soft, after the inflammation control, the tonsils can be reduced . Malignant lymphoma invades the tonsils, which can be bilaterally or unilaterally. It can be asymmetrically swollen. The texture of the sputum is hard and tough. Later, it involves the surrounding tissue. When suspicious, it can be performed by tonsillectomy or biopsy. an examination. 3. Lymph node tuberculosis is a special type of chronic lymphadenitis, swollen lymph nodes are more common in the neck, more with tuberculosis, if accompanied by tuberculous systemic symptoms, such as low fever, night sweats, weight loss, etc., it is not easy to distinguish from malignant lymphoma Lymph node tuberculosis lymph nodes, hard, uneven surface, uneven texture, or cystic due to caseous necrosis, or adhesion to the skin, poor mobility, PPD test was positive. However, it should be noted that patients with malignant lymphoma may have tuberculosis, which may be due to long-term anti-tumor treatment, decreased immunity, and tuberculosis. Therefore, it should be vigilant in clinical practice. Whenever the condition changes, it should be obtained again. Pathological or cytological evidence to avoid misdiagnosis and mistreatment. 4. Sarcoidosis is more common in adolescents and middle-aged people. It can invade lymph nodes and can be swollen with multiple lymph nodes. It is common in the lymph node symmetry enlargement, or in the paratracheal and supraclavicular lymph nodes. The lymph nodes are more than 2cm in diameter. The texture is generally hard, and can also be accompanied by long-term low heat. The diagnosis of sarcoidosis requires biopsy, epithelioid nodules can be found, Kvein test is 90% positive in sarcoidosis, and angiotensin-converting enzyme is elevated in lymph nodes and serum of patients with sarcoidosis. 5. Histiocytic necrotizing lymphadenitis The disease is more common in China, mostly young and middle-aged, and the clinical manifestations are persistently high fever, but the number of peripheral white blood cells is not high, and it is ineffective with antibiotics, which is similar to malignant reticulosis. The lymph nodes of histiocytic necrotizing lymphadenitis are more common in the neck, and the diameter is more than 1 to 2 cm. Quality or soft. Unlike lymph nodes of malignant lymphoma. A lymph node biopsy is required for the diagnosis, and the disease is cured after a few weeks. 6. Central lung cancer invading the mediastinum, thymus tumor can sometimes be confused with malignant lymphoma, the diagnosis depends on the mass biopsy. Read more...