Disease name:
Introduction:
Malignant lymphoma (ML) is an immune cell tumor that occurs in lymph nodes and/or extranodal lymphoid tissues. It is a malignant transformation derived from lymphocytes or tissue cells. It is a group of solid tumors that can be highly cured.
Cause:
(1) Causes of the disease
Malignant lymphomas of many animals such as chickens, mice, cats and cattle have been shown to be caused by viruses. In humans, although it has been considered for many years that certain clinical manifestations of lymphoma such as fever, hyperhidrosis, and increased white blood cells are very similar to infections in many respects, it has not been proven in recent years that some lymphomas are caused by viruses.
Most of the etiology of lymphoma studies began in high-incidence areas or high-risk groups.
1. Viral Human lymphoma was first confirmed to be associated with EBV infection in Burkitt's lymphoma. In Central Africa, the disease mainly occurs in children aged 3 to 12 years old. It is related to certain climatic conditions and can account for more than half of the local children's tumors. Only 5% of the patients are over 20 years old. Although there are scattered patients in other parts of the world, they are rare cases. The genome of Epstein-Barr virus has been found in 98% of Burkitt's lymphoma by cell biology techniques, but only 15% to 20% of Burkitt's lymphomas contain Epstein-Barr virus. The shell antigen antibodies of EB virus in patients in the endemic area were all positive and the titer was high. The risk of developing this tumor in children with positive shell antigen was 30 times that of the control group. Infection with certain mites with Epstein-Barr virus can cause malignant lymphoproliferative lesions similar to Burkitt's lymphoma. Therefore, it is currently believed that this disease is a serious and persistent EB virus infection in children in Africa, the immune function is inhibited, and the oncogene is activated, resulting in the malignant proliferation of B lymphocytes. It is currently believed that malaria transmitted by mosquitoes is only a cofactor, and malaria infection changes the lymphatic network and is susceptible to the triggering of the virus. B cell infection is controlled by T lymphocytes, and viral nuclear proteins (such as EBNA-2, EBNA-3) and membrane proteins (such as LMP-1) can induce B cell proliferation.
Epstein-Barr virus infection is also common in HD patients, but the relationship between the two is still unclear. Epstein-Barr virus infection is associated with nasopharyngeal carcinoma and infectious mononucleosis. There have been many reports in the literature that HD can coexist with the latter or occur in patients who have previously had infectious mononucleosis. Recent studies have found that 50% of RS cells have EBV genes on their surface to form their shell RNA, which is the most common type in mixed cell types. Because of the relationship between lymphoma and EB virus in China, it is also highly valued. Due to the high infection area of Epstein-Barr virus in China, the infection rate of Epstein-Barr virus in the normal population is very high.
Another important finding is the viral cause of adult T-cell lymphoma. As early as 1987, Gallo et al isolated a type C RNA virus from a tumor tissue of a mycosis fungus, called T cell leukemia lymphoma virus (HTLV-1). This is a very special retrovirus with a single-stranded RNA and an outer envelope. The virus has three structural proteins: core protein, envelope protein and enzyme protein (including viral polymerase and reverse transcriptase). It was proved by Gall et al. that the AIDS virus was isolated from the French scholar Montagnier (human acquired immunodeficiency virus, HIV).
To date, this virus (HTLV) has been isolated from tumor specimens from nearly 10 patients with T-cell lymphoma and is considered to be a highly specific virus. At the same time, according to the epidemiological survey of adult T-cell lymphoma, Japanese scholars found that the high incidence occurred in the southern part of the four countries and Kyushu. The peak incidence was in the summer, and the patients were mostly engaged in agriculture, fisheries and forestry, and often had poor nutrition in the past. Factors such as tropical disease infections are likely to be associated with viral and/or filariasis infections. They also isolated RNA viruses independently, called ATLV. After studying ATLV and HTLV, it is also a causative factor of adult T-cell lymphoma/leukemia. However, through a large number of serological studies, there is no positive relationship between T cell lymphoma and HTLV-1 (or ATLV) in China. To date, there have been only 4 cases reported in China related to HTLV-1 (or ATLV).
The detailed mechanism of the virus causing lymphoma is not fully understood. Viral replication is associated with the production of a retro-acting factor (tax) that induces expression of the REL gene and allows cells to proliferate. There are other factors that require the malignant transformation of cells. Many people in the high-incidence area are infected with HTLV-1, but only a small number of T-cell lymphomas occur. Thus supporting host factors including genetic factors may have an important position.
2. The occurrence of immunosuppressive lymphoma is closely related to immunosuppression. Because of the long-term use of drugs to inhibit the immune mechanism in organ transplantation, the incidence of lymphoma is significantly higher than the general population, and the original is more than the extra-outer, a group of reports can be as high as 69%. In addition, central nervous system invasion is also very high (28%) in patients with general lymphoma (1%). The immunosuppressive drugs used also have an effect on the occurrence of lymphoma. In the applicationCyclophosphamideIn the predominant regime, lymphoma accounts for 26% of primary cancer and occurs earlier. And the application of Imulan (AzathioprineThe class only accounts for 11%. Apply anti-CD3Monoclonal antibodiesIn patients, lymphoma accounts for 64% of the second primary cancer. Another fact that has received widespread attention is that many patients with primary immunodeficiency and acquired immunodeficiency (AIDS) are also prone to lymphoma and other tumors. Especially in patients with EB virus infection, the incidence of lymphoma is higher.
3. Bacterial infection In recent years, it has been reported that Helicobacter pylori (Hp) can cause chronic gastritis and gastric cancer, and can also cause high incidence of gastric lymphoma. In some patients, lymphoma can be reduced after antibiotic treatment. Some authoritative organizations in the United States, such as NC-CN in recent years, have adopted antibiotic therapy as the preferred method of mucosa-associated lymphoma (MALT). This is the first example of the use of antibiotics to treat tumors.
4. Environmental factors In the early years, the United States reported that the incidence of lymphoma was several times higher than that of the normal population due to the use of pesticides and pesticides in the midwestern farmers. The US Navy has been involved in the development of lymphoma in paint vessels and veterans who have been exposed to fluoride. High, but it is difficult to explain its mechanism. More definitely, the atomic bomb victims, the Hiroshima residents who have received radiation above 1Gy and those who have been treated with spondylitis, have a higher incidence of lymphoma than the normal population. Patients with HD who have undergone radiation and chemotherapy have a significant increase in the second primary cancer, especially large cell lymphoma, and often invade the digestive tract.
5. Some other congenital immunodeficiency diseases, such asTelangiectasia ataxiaWiscott-Aldreich syndrome, Chediak-Hig syndrome, etc. are also often complicated by malignant lymphoma. Other so-called "immunoinflammatory" diseases such as systemic lupus erythematosus, which have long been treated with immunosuppressive drugs,Rheumatoid arthritisSj?gren syndrome (sjogren's syndrome), immune hemolytic anemia, etc. may also be complicated by malignant lymphoma. The long arm (q) translocation of chromosome 14 is also associated with the development of malignant lymphoma. In addition, long-term use of certain drugs (such as long-known people)Phenytoin, deoxyephedrine, etc.) can also induce lymphoma. The etiology of malignant lymphoma has shown that many factors are related to the occurrence of this disease, and its specific process and detailed mechanism need to be further clarified.
(two) pathogenesis
1.non-Hodgkin's lymphomaThe pathogenesis of lymphocytes varies in stages of lymphocytes, and different stages of tumor cells can occur in the affected lymph nodes or lymphoid tissues. 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, lymphoblastic lymphoma from immature T cells. These are for further study, especially the role of different genes in them.
2.Hodgkin's lymphomaThe pathogenesis of most patients with classic Hodgkin's lymphoma is associated with clonal cytogenetic abnormalities, which vary with different cases, and the abnormalities within the clones are heterogeneous, suggesting chromosomal instability. Many cases show 14q abnormalities, similar to B-cell lymphoma, but t(14;18) abnormalities rarely occur. Two groups used fluorescence in situ hybridization (with or without fluorescent immunophenotyping) and found that RS cells in all Hodgkin's lymphoma cases showed abnormal clone values. In the early reports, Bcl-2 rearrangements were found in about one-third of Hodgkin's lymphoma, but no Bcl-2 rearrangements were detected in other laboratories. Moreover, Bcl-2 rearrangement is also found in highly reactive tissues such as reactive tonsils. The EBV-associated transforming protein is capable of upregulating Bcl-2 in cultured cells, and this evidence further indicates the relationship between Bcl-2 expression and Hodgkin's lymphoma. The conclusions obtained from immunohistochemical studies of Bcl-2 overexpression are not consistent. However, Bcl-2 expression appears to be unrelated to histology, EBV( ) or t(14;18) translocation, and enhancement of Bcl-2 expression may be present in background cells and does not play an important role in the pathogenesis of Hodgkin's lymphoma. . However, a group of researchers applied cytogenetic analysis to clearly confirm the presence of Bcl-2 rearrangement in tumor cells without t(14;18).
Recently, a novel inhibitor of apoptosis, Bcl-X(L), was found in Hodgkin's lymphoma, and Bcl-X(L) was positive in 94% of Hodgkin's lymphoma, and most RS cells were highly expressed. . The rate of expression in non-Hodgkin's lymphoma is low (<20%), except for reticular central lymphoma. Therefore, it is speculated that the abnormal expression of Bcl-X(L) in RS may be the cause of Hodgkin's lymphoma. No correlation was found between Bcl-X (L) and EBV expression. By immunohistochemical analysis, P53 tumor suppressor gene expression has been detected in Hodgkin and other lymphomas of CD30. However, recent studies have found that there are no P53 mutations in Hodgkin and RS cells in 8 Hodgkin's lymphomas.
Recently, Humboldt et al reported that IκBα mRNA was overexpressed in HRS cells from lymph node biopsy samples from patients with HL, and IκBα gene mutation was detected, resulting in a C-terminal truncated protein, suggesting that this protein could not inhibit NF-κB-DNA binding activity. It prevents the apoptosis of HRS cells and triggers proliferation. Therefore it is related to the pathogenesis of HL.
The cytogenetic data of NLPHL is scarce, and the results of cytogenetic abnormalities are also inconsistent. Of the large series of HLs reported by Tilly et al, there is only one NLPHL, which has a 46XY karyotype. Hansmann et al. reported a case of high diploid NLPHL, 6q-, 2l, and several unclear markers. The study found that the DEV cell line originating from NLPHL has the following karyotype abnormalities: 48, XXY, t (3; 14) (3; 22), t (3; 7), del3, -2, 12, mar. Analysis of ploidy of HL, 3 of 5 NLPHL were aneuploid, no tetraploid was detected, and tetraploid was common in classical HL. Bcl-2 gene rearrangement was detected in only a small number of cases, and immunohistochemistry was used to detect Bcl-2 protein expression, and the number of positive cases was small. Based on this, it is speculated that Bcl-2 translocation may not play an important role in the onset of NLPHL.
The origin of tumor cells, it has long been believed that different histological types in HL represent morphological variations of the same disease, with HRS cells in a reactive background, and each tissue subtype has a characteristic cellular composition. In the past 20 years, people have gradually found that the above concepts are only partially correct. For example, nodular lymphocyte-based HL is different from other types of HL and is a different biological disease.
(1) Cellular origin of HRS in classical HL: The earliest immunohistochemical study on Ig expression of IRS, such as Garvin et al in 1974 and subsequent Taylor, etc., their study confirmed that HRS expression of IgG was obtained in HL biopsy specimens, indicating HRS Originated from Ig-producing B cells, but other immunohistochemical studies have shown that HRS originates from non-lymphoid cells. Subsequent to the application of monoclonal antibody technology, CD30 molecules were discovered. It was demonstrated that HRS of classical HL selectively expressed CD30, whereas normal individuals were only expressed in some activated lymphoblasts. This data demonstrates for the first time that HRS is the origin of lymphocytes. Gene level studies showed that clonal Ig gene rearrangement occurred in HRS, and 12 cases were detected in 13 cases of HL in the Rajewsk series. stein also reported that 24 cases were rearranged in 25 cases, which proved that 95% of HLs are B cell origin. .
Sequence analysis demonstrated a high load of somatic mutations in the rearranged V region. Since some classical HLs of HRS cells express one or more T cell antigens and 40% of the cell lines in HL have T cell phenotypes and genotypes, it is speculated that the remaining 5% of classical HL originates from transformed T cells. However, this speculation cannot be confirmed because the rearranged TCR gene has not been detected in HRS cells. Recent studies have found that classical HL originates from germinal center B cells rather than germinal center B cells; B cell line progeny can undergo two independent transformations, one forming HRS cells and the other forming NHL; producing HL transformation Cells that completely altered the morphological and immunophenotype of normal progenitor cells (not expressing CD20, CD10, Bcl-6, and IgM and down-regulating the mutational machinery, expressing CD30 and CD15) and converting to NHL retained more or less B cell lines. The characteristics of the ancestors.
The population of HRS cells in a particular case is completely derived from a single transformed cell and clones proliferate. In the WHO (2001) classification, nodular lymphocyte-based Hodgkin's lymphoma is derived from the B cell of the germinal center of the germinal center, while 98% of the classical Hodgkin's lymphoma is in the differentiation stage of the germinal center. Mature B cells.
(2) Cell origin of lymphocytes and/or histiocytes (H and L) in NLPH: lymphocyte-based HL, a characteristic tumor cell [lymphocytes and/or tissue cells (H and L)] The subtype is related to the huge nodule of the germinal center for progressive transformation. Immunohistochemical studies have shown that H and L cells are a series of B cells. Because they express a large number of B cell markers including CD19, CD20, CD22, CD79a and J chain, and recent molecular studies have also suggested: H and L. Cells are central cells of transformation. In the major clonal populations, immunoglobulin heavy chains continue to undergo somatic hypermutation. In developed countries, EBV is rarely associated with H and L cells and may not be associated with the disease. H and L cells are often surrounded by T cells of CD3, CD4, CD57, CD40, L-, but the significance of this T cell rosette is unclear. NLPHL may co-occur with large cell lymphoma or be converted to large B-cell lymphoma. Numerous studies have shown that at least in some cases, there is a correlation between B-DLCL and NLPHL in cloning. NLPHL may also have nodules or large areas similar to rich tissue cell B cell lymphoma (HRBCL), at least some HRBCL cases originating from NLPHL. This may also be the case with T-cell B-cell lymphoma (TCRBCL). There is little information about the NLPHL cell genes, and the cellular genetic abnormalities reported by each research group are also inconsistent.
(3) Cytokines: The main histological features of Hodgkin's lymphoma are: a considerable amount of collagen sclerosis, inflammatory cells, and malignant RS cells. The cytokines produced by RS cells and background cells lead to differences in subtypes. There is a complex paracrine and autocrine effect between these cells. Various cytokines produced by RS cells and reactive cells affect both RS cells and the surrounding cell environment. For example, transforming growth factor-β1, (TGF-β1) mRNA has been detected in eosinophils of nodular Hodgkin's lymphoma.
Although the role of TGF-β1 is determined by its interaction with other factors and target cells, it can stimulate fibroblast proliferation and produce collagen, which may play an important role in the formation of collagen, the latter is nodular Hodge The characteristics of gold lymphoma. Another cytokine that plays an important role in the pathogenesis of this disease is IL-5. IL-5 is a growth factor for eosinophils, while eosinophils are the primary background cell in some Hodgkin's lymphomas, and IL-5 mRNA is also found in RS cells. In addition, RS also secretes IL-1, IL-9, tumor necrosis factor-α, granulocyte-macrophage colony stimulating factor and macrophage stimulating factor.
IL-6 is present in 10% to 60% of RS cells, which induces plasma cell proliferation and promotes lymphocyte proliferation and maturation. The different histological features of Hodgkin's lymphoma may be the result of a network of various cytokines secreted by RS and reactive background cells such as T lymphocytes, histiocytes, and eosinophils.
symptom:
1. Local manifestations Clinically, most of the malignant lymphomas first invade the superficial and/or mediastinal, retroperitoneal, and mesenteric lymph nodes, and a few may originate in the extranodal organs. The 5101 cases of patients diagnosed with malignant lymphoma admitted to the Cancer Hospital of the Chinese Academy of Medical Sciences from 1958 to 1994. It can be seen that, firstly, 69.6% of the superficial lymph nodes are invaded. It is not difficult to have a good understanding of the disease.
(1) lymphadenopathy: more patients in the early stage showed painless neck lymphadenopathy, and other parts were found later. Lymph nodes can be large from yellow beans to jujube, medium hardness, tough, uniform, full. It is generally non-adhesive to the skin and does not fuse with each other in the early and middle stages. In the later stage, the lymph nodes can grow to a large size, and can also be merged into a large piece, with a diameter of more than 20 cm. Some patients have multiple lymph nodes from the onset of the disease, and it is difficult to determine where the first site is.
(2) Mediastinum: The mediastinum is also one of the most common sites. Most patients often have no obvious symptoms at the beginning. The invaded mediastinal lymph nodes may be a single lymph node enlargement; or multiple lymph nodes may be fused into a giant mass; the outer edge is wavy, invading one side or bilateral mediastinum, and the latter is more common. Compression symptoms can occur in the advanced stage.
(3) Liver and spleen: Primary hepatic malignant lymphoma is rare, and only a few cases have been reported in the literature. It is not uncommon to have a secondary invasion of the liver. The prognosis of liver invasion is poor, and it is worse than systemic symptoms.
(4) Extranodal organs: generally occur in NHL. In rare cases, HD may also have extranodal organs such as bone, pharyngeal lymphatic ring, skin, digestive tract, central nervous system and the like.
2. Whole body performance
(1) systemic symptoms: about 10% of patients can have fever, itchy skin, night sweats and weight loss and other systemic symptoms are the earliest clinical manifestations. As the disease progresses, there is fatigue and anemia. Generally, with the progress of the disease, systemic symptoms can be aggravated. There may be lymphopenia in such patients. The mediastinum and retroperitoneal malignant lymphoma are associated with fever and itchy skin.
Sustained fever, excessive sweating, and weight loss may indicate disease progression, failure of the body's immune function, and poor prognosis. However, some patients have itchy skin and fever without a huge mass. After treatment, the prognosis is better.
(2) Skin lesions: Patients with malignant lymphoma may have a series of non-specific skin manifestations with an incidence of about 13% to 53%. Common psoriasis-like papules, herpes zoster, systemic herpes-like dermatitis, pigmentation, ichthyosis and exfoliative dermatitis. Urticaria, nodular erythema, dermatomyositis, acanthosis, pigmented urticaria, etc. can also occur. It is more common for scratches and skin infections due to itchy skin. In patients with advanced malignant lymphoma, the immune status is low, and skin infections often break down and exudate, forming a systemic scattered skin thickening and scaling.
(3) Anemia: About 10% to 20% of patients with malignant lymphoma have anemia at the time of presentation, and may even occur a few months before the lymphadenopathy. Anemia is more common in patients with advanced disease. Progressive anemia and increased erythrocyte sedimentation rate are important indicators for clinically judging the development of malignant lymphoma.
(4) Neurological manifestations: Patients with malignant lymphoma may have a range of non-specific neurological manifestations, such as progressive multifocal leukoencephalopathy, subacute necrotizing myelopathy, sensory or motor peripheral neuropathy, and multiple myopathy. Wait. The nature of the lesion can be: 1 degeneration; 2 demyelination; 3 infectivity; 4 necrotic or mixed presence.
(5) Low immune function: Due to low immune status in HD patients, especially in advanced patients, central nervous system infections such as Cryptococcus neoformans can occur; blood-borne suppurative meningitis or brain abscess can also occur. Malignant lymphoma invades the brain parenchyma with cerebral hemorrhage.
The diagnosis of malignant lymphoma mainly depends on clinical manifestations, X-ray examination and pathological examination, but pathological examination is essential for the diagnosis and classification of malignant lymphoma.
Diagnostic treatment, in clinical practice, it is often possible to see some patients with long-term weight loss, fatigue or unexplained hypothermia; or in some cases, some people have swollen lymph nodes, due to concerns about biopsy caused by dissemination, and diagnostic radiotherapy. However, a considerable number of patients later confirmed that they were not malignant lymphomas.
Reed-Sternberg cells are characteristic of HL. RS cells originate from B cells and are bulky, cytoplasm rich, and have low nuclear chromatin. There should be at least 2 nuclear lobules or nucleoli (if they are mononuclear, called Hodgkin's cells). The immunophenotype is positive for CD30 and CD15. According to other pathological features, HL is usually divided into four subtypes: nodular sclerosis, mixed cell type, lymphocyte-based and lymphocyte-attenuated; in the WHO classification, another subtype: nodule Sexual lymphocytes are predominant, and their tumor cells resemble popcorn, which is a variant of RS cells.
The basic pathological features of NHL are: the normal structure of lymph nodes disappears and is replaced by tumor tissue; the proliferating lymphocytes are heteromorphic; the tumor cells invade the lymphatic capsule. According to the characteristics of morphological, immunological and molecular biology of tumor cells, NHL can be divided into many subtypes. Currently, the widely used classification methods in the world are REAL classification and WHO classification, while the domestic application is 1982 in the United States. "working plan".
After the lymphoma is diagnosed, the stage of the disease should be based on the Ann Arbor criteria.
2. Diagnostic evaluation The diagnosis of lymphoma relies on pathological examination. Obtaining sufficient and appropriate pathological specimens is the primary condition for correct diagnosis. Lymph node biopsy can be routinely performed in patients with superficial lymphadenopathy. In the mediastinal or intra-abdominal lymph nodes, and the lack of superficial lymphadenopathy, laparotomy or thoracotomy is required to obtain specimens. When the deep lymph nodes fuse into giant pieces, the Tru-Cut needle puncture effect is also quite satisfactory. Only splenomegaly, clinically highly suspected lymphoma, should be splenectomy in time, liver biopsy at the same time to get more diagnostic basis. In the case of liver lesions, hepatic puncture can be performed under CT or ultrasound guidance to obtain the desired liver tissue.
Gastrointestinal microscopy and microscopic biopsy are very important for the diagnosis of gastrointestinal lymphoma, but the biopsy pathology and postoperative pathological results are not completely consistent. The non-conformity rate of a group of cases in Peking Union Medical College Hospital is 25.8%.
A small number of NHL manifested as fever, jaundice, abnormal liver function, decreased whole blood cells or neuro-muscular symptoms in the early stage of the disease. There is no clear tumor block or contraindications for puncture and biopsy. At this time, bone marrow examination is very important. Bone marrow aspiration and biopsy are performed at the same time. If necessary, repeat several times, and try to detect new technologies such as chromosome, immunophenotype and gene rearrangement as soon as possible to confirm the diagnosis at an early date.
The staging of lymphoma is an important basis for the development of treatment options, especially at HL. The current international adoption of the Ann Arbor staging standard (1971, revised by Cotswald in 1989) is mainly applicable to HL. For the NHL, this staging criterion does not predict the prognosis of the disease well, so it is possible to simply make a general staging. One of the problems often encountered when applying Ann Arbor staging is how to determine a localized lesion (stage I) or a diffuse lesion (stage IV) when there is an extranodal organ (or tissue) involved in this literature. Detailed Description. It can be understood that when the whole organ is enlarged and the imaging cannot distinguish a single lesion, it is a diffuse lesion.
Lymphoma is a heterogeneous group of diseases. According to its pathological features, in addition to HL and NHL, there are many subtypes in each category. Through half a century of efforts, pathologists all over the world have developed a variety of classification standards, which were gradually unified into the REAL program in 1994. On the basis of the REAL program, in 2000 the WHO proposed the WHO classification. The WHO classification, based on information provided by morphology, immunology, and genetics, emphasizes that each subtype may become an independent disease, and that subtypes are determined not by individual or group experience, but should be widely available worldwide. Admit. The WHO affirmed that with the advancement of technology and scholars' deeper understanding of lymphoma, the WHO classification will be revised and improved.
Some doctors have thought that the classification of lymphoma subtypes is too cumbersome and has little value for clinical treatment. However, there is increasing evidence that different subtypes of lymphoma may have special treatments. For example, if gastric MALT lymphoma is associated with Helicobacter pylori, antibiotic treatment is effective; inert B-cell lymphoma is suitable for monoclonal antibodies; ALK- anaplastic large cell lymphoma should be autologous hematopoietic stem cell transplantation as early as possible. Therefore, our pathologists and clinicians should learn and accept this taxonomy and actively participate in its further revision.
In general, this type of diagnostic treatment is not appropriate unless there are special indications (for example, if a patient has a large mass, or if there is a long-term fever, a few days of radiation or chemotherapy before surgery to create a surgical resection). The reason is that:
1 The existing radiotherapy and chemotherapy are not specific treatments for malignant lymphoma, and also have inhibitory effects on inflammation, tuberculosis and other granulomas and tumors. Therefore, in fact, these treatments cannot be used to identify the nature of the disease. On the contrary, the diagnosis is more confusing because of concealing contradictions. Sometimes, even biopsy can not make a definite diagnosis due to necrosis of the tissue, which brings difficulties to future treatment;
2 radiotherapy and most of the existing chemotherapy drugs have immunosuppressive effects, which can bring the opposite effect to patients and promote the development of hidden infections;
3 The short- and long-term effects of radiotherapy and chemotherapy (such as skin reactions, myelosuppression, effects on bone development in children, etc.) are not good for patients.
It is the patient who has been diagnosed with malignant lymphoma. During the observation period after treatment, sometimes fever or individual lymph nodes may not be considered as “relapse” without thinking, but other possible causes should be sought. In the recovery period, due to the disease itself and long-term treatment, the immune function is often low, and it is easy to catch a cold or general inflammation, so it is also more prone to fever or a certain part of the lymph nodes. If not treated properly, chemotherapy can be given a great harm to the patient. We have reported (1978) that a patient with HD had a good stage after treatment, but then continued to have fever, the lungs had radial shadows, and various anti-infective and anti-fungal treatments were ineffective, so it was suspected that HD recurred and invaded the lungs. Chemotherapy was given to the Ministry, but it was later confirmed by autopsy as tuberculosis.
diagnosis:
A biopsy failed to confirm the diagnosis and lymphoma should not be ruled out. A total of 13.2% of 200 patients with NHL in Peking Union Medical College Hospital were diagnosed through multiple biopsies. Therefore, it is recommended to consult a number of pathologists in the following situations.
(1) The biopsy specimen is inconsistent with the pathological report of the postoperative specimen.
(2) The external hospital is inconsistent with the pathology report of the hospital.
(3) Multiple biopsy pathology reports are inconsistent.
(4) The pathological results are suspicious and do not match the clinical.
There is no difficulty in the diagnosis of a typical lymphoma. However, clinicians should pay sufficient attention to the extent and stage of disease. After the diagnosis of lymphoma by pathological examination, bone marrow examination, chest and abdomen CT must be performed, and total gastrointestinal barium meal imaging should be performed as much as possible. Ultrasound is inexpensive and easy to perform, but it is less reproducible and lacks long-term preservation images. It is only suitable for primary screening and follow-up after treatment.
Identification
Clinically, malignant lymphoma is often misdiagnosed. For example, 70% to 80% of patients with malignant lymphoma who have a superficial lymph node enlargement are diagnosed with lymphadenitis or lymph node tuberculosis at the time of initial diagnosis, resulting in delay in treatment. The differential diagnosis of malignant lymphoma is of great significance.
Malignant lymphoma should be identified with the following diseases:
1. Chronic lymphadenitis has obvious infections, and often is focal lymphadenopathy, pain and tenderness, generally not more than 2 ~ 3cm, can be reduced after anti-infective treatment. Clinically misdiagnosed as malignant lymphoma is the recurrence of tonsillitis in some children. The superficial lymph nodes are swollen due to bacteremia. When palpation is performed by hand, the tonsils are often softer than the malignant lymphoma. The pus can be squeezed out. The lymph nodes of these children are often swollen by fever and shrink after heat retreat, which can exist for many years without development. However, these can not be regarded as absolute. Some malignant lymphomas, especially HD, may have a history of periodic fever and lymph node enlargement and contraction, so they should be considered comprehensively.
Because many people suffer from enough. Inguinal lymphadenopathy, especially long-standing and unchanged flat lymph nodes, is of great significance. However, if there is no obvious cause on the bilateral trochlear or neck, the supraclavicular lymph nodes, it should be taken seriously. Although it is not certain that it is a malignant lymphoma, it at least marks a systemic lymphoid tissue disease, which should be further examined to determine the nature.
2. Giant lymph node hyperplasia (giant lymph node hyperplasia) is an unexplained lymph node enlargement, mainly invading the chest cavity, with the most mediastinum, and can also invade the hilar and lung. Other areas of invasion include the neck, retroperitoneum, pelvis, armpits, and soft tissues. Patients often have a mass as a sign, and those in the chest may have compression symptoms, but they are often found. There are also systemic symptoms such as fever, anemia, and elevated plasma protein. After the tumor is removed, the symptoms disappear. It is sometimes difficult to distinguish from malignant lymphoma lung lesions based on X-ray examination alone. Gallium (Ga) scanning is sometimes helpful for diagnosis, especially for the identification of pulmonary fibrosis and lung invasion caused by radiotherapy.
3. The pathological and clinical manifestations of HD and NHL have different characteristics. These characteristics are relative and only for clinical reference.
complication:
Complications of malignant lymphoma are mainly seen in anemia, infection, fever, chest tightness, chest pain, cough, shortness of breath, obstruction of swallowing, difficulty breathing, abdominal pain, intestinal obstruction, jaundice, ascites, cirrhosis, hydronephrosis, uremia and neurological symptoms. .
treatment:
Western medicine treatment
1. Principles and strategies for treatment There are three recognized characteristics in the development of clinical oncology: evidence-based medicine, individualization and standardization. Larger research units and collaborative organizations have standardized treatment of lymphoma. The US NCCN proposes to divide lymphoma into: small lymphocytic lymphoma/B-cell chronic lymphocytic leukemia; follicular lymphoma; diffuse large B-cell lymphoma; primary central nervous system lymphoma; cloak cell lymphoma Gastric MALT; Burkitt lymphoma and lymphoblastic lymphoma and other 7 groups. And developed different treatment options.
In particular, they pointed out that it is difficult to treat clonal cell lymphoma, and appropriate clinical trials must be carried out. However, the gastric MALT they believe should be the preferred antibiotic treatment. Individualized treatment of lymphoma should consider other factors besides the type of case. This is age, general condition, blood LDH, extranodal lesions, and staging. The relationship between the so-called high-grade lymphoma international index and prognosis. To some extent, the individualization of lymphoma treatment has become more new.
We believe that for patients with malignant lymphoma, the first treatment should be based on the patient's general condition, pathological type, location of the primary lesion, clinical stage and tumor development trend, etc., to develop a combination of Chinese and Western medicine, local and systemic, righting and evil spirits organic Coordinated comprehensive treatment plan. For patients who have already been treated, according to the subjective and objective conditions of the patient, the response to the previous treatment, the primary and secondary contradictions at each stage are analyzed for comprehensive treatment. Years of experience have shown that focusing on the main tasks at different stages, distinguishing between primary and secondary and syndrome differentiation are the main prerequisites for successful treatment.
Our general strategy in the comprehensive treatment of tumors is: the first stage is full of evil, minimize tumor burden; the second stage is to transfer the focus to the reconstruction of bone marrow and immune function; the third stage is another intensive treatment The tumor residual cells are reduced to a small extent; the fourth phase is converted to improve immune function to consolidate the disease, which is very important in the treatment of lymphoma. Since the 1950s, the therapeutic effect of this disease has gradually improved. In recent years, reasonable and planned comprehensive treatment has been adopted, and the curative effect has been further improved. HD 60% to 80% can be cured, and more than 50% of NHL can be relieved in the long term. This has become a very encouraging area in oncology.
(1) The general condition of the patient: the development of malignant lymphoma is closely related to the patient's ability to resist disease. From the perspective of the motherland medicine, paying attention to distinguishing the patient's reality is also a prerequisite for adopting appropriate treatment.
Many clinical medical workers in our country have experienced from years of clinical practice: pay attention to the internal factors of patients, emphasize the overall concept before treatment, pay attention to protect the patient's own disease resistance during treatment, and actively give corrective treatment after treatment, mobilize and improve patient immunity. Function is of great significance for achieving a good and stable effect. Otherwise, inappropriate treatment can often cause damage to the patient's body.
(2) Pathological classification of tumors: The ideal pathological classification should reflect the proliferation and differentiation of tumor cells and the body's response to tumor growth. Pathological classification is an important factor in determining the treatment plan and so on to a certain extent. It has been mentioned that the subtypes of HD have different clinical development rules, and the prognosis also has certain differences. Appropriate attention should be paid to the treatment arrangements.
(3) Clinical staging: At the current stage, clinical staging is still one of the decisive factors determining the treatment plan, especially radiotherapy. An important task in the clinic is to determine the patients who are truly in stage I and II and the scope of the violation. These patients can be cured by local or regional treatment.
(4) Primary site: Different primary sites determine the pathological type and response to treatment to a certain extent. For example, lymphoma caused by HIV infection is easy to invade the central nervous system, and the primary gastric lymphoma is quite MALT, and it can be treated with antibiotics related to Helicobacter pylori infection, so the prognosis is better;
(5) Trend of tumor development: reflecting the balance between tumor and body. The patient's cellular immune function status is currently an important aspect. Some patients are in stage II, but they are developing rapidly. Even if surgery is possible, they should not be rushed. Instead, radiation or drug treatment should be started first, and surgery should be considered after the tumor is reduced.
(6) Whether there is a huge block: Whether there is a huge block has a great impact on the prognosis of HD. The larger the mass, the worse the response to chemotherapy and radiotherapy, and the more susceptible to residual drug-resistant cells becomes the source of recurrence.
(7) Blood LDH and interleukin-2 receptor levels, tumor cell mdr expression, etc. can determine the outcome of treatment.
In short, how to arrange "attack" and "complement" is a comprehensive analysis of internal and external causes, and how to properly arrange systemic local treatment, we must first analyze and understand whether the whole body spread is the main contradiction or local growth for patients. Is the main problem. It should be said that a considerable number of lymphoma patients, especially those in stage II and IV, have a certain degree of immunological dysfunction and should be noted. The experience of many units in China is that they are opposed to giving large-area irradiation without considering the specific conditions of patients, and they are not in favor of indiscriminate "shock" chemotherapy. For malignant lymphoma with systemic dissemination, combined chemotherapy is needed. After the limitation, a certain dose of radiotherapy is given. In the treatment and after a long time after treatment, the traditional Chinese medicine is given to the treatment of the Chinese medicine, and the treatment effect can often be achieved, and the recovery of the patient's labor ability is also beneficial.
In the development of a comprehensive treatment plan, the departments work closely together to develop a plan: the first treatment is often the key to good results, so it should be carefully discussed, at least the following aspects should be considered:
1 Reasonable application of local and systemic treatment: Radiation therapy can achieve good or even radical effect for cases with low degree of malignancy and early stage; there should be drug treatment mainly for systemic dissemination or advanced cases. HD tends to invade the adjacent lymphatic area and less invade the extranodal organs or tissues, because the lymphatic area of the larger area is better. The spread of NHL often has a “jumping station” phenomenon, which is more likely to invade distant lymph nodes or extranodal nodes. Organs, because most of them require systemic medication. The NHL in the abdominal cavity, especially in the digestive tract, should be surgically resected when possible, and later combined with other treatments to reduce the possibility of obstruction or perforation.
2 combination of evil spirits and righting: after the treatment of radiotherapy or chemotherapy, the combination of traditional Chinese and Western medicine, including effective biological treatment, is conducive to the consolidation of efficacy and recovery of cellular immune function; in combination with traditional Chinese medicine treatment in radiotherapy or chemotherapy can reduce toxicity reaction. Pre-treatment emphasizes the overall concept; pay attention to protect the patient's own disease resistance during treatment, avoid unnecessary over-treatment; actively mobilize and improve the patient's immune function after treatment, which has special significance in the treatment of malignant lymphoma.
3 Sequential application of induction, consolidation and intensive treatment: According to the theory of tumor proliferation kinetics, the number of tumor cells decreased from 1011 to 109, and complete remission occurred in the clinic. The enlarged lymph nodes basically disappeared, but if consolidation treatment is not used, it must be There will be a recurrence within the time. Therefore, after complete remission, consolidation and intensive treatment must be used sequentially, while patients who have not achieved remission should try their best to achieve complete remission, and observe and follow up the patient for a long time to fight for cure.
4 Specific analysis of specific problems: The treatment plan should be adjusted according to various aspects of the patient. The development trend of the disease and the state of the body should be given special attention. At present, some slow-developing HDs are not advocated for excessively strong treatment, so as to avoid excessive suppression of the patient's immune function; for patients with rapid development, they must be given intense treatment in order to achieve complete remission as soon as possible to achieve cure. In addition, patients with superior vena cava compression syndrome and bone marrow invasion should be treated according to specific conditions.
2. Treatment mode Lymphoma treatment has made great progress, and the curative effect is better in the whole malignant tumor, and the cure rate is also higher, but there is a big difference between HD and NHL, especially different types of NHL. It is generally believed that the treatment of NHL can be based on certain principles.
3. The comprehensive treatment of several malignant degrees of NHL is based on the principles and protocols for the comprehensive treatment of low- and medium-grade malignant NHL.
The above content is for reference only, please consult the relevant physician or relevant medical institution if necessary.
prevention:
Because the cause of lymphoma patients is not yet clear, the method of prevention is nothing more than:
1 to minimize infection and avoid exposure to radiation and other harmful substances, especially drugs that have an inhibitory effect on immune function;
2 Appropriate exercise, enhance physical fitness and improve your disease resistance.
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