Non-Hodgkin lymphoma

Introduction to non-Hodgkin's lymphoma Non-hodgkin's lymphoma (NHL) is a major type of malignant lymphoma. The proportion of non-Hodgkin's lymphoma in malignant lymphoma in China is much higher than that of 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 very heterogeneous group of diseases with different causes, pathology, clinical manifestations and treatments. So far, the total cure rate is 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. basic knowledge Sickness ratio: 0.05% Susceptible people: no special people Mode of infection: non-infectious Complications: leukemia, intestinal obstruction, ascites, uremia

The cause of non-Hodgkin's lymphoma

Genetic abnormalities (20%):

Cytogenetic studies have found that patients with non-Hodgkin's lymphoma have chromosomal abnormalities and thus become a high-risk group for malignant lymphoma.

Immunodeficiency disease (30%):

Primary immunodeficiency syndrome (PIDS) is one of the highest risk factors for malignant tumors in humans, and acquired immunodeficiency disease or homologous secondary to human immunodeficiency virus (HIV) infection The sustained suppression of immunity caused by organ transplantation and certain non-neoplastic diseases has caused a marked increase in lymphoproliferative diseases.

Pathogenesis:

Due to the different stages of lymphocyte differentiation, different stages of tumor cells may occur in the invaded lymph nodes or lymphoid tissues. In the same lesion, there may be poorly differentiated tumor cells or cells with more mature differentiation. The progression of the lesion, the histological type of malignant lymphoma may be transformed, such as nodular type can be converted 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, B lymphocytes in 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, CD4-positive, including adult T-cell lymphoma. (ATL), mycosis fungoides, Sezary syndrome, most so-called peripheral T-cell lymphoma (diffuse large cells in the international work classification, immunoblasts and mixed lymphoma) and more than half of T-cell chronic lymphocytes Leukemia, there are some peripheral T-cell lymphoma, nearly half of T-cell chronic lymphocytic leukemia and some T lymphoproliferative diseases, CD8 positive.

B-cell lymphoma has fewer specific antibodies, but has surface immunoglobulin expression. The earliest B cells have CD10 and CD19 on the surface, and there are terminal transferases in the cell and recombination of heavy-bond genes. , the production of heavy bonds in the cytoplasm, the reorganization of the K light bond gene, the recombination of the light bond gene and the loss of the terminal transferase, which represent the development of the pre-B cell stage, and the expression of CD10 after cell loss becomes immature. B cells have IgM expression on the surface, and IgD and IgM are produced on the cell surface expressing CD21 receptor (C3d) membrane. The developmental stages of all B cells occur under antigenic stimulation, and the immunoglobulin gene is stimulated by antigen. It is activated and secreted. After that, the cells lose CD21, CD20 and surface immunoglobulin, and the plasma cells are labeled with PC-1 and PC-2 to secrete immunoglobulin, which is the development process of cell follicle center B cells, which is malignant. After the change, it becomes lymphocytic lymphoma.

The maturation of B cells in the follicular center and the initiation of immunoglobulin genes are regulated by T helper cells, but there are also some unidentified B lymphocytes. The B cells in the mantle cell area seem to be relatively less affected by T cells, which are CD5 positive. This 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, giant balls. Proteinemia (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 rather than the filter. B cells in the center of the bubble.

The immunophenotyping and clinical manifestations of some lymphomas are still very confusing. Diffuse large cell lymphomas 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 Cellular lymphoma is derived from mature T cells in terms of immunophenotype, but clinical manifestations are very dangerous, like lymphoblastic lymphoma from immature T cells, which are subject to further study, especially the role of different genes.

Non-Hodgkin's lymphoma prevention

Appropriate exercise, enhance physical fitness and improve your disease resistance. Mainly for the prevention of various factors that may lead to malignant lymphoma, it is currently considered that the loss of normal immune surveillance function, the tumorigenic effect of immunosuppressants, the activity of potential viruses and certain physical (such as radiation), chemical (such as Long-term application of antiepileptic drugs, adrenocortical hormones, may lead to the proliferation of lymphatic network, and eventually malignant lymphoma. Therefore, pay attention to personal and environmental hygiene, avoid drug abuse, and pay attention to personal protection when working in a harmful environment. Wait.

Non-Hodgkin's lymphoma complications Complications leukemia intestinal obstruction ascites uremia

Organ infiltration is more extensive, bone marrow and peripheral blood can be affected. The more frequently invaded sites are Wei's pharyngeal ring, gastrointestinal tract, testis and intra-abdominal lymphoid tissue, and often invade bone marrow tissue and leukemia-like blood changes, most common Complications include infection, fever, chest tightness, chest pain, short cough, shortness of breath, obstruction of swallowing, difficulty breathing, abdominal cramps, intestinal obstruction, jaundice, ascites, cirrhosis, renal pelvis and stagnant water, uremia, anemia, headache, visual impairment, etc. These are the clinical manifestations of NHL, but also its complications.

Symptoms of non-Hodgkin's lymphoma Common symptoms Bone pain, abdominal pain, increased intracranial pressure, mediastinal lymphadenopathy, weight loss, lymph node swelling, night sweats

The disease can be seen at any age, and the clinical manifestations can be summarized as follows:

1. Superficial lymph nodes or nodules, masses: the most common first clinical manifestations, accounting for 60% to 70% of all cases, especially cervical lymphadenopathy (49.3%), followed by armpits, Inguinal lymph nodes (12.9%, 12.7%), lymph nodes vary in size, often asymmetrical, solid and elastic, and no tenderness. In low-grade lymphoma, lymph nodes are mostly scattered, non-adhesive, and easy to move. Multiple lymph nodes, but invasive or highly aggressive lymphoma, rapid progression, lymph nodes often fuse into a mass, sometimes adhesion to the basal and skin, and may have local soft tissue infiltration, compression, edema performance.

2. Deep lymph nodes in the body: the corresponding symptoms caused by infiltration, compression, obstruction or tissue destruction due to their occurrence in different parts. For example, mediastinum, hilar lymph node mass can cause chest tightness, chest pain, difficulty breathing, Clinical manifestations such as superior vena cava compression syndrome, intra-abdominal (mesomembranous lymph nodes, retroperitoneal lymph nodes) mass, can cause abdominal pain, abdominal mass, intestinal obstruction, ureteral obstruction, renal effusion and other performance.

3. Hyperplasia and mass of extranodal lymphoid tissue: It can also cause corresponding symptoms due to different parts. At the time of initial diagnosis, it is only characterized by extranodal lesions, and no superficial lymph node enlargement accounts for 21.9%. Extranodal lesions are most common with pharyngeal ring. Common, manifested as tonsil tonsil or pharyngeal mass, gastrointestinal submucosal lymphoid tissue can be violated and cause abdominal pain, abdominal mass, gastrointestinal obstruction, hemorrhage, perforation, etc., the liver may be swollen when invaded by lymphoma Large, 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 brain is violated, Can cause headache, visual impairment and other symptoms of increased intracranial pressure, lesions can also oppress the peripheral nerve-induced neural crest, such as facial nerve spasm, can also invade the spinal canal, causing spinal cord compression and paraplegia, some types of non-Hodgkin's lymphoma , especially T-cell lymphoma, easy to have skin infiltration, nodules or tumors, mycosis fungoides and Sézary syndrome are special types of cutaneous T-cell lymphoma, and there is a type of extranodal lymphoma Adenoma, a nasal and nasal type of NK/T-cell lymphoma, has been called "neutral necrotic granuloma", "central vascular lymphoma", the most common starting site in the clinic is the nasal cavity, followed by the ankle, nose. Pharynx 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. Tissue type lymphoma 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), but 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 body weight common in the late stages of the disease Decreased, sometimes it is difficult to distinguish whether it is the clinical manifestation of the disease, or the consequences of long-term treatment (chemotherapy, radiotherapy), or combined infection due to impaired advanced immune function.

Non-Hodgkin's lymphoma examination

Laboratory inspection

1. Peripheral blood: early patients with more normal blood, secondary autoimmune hemolysis or tumor involving bone marrow can cause anemia, thrombocytopenia and hemorrhage, about 9% to 16% of patients can develop leukemia, common in diffuse small lymphocytes Lymphoma, follicular lymphoma, lymphoblastic lymphoma and diffuse large cell lymphoma.

2. Biochemical examination: there may be erythrocyte sedimentation rate, serum lactate dehydrogenase, 2-microglobulin and alkaline phosphatase increased, monoclonal or polyclonal immunoglobulin increased, the above changes can often be used as tumor burden and disease detection indicators .

3. ESR: ESR increases in the active phase, and the remission period is normal. It is a simple method for determining the remission period and the activity period.

4. Pathological biopsy: It is the main basis for the diagnosis of MHL and pathological types. The disease can only be diagnosed by histological examination of the excised tissue. The general diagnostic criteria for histology is the destruction of the structure of normal lymph nodes, as well as the envelope and Adjacent fat is invaded by typical tumor cells.

5. Immunological phenotypic detection: monoclonal antibody immunophenotyping can identify the cell lineage and differentiation level of lymphoma cells, and commonly used monoclonal antibody markers including diagnosis and typing include CD45 (white blood cell common antigen) for identification. Its leukocyte origin; CDl9, CD20, CD22, CD45RA, CD5, CD10, CD23, immunoglobulin light chain and are used to identify B lymphocyte phenotype; CD2, CD3, CD5, CD7, CD45RO, CD4, CD8, etc. Identification of T lymphocyte phenotype; CD30 and CD56 were used to identify anaplastic large cell lymphoma and NK cell lymphoma, respectively, CD34 and TdT are common in lymphoblastic lymphoma phenotype, immune peroxidase test: determination of white blood cell common antigen ( CD45) exists and excludes metastatic cancer. This method can be used on fixed tissues to determine leukocyte common antigen. Most surface markers can also be examined on fixed tissues using immunoperoxidase method, however gene rearrangement and cells Genetic testing requires fresh tissue.

6. Genetics: 90% of non-Hodgkin's lymphomas have non-random karyotype abnormalities, usually chromosomal translocations, partial deletions and amplifications, etc. Different types of non-Hodgkin's lymphomas have According to their respective cytogenetic features, non-Hodgkin's lymphoma is a monoclonal malignant proliferation that occurs in a single parental cell. The gene rearrangement of tumor cells is highly consistent. IgH gene rearrangement is often used as a gene marker for B cell lymphoma, TCR . Or gene rearrangement is often used as a genetic marker for T-cell lymphoma, and the positive rate can reach 70%-80%. Cytogenetics and gene markers can be used for the diagnosis, classification and microscopic lesions of non-Hodgkin's lymphoma. Detection.

7. Bone marrow: early normal, bone marrow can change when the bone marrow is infiltrated in the late stage. If lymphoma cells are found, it can be called lymphoma leukemia.

.Film degree exam

1 chest radiograph lateral position, abdominal pelvic CT scan, chest CT scan, total gastrointestinal angiography, MRI, brain, spinal MRI.

2.B super-thoracic, abdominal B-ultrasound, lymph node B-ultrasound.

3. Bone scan.

4. Lymphangiography.

5. Gastrointestinal examination.

Diagnosis and identification of non-Hodgkin's lymphoma

diagnosis

1. The diagnosis of this disease depends on histological biopsy (including immunohistochemistry and molecular cytogenetic examination). These histology, immunology and cytogenetic examination can not only confirm the NHL, but also make a classification diagnosis. It is important to understand the malignancy of the disease, to estimate the prognosis and to choose the right treatment.

Any lymph node with no obvious infection should be considered. If the swollen lymph nodes are full, tough and so on, the disease should be considered. Sometimes the swollen lymph nodes can be temporarily prevented by anti-inflammatory measures. Smaller, and then grow up again; some patients with superficial lymph nodes are not large, but more prolonged fever, night sweats, weight loss and other symptoms, after a period of time can be characterized by para-aortic lymphadenopathy.

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, including the differentiation of pseudolymphoma caused by phenytoin. The diagnosis of NHL depends on biopsy of the diseased lymph nodes or related tissues. The pathological diagnosis should include at least two parts, namely histological classification. And the immunophenotype of tumor cells, if necessary, immunoglobulin and T cell receptor gene rearrangement analysis, as well as cytogenetic testing, the usual diagnostic criteria for the destruction of the structure of normal lymph nodes, and Membrane and adjacent fat are invaded by typical tumor cells. Phenotypic examination can determine the source of the cell and its subtypes, help to determine the prognosis, and may also be valuable for determining treatment options. By immunoperoxidase test (usually used for Differential diagnosis of differentiated malignant tumors) Determination of the presence of white blood cell common antigen (CD45), excluding metastatic cancer. This method can be used on fixed tissues to determine white fine Cellular public antigens. Most surface markers can also be examined on fixed tissues using the immunoperoxidase method. However, genetic rearrangements and cytogenetic examinations require fresh tissue.

Differential 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, as specified below:

1. Chronic lymphadenitis: general chronic lymphadenitis has infections, in acute infections, such as athlete's foot infection, can cause ipsilateral inguinal lymphadenopathy, or with red, swollen, hot, pain and other acute manifestations, or Only lymph nodes with pain, after the acute phase, the lymph nodes shrink, the pain disappears, usually the lymph nodes of chronic lymphadenitis are small, about 0.5 ~ 1.0cm, the texture is soft, flat, more active, and the lymph nodes of malignant lymphoma It has the characteristics of large, fullness and toughness, and the biopsy is removed if necessary.

2. Acute suppurative tonsillitis: In addition to different degrees of fever, tonsils are mostly bilateral, red, swollen, painful, and have attached pus moss, the texture of the sputum is soft, after inflammation control, tonsils can be Narrowing, and malignant lymphoma invading the tonsils, can be bilateral or unilateral, or asymmetrically swollen, the texture of the sputum is hard, tough, and later involved the surrounding tissue, suspicious when the tonsillectomy or biopsy pathology Histological examination.

3. Lymph node tuberculosis: for special 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. and malignant lymphoma is not easy The difference is that the lymph nodes of the lymph node tuberculosis are swollen, the quality is hard, the surface is not smooth, the texture is uneven, or it is cystic due to caseous necrosis, or adhesion to the skin, the activity is poor, and the PPD test is positive.

However, it should be noted that patients with malignant lymphoma may have tuberculosis, which may be due to the long-term anti-tumor treatment, the body's immunity is reduced, and thus suffering from tuberculosis and other diseases, so the clinical should be vigilant. When the condition changes, it should be obtained again. Pathological or cytological evidence to avoid misdiagnosis and mistreatment.

4. Sarcoidosis: more common in adolescents and middle-aged people, more invasion of lymph nodes, multiple lymph nodes, common in the hilar lymph node symmetry enlargement, or involvement of paratracheal and supraclavicular lymph nodes, lymph nodes more than 2cm in diameter Within the texture, the texture is generally hard, may also be associated with long-term low fever, the diagnosis of sarcoidosis requires biopsy, epithelioid nodules can be found, Kvein test is 90% positive in sarcoidosis, angiotensin-converting enzyme in nodules The lymph nodes and serum of the patients were elevated.

5. Histiocytic necrotizing lymphadenitis: The disease is more common in China, mostly young and middle-aged, clinical manifestations of persistent high fever, but the number of peripheral white blood cells is not high, with antibiotic treatment is ineffective, similar to malignant reticulosis, tissue Lymph node enlargement of cellular necrotizing lymphadenitis, more common in the neck, more than 1 ~ 2cm in diameter, moderate or soft, different from the lymph nodes of malignant lymphoma, confirmed lymph node biopsy, the disease after several weeks Its getting hotter.

6. Central lung cancer invades the mediastinum, thymic tumor: sometimes confused with malignant lymphoma, the diagnosis depends on the tumor biopsy.

7. Identification of Hodgkin's lymphoma The clinical manifestations of non-Hodgkin's lymphoma are very similar to those of Hodgkin's lymphoma. In fact, it is difficult to make a clear differential diagnosis from clinical manifestations, only histopathological examination will be The two clearly distinguish the diagnosis, but there are some different manifestations in the clinical.

Must also 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) ), as well as other diseases that cause lymphadenopathy, including the identification of pseudolymphoma caused by phenytoin.

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