Malignant lymphoma

Introduction to malignant lymphoma 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. Mainly manifested as painless lymphadenopathy, hepatosplenomegaly, all organs and organs of the body can be affected, with fever, night sweats, weight loss, itching and other systemic symptoms. basic knowledge The proportion of illness: 0.003% Susceptible people: no specific people Mode of infection: non-infectious Complications: anemia, abdominal pain

Cause of malignant lymphoma

Virus factor (30%):

Human lymphoma is the first to be confirmed that Burkitt lymphoma is associated with EB virus infection. In Central Africa, this 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 local children's tumors, only 5%. The patient is over 20 years old and has sporadic patients in other parts of the world, but it is a rare case. It has been proven by cell biology techniques that the genome of Epstein-Barr virus can be found in 98% of Burkitt's lymphoma, but it is distributed. Only 15% to 20% of Burkitt's lymphomas contain Epstein-Barr virus, and all of the Epstein-Barr virus antibody antigens in the endemic areas are positive, and the titer is high. The risk of such tumors in children with positive shell antigen is 30 in the control group. Times, infection with certain mites with Epstein-Barr virus can cause malignant lymphoproliferative lesions similar to Burkitt's lymphoma. Therefore, it is currently considered that this disease is a severe and persistent EB virus infection in African children in childhood, and immune function is inhibited. The oncogene is activated, leading to the malignant proliferation of B lymphocytes. It is currently believed that malaria transmitted by mosquitoes is only a cofactor, and malaria infection makes The reticular system changes, it is susceptible to the triggering of the virus, and the infection of B cells is controlled by T lymphocytes. The nuclear proteins (such as EBNA-2, EBNA-3) and membrane proteins (such as LMP-1) can be used. Induction of 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 be followed. Coexisting or occurring in patients with previous 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 in mixed cell types. The relationship between lymphoma and Epstein-Barr virus in China is also highly valued. Due to the high infection area of Epstein-Barr virus in China, the infection rate of Epstein-Barr virus in 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 C-type RNA virus from a tumor of mycosis fungus, called T-cell leukemia lymphoma virus (HTLV-1). This is a very special retrovirus, the core is a single strand of RNA, the outer envelope, the virus has core protein, envelope protein and enzyme protein (including viral polymerase and reverse transcriptase) three structural proteins The AIDS virus (human acquired immunodeficiency virus, HIV), which was isolated from the French scholar Montagnier by Gall et al., has been isolated from tumor specimens of nearly 10 patients with T-cell lymphoma (HTLV). At the same time, according to the epidemiological investigation of adult T-cell lymphoma, Japanese scholars found that the incidence is high in the southern part of the four countries and Kyushu. The peak incidence is in the summer, and the patients are mostly engaged in agriculture and fisheries. And forestry, and often have poor nutrition conditions in the past and are susceptible to infection by tropical diseases. Considering that it is likely to be associated with viral and/or filariasis infections, they also independently isolated RNA viruses, called ATL. V, after studying ATLV and HTLV, is also a causative factor of adult T-cell lymphoma/leukemia, but through a large number of serological studies, China's T-cell lymphoma has no positive relationship with HTLV-1 (or ATLV). There are only 4 cases reported in China related to HTLV-1 (or ATLV).

The detailed mechanism of the virus causing lymphoma is not fully understood. The replication of the virus is related to the production of a retro-acting factor (tax), which induces the expression of the REL gene, which causes the cell to proliferate, and requires other factors to cause malignant transformation of the cell. Many people in the high-incidence area are infected with HTLV-1, but only a small number of T-cell lymphomas occur, so supporting host factors including genetic factors may have an important position.

Immunosuppression (30%):

The occurrence of lymphoma is closely related to immunosuppression. Because organ transplantation requires long-term medication to suppress the immune mechanism, the incidence of lymphoma is significantly higher than that of the general population, and there are more primary infections. A group of reports can be as high as 69%. In addition, the central nervous system is also invaded (28%) in patients with general lymphoma (1%). The immunosuppressive drugs used also have an effect on the occurrence of lymphoma. In the cyclophosphamide-based regimen, lymphoma accounts for 26% of primary cancers occur earlier, and only 11% of them use imamidine (azathioprine). In patients with anti-CD3 monoclonal antibodies, lymphoma accounts for 64% of the second primary cancer. %, another fact that has received extensive 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 rate is higher.

Bacterial infection (30%):

In recent years, it has been reported that Helicobacter pylori (Hp) can cause chronic gastritis, 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 have developed in recent years. Among the treatment specifications, antibiotic treatment has been the preferred method for mucosal-associated lymphoma (MALT), which is the first example of antibiotic treatment of tumors.

Environmental factors (5%):

In the early years of the United States, 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 paint vessels and veterans who have been exposed to fluoride. The incidence of lymphoma is also high, but very It is difficult to explain the mechanism. It is relatively certain that 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. They have received radiation in the clinic. And the chemotherapeutic HD patients have a significant increase in the second primary cancer, especially large cell lymphoma, and often invade the digestive tract.

Malignant lymphoma prevention

1 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.

Malignant lymphoma complications Complications, anemia, abdominal pain

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. .

Malignant lymphoma symptoms Common symptoms Lymphatic rupture fatigue Myelosuppression Low fever Liver function abnormalities Mediastinal lymph node hyperplasia Superficial lymph nodes Progressive swelling Hair scars

Partial performance

Clinically, most of the malignant lymphomas first invade the superficial and/or mediastinum, retroperitoneum, mesenteric lymph nodes, and a few can be primary in the extranodal organs. 5101 cases admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from 1958 to 1994 were diagnosed as malignant. Among the patients with lymphoma, the first site, it can be seen that the first episode of lymph node involvement is 69.6%. It is not difficult to diagnose 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, plump, general It has no adhesion to the skin, does not fuse with each other in the early and middle stages, and can be active. 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. Large, it is difficult to determine where the starting position.

(2) mediastinum: mediastinum is also one of the most common sites, most patients often have no obvious symptoms at the beginning, the mediastinal lymph nodes may be a single lymph node enlargement; or multiple lymph nodes may be merged into a giant mass; It is wavy and invades one side or both sides of the mediastinum. The latter is more common, and compression symptoms may occur in the late stage.

(3) Liver and spleen: Primary hepatic malignant lymphoma is rare. There are only a few reports 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, with the development of the disease, fatigue and anemia, generally with the progress of the disease, systemic symptoms can Exacerbation, there may be lymphopenia in these patients, mediastinal and retroperitoneal malignant lymphoma with fever, more itchy skin.

Sustained fever, excessive sweating, weight loss, etc. may indicate disease progression, failure of the body's immune function, and poor prognosis, but some patients have itchy skin, fever without a large mass, and rapidly improve after treatment. The prognosis is better.

(2) skin lesions: patients with malignant lymphoma may have a series of non-specific skin manifestations, the incidence rate is about 13% to 53%, common psoriasis-like papules, herpes zoster, systemic herpes-like dermatitis, pigmentation, scales and exfoliative dermatitis can also occur urticaria, nodular erythema, dermatomyositis, acanthosis, pigmented urticaria, etc. As for scratches and skin infections caused by itchy skin, it is more common, advanced malignant Lymphoma patients with low immune status, skin infections often break down, exudate, the formation of systemic scattered skin thickening, desquamation.

(3) Anemia: About 10% to 20% of patients with malignant lymphoma have anemia at the time of presentation, and may even occur in the first few months before lymphadenopathy. Patients with advanced disease are more likely to have anemia. Progressive anemia and ESR are clinical. An important indicator for 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. Etc., the nature of the lesion can be: 1 degeneration; 2 demyelination; 3 infectious; 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, malignant lymphoma can also occur Invasion of the brain parenchyma may be associated with cerebral hemo

Examination of malignant lymphoma

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. 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; CD19, 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. T lymphocyte phenotype was identified; CD30 and CD56 were used to identify anaplastic large cell lymphoma and NK cell lymphoma, respectively, and CD34 and TdT were common in lymphoblastic lymphoma phenotype.

4. 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.

5. Pathological examination: Malignant lymphoma should generally be confirmed by pathological examination. Because the morphology of the cells should not be observed under the microscope, and the structure and interstitial cell reaction of the entire lymph node should be observed, it is best to take a complete lymph node examination. As much as possible, do not take part of the lymph nodes.

For the same reason, needle biopsy sometimes has some reference value for diagnosis, but often does not provide enough material to make a comprehensive diagnosis. In addition, needle aspiration is easy to cause hematoma.

The possibility of malignant lymphoma should be emphasized in the following situations. It is best to take lymph nodes early for pathological examination.

(1) Progressive lymphadenopathy without clear cause: especially when the site, hardness, and activity are consistent with the characteristics of the aforementioned malignant lymphoma.

(2) "Lymph node tuberculosis", "chronic lymphadenitis" when the regular course of anti-tuberculosis or general anti-infective treatment is invalid.

(3) Although the lymph nodes and fever are repeated, the general trend is progressive.

(4) Unexplained long-term hypothermia or periodic fever should consider the possibility of malignant lymphoma: especially with itchy skin, sweating, weight loss, and the discovery of superficial lymphadenopathy, especially on bilateral trochlear lymphadenopathy. Time.

Note when taking lymph node biopsy:

1 Because the general patient often has individual parts such as groin, submandibular and other lymph node inflammation, so when choosing lymph nodes, it should be taken faster, the texture is tough and full, in line with the characteristics of malignant lymphoma, the part is neck, underarm and It is better on the trolley.

2 should try to avoid extrusion.

3 should be fixed as soon as possible after removal.

4 If necessary, several parts can be taken from different parts.

5 If the inguinal lymph nodes are taken, the contrast agent should have an effect on the lymph nodes before lymphography.

6 If there are several lymph nodes in a lymphatic area, larger ones should be selected, but sometimes large lymph nodes often have central necrosis.

6. ESR: The active period increases and the remission period is normal. It can often be used to determine the remission and active phases of malignant lymphoma.

Film degree exam

1. X-ray examination: X-ray examination often has important reference value for the diagnosis of malignant lymphoma. For patients considering malignant lymphoma, the routine X-ray examination is performed including the posterior anterior and lateral slices of the chest. If necessary, with tomography, the main purpose is to observe the hilar, mediastinum, tracheal carina and internal milk chain lymph nodes, as well as to observe the presence or absence of invasion in the lungs, lymphography of the lower extremities to determine whether the pelvic and retroperitoneal lymph nodes are invaded. It is an indispensable basis for clinical staging. In addition, according to clinical symptoms and signs, it is possible to photograph the skeletal phase of suspected invaded sites, gastrointestinal barium examination, inferior vena cava angiography and intravenous pyelography, combined with the patient's age and clinical manifestations. And experimental results, for the bone, digestive tract, mediastinum and urinary tract malignant lymphoma often lead to a preliminary diagnosis.

2. CT, MRI, B-ultrasound is very helpful for the detection of lesions in the mediastinal retroperitoneum and other hidden parts.

Diagnosis and differentiation of malignant lymphoma

Diagnosis can be based on medical history, clinical symptoms, and laboratory tests.

diagnosis

1. Diagnostic criteria: The diagnosis of lymphoma is based on pathological examination.

Reed-Sternberg cells are characteristic of HL. RS cells originate from B cells. They 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 depends on pathological examination, and obtaining adequate 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.

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.

Differential diagnosis

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: more obvious infections, and often focal lymphadenopathy, pain and tenderness, generally not more than 2 ~ 3cm, can be reduced after anti-infective treatment, clinically misdiagnosed as malignant lymphoma Some children have repeated tonsillitis episodes, due to bacteremia caused by superficial lymphadenopathy, the palpation of the tonsils is often softer than the malignant lymphoma invading the tonsils, sometimes extruding pus, these children The lymph nodes are often swollen by fever, and shrink after heat retreat. They can exist for many years without development, but these can not be regarded as absolute. Some malignant lymphomas, especially HD, may also have periodic fever and lymph node enlargement. Large, narrowed history, so it should be considered comprehensively.

Because many people suffer from athlete's foot, inguinal lymphadenopathy, especially the long-standing and unchanged flat lymph nodes, there is no significant significance, but there is no obvious cause of bilateral trochlear or neck, supra-sacral lymph nodes, should pay attention to 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: an unexplained lymph node enlargement, mainly invading the thoracic cavity, with the most mediastinum, and can also invade the hilum and lung. Other affected parts have neck and retroperitoneum. , pelvic cavity, armpit and soft tissue, patients often with lumps as their signs, those in the chest can appear compression symptoms, but often found, there are fever, anemia and plasma protein increased systemic symptoms, after the tumor is removed, the symptoms disappear It is sometimes difficult to distinguish from malignant lymphoma and lung lesions based on X-ray examination. Gallium (Ga) scan 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.

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