Gastric malignant lymphoma

　　Gastric malignant lymphoma is related to viral infection, and Helicobacter pylori infection plays an important role in its occurrence. The specific causes and mechanisms will be described as follows.

　　The causes of gastric malignant lymphoma

　　The etiology of gastric malignant lymphoma is still unclear. Some scholars believe that it may be related to the infection of certain viruses; it has been found that patients with malignant lymphoma have a low level of cellular immune function, so it is speculated that under the infection of certain viruses, there may be a disorder and imbalance in cellular immune function, leading to the onset of the disease. In addition, gastric lymphoma originates from the submucosal or固有lymphatic tissue, which is not exposed to the gastric cavity and does not come into direct contact with carcinogens in food. Therefore, its etiology is different from that of gastric cancer, and it is more likely related to systemic factors causing atypical hyperplasia of local gastric lymphatic tissue.

　　In recent years, the relationship between gastric malignant lymphoma and Helicobacter pylori (Hp) infection has received extensive attention. Parsonnet et al. found that the HP infection rate in patients with gastric malignant lymphoma, including gastric mucosa-associated lymphoid tissue (MALT), was 85%, while in the control group it was only 55%, suggesting that HP infection is associated with the occurrence of gastric lymphoma. Clinical microbiological and histopathological studies have shown that the acquisition of gastric mucosal MALT is due to the body's immune response after HP infection. The chronic infection state of HP stimulates the aggregation of mucosal intraepithelial lymphocytes, leading to a series of autoimmune reactions that activate immune cells and their active factors such as IL-2, causing the hyperplasia of lymphoid follicles in the gastric mucosa, laying the foundation for the occurrence of gastric lymphoma. The occurrence of MALT is related to HP infection, and eradication of HP treatment can cause MALT regression, which has attracted people's attention. Bayerdorffer E et al. reported that in 33 patients with primary low-grade malignant MALT lymphoma and Hp gastritis, radical HP treatment was performed, and the results showed that more than 80% of the patients had complete disappearance of the tumor after eradication of HP infection. However, advanced tumors or those that migrate to high-grade malignancy do not respond to the cure of HP infection, which further suggests that the development of primary low-grade malignant MALT lymphoma may be related to HP chronic infection. However, the long-term efficacy of HP eradication treatment for gastric MALT lymphoma still requires long-term follow-up studies, and the relationship between low or absent gastric acid and gastric lymphoma remains uncertain.

　　2.of gastric malignant lymphomaPathogenesis

　　Gastric malignant lymphoma can occur at any part of the stomach, most commonly in the gastric body and antrum, the lesser curvature and posterior wall. The lesions are usually large, sometimes showing multicentricity. They often start localized to the mucosa or submucosa and can gradually extend to the duodenum or esophagus on both sides, and can also gradually involve the entire gastric wall layer by layer and adjacent surrounding organs, often accompanied by perigastric lymph node metastasis, and there can be significant regional lymph node enlargement due to reactive hyperplasia.

　　1. Gross morphological characteristics It is difficult to distinguish from gastric cancer by gross examination. Friedma classified the gross morphology of primary gastric lymphoma into the following types:

　　(1) Ulcerative type This is the most common type. Lymphoma can present with multiple ulcers, which are relatively superficial, with diameters ranging from several centimeters to more than ten centimeters. The bottom of the ulcer is uneven, and there may be grayish yellow necrotic material covering it, with elevated and hard edges, and the surrounding folds thickened and thickened, appearing radiating.

　　(2) Infiltrative type The gastric wall shows localized or diffuse infiltration and hypertrophy, with thickened and prominent folds, and the gastric glands increase in size and appear granular. The mucosa and submucosa are extremely thickened, becoming grayish white, and the muscular layer is often infiltrated and separated, even destroyed, and the subserosal layer is often involved as well.

　　(3) Nodular type The gastric mucosa has multiple scattered small nodules with a diameter of half a centimeter to several centimeters. The mucosal surface usually has superficial or deep ulcers. The gastric mucosal folds between the nodules are often thickened, and the nodules are located between the mucosa and submucosa, often extending to the serosal surface, appearing grayish white, indistinct, thickened, and even forming large folds.

　　(4) Polypoid type Less common. Form limited masses under the gastric mucosa, protruding into the gastric cavity as polypoid or mushroom-like.

　　(5) Mixed type In a single case specimen, two or three types of lesion forms exist simultaneously.

　　2. Histological characteristics

　　(1) High differentiation lymphocyte type:Maturation of lymphocytes proliferation, usually without the histological characteristics of malignant cells.

　　(2) Low differentiation lymphocyte type:Lymphocytes show varying degrees of immaturity.

　　(3) Mixed cell type:Contains lymphocytes and histiocytes, and these tumors are usually nodular.

　　(4) Histiocytic type:Tumor proliferation with differentiation and maturation of histiocytes at different stages.

　　(5) Undifferentiated type:Tumor proliferation of primitive reticulum cells without obvious differentiation into tissue cells or lymphocyte systems.

　　3. Pathological histological classification

　　(1) Histological classification:Gastric malignant lymphoma is mainly divided into 3 types, namely lymphosarcoma, reticulum cell sarcoma, and Hodgkin's disease. Lymphosarcoma is the most common.

　　(2) Immunological classification (luke sand collins):Malignant lymphoma is divided into U cell type (non-B non-T cells, i.e., undetermined cells), T cell type, B cell type, and M cell type (monocytes, histiocytes). Most non-Hodgkin's lymphomas belong to the B cell type, and most low-grade malignant non-Hodgkin's lymphomas also belong to the B cell type; T cell type is mostly highly malignant and highly invasive, and Hodgkin's disease is mostly of this type; U cell type has a higher degree of malignancy and is insensitive to chemotherapy.

　　4. Clinical staging:Determining the clinical stage of gastric malignant lymphoma is of great significance for selecting treatment plans and predicting the prognosis of patients.

　　Gastric malignant lymphoma can cause abdominal pain, distension, intestinal obstruction, and bleeding due to gastrointestinal infiltration. When the tumor invades the mucosa, it can cause erosion, ulceration, hemorrhage, or perforation. Malignant lymphoma lacks fibrous components, is soft in texture, and is not easy to cause obstruction even when the tumor is large.

　　Gastric malignant lymphoma mainly manifests as symptoms such as abdominal pain, weight loss, vomiting, anemia, etc. The most common signs are tenderness in the upper abdomen and abdominal masses. The specific symptoms and weight changes are described as follows.

　　Firstly,of gastric malignant lymphomaSymptoms

　　1. Abdominal pain:The most common symptom of gastric malignant lymphoma is abdominal pain. Data show that the incidence of abdominal pain is over 90%. The nature of the pain is not fixed, ranging from mild discomfort to severe abdominal pain. There are even cases where patients seek medical attention due to acute abdomen. The most common are dull pain and distension, which can be exacerbated by eating. The initial impression is usually peptic ulcer disease, but antacids often cannot alleviate the pain, and the abdominal pain may be caused by primary injury to the surrounding nerves or compression by enlarged lymph nodes due to malignant lymphoma.

　　2. Weight loss:About 60% of cases are caused by the extensive consumption of nutrients by tumor tissue and a decrease in appetite for intake, with severe cases presenting as cachexia.

　　3. Vomiting:Related to incomplete pyloric stenosis caused by tumors, with lesions in the antrum and prepyloric area more prone to occur.

　　4. Anemia:More common than gastric cancer, it may sometimes be accompanied by hematemesis or melena.

　　2.of gastric malignant lymphomaSigns

　　Upper abdominal tenderness and abdominal mass are the most common signs of the disease. In cases with metastasis, liver and spleen enlargement may occur, and a small number of patients may have no signs at all.

　　The misdiagnosis rate at the initial clinical diagnosis is very high, with literature reports reaching over 80%, and the main reasons are mainly two:

     1. The incidence of the disease is low, which leads to a lack of sufficient vigilance among clinicians.

     2. There are not many specific signs in clinical manifestations and auxiliary examinations.

　　Gastric malignant lymphoma is mainly prevented by vaccination against viral infection, and daily living habits are also crucial for the prevention of the disease. The specific preventive and control measures are as follows:

　　1. Prevent virus invasion

　　By taking measures such as vaccination (such as hepatitis vaccine), promoting sleep, and frequent exercise, a defense line can be established in the body to prevent any opportunity for virus invasion.

　　2. Strengthen the body's immune system

　　Eat well three meals a day, consume enough nutrients related to immunity, prevent malnutrition; take reasonable medication and try to avoid drugs that damage the immune system, such as antibiotics and corticosteroids.

　　3. Pay attention to food hygiene

　　Do not eat moldy food, eat less preserved, fried, and high-fat foods, quit smoking (including second-hand smoke), and drink moderately, but never overdo it.

　　4. Purify the environment

　　Home decoration should strive for environmental protection, use mobile phones and computers correctly, and control ionizing radiation within the permitted range.

　　5. Avoid harmful chemicals

　　If hair dyes are not used or used less, and fruits and vegetables are treated to remove pesticides and other anti-pollution treatments.

　　6. Moderate sunbathing

　　Sunbathing has a significant preventive effect on lymphoma, but it should not be overexposed, otherwise it may trigger the possibility of skin cancer.

　　7. High-risk groups

　　If there are genetic factors or the elderly and weak, it is advisable to eat some anti-malignant lymphoma foods and alkaline foods with high alkaline content.

　　Gastric malignant lymphoma is less common, and its history and symptoms are lacking in specificity, making diagnosis quite difficult. Once diagnosed, the lesion is often large. The time from onset to diagnosis in patients with primary gastric lymphoma is usually long, with literature reporting that about 50% of patients exceed 6 months, and about 25% exceed 12 months. Although diagnosis is difficult, it is still possible to make a correct diagnosis in time through careful examination and analysis. The main examination methods for the diagnosis of gastric lymphoma at present include:

　　1. Histopathological examination and immunohistochemical examination

　　1. Gross morphology

　　Gastric malignant lymphoma is divided into ulcerative type, multiple nodular type, polypoid type, and mixed type, which is difficult to distinguish from gastric cancer. In advanced cases, there are huge gyral changes, similar to hypertrophic gastritis.

　　2. Histological type

　　Most primary gastric lymphomas are non-Hodgkin lymphoma, with B-cell and T-cell lymphomas being rare, and Hodgkin's disease is rare.

　　3. Degree of differentiation

　　Primary gastrointestinal B-cell lymphoma is most commonly associated with mucosa-associated tissue (MALT) lymphoma, which is further divided into low-grade and high-grade subtypes.

　　(1) B-cell low-grade malignant MALT lymphoma:

　　① The tumor is mainly composed of centrocyte-like cells (CLL). The tumor cells are moderately small, the nuclei are slightly irregular, the chromatin is relatively mature, the nucleoli are not obvious, and they resemble small cleaved cells.

　　② Tumor cells invade and destroy the covering epithelial cells and glandular epithelial cells, forming mucosal epithelial damage.

　　③ Common lymphoid follicle structure or reactive lymphoid follicles are found within the tumor, tumor cells infiltrate the lamina propria, submucosa, and muscularis, and often involve mesenteric lymph nodes.

　　④ Immunohistochemistry shows that CD21, CD35, CD20, bcl-2 are often positive, CD5, CD10 are negative, and low-grade malignant MALT lymphoma must be differentiated from benign gastric lymphoid tissue proliferation first. Benign lymphoid tissue proliferation often contains other inflammatory cells in addition to mature lymphocytes, often showing lymphoid follicles with germinal centers, often with fibrous connective tissue proliferation, local lymph nodes show no lymphoma changes, and immunohistochemistry shows polyclonal lymphocyte components.

　　(2) B-cell high-grade malignant MALT lymphoma:In low-grade malignant MALT lymphoma, there are relatively obvious high-grade transformation foci, which are manifested as enlargement of tumor cells, irregular increase of nuclei, and transformed lymphocyte-like cells (centroblasts) with nucleoli, frequent nuclear division, or Reed-Sternberg-like cells may be seen.

　　Two: X-ray Barium Examination

　　X-ray barium examination is the main method for diagnosing gastric lymphoma, although X-ray examination often cannot provide a clear diagnosis of malignant lymphoma, but for more than 80% of gastric lesions, a diagnosis of malignant lesions can be made through this examination, thus further examination can be conducted.

　　The manifestation of gastric malignant lymphoma under X-ray barium examination is often non-specific. It often involves most of the stomach and grows in a diffuse and infiltrative pattern, often accompanied by ulcer formation. If there are multiple irregularly shaped circular filling defects in the X-ray findings, resembling pebble-like changes, then there is a relatively definite diagnostic value. In addition, the following signs should also be considered as possible gastric lymphoma: multiple malignant ulcers; large and shallow ulcers on the posterior wall of the stomach, on the greater curvature; extremely hypertrophied mucosal folds around filling defects or shadowy defects; thickened, rigid gastric wall, but peristalsis can still pass through; large mass, slight change in gastric shape, but does not cause obstruction; tumor extension beyond the pylorus to involve the duodenum.

　　Three: Fiberoptic Endoscopic Examination

　　To clearly diagnose lymphoma before surgery, fiberoptic gastroscopy is increasingly widely used. The macroscopic types of gastric lymphoma observed by gastroscopy often resemble gastric cancer, making it difficult to make a diagnosis based on the gross appearance of these tumors, and a definitive diagnosis still relies on biopsy. If the lesion is submucosal, it is difficult to obtain positive tissue samples from the tumor below the mucosa, so the positive rate of biopsy is often not as high as that of gastric cancer. Under gastroscopy, gastric malignant lymphoma can be seen to have hypertrophy of mucosal folds and edema, or multiple superficial ulcers, which must be differentiated from hypertrophic gastritis and early gastric cancer with concave lesions. Sometimes, certain ulcerative malignant lymphomas can heal temporarily and be difficult to distinguish from gastric ulcer disease, if the malignant lymphoma presents as ulcerative lesions, then a definitive diagnosis can be obtained by direct cell brush technique or by directly snipping the tumor tissue for biopsy.

　　4. Endoscopic ultrasound examination

　　Endoscopic ultrasound can clearly display the various layers of the gastric wall, thus seeing the infiltration situation of gastric lymphoma. This technology can reach a sensitivity of 83% and a positive rate of 87% in the examination of upper gastrointestinal malignant tumors, and can also clearly determine the situation of lymph node metastasis around the stomach.

　　5. Gray-scale ultrasound and CT examination

　　It can be seen that the gastric wall is thickened in nodular form, which can determine the location, extent, and response to treatment of the lesion. Ultrasound examination of gastric lymphoma that presents as an abdominal mass can assist in diagnosis.

　　Gastric malignant lymphoma should eat more light, easy-to-digest foods, and pay attention to cleanliness and hygiene in daily life. The specific description is as follows:

1. Diet for gastric malignant lymphoma

　　1. Diet should be light

　　Patients with gastric malignant lymphoma should persist in eating light, easy-to-digest, and nutritious foods, and they should also pay attention to a reasonable diet, balanced allocation, attention to the mix of meat and vegetables, coarse and fine, and the more food varieties, the better.

　　2. Stay away from spicy foods

　　Do not drink stimulant drinks, and avoid eating large amounts of spicy foods such as scallions, garlic, ginger, cinnamon, and other pungent and刺激性 foods, as well as greasy, fried, moldy, preserved foods, and foods such as rooster and pork head meat, and seafood.

　　2. Daily precautions for gastric malignant lymphoma

　　1. Pay attention to living habits, create a suitable living environment, engage in moderate exercise, and avoid overexertion.

　　2. Keep the skin clean, wash with warm water every day.

　　3. Avoid cold, greasy, and spicy foods, and quit smoking and drinking.

　　For primary gastric lymphoma, comprehensive treatment should be adopted with surgical resection as the main approach. The specific methods are briefly described as follows.

　　1. Treatment of gastric malignant lymphoma

　　The resection rate and 5-year survival rate after surgery for primary gastric lymphoma are better than those for gastric cancer, and it also has a good response to radiotherapy and chemotherapy. Therefore, comprehensive treatment should be adopted for primary gastric lymphoma, with surgical resection as the main approach.

　　Due to the lack of specific clinical signs of primary gastric lymphoma, the accuracy of preoperative diagnosis and intraoperative judgment is relatively low. The diagnosis is mainly confirmed by biopsy during surgical exploration, and the clinical stage is determined according to the size and extent of the lesion, in order to further select a reasonable and appropriate treatment plan.

　　1. Surgical treatment:The surgical principles are basically similar to those for gastric cancer. Most scholars hold a positive attitude towards the resection of primary gastric lymphoma.

　　For lesions in stages I and II1E, surgical treatment is the main approach due to the localized nature of the lesions. The goal is to achieve radical resection of the primary tumor and adjacent regional lymph nodes, followed by adjuvant chemotherapy or radiotherapy to achieve cure. For patients in stages II2E, IIIE, and IV, combined chemotherapy and radiotherapy are the main treatments. If the patient's condition permits, it is advisable to remove the primary tumor as much as possible to improve the effectiveness of postoperative chemotherapy or radiotherapy and to avoid complications such as bleeding or perforation caused by it.

　　The extent of gastric resection for gastric lymphoma should be determined according to the size, location, and macroscopic morphological characteristics of the lesion. Generally, subtotal gastrectomy is performed for polyps or nodular masses limited to the gastric wall. Sometimes, the boundary of localized lymphoma may be difficult to identify, so it is necessary to perform frozen section examination of the distal and proximal margins of the resected specimen during surgery. If there is tumor in the biopsy, a more extensive resection is required. If the tumor invades or extends over a wide range, the boundary is unclear, or there are multiple foci in the gastric wall, total gastrectomy should be performed. For cases suspected of malignant lymphoma before or during surgery, even if the tumor is large or there is adhesion around it, surgery should not be easily abandoned. Biopsy can be performed during surgery, and if it is confirmed to be malignant lymphoma, efforts should be made to resect it, as it is technically possible and often achieves good efficacy. Even for tumors that require total gastrectomy, the 5-year survival rate can still reach 50%.

　　Gastric malignant lymphoma can cause serious complications such as obstruction, bleeding, and perforation. If radical resection is not possible, palliative resection should be attempted; the success rate of palliative resection for inoperable cases is about 50%. Palliative resection not only helps prevent or alleviate complications but also the residual metastatic tumors may have the potential to regress naturally. There are also reports that radiotherapy can be used as an adjuvant after palliative resection, and some cases can still achieve long-term survival, therefore, palliative resection for gastric malignant lymphoma should be more aggressive than for gastric cancer. For cases where palliative resection cannot be performed, tumor localization can be performed during surgery, followed by postoperative radiotherapy, which often achieves certain efficacy. Lymph node metastasis is the main route of metastasis for gastric lymphoma, accounting for about 50%, so corresponding regional lymph nodes should be removed during radical surgery.

　　2. Radiotherapy:Considering the radiosensitivity of lymphoma, radiotherapy is usually used as adjuvant treatment after surgery or as treatment for advanced lesions that cannot be resected. There is a divergence of opinions on the value of postoperative radiotherapy. Some scholars advocate that radiotherapy should be limited to inoperable lesions, postoperative residual or recurrent tumors. While others insist that postoperative radiotherapy should be given regardless of whether the tumor or lymph node metastasis occurs, arguing that surgeons cannot accurately estimate the presence or extent of lymph node metastasis during surgery. In summary, the success of radiotherapy depends on precise localization and staging of the lesion. The general dose of radiation is 40 to 45 Gy, while the dose for the adjacent areas invaded by the tumor is 30 to 40 Gy.

　　3. Chemotherapy:Primary gastric lymphoma is different from gastric cancer, and its sensitivity to chemotherapy is well known. Chemotherapy can be used as an adjuvant treatment after surgery to further consolidate and improve the efficacy. It is usually used to treat malignant lymphoma with combined chemotherapy methods. Commonly used and effective combined chemotherapy regimens include MOPP, COPP, and CHOP, among others. In recent years, a considerable number of combined chemotherapy regimens have been used in clinical or clinical experimental treatments, in addition to MOPP and other regimens, mainly including ABVD, CVB, SCAB, VABCD, M-BACOD, and so on. It is reported that all of them have achieved a high 5-year survival rate.

　　Before chemotherapy, a reasonable treatment plan should be formulated on the basis of a comprehensive understanding and analysis of the pathological type of the disease, the clinical stage, the extent of the lesions, and the overall condition of the body, in order to increase the efficacy, prolong the remission period, and the tumor-free survival period.

　　(1) MOPP regimen:

　　M Mustard 6mg/m2 and vincristine 1.4mg/m2 are administered intravenously on the first and eighth days.

　　Procarbazine (methylbenzhydrazine) 100mg/m2 and prednisone 40mg/m2 are taken orally from the first to the fourteenth day, once a day.

　　Every 28 days is a cycle, and it is used for more than 6 cycles. Prednisone (Prednisone) is only given in the first, third, and fifth cycles.

　　(2) COPP regimen:

　　Cyclophosphamide 650mg/m2 and vincristine 1.4mg/m2 are administered intravenously on the first and eighth days.

　　Procarbazine 100mg/m2 and prednisone 30mg/m2 are taken orally for 14 consecutive days.

　　Every 28 days is a cycle, with a total of 6 cycles.

　　(3) CHOP regimen:

　　Cyclophosphamide 500mg/m2, doxorubicin (adriamycin) 40mg/m2, and vincristine 1.4mg/m2 are administered intravenously on the first day. Prednisone 30mg/m2 is taken orally from the first to the fifth day.

　　Every 21 days is a cycle, with a total of 6 cycles.

　　Second, the Prognosis of Gastric Malignant Lymphoma

　　The prognosis of gastric malignant lymphoma is related to the clinical stage of the tumor (specifically including the size of the tumor, the extent of infiltration, the degree of lymph node metastasis, and whether there is distant metastasis), the pathological type of the tumor, and the treatment method.

　　Generally, the relationship between the clinical stage of the tumor and the prognosis is closer than that of the tumor's histological type. The 5-year survival rate of patients in the IIE stage is more than 75%, the IIIE stage is about 50%, the IIIIE stage is about 31%, and the IV stage is about 27%.

　　The size of gastric malignant lymphoma is also related to the prognosis. For tumors with a diameter of 5 to 8 cm, 80% can be cured, and the cure rate decreases as the tumor size increases. For tumors larger than 12 cm, the cure rate is only 37%.

　　Although there are reports that the 5-year survival rate of gastric malignant lymphoma with lymph node metastasis after surgery can reach 40% to 50%, it is generally believed that the efficacy of those without lymph node metastasis is significant, and their 5-year survival rate is about twice as high as those with lymph node metastasis.