Overview
Thymus is an important immune origin of human body, which is derived from the endoderm of the 3rd (or 4th) gill arch during embryonic period, and is a derivative of primitive foregut epithelial cells, which is attached to the anterior mediastinum with embryonic growth and development. Thymic tumors originating from thymic epithelial cells or lymphocytes are the most common, accounting for 95% of thymic tumors and ranking 1st to 3rd in the whole mediastinal tumors. In a group of 1064 mediastinal tumors in the United States, thymoma was the first one accounting for 21.14% of the domestic reports, mostly led by teratoma. In a group of 14 domestic reports of 2720 mediastinal tumors, thymoma was the third after teratoma and neurogenic tumor, accounting for 22.37%.
Pathological changes
Pathologically, thymoma is named after the cellular component that accounts for more than 80% of the tumor. They are divided into epithelial cell type and mixed epithelial cell lymphocyte type. It is difficult to distinguish benign or malignant thymoma purely from pathological morphology, and it is more appropriate to classify invasive and non-invasive thymoma according to clinical manifestations, visual observation during surgery and pathological morphological characteristics. However, it is customary to refer to benign and malignant thymomas. The differentiation between benign and malignant thymoma A is based on the clinical presentation and the findings during surgery.
During surgery, attention should be paid to
1.Whether the tumor has an intact envelope or not;
2.Whether the tumor has aggressive growth;
3. whether there is distant metastasis and intra-thoracic implantation; the anomaly of cell morphology under microscope, and the comprehensive analysis can reach the correct conclusion. If the tumor has a complete fiber envelope at the time of surgery, and the tumor grows within the envelope without adhesion and infiltration with the surrounding organs, it is benign or non-invasive thymoma if it can be easily removed by surgery. When the tumor invades out of the envelope and invades the surrounding organs or tissues (pericardium, pleura, lung and blood vessels, etc.), and cannot be removed or completely removed by surgical operation, or if intra-thoracic implantation or pleural metastasis is found at the time of operation, it is considered malignant or invasive thymoma.
Clinical manifestations]
Like any mediastinal tumor, the clinical symptoms of thymoma arise from the compression of surrounding organs and the symptoms specific to the tumor itself – the combined syndrome. Small thymoma has no clinical complaints and is not easily detected. When the tumor grows to a certain size, the common symptoms are chest pain, chest tightness, cough and anterior chest discomfort. The nature of chest pain is not characteristic, the degree varies and the location is not specific, generally speaking, it is mild and often treated symptomatically without further examination. If the symptoms persist for a long time, some patients may undergo X-ray examination, or some patients may find mediastinal mass shadows during chest X-ray or chest radiography. The overlooked thymoma often grows to a large size at this time, compressing the veins or showing signs of superior vena cava obstruction syndrome. Severe chest pain, rapid worsening of symptoms within a short period of time, severe irritating cough, dyspnea due to pleural effusion, shortness of breath due to pericardial effusion, and skeletal pain of peripheral concern all suggest the possibility of malignant thymoma or thymic carcinoma.
The unique manifestation of thymoma is the combination of certain syndromes, such as myasthenia gravis (MG), simple red blood cell aplastic anemia (PRCA), hypoglobulinemia, nephritis nephritis syndrome, rheumatoid arthritis, dermatomyositis, lupus erythematosus, and megalophagia.
[Diagnosis].
X-ray examination is an important method to detect and diagnose mediastinal tumor. In the orthopantomogram of chest, thymoma often appears as a round or oval dense shadow of widened septum on one side or protruding to one side of the chest cavity, more to the right than to the left, and also to both sides of the chest cavity. The protrusion to the left is often obscured by the aortic bulb, while the protrusion to the right may overlap with the superior vena cava. The edges of the mass are clear and sharp, and some of them are lobulated. The lateral image shows a substantial mass with uniform density in front of the great vessels of the heart behind the sternum. A few thymomas show striated, punctate, massive and shapeless calcifications, which are less calcified than teratomas. Some thymomas are flattened over the great vessels of the heart and are the most difficult to diagnose on x-ray. Lateral lesion tomography is a simple and economical way to identify thymoma, showing the presence, size, and density of the tumor, and is particularly useful when complex examinations are not available.
Chest CT is an advanced and sensitive method to examine mediastinal tumors. It can accurately show the location, size, protrusion to one side or both sides, the edge of tumor, the presence or absence of surrounding infiltration, and the determination of surgical resectability. If the tumor location is complicated, magnetic resonance examination can be considered, which can observe the tumor morphology and relationship with blood vessels in three dimensions.
Differential diagnosis
Although there are many kinds of examinations, sometimes there are still cases that are difficult to be diagnosed clinically. It has been suggested to perform superior vena cava or nameless vein angiography and mediastinal inflatable angiography, but they are seldom used recently because of the complicated operation. Common lesions that need to be differentiated from thymoma include teratoma and ascending aortic aneurysm. Teratomas often occur in middle-aged and young adults and may be asymptomatic or may have recurrent pulmonary infections, sometimes with a history of coughing up hair or grease-like material, and may have calcified teeth or bone within the mass on X-ray.
It is reported in the literature that mediastinal tumors are mistaken for ascending aortic aneurysms, or ascending aortic aneurysms are misdiagnosed as thymic aneurysms. In the lateral phase of the chest, the ascending aortic aneurysm appears as a round shadow along the left ventricle, and the mass can be seen on chest X-ray as a distending pulsation. In recent years, magnetic resonance imaging (MRI) has been gradually increasing in clinical application, which has special value for the diagnosis of cardiac macrovascular malformation3 and hemangioma, and is a sensitive and effective examination method to distinguish mediastinal tumor from ascending (descending) aortic aneurysm.
【Treatment measures
1.Treatment principle: Thymoma should be surgically removed once diagnosed. The reason is that the tumor continues to grow and enlarge, compressing the neighboring tissues and organs to produce obvious clinical symptoms; it is difficult to judge the benignity and malignancy of the tumor simply from clinical and X-ray performance; moreover, benign tumor can also be malignant. Therefore, no matter benign or malignant thymoma, it should be removed as soon as possible. The pathological biopsy of malignant thymoma that can be resected can guide the postoperative treatment, and the postoperative radiation therapy of partially resected tumor can relieve the symptoms and prolong the survival of patients.
2. Incision selection: For small thymoma protruding to one side, the anterior external intercostal thoracic incision is mostly used, while for larger tumor protruding to both sides, the anterior median thoracic incision can be used. In recent years, the use of anterior median thoracic incision has increased, in addition to the removal of thymoma at the same time remove the contralateral thymus, in order to prevent the possibility of severe muscle weakness in the future. A bilateral transverse thoracic incision across the sternum has also been used in spring to remove the tumor. The anterior median thoracic incision does not enter the thoracic cavity, which reduces postoperative interference with the patient’s respiratory function and avoids postoperative respiratory complications. Some people remove thymoma through cervical incision. The indications are old patients, contraindication to open chest, small size of tumor and close to the neck.
3. Problems that should be noted during surgery: for benign thymoma without adhesions, there is no difficulty in complete removal and the surgery can be completed successfully, but in some complicated cases, the difficulty should be fully estimated during surgery. Malignant thymoma should be explored first to find out the relationship between the tumor and the surrounding organs before dissection. Thymoma is located at the base of the mediastinum and at the junction of heart and large blood vessels; malignant thymoma can infiltrate into the surrounding adhesions; when the tumor grows, the neighboring tissues and organs are pushed and the normal anatomical relationship is changed; fibrous connective tissue adhesions thicken, making it difficult to distinguish from blood vessels. All of these may cause hemorrhage due to accidental injury of blood vessels during surgery. Operators should be alert to this problem.
The determination of resectability of the tumor is an important issue to be considered during surgery. When the tumor has invaded the innominate vein or superior vena cava, or the blood vessels are encapsulated in the tumor, or the tumor is frozen with the surrounding tissues, then a cautious attitude should be taken to abort the operation and only pathological biopsy should be taken and postoperative radiation therapy should be given. If the tumor is infiltrated with large blood vessels, but still separable, it can be dissected gradually, from shallow to deep, from easy to difficult, firstly to loosen it, then to free the tumor, and finally to remove it after clamping at its tip.
Every fibrous tissue or cord should be clamped and cut off during dissection to avoid damaging the blood vessels and making the surgery more difficult. If the blood vessels are accidentally damaged, do not panic and blindly clamp to stop the bleeding. You can first use gauze pad to compress out the enemy rupture, prepare the suction device, and at the same time speed up the blood transfusion, after aspirating the blood accumulated in the operation field, identify the site and scope of the injury, and then decide whether to directly suture or repair.
If the tumor protrudes from one side of the chest to the opposite side or the tumor extends prominently to the neck, it should be dissected and separated under direct vision. Sometimes some blood vessels traverse through it or there are blood vessels supplying the tumor, blind blunt separation may cause bleeding. If the tumor invades the pericardium, the pericardium can be cut in the normal part and fingers can be stretched in the pericardial cavity to help remove the tumor or the pericardium can be removed together with the tumor.
4.Surgical treatment result No matter benign or malignant thymoma treatment, mainly is surgical resection, only when the resection is incomplete or failed to resect thymoma, then consider radiotherapy, chemotherapy on thymoma base is minimal.
The relationship between surgical resection rate and tumor size. Generally speaking, the larger the tumor, the lower the resection rate, which is consistent with the general conclusion of surgical oncology, but the size of the tumor is not the only indicator of resectability. Sometimes large tumors can be resected, but smaller ones cannot. In addition to tumor size, the severity of tumor invasion, especially invasion of peripheral vessels, such as superior vena cava, innominate vein and aorta, greatly affects the surgical resection rate. When the tumor grows around the blood vessels and freezes, even a medium-sized tumor can not be completely resected.
5.Radiation therapy for thymoma Malignant thymoma even if the tumor has been removed cleanly by the naked eye, the tumor bed still needs to be completed, and if there is residual tumor tissue not cut or not removed during the surgery, the dose needs to be increased, generally 60Gy (6000rad). It has been suggested that benign thymoma also has a few recurrences, so it is suggested that benign thymoma should also be irradiated with 30-40Gy (3000-4000rad) as a preventive treatment. The results of radiotherapy for thymoma are generally not very satisfactory, and it is difficult to comment on them because the results reported in different places are far apart.
Complications
1, myasthenia gravis (MG) has long been found to be related to the thymus (or thymoma). Myasthenia gravis can be clinically divided into 3 types, such as eyelid drooping, long-lasting fatigue, double vision, for the eye muscle type; upper limb extension can not last, walking a little far need to sit down to rest, for the trunk type; chewing and swallowing effort, and even respiratory muscle paralysis, for the medulla oblongata type. The most dangerous clinical condition is myasthenia gravis, in which the patient must be assisted by artificial respiration because of respiratory muscle paralysis.
It is believed that myasthenia gravis is an autoimmune disease, mainly due to the mutation of the thymus gland by certain stimuli, which cannot control certain forbidden cell lines and allows them to differentiate and proliferate, resulting in an immune response to its own components (transverse muscle) and myasthenia gravis. Treatment of myasthenia gravis has been using anti-acetylcholinesterase drugs, such as pyridostigmine, for many years, and in recent years immunosuppressive drugs, such as hormones and cyclophosphamide, have been added. The indications for surgical treatment of myasthenia gravis are patients with myasthenia gravis with or without thymoma, taking anti-acetylcholinesterase drugs with increasing doses without symptom reduction, or myasthenia gravis crisis and recurrent respiratory infections.
2. Pure red blood cell aplastic anemia (PRCA)
One of the coexisting diseases with thymoma is pure red blood cell aplastic anemia. Pure red reoccurrence can be primary and the cause is unclear. It can also be secondary to drugs, infections and tumors. Experimental studies suggest that PRCA is an autoimmune disease with unknown causes leading to an autoimmune response to red blood cell antigens that can be present in the human thymus. Thymoma itself does not have a direct effect on red blood cell growth; it may be the case that thymoma enhances the sensitivity of the immune system or that thymoma is induced by a highly sensitive proliferative system.
3. Nephrotic syndrome nephritis The relationship between nephrotic syndrome nephritis and thymoma is unknown. Nephrotic syndrome can be part of the systemic manifestations of certain tumors, such as Hodgkin’s disease. The possible explanation is that thymoma forms a cross-reaction with the antigen-antibody complex of glomerulonephritis.