Introduction:
Gastrointestinal stromal tumor(Gastrointestinal Stromal Tumors, GISTs) are a type of tumor that originates in the mesenchymal tissue of the gastrointestinal tract and accounts for most of the tumors in the digestive tract. As a newer concept, stromal tumors should cover the so-called "gastrointestinal leiomyomas" or "gastrointestinal leiomyosarcoma". However, as a tumor of mesenchymal tissue, the concept of gastrointestinal leiomyoma or sarcoma has not been ruled out, but in the current clinical pathological diagnosis, these tumors account for only a small part of the gastrointestinal mesenchymal tumor. .
Cause:
Gastrointestinal mesenchymal tumors are only a minority in gastrointestinal tumors, but they are numerous and complex. In the past, due to the limitations of pathological techniques, many gastrointestinal tract spindle cells with smooth muscle fibers or nerve bundles were often diagnosed as smooth muscle-derived tumors or neurogenic tumors. Current studies suggest that most of these are c-kit-positive or CD34-positive mesenchymal tumors of the interstitial cells of Cajal (ICC), the current defined gastrointestinal stromal tumor, and smooth muscle origin. Or neurogenic tumors account for only a very small number.
In 1960, Matin et al first reported six cases of cytoplasmic round or polygonal cell tumors of the stomach wall, named gastric epithelioid leiomyoma; in 1962, Stout reported 69 cases of gastric mesenchymal tumors, called "Singular leiomyomas" or "smooth muscle myblastoma"; in 1969, it was called epithelioid smooth muscle myblastoma in the WHO classification of tumors, although there is doubt that evidence of smooth muscle was not found under electron microscope, but Not paid enough attention. In 1983, Mazur and Clark found that most gastrointestinal stromal tumors lack the characteristics of smooth muscle cells, and proposed the concept of gastrointestinal stromal tumors. GIST was defined as including all gastrointestinal tract spindle cells with biological behavior and unknown origin. . Since then, the concept of gastrointestinal stromal tumor (GIST) has gradually become recognized and accepted by most people. In 1998, Kindblon and other studies showed that GIST was similar to Cajal cells around the gastrointestinal myenteric plexus, and all of them were positive for c-kit gene, CD117 and CD34. ICC is a gastrointestinal pacemaker cell, so it is called a Gastrointestinal Pacemaker Cell Tumor (GIPACT). However, GIST can occur outside the gastrointestinal tract, such as the omentum, mesentery, etc., and GIST tumor cells have no ICC function, so it is currently believed that GIST may not originate from ICC, but originated from precursor cells homologous to ICC (middle leaves) Stem cells), which may also explain focal myogenic marker expression in some tumor cells. Therefore, most authors currently disapprove of replacing the GIST naming with the GIPACT naming. At this stage, it is more appropriate to use the GIST name.
Pathological features
1, the general form
Tumors vary in size, ranging from 0.2cm to 44cm. They originate from the inner muscular layer of the gastrointestinal tract and can grow into the cavity, outside the cavity or simultaneously into the cavity and outside the cavity. The growth into the cavity can form an ulcer, and thus can be classified into an intraluminal type, an intramural type, a dumbbell type, an extraluminal type, and an intra-abdominal gastrointestinal type according to the position of the main body of the tumor. Most tumors are inflated, with clear boundaries, hard and brittle; cut fish-like, gray-red, with secondary changes such as hemorrhage, necrosis, and cystic changes in the center. The number of tumors can be multiple.
2, histological characteristics
GISTs are mainly composed of spindle cells and epithelioid cells. Both cells can appear in different tumors at the same time, but the morphological changes range. According to the number of two kinds of cells, it can be divided into a spindle cell type, an epithelioid cell type, and a fusiform and epithelial cell hybrid type. The arrangement of tumor cells is also diverse, mostly in bundles and slabs. The morphological changes of the stomach and small intestine are large, and the morphological changes of the rectum are small, and most of them are spindle-shaped cell types, which are arranged in a cross-bundle. Tumor cell differentiation can vary, and nuclear vacuole cells and sign-like cells can appear.
3. Immunohistochemical features
Immunohistochemical studies of GISTs indicate that CD117 (c-kit) and CD34 are important markers. 80-100% of GISTs CD117 was diffusely expressed, while smooth muscle cells and nerve fibers did not express CD117. In 60-80% of GISTs tumor cells, CD34 was diffusely positive, and benign GISTs had higher CD34 expression. CD34 has strong expression and is of great value in distinguishing between GISTs and leiomyomas or neurogenic tumors. When CD34 is positively expressed, CD117 is also positively expressed. The expression of CD117 and CD34 had no significant relationship with tumor location, biological behavioral cell differentiation and prognosis. In addition, GISTs may also have expression of myogenic or neurogenic markers, such as 2-SMA, desim, S-100, and the like. However, the positive rate is low, and most of them are focally positive.
symptom:
Clinical manifestation
GISTs are the most common mesenchymal tumors in the gastrointestinal tract, accounting for 1 to 3% of gastrointestinal malignancies. The estimated annual incidence is about 1 to 2/10000, which is more common in middle-aged and elderly patients, and less common in patients under 40 years old. There was no significant difference in the incidence of men and women. Most GISTs occur in the stomach (50-70%) and the small intestine (20-30%), the colorectal accounts for about 10-20%, and the esophagus accounts for 0-6%. It is rare after the mesentery, omentum and abdominal cavity.
The symptoms of GISTs depend on the size and location of the tumor and are usually non-specific. Gastrointestinal bleeding is the most common symptom. In the esophagus, symptoms of dysphagia are often common. Some patients have a perforation of the intestine, which increases the risk of abdominal implants and local recurrence.
About 11% to 47% of patients with GISTs had a metastasis at the first visit. Metastases are mainly in the liver and abdominal cavity, and lymph nodes and extra-abdominal metastases are rare even in more advanced patients. Metastases can even occur 30 years after primary tumor resection. Small intestine GISTs have the highest degree of malignancy and lymph node metastasis, while esophage GISTs have a low degree of malignancy. Therefore, strictly speaking, GISTs are not benign, or at least a class of malignant tumors including potential malignancy.
diagnosis:
CT, endoscopic ultrasonography, and gastrointestinal angiography can assist in the judgment of GISTs size, local infiltration, metastasis, and location.
According to the patient's gastrointestinal bleeding or clinical manifestations from time to time, combined with endoscopic examination such as gastroscopy, colonoscopy, non-mucosal tumor results, CT or endoscopic ultrasound showed tumors occurring in the gastrointestinal wall, can make a preliminary diagnosis. Gastrointestinal angiography can help diagnose the exact location and approximate extent of the tumor in the gastrointestinal tract. However, clinical diagnosis is not enough to confirm the diagnosis of GISTs. The diagnosis of GISTs ultimately requires pathological sections and immunohistochemistry results. Typical immunohistochemical phenotypes of GISTs are positive for CD117 and CD34. SMA was positive in nearly 30% of cases, and S-100 and Desmin intermuscular protein were positive in a small number of cases. However, a small number of cases (<5%) were negative for CD117 and there were some CD117-positive non-GISTs tumors. Therefore, the immunohistochemical diagnosis of GISTs is not absolute. It is still necessary to combine clinical and general pathological results, and sometimes it is necessary to exclude other tumors by immunohistochemistry.
Identification
GISTs often need to be identified with the following tumors, which often have clinical manifestations similar to GISTs.
1, gastrointestinal leiomyomas / sarcoma GISTs mostly diffuse positive expression of CD117 and CD34, SMA does not express or focal expression, while leiomyomas / sarcoma CD117 and CD34 negative expression, SMA diffuse positive expression.
2. S-100 expression was found in a small number of cases of gastrointestinal schwannomas GISTs, while gastrointestinal schwannomas S-100 was diffusely positive, and CD117 and CD34 were negative.
3. The gastrointestinal autonomic neuroma CD117, CD34, S-100, SMA and Desmin were negatively expressed, and neurosecretory granules were observed under electron microscope.
Judging the malignant degree of GISTs In addition to clinical local infiltration, metastasis, recurrence and other factors, the tumor site is also a consideration. Generally speaking, the GISTs of the stomach, esophagus and rectum are less malignant, while the small intestine and colon are more malignant. The size of the tumor and the number of mitotic divisions are also one of the criteria for judging the degree of malignancy of GISTs.
treatment:
Western medicine treatment
Traditional GISTs are mainly treated with surgery. Although recent progress has been made in the pathology and basic research of GISTs, new chemotherapeutic drugs have made some progress, but surgical treatment is still the best treatment for clinical cure.
1, surgical treatment and principles
Due to the potential malignancy of GISTs, clinically suspected GISTs should be performed according to the principle of malignant tumor surgery. Because GISTs are often brittle, blood supply is abundant, and blood and peritoneal metastasis, special attention should be paid to avoid tumor rupture and extrusion. Intestinal GISTs should be ligated to supply and return blood vessels. Intraoperative biopsy should not be performed on suspicious cases unless the tumor cannot be cured.
GISTs are generally not suitable for tumor removal. The GISTs of the stomach may be less than 3 cm in diameter or at least 3 cm in diameter. The margin of margin is at least 3 cm from the tumor; 3 to 5 cm should be wedge resection or partial resection of the stomach. The margin is at least 5 cm from the tumor. Patients with a diameter > 5 cm should be operated according to the gastric cancer D2 sweeping range. Small intestinal GISTs reported a lymph node metastasis rate of 7 to 14%, so it is recommended to perform routine lymphadenectomy, at least 10 cm from the tumor. For rectal GISTs, especially the lower GISTs, sometimes the operation is very difficult. Because it is difficult to judge the degree of malignancy before surgery, for the diameter <3cm, consider keeping the anus as much as possible; for the diameter >5cm or postoperative recurrence, it should be sufficient before surgery. Under the premise of soliciting the patient's wishes, make choices in anal sphincter and enlarged surgery. For local infiltration or distal metastases, combined with organ resection should be performed under the premise of radical treatment.
2, chemotherapy
Traditional chemotherapy GISTs are treated as leiomyosarcoma. The commonly used regimen is doxorubicin + cisplatin (AD regimen). The clinical remission rate is <10%, and the curative effect is not good.
Imatinib(Imatinib) chemotherapy. Imatinib is an inhibitor of c-kit kinase activity and was first used in clinical practice in 2000. It is mainly used for patients who cannot undergo radical surgery, as well as for high-risk GISTs. The application method is 400 to 800 mg/day for 12 to 24 months. According to the phase II clinical study, PR reached 63% and SD reached 20%; the phase III clinical study lacked long-term follow-up reports, but it was reported that the PFS in June exceeded 70%. Imatinib was used for neoadjuvant chemotherapy for GISTs, and a small sample was successfully reported.
prevention:
Prognosis
The overall 5-year survival rate of GISTs was 35%, the 5-year survival rate of complete tumor resection was 50-65%, and the survival rate of unresectable patients was <12 months. Tumor location, size, number of mites, and age were all associated with prognosis. Esophage GISTs have the best prognosis, while small intestine GISTs have the worst prognosis.
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