Gastrointestinal stromal tumor (GIST) is a clinically heterogeneous disease with highly variable malignant potential. GIST can occur throughout the gastrointestinal tract, most of it in activating mutations of KIT or platelet-derived growth factor A (PDGFRA) genes, and it was mainly diagnosed by cell morphology and immunohistochemistry [1]. In this case, a large number of spindle cells were seen in the tumor (Fig. 2), and immunohistochemistry showed that CD117 and Dog-1 were positive (Fig. 3a and 3b). CgA and CD56 were negative, excluding neurogenic tumors, Desmin and S-100 were negative, excluding smooth muscle tumors[5]. Therefore, this case was diagnosed as GIST in jejunum. However, in this case, chronic inflammation and GIST appeared in the same site. To clarify their relationship is very helpful for the diagnosis and treatment of the disease and the prevention of GIST. There were three possibilities for their relationship: i) inflammation caused GIST; ii) GIST caused inflammation; iii) GIST and inflammation coexist alone.
i). This study supported GIST caused by repeated stimulation of chronic inflammation. This patient developed intermittent abdominal pain and fever after abdominal trauma, and the recurrence occurred within six years, which was relieved by oral non-steroidal anti-inflammatory drugs at home. While gastrointestinal stromal tumors caused obvious symptoms at 5 cm-10cm[6, 7]. Combined with the long duration of symptoms in this case, abdominal pain and fever can only be caused by repeated stimulation of inflammation caused by perforation after trauma; CT of the admitted abdomen revealed a solid cystic mass in the upper and middle abdomen, mainly cystic, with separation seen inside, and the solid part and separation of the enhanced scan were significantly enhanced. The boundary between the mass and the surrounding intestine was unclear, and a small amount of air density was seen in the surrounding area. Fat interstitial density increased and a small amount of flocculent density shadow was seen (Fig. 1a). During surgery, the tumor envelope on the contralateral side of the small intestine mesentery was intact, with omentum wrapping around it (Fig. 1b); The general anatomy of the isolated tumor (Fig. 1c) showed that the tumor envelope was intact, and perforation, inflammatory tissue, and a little pus can be seen at the edge of the tumor, combined with the patient’s injury history, it is considered that the inflamed tissue contains GIST, and the small amount of gas is considered to be caused by intestinal perforation. Although there are reports in the literature that GIST can have rare clinical symptoms such as intestinal obstruction, perforation or rupture, abscess and intestinal fistula, etc., it is reported that GIST with the above-mentioned symptoms usually has a tumor diameter greater than 5 cm, even greater than 10 cm[6, 7]. And necrosis of small intestine GIST is generally central liquefaction necrosis [8]; Therefore, it is considered that inflammation stimulus and perforation accompanied with formation of abscess cavity after injury, and speculated that the chronic inflammation of the tumor edge is caused by infection caused by trauma. HE staining of postoperative sections showed tumor cells (Fig. 2b) and a large number of inflammatory cells (Fig. 2c); Recent studies reported that inflammation caused KIT or PDGFRA gene mutations[9, 10], Lisa W. Witten et al.[9] reported that miR-155 overexpression played an important role in inflammation and found that the KIT gene was mutated; Huss S et al.[10] reported that inflammatory fibrous polyps often accompany PDGFRA exons 12 and 18 Mutations, and the membrane receptor KIT or PDGFRA mutations can lead to uncontrolled cell growth and stromal tumor formation [2]. Therefore, this case report believes that trauma caused inflammation, which can lead to mutations in KIT or PDGFRA genes, and further leaded to the formation of gastrointestinal stromal tumors. The general anatomy of the tumor (Fig. 1c) showed that the tumor capsule was intact, with a little pus and inflammatory tissue at the edge of the perforation. Therefore, it is considered that inflammation irritation and perforation accompanied with abscess formation after injury. The above speculates that the chronic inflammation of the tumor margin is caused by infection caused by trauma.
ii). Does GIST cause inflammation? The most common symptoms of GIST are bleeding into the intestine or abdominal cavity, anemia, and abdominal pain, other symptoms include indigestion, nausea or vomiting, constipation or diarrhea, frequent urination, and fatigue [1]. There are reports in the literature that GIST can have rare manifestations such as intestinal obstruction, perforation or rupture, abscess and intestinal fistula [11, 12]. However, if it is inflammation caused by GIST, such as abscess formation, it is usually acute and often accompanied by tumor central necrosis and rupture [8]. This patient has been suffering from intermittent abdominal pain and fever for 6 years, and the pathological examination of the capsule is intact. The tumor has no signs of necrosis or ulceration. A large number of inflammatory packages are seen on the edge of the tumor, suggesting that chronic inflammation is caused by repeated stimulation. For example, Chen et al.[12] and Misawa S et al. [13] reported the appearance of necrotic ulcers or abscesses in GIST. The tumor was large and had acute inflammation symptoms, which was inconsistent with the persistence of repeated chronic inflammation in this case. The above view does not support the formation of inflammation caused by GIST.
iii). If GIST occurs and chronic inflammation caused by trauma independently of each other, they usually occur in different locations. but this case occurs in the same location, although studies have reported the possibility of GIST and inflammation being parallel to each other[14]. Theodoropoulos GE et al. [15]reported that a patient with ulcerative colitis was diagnosed with GIST after surgery due to jejunoileum intussusception, but another study found that patients with inflammatory bowel disease (IBD) had an increased risk of cancer, especially it is for patients taking immunosuppressive agents[16]. Most cancers occur in the site of inflammation and have experienced the sequence of inflammation-dysplasia-cancer [17, 18]. Many studies [18, 19]reported that some inflammatory factors can change the tumor microenvironment and promote tumor survival. Cavnar MJ. [20]found that depletion of tumor-associated macrophages with similar functions to type I macrophages can increase tumor size in GIST mice. The above view does not support the independent occurrence of chronic inflammation and GIST, and it supports the possibility that chronic inflammation may cause GIST to be generated by repeated long-term stimulation of chronic inflammation.
For the treatment of GIST, surgery is the first treatment option. Tyrosine kinase inhibitors such as imatinib are used for neoadjuvant treatment of potentially resectable tumors and high-risk tumors after surgery, or as palliative treatment. The prognosis of the patient depends on the size of the tumor, the mitotic image, and the preservation of the pseudocapsule. In this case, the diameter of the tumor was 4.8 cm, and the mitotic figure > 5/50 HPF was defined as a medium-to-high prognosis risk factor. Imatinib was taken orally after the operation, and no recurrence was found after one year of follow-up.
In summary, we reported a case of intestinal perforation caused by trauma, which resulted in abscess formation accompanied by long-term chronic inflammation. GIST is mainly formed by activating mutations of the membrane receptor KIT or PDGFRA [2]. We speculate that long-term chronic inflammation can lead to activating mutations of membrane receptor KIT or PDGFRA, which in turn leads to the formation of GIST. Early detection and timely removal of the inducement of repeated chronic inflammation caused by trauma can effectively prevent the occurrence of GIST.