Gist Tumor Manifested with Digestive Tract Bleeding: Case Report and Literature Review

ABSTRACT


INTRODUCTION
Gastrointestinal stromal tumors (GIST) are a subgroup of mesenchymal tumors that origins from soft tissues and have their primary origin in the interstitial Cajal cells [1].Despite being known as the most common mesenchymal neoplasms of the digestive tract, they only represent between 1-3% of malignant gastrointestinal neoplasms [2].This type of tumors usually affect the gastrointestinal tract in most cases (80%), with the stomach as the most frequent location, followed by duodenum, jejunum, colon and rectum [3]; Less frequently occurs outside the gastrointestinal tract, being the mesentery and retroperitoneum the most frequent sites of presentation [4].The clinical picture, laboratory and image studies similarly to the majority of gastrointestinal tumors are not specific, so the final diagnosis falls on histopathological analysis by biopsy, which must be obtained with special care due to the risk of rupture of the tumor capsule and consequently the tumoral dissemination.Of special importance is the association with the oncogenic mutation in the KIT gene, which is regulated by tyrosine kinase activity.In tumors unresectables, tyrosine kinase inhibitors such as imatinib have an important role in the treatment because they significantly improved the prognosis in the last years, before they being integrated into the treatment the mortality in unresectable tumors was very high.Hence the importance of and adequate suspected diagnosis and timely treatment that is the principal point to treat in this review so we will comment key points to improve the survival of GIST.

CASE REPORT
We present a case of a 48-year-old male with no chronic degenerative diseases or personal pathological history of importance for the current condition who reports that his condition began a month prior to his admission with presence of a feeling of early progressive satiety, asthenia and anorexia with subsequent appearance of evacuations with melenic characteristics in a small quantity which subsided spontaneously, however after the recurrence of the evacuations in greater quantity, additionally to disabling asthenia and adynamia, he went to the emergency department of our hospital being admitted without clinical Corresponding Author: Rodolfo Martín Ruiz Ravelo signs of hemodynamic instability, vital signs within normal parameters, during his initial evaluation the following laboratories were performed: TP 13.1s, INR 1.1, TPT 24.3s, Leukocytes 7.1k/Ul, Hemoglobin 5.5 g/dL, Hematocrit 20.8% V.C.M. 93.7%, H.C.M. 24.8, Platelets 370k/IU, ALT 23.1 U/L AST 19.3 U/L BD 0.23 mg/dL BI 0.41 mg/dL BT 0.64 mg/dL.Due to the hemoglobin value a transfusion of 2 erythrocyte concentrates was required and upper endoscopy were performed, in which at the minor gastric curvature a tumor with exophytic characteristics were observed, approximately of 40mm of diameter with an apical erosion and visible vessel (Fig 1).Adjacent to this main lesion, another elevated and ulcerated area with fibrin and raised borders were observed, the rest of the gastric mucosa were seen without alterations.Biopsies of the lesion were not taken due to having a visible central vessel and due to suspicion of a GIST submucosal tumor by macroscopic characteristics, in order to avoid tumor dissemination due to the friability that these lesions may have.Therefore, as part of the diagnostic extension protocol of said tumor, a simple and contrasted thoracoabdominal computed tomography (CT) was requested, revealing a collapsed stomach, which was difficult to assess, with an internal irregular lesion, with lobulated edges, isodense with apparently heterogeneous reinforcement dependent on the stomach lower wall and projecting towards lumen, with approximate measurements in the axial plane of 5.After evaluation and reporting of complete tumoral resection with resection edges free of neoplasia and non-invasion to surrounding lymph nodes, a complete cure was considered in our patient who, due to being a low-risk GIST tumor it didn´t need treatment with tyrosine kinase inhibitors, however, given the high recurrence rate reported in these tumors despite a successful treatment, long-term follow-up were performed.
After 6 months of post-surgical follow-up, the patient was found to be completely asymptomatic with no data suggestive of recurrence.The principal immunohistochemical characteristic for GISTs is that in up to 95% of cases they express the specific tyrosine kinase growth factor, better known as the KIT proto-oncogene, that express CD117, in a lesser proportion they also express CD34, desmin and S-100 [14].However, there are 5% of cases in which the tumor is negative for CD117, CD34, desmin and S-100; So in these cases additional tests come into role for diagnosis consisting of DOG1 staining, KIT gene mutation or mutations in the platelet growth factor receptor alpha gene (PDGFRA) [15].The differential diagnosis of GIST is with other types of tumors such as carcinoma, metastatic melanoma, clear cell sarcoma, among others [16].

Malignancy risk Tumoral size Mitosis/Field
Very low < 2 cm > 5 Low 2 -5 cm < 5 The treatment of choice in non-metastatic GIST is complete surgical resection with safety margins of 1-2 cm, which represents the success in up to 95% of cases [17], always taking care to preserve the tumor capsule.Despite adequate treatment none patient is exempt from tumoral recurrence, hence the importance of close follow-up despite successful resection of the GIST.The recurrence rate depends on the quality of tumor resection, being 40% in patients with a complete tumor resection with surgical margins free of disease and up to almost 100% in patients who present capsular rupture during the procedure [18], so the resections always need to be carried out with special care.With unresectable gastrointestinal stromal tumors, the importance of their positivity in tyrosine kinase expression have an important role in the pathogeny, so the since of inclusion of tyrosine kinase inhibitors these revolutionized the treatment and improved the prognosis of advanced GISTs [19].

Intermediate
Treatment with tyrosine kinase inhibitors consists in neoadjuvant and adjuvant treatment.The assessment of neoadjuvant treatment is generally carried out one month after initiation with a CT to assess the reduction in tumoral size, the perfect time to perform the surgical intervention is between 6-12 months after the start of imatinib, which is the time of maximum response to treatment [20].
The length of treatment, even if it is neoadjuvant or adjuvant, generally maintains for up to 36 months, but in cases of tumoral rupture, due to the high risk of recurrence it can even be maintained for life [21].
The prognosis generally depends on the interaction of three main components: Size, location and mitotic tumoral index [22].It is considered that from 5 cm in tumor size, as well as a mitotic index greater than 5/50 per field, the risk of generating local and distant metastases are greater [23], so the GISTs are classified according to their potential to generate metastases into four degrees of malignancy (Table 1) [24].However, there have been cases in which, despite a small tumoral size and low mitotic index these tumors express a malignant behavior are seen, so it is always important to try to provide definitive treatment and adequate follow-up.
The follow-up of low-risk tumors is carried out by CT every six months for five years and those with high or intermediate risk needs a CT every three or four months for the first three years, subsequently every six months until the fifth year and annually for another five years [25].

CONCLUSION
In conclusion, GISTs are tumors that have a very low incidence and that in most of cases have an unspecific presentation, so their diagnostic suspicion is very low.It´s especially important in cases when they presents with symptomatology perform a timely diagnostic-therapeutic approach with image studies in order to demonstrate distant dissemination, tumoral resection and histopathological analysis with immunohistochemistry, since it has been seen that the risk of malignancy and recurrence is variable depending on tumoral size, mitosis per field and the successfully resection with adequate security margins.Another point to take account is the therapeutic effectiveness of tyrosine kinase inhibitors, so we must not leave aside the use of imatinib as a neoadjuvant or adjuvant treatment to improve the success rates in those tumors who are unresectable or with a high risk of recurrence.

Figure 1 .
Figure 1.Upper endoscopy showing an exophytic tumor with central ulceration at the level of the lesser gastric curvature.
2 x 4.8 cm (Fig 2) suggestive of a neo-formative process, tumor lesions on peripheral lymph nodes were not detected.

Figure 2 .
Figure 2. Contrast-enhanced abdominal tomography, we observed an intragastric tumor that tends to occlude practically all of gastric lumen (Arrows) .

Figure 3 .
Figure 3. Histopathological staining with hematoxylin and eosin where multiple polymorphic cells with an epithelioid appearance are seen.

Figure
Figure 4. Histopathology with Immunohistochemistry where CD117 (C-kit) shows cytoplasmic immunostaining with a Golgi pattern without evidence of increased mitotic activity.