Systemic therapy in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.

Gastric IgG4-related disease mimicking a gastrointestinal stromal tumor in a child: A case report

BACKGROUND Gastric IgG4-related disease(IgG4-RD)is rarely encountered in clinical practice,and especially more so among pediatric patients.To our knowledge,this is the first report of IgG4-RD presenting as a calcifying gastric mass in a child.We describe how this entity was difficult to differentiate from a gastrointestinal stromal tumor(GIST)imaging-based approaches.Therefore,this case highlights the importance of considering IgG4-RD in the differential diagnosis of gastric tumor before performing surgical resection,especially to distinguish it from malignancy to avoid unnecessary surgery.CASE SUMMARY The patient suffered from epigastric pain for several days.Panendoscopy and computed tomography scan revealed a submucosal tumor.Differential diagnoses included GIST,leiomyoma,teratoma,and mucinous adenocarcinoma.However,laparoscopic proximal gastrectomy allowed for the definitive diagnosis of IgG4-related stomach disease.CONCLUSION We emphasize the importance of considering IgG4-RD in the differential diagnosis of gastric submucosal tumors before performing surgical resection.

GASTROINTESTINAL STROMAL TUMORS OF THE ANORECTUM——A SPECIAL ENTITY: GISTs OF THE ANORECTUM

Objective： Until recently gastrointestinal stromal tumor （GIST） has been separated from other mesenchymal neoplasms and categorized as a special entity. Morphology of tumor cells and immunohistochemical findings with CD117 are crucial in the pathological diagnosis of GISTs. Newly developed drug imatinib mesylate （formerly called STI571） has been proved effective for GISTs. The distinction of GISTs and other mesenchymal tumors has great clinical significance, especially for lesions located in the anorectum. Methods： The authors searched the database of Peking University, School of Ontology for patients with anorectal neoplasms treated from January 1995 to June 2002. Information of 12 patients with anorectal mesenchymal tumors was collected. The patients were reevaluated and discussed according to current criteria of GISTs with clinical data and immunohistochemical findings. Results： Six patients （including 3 males） were finally diagnosed as anorectal GISTs. The median age of those patients was 59.5 years （27～69）. The symptoms were not specific. Three cases with original diagnosis of leiomyoma or leiomyosarcoma were actually GISTs. A total of six anorectal GISTs was found comprising about 1.06% of patients with anorectal neoplasmas in the same period. Besides CD117, CD34 and vimentin were also expressed in majority of these patients. Five of the six patients underwent surgical resection one of which received neoadjuvant chemotherapy before resection Conclusion： Anorectal GISTs should be considered as a special entity using current diagnostic criteria. Surgical resection remains the primary therapeutic strategy. Neoadjuvant imatinib mesylate may be helpful in sphincter-sparing operations and improvement of the quality of life for these patients.

Relationship between multi-slice computed tomography features and pathological risk stratification assessment in gastric gastrointestinal stromal tumors

BACKGROUND Computed tomography(CT)imaging features are associated with risk stratification of gastric gastrointestinal stromal tumors(GISTs).AIM To determine the multi-slice CT imaging features for predicting risk stratification in patients with primary gastric GISTs.METHODS The clinicopathological and CT imaging data for 147 patients with histologically confirmed primary gastric GISTs were retrospectively analyzed.All patients had received dynamic contrast-enhanced CT(CECT)followed by surgical resection.According to the modified National Institutes of Health criteria,147 lesions were classified into the low malignant potential group(very low and low risk;101 lesions)and high malignant potential group(medium and high-risk;46 lesions).The association between malignant potential and CT characteristic features(including tumor location,size,growth pattern,contour,ulceration,cystic degeneration or necrosis,calcification within the tumor,lymphadenopathy,enhancement patterns,unenhanced CT and CECT attenuation value,and enhancement degree)was analyzed using univariate analysis.Multivariate logistic regression analysis was performed to identify significant predictors of high malignant potential.The receiver operating curve(ROC)was used to evaluate the predictive value of tumor size and the multinomial logistic regression model for risk classification.RESULTS There were 46 patients with high malignant potential and 101 with low-malignant potential gastric GISTs.Univariate analysis showed no significant differences in age,gender,tumor location,calcification,unenhanced CT and CECT attenuation values,and enhancement degree between the two groups(P>0.05).However,a significant difference was observed in tumor size(3.14±0.94 vs 6.63±3.26 cm,P<0.001)between the low-grade and high-grade groups.The univariate analysis further revealed that CT imaging features,including tumor contours,lesion growth patterns,ulceration,cystic degeneration or necrosis,lymphadenopathy,and contrast enhancement patterns,were associated with risk stratification(P<0.05).According to binary logistic regression analysis,tumor size[P<0.001;odds ratio(OR)=26.448;95%confidence interval(CI):4.854-144.099)],contours(P=0.028;OR=7.750;95%CI:1.253-47.955),and mixed growth pattern(P=0.046;OR=4.740;95%CI:1.029-21.828)were independent predictors for risk stratification of gastric GISTs.ROC curve analysis for the multinomial logistic regression model and tumor size to differentiate high-malignant potential from low-malignant potential GISTs achieved a maximum area under the curve of 0.919(95%CI:0.863-0.975)and 0.940(95%CI:0.893-0.986),respectively.The tumor size cutoff value between the low and high malignant potential groups was 4.05 cm,and the sensitivity and specificity were 93.5%and 84.2%,respectively.CONCLUSION CT features,including tumor size,growth patterns,and lesion contours,were predictors of malignant potential for primary gastric GISTs.

Optical second-harmonic generation imaging for identifying gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors arising in the digest tract.It brings a challenge to diagnosis because it is asymptomatic clinically.It is well known that tumor development is often accompanied by the changes in the morphology of collagen fibers.Nowadays,an emerging optical imaging technique,second-harmonic generation(SHG),can directly identify collagen fibers without staining due to its noncentrosymmetric properties.Therefore,in this study,we attempt to assess the feasibility of SHG imaging for detecting GISTs by monitoring the morphological changes of collagen fibers in tumor microenvironment.We found that collagen alterations occurred obviously in the GISTs by comparing with normal tissues,and furthermore,two morphological features from SHG images were extracted to quantitatively assess the morphological difference of collagen fibers between normal muscular layer and GISTs by means of automated image analysis.Quantitative analyses show a significant difference in the two collagen features.This study demonstrates the potential of SHG imaging as an adjunctive diagnostic tool for label-free identification of GISTs.

Neurofibromatosis type 1 with multiple gastrointestinal stromal tumors:A case report

BACKGROUND Neurofibromatosis type 1(NF1)is characterized by café-au-lait patches on the skin and the presence of neurofibromas.Gastrointestinal stromal tumor(GIST)is the most common non-neurological tumor in NF1 patients.In NF1-associated GIST,KIT and PDGFRA mutations are frequently absent and imatinib is ineffective.Surgical resection is first-line treatment.CASE SUMMARY A 56-year-old woman with NF1 was hospitalized because of an incidental pelvic mass.Physical examination was notable for multiple café-au-lait patches and numerous subcutaneous soft nodular masses of the skin of the head,face,trunk,and limbs.Her abdomen was soft and nontender.No masses were palpated.Digital rectal examination was unremarkable.Abdominal computed tomography was suspicious for GIST or solitary fibrous tumor.Laparoscopy was performed,which identified eight well-demarcated masses in the jejunum.All were resected and pathologically diagnosed as GISTs.The patient was discharged on day 7 after surgery without complications.No tumor recurrence was evident at the 6-mo follow-up.CONCLUSION Laparoscopy is effective for both diagnosis and treatment of NF1-associated GIST.

Sunitinib-induced hyperammonemic encephalopathy in metastatic gastrointestinal stromal tumors:A case report

BACKGROUND Sunitinib,a multi-targeted tyrosine kinase inhibitor(TKI),has been approved for the salvage treatment of gastrointestinal stromal tumors(GIST).Hyperammonemic encephalopathy is a rare but severe complication of sunitinib use.Here,we present the case of a 66-year-old male with metastatic GIST without underlying liver cirrhosis who developed sunitinib-induced hyperammonemic encephalopathy.CASE SUMMARY A 66-year-old male with metastatic GIST was admitted because of reduced consciousness.Imatinib was administered as the first-line systemic therapy.He experienced repeated episodes of peritonitis due to tumor perforation,and surgery was performed.Progressive disease was confirmed based on increased liver metastasis,and sunitinib was initiated as a salvage treatment.However,23 d after the third course of sunitinib,he presented to the emergency room with an episode of altered consciousness and behavioral changes.Based on the patient clinical history and examination findings,sunitinib-induced encephalopathy was suspected.Sunitinib was discontinued,and the patient was treated for hyperammonemia.The patient had a normal level of consciousness four days later,and the serum ammonia level gradually decreased.No further neurological symptoms were reported in subsequent follow-ups.CONCLUSION TKI-induced hyperammonemic encephalopathy is potentially life-threatening.Patients receiving TKIs experiencing adverse reactions should undergo systemic evaluation and prompt treatment.

Gastrointestinal Stromal Tumors (GISTs), Surgical Management and Clinical Outcome

Introduction: This study investigated the incidence, surgical management and outcome of Gastrointestinal Stromal Tumors (GIST) in Upper Egypt. Methods: A retrospective review of all GIST patients admitted a South Egypt Cancer Institute between Jan. 2010 and Dec. 2015 was conducted. Patients’ demographics, clinical presentation, tumor characteristics, radiological, pathological and immunohistochemical findings, surgical procedures, recurrence and mortality were recorded. Results: A total of 36 GIST patients were identified, stomach was the most common site (27.8%) followed by the small intestine (19.4%) and the large intestine (16.7%). The mean age at time of diagnosis as 52.8 ± 14.4 (ranged from 17 to 76 years). Of these 36 cases, 20 (55.6%) cases were males and 16 (44.4%) cases were females with a ratio of 1.2:1. About 22 cases (61.1%) presented with primary tumors, eight cases (22.2%) had primary tumors and metastases, three cases (8.35) presented with recurrent mass, whereas one case (2.2%) presented either with recurrent mass and metastases or metastases only. The majority of cases (22) had tumorsize >5 cm. Patients were stratified as high, intermediate, low and very low risk (50.6%, 30.6%, 11.1% and 2.8%, respectively). Almost all the cases were surgically managed and 75% were completely resectable. During follow up (average 26.5 months), 22 patients showed complete recovery, 7 had recurrent or metastatic disease and 2 died due to liver metastasis. Conclusion: The incidence of GIST in Upper Egypt is apparently low. Surgical resection is the preferred choice of treatment. The demographic data of GIST patients in South Egypt Cancer institute were similar to those published in the literature. Other prospective studies are required to assess the prognosis and the effect of treatment.

Management Colorectal Gastrointestinal Stromal Tumors (Gists) in Surabaya

Introduction: Colorectal gastrointestinal stromal tumors (GISTs) mesenchymal tumor is very uncommon. GISTs effect mostly on the stomach and small intestine and rarely occur in the colon, rectum and esophagus, that originating from precursors of the interstitial cells that originate of Cajal. The symptoms of gastrointestinal stromal tumor depend on the site and size of the tumor, and may include abdominal pain, gastrointestinal bleeding or signs of obstruction;small tumors may, however, be asymptomatic. Some of the patients with gastrointestinal stromal tumor have bloody stools, obstruction and abdominal pain as the commonest manifestation. Immunocytochemical staining for CD117 is helpful in confirming the diagnosis. Case presentation: We report 3 new cases of GISTs: two occurred at the rectal and the other at descending Colon. Two cases are over 50 years of age and, and all cases the chief complain of bowel obstruction, abdominal pain in two cases, and one case with anemia and urine retention. All the patients were operated and were permormed pathology examinatiom. All case ware positive result for immunocytochemical staining CD117. All cases we had presented had size more than 5 cm are considered as unfavorable prognostic factors to Fletcher criteria, all patients scheduled for chemotherapy with Glivec but just one patient continued to used Glivec. Post surgery follows up one patient post milles with urinary incontinence complaints found and that patients are trained to CIC (intermittent catheterization). Conclusion: Colorectal gastrointestinal stromal tumors are very rare and can present as mass abdomen. Resection and chemotherapy are the treatment of choice.

A gist of gastrointestinal stromal tumors: A review

Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mes-enchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularlytargeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.

TATA-box-binding protein-associated factor 15 is a novel biomarker that promotes cell proliferation and migration in gastrointestinal stromal tumor

BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic targets for GIST.TATA-boxbinding protein-associated factor 15(TAF15)contributes to the progress of various tumors,while the role and molecular mechanism of TAF15 in GIST progression are still unknown.AIM To explore new molecular therapeutic targets for GIST and understand the biological role and underlying mechanisms of TAF15 in GIST progression.METHODS Proteomic analysis was performed to explore the differentially expressed proteins in GIST.Western blotting and immunohistochemical analysis were used to verify the expression level of TAF15 in GIST tissues and cell lines.Cell counting kit-8,colony formation,wound-healing and transwell assay were executed to detect the ability of TAF15 on cell proliferation,migration and invasion.A xenograft mouse model was applied to explore the role of TAF15 in the progression of GIST.Western blotting was used to detect the phosphorylation level and total level of RAF1,MEK and ERK1/2.RESULTS A total of 1669 proteins were identified as differentially expressed proteins with 762 upregulated and 907 downregulated in GIST.TAF15 was selected for the further study because of its important role in cell proliferation and migration.TAF15 was significantly over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with larger tumor size and higher risk stage of GIST.TAF15 knockdown significantly inhibited the cell proliferation and migration of GIST in vitro and suppressed tumor growth in vivo.Moreover,the inhibition of TAF15 expression significantly decreased the phosphorylation level of RAF1,MEK and ERK1/2 in GIST cells and xenograft tissues,while the total RAF1,MEK and ERK1/2 had no significant change.CONCLUSION TAF15 is over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with a poor prognosis of GIST patients.TAF15 promotes cell proliferation and migration in GIST via the activation of the RAF1/MEK/ERK signaling pathway.Thus,TAF15 is expected to be a novel latent molecular biomarker or therapeutic target of GIST.

Results of the Management of Gastrointestinal Stromal Tumors (GIST): About 6 Cases at the Vichy Hospital Center (France)

The aim of our study was to analyze the results of surgical management of gastrointestinal stromal tumors (GIST) at the Vichy Hospital Center. Methodology: Between 2010 and 2020, the data of 6 patients operated at the Vichy Hospital Center for GIST were analyzed. The parameters studied were: age, sex, antecedents, discovery circumstances, imagery, surgical procedure, anatomopathological data, the follow-up and the morbidity-mortality. Results: There were 5 men and one woman with an average age of 72.16 years [58 - 80 years]. The average time of evolution was 8 months (0 - 14 months). The diagnosis was fortuitous in 2 cases. Atypical abdominal pain was the main symptom in 3 cases. One case was received in a clinical picture of peritoneal irritation syndrome. Echo-endoscopy with biopsy specimen histology made it possible to make the diagnosis in 5 cases and the surgical specimen in 1 case. The fusiform type was the predominant histological form. The stomach was the most common location. The average size of GISTs was 7.3 × 4 cm with a positive C Kit in all patients. Neoadjuvant chemotherapy was performed on one patient. Surgery was curative and was done laparoscopically on 4 patients. Adjuvant chemotherapy based on Imatinib at a rate of 400 mg/d in 3 patients was initiated. One patient presented a fistula of the esophagus-jejunal anastomosis on D6 post operation controlled by a drainage and an antibiotic therapy. Mortality was zero. During the surgery, all of the patients were followed up with surgeon, oncologist. Conclusion: GISTs are the most common mesenchymal tumors of the digestive tract with a preferential gastric location. Laparoscopic surgery, with advances in molecular biology and the introduction of targeted therapy has improved the management of these tumors in terms of morbidity and mortality.

Raf kinase inhibitor protein combined with phosphorylated extracellular signal-regulated kinase offers valuable prognosis in gastrointestinal stromal tumor

BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.Tyrosine kinase inhibitors,such as imatinib,have been used as first-line therapy for the treatment of GISTs.Although these drugs have achieved considerable efficacy in some patients,reports of resistance and recurrence have emerged.Extracellular signal-regulated kinase 1/2(ERK1/2)protein,as a member of the mitogen-activated protein kinase(MAPK)family,is a core molecule of this signaling pathway.Nowadays,research reports on the important clinical and prognostic value of phosphorylated-ERK(P-ERK)and phosphorylated-MAPK/ERK kinase(P-MEK)proteins closely related to raf kinase inhibitor protein(RKIP)have gradually emerged in digestive tract tumors such as gastric cancer,colon cancer,and pancreatic cancer.However,literature on the expression of these downstream proteins combined with RKIP in GIST is scarce.This study will focus on this aspect and search for answers to the problem.AIM To detect the expression of RKIP,P-ERK,and P-MEK protein in GIST and to analyze their relationship with clinicopathological characteristics and prognosis of this disease.Try to establish a new prognosis evaluation model using RKIP and PERK in combination with analysis and its prognosis evaluation efficacy.METHODS The research object of our experiment was 66 pathologically diagnosed GIST patients with complete clinical and follow-up information.These patients received surgical treatment at China Medical University Affiliated Hospital from January 2015 to January 2020.Immunohistochemical method was used to detect the expression of RKIP,PERK,and P-MEK proteins in GIST tissue samples from these patients.Kaplan-Meier method was used to calculate the survival rate of 63 patients with complete follow-up data.A Nomogram was used to represent the new prognostic evaluation model.The Cox multivariate regression analysis was conducted separately for each set of risk evaluation factors,based on two risk classification systems[the new risk grade model vs the modified National Institutes of Health(NIH)2008 risk classification system].Receiver operating characteristic(ROC)curves were used for evaluating the accuracy and efficiency of the two prognostic evaluation systems.RESULTS In GIST tissues,RKIP protein showed positive expression in the cytoplasm and cell membrane,appearing as brownish-yellow or brown granules.The expression of RKIP was related to GIST tumor size,NIH grade,and mucosal invasion.P-ERK protein exhibited heterogeneous distribution in GIST cells,mainly in the cytoplasm,with occasional presence in the nucleus,and appeared as brownish-yellow granules,and the expression of P-ERK protein was associated with GIST tumor size,mitotic count,mucosal invasion,and NIH grade.Meanwhile,RKIP protein expression was negatively correlated with P-ERK expression.The results in COX multivariate regression analysis showed that RKIP protein expression was not an independent risk factor for tumor prognosis.However,RKIP combined with P-ERK protein expression were identified as independent risk factors for prognosis with statistical significance.Furthermore,we establish a new prognosis evaluation model using RKIP and P-ERK in combination and obtained the nomogram of the new prognosis evaluation model.ROC curve analysis also showed that the new evaluation model had better prognostic performance than the modified NIH 2008 risk classification system.CONCLUSION Our experimental results showed that the expression of RKIP and P-ERK proteins in GIST was associated with tumor size,NIH 2008 staging,and tumor invasion,and P-ERK expression was also related to mitotic count.The expression of the two proteins had a certain negative correlation.The combined expression of RKIP and P-ERK proteins can serve as an independent risk factor for predicting the prognosis of GIST patients.The new risk assessment model incorporating RKIP and P-ERK has superior evaluation efficacy and is worth further practical application to validate.

Synchronous occurrence of gastric cancer and gastrointestinal stromal tumor: A case report and review of the literature

BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer(GC)occurring synchronously with gastrointestinal stromal tumor(GIST).CASE SUMMARY We report 19 patients with concurrent GC and GIST(17 male and 2 female,median age 62 years).GC was most often located in the lower third of the stomach.GIST was diagnosed preoperatively in four patients.GIST was most often located in the gastric body(n=8,42%).The most common growth pattern in GIST was extraluminal(n=12,63%).The positive expression rates of CD117 and CD34 in GIST were 100% and 95%,respectively.Most patients with GIST(n=17,89%)were very low or low risk.There was no recurrence of GIST during follow-up.The 3-year cumulative survival rate was 73.9%,and the 5-year cumulative survival rate was 59.2%.The combined analysis of this study and literature reports(47 reports,157 patients)found that GC and GIST were usually located in the lower third(42%)and middle third(51%)of the stomach.GC was usually early(stage I:42%),poorly differentiated(42%)intestinal-type adenocarcinoma(51%).GISTs were primarily small in diameter(median:1.2 cm)and very low or low risk(89%).CONCLUSION Synchronous GC and GIST may not be rare.They have specific clinicopathological characteristics,and may have mutual inhibition in pathogenesis and progression.

Histopathologic and Immunohistochemical Analysis of 66 Cases of Gastrointestinal Stromal Tumor

Background and Objective: To investigate the histopathological characteristics and immunohistochemistry of gastrointestinal stromal tumors (GIST). Immunohistochemistry (IHC) refers to the expression and meaning of CD117, DOG-1, CD34. Methods: Sixty-six gastrointestinal stromal tumor (GIST) samples with complete clinical data and definite clinicopathological diagnosis were collected from the Seventh Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022. Retrospective analysis was performed on the pathological data of 66 patients with GIST, and the histopathology and IHC were analyzed and summarized. Results: Among the 66 cases, 46, 14, 1, 5 were found in the stomach, small intestine, large intestine, and gastroenteral area. There were 45 cases (97%), 11 cases (79%), 1 case (100%), 5 cases (100%) in order of fusiform cell type. There were 1 case (3%), 2 cases (14%), 0 case, 0 case of upper dermatiform;Mixed type in 0 case, 1 case (7%), 0 case, 0 case;CD117 positive 66 cases (100%), DOG-1 positive 66 cases (100%), CD34 positive 61 cases (92%), CD117 and/or CD34 negative 5 cases (8%);CD34, CD117 and DOG-1 were negative simultaneously in 0 case. 19 cases (28%) were positive for SMA and 7 cases (11%) were positive for S-100. Conclusion: Fusiform cell type is the common type of GIST, followed by epithelioid type and mixed type, but the tumor sites are different, and the comparison cases are not completely the same. CD117, DOG-1 and CD34 are high surface in GIST, and the combination of SMA, S-100 and histomorphology can be used to diagnose most GIST.

Rare rectal gastrointestinal stromal tumor case:A case report and review of the literature

BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare tumors of the gastrointestinal tract accounting for less than 1%of all gut tumors.GISTs occurring in the rectum are extremely rare,and these usually present at an advanced stage compared with other sites.CASE SUMMARY A 60-year-old male who presented with features of sensations of rectal tenesmus was referred to our department with a mass in the lower rectum that was detected during a routine checkup.Colonoscopy,transrectal ultrasound,perianal magnetic resonance imaging and ultrasonic contrast were used to diagnose the rectum GIST,and then the patient underwent complete transanal resection using the ultrasonic scalpel.The patient was discharged ten days after the operation and was defined as low risk.Therefore,he had no need to receive subsequent adjuvant therapies,and he had not suffered any anal dysfunction or had any evidence of recurrence at follow up.CONCLUSION Surgical resection with histologically negative margins is the standard curative treatment for rectal GISTs.Appropriate surgical techniques based on the location,size,and resectability of the tumor should attract great attention from clinicians.

Factors associated with gastrointestinal stromal tumor rupture and pathological risk:A single-center retrospective study

BACKGROUND Gastrointestinal stromal tumor(GIST)is a rare gastrointestinal mesenchymal tumor with potential malignancy.Once the tumor ruptures,regardless of tumor size and mitotic number,it can be identified into a high-risk group.It is of great significance for the diagnosis,treatment,and prognosis of GIST if non-invasive examination can be performed before surgery to accurately assess the risk of tumor.AIM To identify the factors associated with GIST rupture and pathological risk.METHODS A cohort of 50 patients with GISTs,as confirmed by postoperative pathology,was selected from our hospital.Clinicopathological and computed tomography data of the patients were collected.Logistic regression analysis was used to evaluate factors associated with GIST rupture and pathological risk grade.RESULTS Pathological risk grade,tumor diameter,tumor morphology,internal necrosis,gas-liquid interface,and Ki-67 index exhibited significant associations with GIST rupture(P<0.05).Gender,tumor diameter,tumor rupture,and Ki-67 index were found to be correlated with pathological risk grade of GIST(P<0.05).Multifactorial logistic regression analysis revealed that male gender and tumor diameter≥10 cm were independent predictors of a high pathological risk grade of GIST[odds ratio(OR)=11.12,95%confidence interval(95%CI):1.81-68.52,P=0.01;OR=22.96,95%CI:2.19-240.93,P=0.01].Tumor diameter≥10 cm,irregular shape,internal necrosis,gas-liquid interface,and Ki-67 index≥10 were identified as independent predictors of a high risk of GIST rupture(OR=9.67,95%CI:2.15-43.56,P=0.01;OR=35.44,95%CI:4.01-313.38,P<0.01;OR=18.75,95%CI:3.40-103.34,P<0.01;OR=27.00,95%CI:3.10-235.02,P<0.01;OR=4.43,95%CI:1.10-17.92,P=0.04).CONCLUSION Tumor diameter,tumor morphology,internal necrosis,gas-liquid,and Ki-67 index are associated with GIST rupture,while gender and tumor diameter are linked to the pathological risk of GIST.These findings contribute to our understanding of GIST and may inform non-invasive examination strategies and risk assessment for this condition.

Unusual breast metastasis of gastrointestinal stromal tumor:A case report and literature review

BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most frequent mesenchymal tumors of gastrointestinal tract.The most common sites of metastases are the liver and the peritoneum,whereas breast metastases from GIST are extremely rare.We present a second case of GIST breast metastasis.CASE SUMMARY We found a case of breast metastasis from rectum GIST.A 55-year-old female patient presented with rectum tumor with multiply liver lesions and metastasis in the right breast.Abdominal-perineal extirpation of rectum was performed,histology and immunohistochemistry study showed GIST,mixed type with CD117 and DOG-1 positive staining.The patient was taking imatinib 400 mg for 22 mo with stable disease.Because of growth of the breast metastasis the treatment was changed twice:The dose of imatinib was doubled with further progression in the breast lesion and then the patient was receiving sunitinib for 26 mo with partial response in the right breast and stable disease in the liver lesions.The breast lesion increased and right breast resection was done–surgery on local progression,the liver metastases were stable.Histology and immunohistochemistry studies revealed GIST metastasis,CD 117 and DOG 1 positive with KIT exon 11 mutation.After surgery the patient resumed imatinib.Until now the patient has been taking imatinib 400 mg for 19 mo without progression,last follow up was in November 2022.CONCLUSION GISTs breast metastases are extremely rare,we described the second case.At the same time second primary tumors have been reported frequently in patients diagnosed with GISTs and breast cancer is one of the most common second primary tumors in patients with GISTs.That is why it is very important to distinguish primary from metastatic breast lesions.Surgery on local progression made it possible to resume less toxic treatment.

Rectal gastrointestinal stromal tumors:Imaging features with clinical and pathological correlation

AIM:To investigate computed tomography(CT) and magnetic resonance imaging(MRI) manifestations of rectal gastrointestinal stromal tumors(GISTs) in order to enhance the recognition of these rare tumors.METHODS:Fourteen patients with pathologically proven rectal GISTs were retrospectively reviewed.Patient histories were retrospectively reviewed for patient age,gender,presenting symptoms,endoscopic investigations,operation notes and pathologic slides.All tumors were evaluated for CD117,CD34 expression,and the tumors were stratified according to current criteria of the National Institutes of Health(NIH).In all cases the first pre-operation imaging findings(CT and MRI,n = 3;MRI only,n = 8;CT only,n = 3) were analyzed by two experienced radiologists by consensus,which include:tumor size,shape,CT density(hypodense,isodense and hyperdense),MRI signal intensity(hypointense,isointense and hyperintense),epicenter(intraluminal or extraluminal),margin(well-defined or ill-defined),internal component(presence of calcifications,necrosis,hemorrhage or ulceration),pattern and degree of enhancement,invasion into adjacent structures.After review of the radiologic studies,clinical and pathological findings were correlated with radiological findings.RESULTS:The patients,13 men and 1 woman,were aged 31-62 years(mean = 51.5 ± 10.7 years).The most common initial presentation was hematochezia(n = 6).The mean tumor diameter was 5.68 ± 2.64 cm(range 1.5-11.2 cm).Eight lesions were round or oval,and 6 lesions were irregular.Eleven lesions were welldefined and 3 had ill-defined margins.Ten tumors were extraluminal and 4 were intraluminal.The density and MR signal intensity of the solid component of the lesions were similar to that of muscle on unenhanced CT(n = 6) and T1-weighted images(n = 11),and hyperintense on T2-weighted MR images.Calcification was detected in 2 tumors.Following intravenous injection of contrast media,3 lesions had mild enhancement and 11 lesions had moderate enhancement.Enhancement was homogenous in 3 lesions and heterogeneous in 11.In 1 of 11 patients who underwent both CT and MRI,the tumor was homogenous on CT scan and heterogeneous on MRI.Eight patients were classified as high risk according to the modified recurrent risk classification system of NIH.CONCLUSION:Rectal GISTs usually manifest as large,well-circumscribed,exophytic masses with moderate and heterogeneous enhancement on CT and MRI.The invasion of adjacent organs,bowel obstruction and local adenopathy are uncommon.

Molecular basis and management of gastrointestinal stromal tumors

Molecularly targeted agents have dramatically impacted the management of several cancers. Targeting KIT has led to a new treatment paradigm in gastrointestinal stromal tumors (GISTs). KIT is a cell surface receptor with tyrosine kinases that, upon binding of its ligand, stem cell factor, activates various signaling pathways. Imatinib and sunitinib, both tyrosine kinase inhibitors directed to KIT, were approved for firstand secondline treatment of metastatic and unresectable GISTs. In this article, we will review the molecular pathogenesis of GISTs followed by a discussion of imatinib and sunitinib’s role in the treatment of GISTs. Finally, we will introduce novel therapeutic options for imatiniband sunitinib-resistant GISTs.