Two different mutational types of familial gastrointestinal stromal tumors:Two case reports

BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract,and cases of GISTs tend to be of the disseminated type,with a global incidence of 10 to 15 cases/million each year.The rarer familial GISTs,which often represent a population,differ in screening,diagnosis,and treatment.Familial GISTs include primary familial GISTs with predominantly KIT/PDGFRA mutations and wild-type GISTs.However,whether the same genetic family has different phenotypes has not been reported.CASE SUMMARY We report two cases of rare GISTs in the same family:A male patient with the V561D mutation in exon 12 of the PDGFRA gene,who has been taking the targeted drug imatinib since undergoing surgery,and a female patient diagnosed with wild-type GIST,who has been taking imatinib for 3 years since undergoing surgery.The favorable prognosis of these patients during the 7-year follow-up period validates the accuracy of our treatment strategy,and we have refined the entire process of diagnosis and treatment of familial GISTs in order to better manage this rare familial disease.CONCLUSION Different mutation types of familial GISTs in the same family are very rare,thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.

Extragastrointestinal stromal tumors with diffuse membranous distribution with bleeding:A case report

BACKGROUND Extragastrointestinal stromal tumors(EGIST)and gastrointestinal stromal tumors are of similar pathological type and form.Here we report a rare case of EGIST diffusely distributed in membranous tissue in abdominal cavity,the feature of which included diffuse tumors at membranous tissue in entire abdominal cavity and spontaneous bleeding of the tumors.CASE SUMMARY The patient was a 71-year man and hospitalized due to continuous pain at lower abdomen for more than 10 days.Upon physical examination,the patient had flat and tough abdomen with mild pressing pain at lower abdomen,no obvious abdominal mass was touchable,and shifting dullness was positive.Positron emission tomography-computed tomography(CT)showed that in his peritoneal cavity,there were multiple nodules of various sizes,seroperitoneum,multiple enlarged lymph nodes in abdominal/pelvic cavity and right external ilium as well as pulmonary nodules.Plain CT scanning at epigastrium/hypogastrium/pelvic cavity+enhanced three-dimensional reconstruction revealed multiple soft tissue nodules in abdominal/pelvic cavity,peritoneum and right groin.Tumor marker of carbohydrate antigen 125 was 808 U/mL,diffuse tuberous tumor was seen in abdominal/pelvic cavity during operation with hematocelia,and postoperative pathological examination confirmed EGIST.Imatinib was administered with better therapeutic effect.CONCLUSION Gene testing showed breast cancer susceptibility gene 1 interacting protein C-terminal helicase 1 and KIT genovariation,and the patient was treated with imatinib follow-up visit found that his clinical symptoms disappeared and the tumor load alleviated obviously via imageological examination.

Computed tomography radiogenomics:A potential tool for prediction of molecular subtypes in gastric stromal tumor

BACKGROUND Preoperative knowledge of mutational status of gastrointestinal stromal tumors(GISTs)is essential to guide the individualized precision therapy.AIM To develop a combined model that integrates clinical and contrast-enhanced computed tomography(CE-CT)features to predict gastric GISTs with specific genetic mutations,namely KIT exon 11 mutations or KIT exon 11 codons 557-558 deletions.METHODS A total of 231 GIST patients with definitive genetic phenotypes were divided into a training dataset and a validation dataset in a 7:3 ratio.The models were constructed using selected clinical features,conventional CT features,and radiomics features extracted from abdominal CE-CT images.Three models were developed:ModelCT sign,modelCT sign+rad,and model CTsign+rad+clinic.The diagnostic performance of these models was evaluated using receiver operating characteristic(ROC)curve analysis and the Delong test.RESULTS The ROC analyses revealed that in the training cohort,the area under the curve(AUC)values for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic)for predicting KIT exon 11 mutation were 0.743,0.818,and 0.915,respectively.In the validation cohort,the AUC values for the same models were 0.670,0.781,and 0.811,respectively.For predicting KIT exon 11 codons 557-558 deletions,the AUC values in the training cohort were 0.667,0.842,and 0.720 for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic),respectively.In the validation cohort,the AUC values for the same models were 0.610,0.782,and 0.795,respectively.Based on the decision curve analysis,it was determined that the model_(CT sign+rad+clinic)had clinical significance and utility.CONCLUSION Our findings demonstrate that the combined modelCT_(sign+rad+clinic)effectively distinguishes GISTs with KIT exon 11 mutation and KIT exon 11 codons 557-558 deletions.This combined model has the potential to be valuable in assessing the genotype 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.

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

Postoperative encapsulated hemoperitoneum in a patient with gastric stromal tumor treated by exposed endoscopic full-thickness resection: A case report

BACKGROUND Gastric stromal tumors,originating from mesenchymal tissues,are one of the most common tumors of the digestive tract.For stromal tumors originating from the muscularis propria,compared with conventional endoscopic submucosal dissection(ESD),endoscopic full-thickness resection(EFTR)can remove deep lesions and digestive tract wall tumors completely.However,this technique has major limitations such as perforation,postoperative bleeding,and post-polypectomy syndrome.Herein,we report a case of postoperative serous surface bleeding which formed an encapsulated hemoperitoneum in a patient with gastric stromal tumor that was treated with exposed EFTR.Feasible treatment options to address this complication are described.CASE SUMMARY A 47-year-old male patient had a hemispherical protrusion found during gastric endoscopic ultrasonography,located at the upper gastric curvature adjacent to the stomach fundus,with a smooth surface mucosa and poor mobility.The lesion was 19.3 mm×16.1 mm in size and originated from the fourth ultrasound layer.Computed tomography(CT)revealed no significant evidence of lymph node enlargement or distant metastasis.Using conventional ESD technology for mucosal pre-resection,exposed EFTR was performed to resect the intact tumor in order to achieve a definitive histopathological diagnosis.Based on its morphology and immunohistochemical expression of CD117 and DOG-1,the lesion was proven to be consistent with a gastric stromal tumor.Six days after exposed EFTR,CT showed a large amount of encapsulated fluid and gas accumulation around the stomach.In addition,gastroscopy suggested intracavitary bleeding and abdominal puncture drainage indicated serosal bleeding.Based on these findings,the patient was diagnosed with serosal bleeding resulting in encapsulated abdominal hemorrhage after exposed EFTR for a gastric stromal tumor.The patient received combined treatments,such as hemostasis under gastroscopy,gastrointestinal decompression,and abdominal drainage.All examinations were normal within six months of follow-up.CONCLUSION This patient developed serous surface bleeding in the gastric cavity following exposed EFTR.Serosal bleeding resulting in an encapsulated hemoperitoneum is rare in clinical practice.The combined treatment may replace certain surgical techniques.

Effect and safety of ripretinib in the treatment of advanced gastrointestinal stromal tumor:A systematic review and metaanalysis

BACKGROUND Imatinib(IMA)has received approval as the primary treatment for gastrointestinal stromal tumors(GIST).Nonetheless,approximately half of the patients with advanced GIST show disease advancement following IMA treatment.Presently,the efficacy of secondary and tertiary medications in addressing various GIST secondary mutations is somewhat restricted.Consequently,there is a significant medical demand for the creation of kinase inhibitors that extensively block secondary drug-resistant mutations in advanced GIST.Ripretinib(RPT)is a new,switch-control tyrosine kinase inhibitors that can suppress different mutations of KIT and PDGFRA via a dual mechanism of action.AIM To investigate the literature on RPT to assess an effective,safe,and successful treatment strategy against advanced GIST.METHODS The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.PubMed,Embase,Cochrane,Web of Science and ClinicalTrials.gov databases were screened from January 1,2003 to May 1,2024.RESULTS A total of 4 studies were included,with a total of 507 patients enrolled.The objective response rate(ORR)of the RPT-treated advanced GIST was 17%(95%CI:0.11-0.27),while the disease control rate(DCR)was 66%(95%CI:0.59-0.73).The overall occurrence of adverse events with varying degrees was 97%(95%CI:0.93-1),whereas that of grade≥3 adverse reactions was 42%(95%CI:0.28-0.63).The sensitivity analysis revealed that omitting some studies did not yield statistically notable variances in the aggregate data regarding the ORR,DCR,and the occurrence of adverse events of grade 3 or higher.The publication bias was absent because no significant asymmetry was observed in Begg’s funnel plot in all studies.CONCLUSION RPT has favorable efficacy profiles in GIST patients,but the adverse reactions are obvious,and patient management needs to be strengthened to achieve better safety and tolerability.

Advancing gastrointestinal stromal tumor management: The role of imagomics features in precision risk assessment

BACKGROUND Gastrointestinal stromal tumors(GISTs)vary widely in prognosis,and traditional pathological assessments often lack precision in risk stratification.Advanced imaging techniques,especially magnetic resonance imaging(MRI),offer potential improvements.This study investigates how MRI imagomics can enhance risk assessment and support personalized treatment for GIST patients.AIM To assess the effectiveness of MRI imagomics in improving GIST risk stratification,addressing the limitations of traditional pathological assessments.METHODS Analyzed clinical and MRI data from 132 GIST patients,categorizing them by tumor specifics and dividing into risk groups.Employed dimension reduction for optimal imagomics feature selection from diffusion-weighted imaging(DWI),T1-weighted imaging(T1WI),and contrast enhanced T1WI with fat saturation(CET1WI)fat suppress(fs)sequences.RESULTS Age,lesion diameter,and mitotic figures significantly correlated with GIST risk,with DWI sequence features like sphericity and regional entropy showing high predictive accuracy.The combined T1WI and CE-T1WI fs model had the best predictive efficacy.In the test group,the DWI sequence model demonstrated an area under the curve(AUC)value of 0.960 with a sensitivity of 80.0%and a specificity of 100.0%.On the other hand,the combined performance of the T1WI and CE-T1WI fs models in the test group was the most robust,exhibiting an AUC value of 0.834,a sensitivity of 70.4%,and a specificity of 85.2%.CONCLUSION MRI imagomics,particularly DWI and combined T1WI/CE-T1WI fs models,significantly enhance GIST risk stratification,supporting precise preoperative patient assessment and personalized treatment plans.The clinical implications are profound,enabling more accurate surgical strategy formulation and optimized treatment selection,thereby improving patient outcomes.Future research should focus on multicenter studies to validate these findings,integrate advanced imaging technologies like PET/MRI,and incorporate genetic factors to achieve a more comprehensive risk assessment.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.