Mesenchymal Tumors Of Gastrointestinal Tract Research Articles

Our experience with gastrointestinal stromal tumors at tertiary care hospital in central India: A retrospective observational study

Gastrointestinal stromal tumors (GISTs) are the commonest mesenchymal tumor of gastrointestinal tract. Commonly found in Stomach and Small intestine, may present as E GIST. A case series of 30 patients over a period of 3 years managed at Government medical college and hospital. A Retrospective study of the GIST cases. Around 30 patients who were diagnosed having GIST, there records were compiled. Data analysis of all patients in terms of demographics, clinical presentation, location of the tumor, management has been done. Presented with varied complaints such as pain in abdomen, lump in abdomen, upper/lower GI bleeding, weight loss, obstruction perforation, hematuria and retention of urine depending upon the site involved. Sites involved were small bowel (16), Stomach (10), Colon (1), Rectosigmoid (1), retroperitoneum (1) and omentum (1). Half the cases took imatinib including neoadjuvant and post operative cases and rest lost to follow up. Surgery being the main stay of treatment.

Malignant Extra-Gastrointestinal Stromal Tumor of the Mesentery

Gastrointestinal stromal tumors (GISTs), the commonest mesenchymal tumors of gastrointestinal tract are often described to take origin from the interstitial cells of Cajal (ICC) or its precursor cells. Rarely these tumors do arise in structures other than the alimentary tract like omentum, mesentery, retroperitoneum, etc., of varying malignant potential and are known as extra-gastrointestinal stromal tumors (eGISTs).This is a case report of a 70-year-old female with multicentric malignant eGISTs arising in the mesentery of ileum. On laparotomy, a large mass of 20 × 15 cm was found in the small bowel mesentery without involvement of the adjacent ileum, with multiple other small nodules resembling lymph nodes, present adjacent to it. Histopathological study of the excised lump, confirmed the mass to be malignant eGIST without involvement of the adjacent ileum, with cluster differentiation (CD)117 positive and of high-risk stratification. The mesenteric nodule was confirmed on histopathology to be malignant eGIST, similar to that of that of the primary, without any lymphoid tissue. Adjuvant imatinib mesylate treatment was started immediately postoperation with the patient doing well at 1 year of follow-up. We report this case, due to the rare occurrence of multifocal malignant eGISTS of small bowel mesentery, which is yet to be reported. The existing literature is unclear regarding the clinicopathology and management of multifocal malignant stromal tumors of the mesentery.

Gastrointestinal stromal tumours (GIST) — 2018

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of gastrointestinal tract. Advances in the understanding of the pathologic-molecular mechanisms of GIST pathogenesis have emerged GIST as a model of targeted therapy in oncology. The paper describes advances in diagnostics and therapy of these tumours based on new scientific basis. Radical surgery is still the mainstay treatment for primary, localized, resectable GISTs, although high percentages of the patients after potentially curative operations develop recurrent or metastatic disease; thus all GIST should be evaluated for potential adjuvant therapy with imatinib. In inoperable/metastatic lesions the treatment of choice is tyrosine kinase inhibitor — imatinib mesylate In case of disease progression the increase of imatinib dose to 800 mg daily is recommended and if further progression exists — sunitinib in the initial dose 50 mg daily should be introduced, thereafter sorafenib/regorafenib or clinical trial with new drugs (e.g. BLU-285 or DCC2618).

Difficulties of diagnosis of GIST. Case histories of three patients with GIST

Introduction: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of gastrointestinal tract. It was named at first by Mazur and Clark in 1983. The GIST is rare tumor of gastrointestinal tract (2,2% of all tumors). The malignant version of GIST is the largest part of GI-sarcomas. These tumors can be lethal; depends of tumor size, mitotic index and location. The incidence rate of GIST nowdays is increasing. This fact may be explaned by better understanding of the pathobiology and the central role of activating Kit mutations in the pathogenesis. Nowdays specific diagnostic immunhistochemical examination is generally avaiable. The incidence rate is around 13-15-17 per million of inhabitants. 20-30% of cases are malignant. There is no difference between of female and male.

Mechanisms of the resistance of gastrointestinal stromal tumors to imatinib

The review describes the modern concepts of the primary and secondary (acquired) resistance of gastrointestinal stromal tumors to the targeted drug imatinib. Gastrointestinal stromal tumors are the mesenchymal tumors of gastrointestinal tract that originate from interstitial cells of Cajal or their stem cell precursors. Up to 85 % of gastrointestinal stromal tumors have the mutations of KIT gene that lead to ligand-independent activation of this tyrosine kinase. Imatinib is an inhibitor of KIT tyrosine kinase which is hyperexpressed in 70-85 % of cases on the cell membrane of gastrointestinal stromal tumors. Despite the high effectiveness of imatinib in gastrointestinal stromal tumors, up to 15 % of patients do not respond to this therapy, and over 50 % of patients acquire the resistance to this drug 2 years after initiation of target therapy with imatinib. The mechanisms of primary resistance include basically the mutational status of KIT, PDGFRA and, rarely, mutations of SDH, NF1, BRAF, PI3K3CA, CBL, and KRAS. The mechanisms of secondary resistance of tumor cells to imatinib are not restricted to the secondary mutations of KIT and PDGFRA, but also might be due to the loss of KIT expression associated by overexpression of the alternative receptor- and non-receptor tyrosine kinases, such as MET, AXL, FGFR2α, FAK, etc. Alternative mechanisms of acquired resistance might be due to the mutations of BRAF gene.

KIT exon 11 and PDGFRA exon 18 gene mutations in gastric GIST: proposal of a short panel for predicting therapeutic response

BackgroundGIST is the most common mesenchymal tumor of gastrointestinal tract and is more frequent in stomach. Its main mutations affect KIT and PDGFRA genes. Full genetic analysis panels are currently used to study mutations in GIST and other tumors. Considering that in gastric GIST KIT gene mutations in exon 11 are sensitive to IM whereas PDGFRΑ gene mutations in exon 18 (D842V) are resistant to the same drug, the aim of this study is to focus on these two molecular targets as a short alternative panel for predicting therapeutic response in gastric GIST which might optimize resources.MethodsThe genotypes of 38 cases of primary GIST were determined by performing bidirectional DNA sequencing.ResultsExon 11 of KIT gene showed mutations in 65.3% and the exon 18 of PDGFRA gene showed 9% of cases. So it was possible to determine a subgroup of tumors which presented mutations in KIT exon 11 and PDGFRA exon 18.ConclusionConsidering all of the foregoing analyzed globally, the application of short panel has impact on the cost and time of release of results to the physician, allowing a rapid approach to patients eligible for treatment with the target therapy.

Gastrointestinal schwannomas: a rare but important differential diagnosis of mesenchymal tumors of gastrointestinal tract

BackgroundSchwannomas of gastrointestinal tract are rare, mostly benign and notably different neoplasms from conventional schwannomas that arise in soft tissue or the central nervous system. These tumors are of clinical importance since they should always be considered in the differential diagnosis of submucosal lesions of gastrointestinal tract.MethodsSeven patients with a pathologically proven gastrointestinal schwannoma were identified in our series of mesenchymal tumors and reviewed retrospectively. Clinicopathological and immunohistochemical parameters along with the follow-up results were analysed.ResultsThe series included two males and five females, with a mean age 69 years (range, 39–81). Most patients were asymptomatic on presentation, except for two patients with abdominal pain. In the other cases (n = 5), the tumor was an incidental finding during other medical, imaging or surgical procedures. The tumors were located in the stomach (n = 4) and in the small intestine (n = 3) with an average size of 29 mm (range, 12–70). A preoperative diagnosis was achieved only in one case with a CT-guided core biopsy. Otherwise the clinical, intraoperative, endoscopic or radiological findings were unspecific. Patients with gastric tumor underwent either laparoscopic (n = 2) or open (n = 2) gastric wedge resection of the tumor; in the cases of intestinal tumor (n = 3) a segmentectomy was performed. Pathological examination revealed solid homogenous tumors, which were highly cellular and composed of spindle cells with positive staining for S100 protein, and confirmed the diagnosis of schwannoma. All tumors were negative for c-Kit, smooth muscle actin, desmin and DOG-1 and showed very low proliferation index. There were negative resection margins and no malignant variants were recognized. At an average follow-up of 60 months (range, 24–185) all patients were free of disease with no signs of recurrence or metastases and acceptable gastrointestinal function.ConclusionsSchwannomas are rare, slow-growing and mostly asymptomatic gastrointestinal mesenchymal tumors. They are difficult to be diagnosed preoperatively as endoscopic and radiological findings are nonspecific but histological and immunohistochemical features are of paramount importance to differentiate between benign and malignant schwannomas, or other spindle cell sarcomas. The treatment of choice is complete surgical excision without a conclusive preoperative diagnosis, and the long-term outcome is excellent as these lesions are mostly benign.

Small Molecules in Rare Tumors: Emerging Role of MicroRNAs in GIST.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of gastrointestinal tract. GISTs have very different clinical phenotypes and underlying molecular characteristics that are not yet completely understood. microRNAs (miRNAs) have been shown to participate in carcinogenesis pathways through post-transcriptional regulation of gene expression in different tumors. Over the last years emerging evidence has highlighted the role of miRNAs in GISTs. This review provides an overview of original research papers that analyze miRNA deregulation patterns, functional role, diagnostic, therapeutic and prognostic implications in GIST as well as provides directions for further research in the field.

Mesenchymal Tumors of Gastrointestinal Tract- The Role of Immunohistochemistry in Characterizing Specific Tumors

Mesenchymal Tumors of Gastrointestinal Tract- The Role of Immunohistochemistry in Characterizing Specific Tumors

Syndromic gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of gastrointestinal tract. They feature heterogeneous triggering mechanisms, implying relevant clinical differences. The vast majority of GISTs are sporadic tumors. Rarely, however, GIST-prone syndromes occur, mostly depending on heritable GIST predisposing molecular defects involving the entire organism. These conditions need to be properly identified in order to plan appropriate diagnostic, prognostic and therapeutic procedures.Clinically, GIST-prone syndromes must be thought of whenever GISTs are multiple and/or associated with accompanying signs peculiar to the background tumorigenic trigger, either in single individuals or in kindreds. Moreover, syndromic GISTs, individually considered, tend to show distinctive features depending on the underlying condition. When applicable, genotyping is usually confirmatory.In GIST-prone conditions, the prognostic features of each GIST, defined according to the criteria routinely applied to sporadic GISTs, combine with the characters proper to the background syndromes, defining peculiar clinical settings which challenge physicians to undertake complex decisions. The latter concern preventive therapy and single tumor therapy, implying possible surgical and molecularly targeted options.In the absence of specific comprehensive guidelines, this review will highlight the traits characteristic of GIST-predisposing syndromes, with particular emphasis on diagnostic, prognostic and therapeutic implications, which can help the clinical management of these rare diseases.

Clinicopathological impact of protein phosphatase 2, regulatory subunit A, alpha mutations in gastrointestinal stromal tumors.

10536 Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in gastrointestinal tract. Approximately 85-90% of GISTs are harboring oncogenic mutations in KIT or...

The importance of mutational status in prognosis and therapy of GIST

GIST (gastrointestinal stromal tumor) are the most common mesenchymal tumors in gastrointestinal tract and are thought to derive from the cells of Cajal or their precursors that have a constitutional mutation in KIT and PDGFRA genes. There are KIT and PDGFRA genes mutations detected before the start of therapy that are believed to be related to GIST pathogenesis and some secondary mutations causing drug resistance and progression of disease. The most common KIT mutations are detected in exon 11 (66-71%), exon 9 (10-13%), exon 13,14,17 (1% each). PDGFRA mutations (8%) are described in exon 18 (5-6%), 12 (1%) and 14 (1%). No mutations are detected in 5-10% of tumors and those subtypes are called wild type GIST (WT). Imatinib mesilate is a selective inhibitor of KIT and PDGFRA with an antityrosine kinase activity (TKI) used in advanced or metastatic GIST as well as in adjuvant setting after complete resection of neoplasm. Imatinib has radically changed the therapy and prognosis of GIST, but sensitivity of the disease is different on the basis of leading mutations. GIST KIT exon 11 mutated manifests response rate in 80% of cases, exon 9 in 40% and GIST WT in 14%. PDGFRA shows a mild sensitivity to drug (66%) except the exon 18 D842 V mutation which is totally resistant. Unfortunately up to 15% of GIST have a primary resistance to imatinib that means progression of the disease within 6-12 months after the start of therapy. Another 40-50% of GIST develops a secondary resistance after >24 months of TKI treatment. Biopsy of progressing GIST shows multiple clonal origins with distinct mutational changes. Secondary resistance occurs almost exclusively in KIT mutated GIST with the appearances of T670I gatekeeper secondary mutation and less common in 14, 17, 18 exons. After progression of disease second line therapy is represented by sunitinib malate that overcomes the most common resistant mutations excepted PGDFRA D842V. Again, after few months of treatment, new different mutations appear and the disease progresses. Regorafenib is the third line therapy but too few data relates mutational status and regorafenib activity. In adjuvant setting only imatinib has a role. Two important studies (the USA ACOSOG Z 9001 and the German-Scandinavian study) fail to demonstrate that a specific mutation can predict a better DFS and OS in treated patients. On the contrary, volume of the tumor, number of mitosis and site of GIST are strong prognostic and predictive factors. In conclusion mutational analysis in GIST is at present more useful in metastatic setting than in adjuvant therapy. The insurgence of primary and secondary mutations during therapy is a fundamental step for disease progression.

Utility of immunohistochemical investigation of SDHB and molecular genetic analysis of SDH genes in the differential diagnosis of mesenchymal tumors of GIT.

Loss of expression of beta subunit of succinate dehydrogenase (SDHB) was proved to be present in a subgroup of KIT/PDGFRA wt gastrointestinal stromal tumors (GISTs). To evaluate possible diagnostic utility of SDHB immunohistochemistry in the differential diagnostics of mesenchymal tumors of gastrointestinal tract (GIT), 11 cases of KIT/PDGFRA wt GISTs, 12 gastric schwannomas (GSs), 20 solitary fibrous tumors (SFTs), 4 leiomyomas (LMs), 16 leiomyosarcomas (LMSs), 5 synovial sarcomas (SSs), 3 endometrioid stromal sarcomas (ESSs), and 1 ileal inflammatory myofibroblastic tumor (IMT) were investigated for SDHB immunoexpression together with molecular genetic analysis of genes encoding succinate dehydrogenase (SDH). Three recent cases of KIT/PDGFRA mutant GISTs were used as controls. Among the 11 KIT/PDGFRA wt GISTs, 6 expressed SDHB, 1 of them harboring a sequence change of SDHD. All SDHB-negative cases were SDHB-D wt. In 1 of the control GIST cases molecular genetic analysis revealed an SDHD sequence change in addition to a mutation in KIT exon 11. No SFT was truly SDHB-negative, but in 2 of them the staining was impossible to analyze. Furthermore, 1 SFT carried an SDHB and another 1 SDHD sequence change. All GSs, LMs, LMSs, SSs, ESSs, and IMT were SDHB-positive or non-analyzable, and SDHB-D wt. Additional factors may play a role in regulating expression of SDHB. Furthermore, SDHB immunohistochemistry alone may be misleading in excluding tumors other than GIST (especially SFT) in the differential diagnosis of KIT/PDGFRA wt mesenchymal tumors of GIT.

Commentary to: Atypical Presentation of Gastrointestinal Stromal Tumours—A Case Report by Kalpana Raja et al.

Dear Sir, I read the case report “ATYPICAL PRESENTATION OF GASTROINTESTINAL STROMAL TUMOURS—A CASE REPORT” written by authors: Kalpana Raja, Bhawna Dev, Roy Santosham, and Joseph Santhosh, which was received 26th Feb. 2010/Accepted 4th June 2012/Published on line: 21st June 2012 7 Print Publication in Indian J Surg ( June 2013) 75 (suppl 1): S185–S187. It is really confusing whether gastrointestinal stromal tumors (GIST) are benign or highly malignant. Authors in their case report mention that GIST are benign mesenchymal tumours of gastrointestinal tract, as per the Abstract and their Discussion, while in their conclusion they mention that GISTs are highly malignant. Hence, I would like to draw the attention of authors that, essentially, to start with, GISTs are benign when they are microscopic or very small, i.e., <2 cm in size, if arising from stomach and are usually incidentally detected but when they attain large size or they become symptomatic they are mostly malignant GIST. According to NCCN Guidelines 2014, most GISTs behave in an indolent manner, and those smaller than 2 cm in size are almost universally benign, but similar lesions of small intestine tend to be more aggressive than Gastric GISTs. So, tumor size less than or equivalent to 2 cm with a mitotic rate of 5 mitosis per 50 high-power field on microscopic examination are to be considered as benign; otherwise, most are considered as malignant GISTs [1]. Secondly, GISTs are the most common mesenchymal neoplasms of the gastrointestinal tract resulting from mutation in one of the receptor protein tyrosin kinase (KIT—called CD 117).Most GISTs (90–95 %) are KIT-positive; hence, CD 117 is quite diagnostic of GIST, but it does not mean that CD 117 positivity is associated with malignant behavior of GIST. Also, CD 117 is the most important immunohistochemical marker than CD 34 which is positive in <80 % cases of GIST [2–4].

Synchronous GIST of jejunum and neuroendocrine tumor of duodenum: A rare case report

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of gastrointestinal tract, although it comprises only 0.1-3% of all gastrointestinal neoplasms. The majority of the neuroendocrine tumors of small intestine occur in adults and most of them are located in ileum followed by jejunum and duodenum. We present a case of synchronous GIST of jejunum and neuroendocrine tumor of duodenum in an elderly adult male patient without any associated syndrome. Although a Synchronous occurrence of gastrointestinal tumors without any coexisting syndromes is rare, a complete workup should be done to rule it out in any gastrointestinal tumors. To the best of our knowledge this is the first case to be reported in literature.

Gastrointestinal Stromal Tumor in Sigmoid Colon at a Tertiary Care Hospital: A Case Report

Gastrointestinal stromal tumors (GISTs) are the mesenchymal tumors representing the most common mesenchymal neoplasm of gastrointestinal tract. However, GIST is recognized tumor entity and the literature on these stromal tumors has rapidly expanded. This present case report has been found in Dhaka at a tertiary care hospital in a male patient. The patient was operated at the local area before admitted at this hospital where he was misdiagnosed. In this hospital the diagnosis was confirmed by histopathologically. Surgical resection was performed laparoscopically by a skilled surgical team. DOI: http://dx.doi.org/10.3329/jssmc.v5i1.16224 J Shaheed Suhrawardy Med Coll, 2013;5(1):59-62

P-0128 - Characteristics and Outcome of Gastrointestinal Stromal Tumors (Gist): a Single Center Experience Over a Decade

Background: GISTs are the most common mesenchymal tumors of gastrointestinal tract (GI) and account for 0,1% to 0,3% of all GI tumors. Their biological behavior is difficult to predict, ranging from clinically benign to malignant. Tumor size, mitotic rate, and anatomic location correlate with potential malignancy and recurrence rate. Treatment with tyrosine kinase inhibitors has revolutionized therapy for gists, but complete resection remains the treatment of choice. Our aim is to analyze the outcome of 52 patients with gastrointestinal stromal tumor (GIST) who were treated at a single

Evaluation of mesenchymal tumors of gastrointestinal tract with special reference to gastrointestinal stromal tumors – A tertiary care center experience

Evaluation of mesenchymal tumors of gastrointestinal tract with special reference to gastrointestinal stromal tumors – A tertiary care center experience

Evaluation of mesenchymal tumors of gastrointestinal tract with special reference to gastrointestinal stromal tumors – A tertiary care center experience

Background: Gastrointestinal tumors (GISTs) have attained significance in recent years because of their dramatic response to imatinib. Imatinib acts by inhibiting the proliferation and inducing apoptosis of GIST cells which express by activating c-kit mutation. GISTs with activating c-kit mutation show positivity for CD117 marker immunohistochemically. In this study, we analyzed the mesenchymal tumors of gastrointestinal tract morphologically and immunohistochemically. Materials And Methods: In this single-institutional retrospective study from January 1995 to April 2010, 52 mesenchymal tumors of gastrointestinal tract were included. Initially they were grouped under smooth muscle and stromal tumors based on their morphology and immunoreactivity for smooth muscle markers. Later on, they were subjected to additional immunostaining by CD117. Based on this, the mesenchymal tumors were reclassified. Results: In our study, the median age was 50 years (range 20-86 years). Stomach was the most common site ( n = 13). After CD117 immunostaining, 16 cases which were originally grouped under smooth muscle tumors were reclassified as GISTs. Conclusion: GISTs showing CD117 positivity are the largest group of mesenchymal tumors of gastrointestinal tract. Categorization of tumors as GIST helps to consider the patients for potential imatinib therapy.

Primary Extra-Gastrointestinal Stromal Tumor (GIST) arising from mesentery of small bowel and presenting as abdominal mass: A rare entity

Introduction: Majority of mesenchymal tumors of gastrointestinal tract are Gastrointestinal Stromal Tumor (GIST). It is, however, a rare tumor, accounting for less than 1% of primary gastrointestinal (GI) neoplasms. Though, these tumors are refractory to conventional chemotherapy or radiotherapy but show a good response to targeted adjuvant chemotherapy with tyrosine kinase inhibitors following surgical resection. Case Report: we report here a case of primary Extra-GIST tumor arising from mesentry of small bowel near duodeno-jejunal junction in a 69 years old male patient. The patient presented with a palpable mass in upper abdomen for past 15 days. On examination, a non-tender mobile lump of size around 17 × 10 cm, with bosselated surface and firm in consistency was palpable involving epigastric, left hypochondrium and umbilical region. Contrast enhanced computed tomography of abdomen revealed a heterogenous mesentric mass. On surgical intervention a mass was found involving mesentery near dudenojejunal junction without involvement of gastrointestinal tract. Complete surgical resection of the tumor was done and adjuvant chemotherapy with Imatinib mesylate was started as HPE revealing GIST with mitotic index of >10/50 HPF and 17 × 10 cm size placed the patient in high risk category. Patient was discharged on 12th of post-operative day with advice of regular follow-up. Conclusion: GIST occurrence is not restricted to bowel but can involve unusual sites also. The mainstay of treatment remains surgical resection with adequate margin. In cases where tumour has malignant potential (high mitotic figures on histopathology) adjuvent treatment with tyrosine kinase may prevent or delay relapse.