Search Results (171)

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors primarily located in the stomach and small intestine; their occurrence in the terminal ileum is particularly rare. Although GISTs can develop throughout the gastrointestinal tract, cases of perforation in elderly individuals are even less common, posing significant diagnostic and therapeutic challenges. This case report describes an 86-year-old male patient with an acute abdomen caused by a terminal ileum perforated GIST requiring urgent surgical intervention. An immunohistochemical examination of the tumor confirmed a GIST with a GILT (gastrointestinal leiomyogenic tumor) immunophenotype. The rarity of this condition makes it diagnostically challenging, as its symptoms are often nonspecific, and GISTs are frequently overlooked, particularly in older patients. This case supplements the existing literature by emphasizing the importance of considering GIST perforation in the differential diagnosis of an acute abdomen, even in elderly patients and in rare anatomical locations. Full article

This case represents a relatively rare localization of a gastrointestinal stromal tumor involving the distal esophagus with a very unusual mode of metastatic spread to the lymph nodes and bone structures. Diagnostic follow-up showed the effect of tyrosine kinase inhibitor therapy on metastatic lesions, highlighting the necessity of comprehensive diagnostic evaluation in patients with atypical presentations and contributing to the improvement of therapeutic strategies in complex clinical scenarios. Full article

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, primarily driven by activating mutations in KIT (CD117) and platelet-derived growth factor receptor alpha (PDGFRA). The introduction of tyrosine kinase inhibitors (TKIs), especially imatinib, has significantly transformed GIST treatment. However, the emergence of both primary and secondary resistance to imatinib presents ongoing therapeutic challenges. This review comprehensively explores the mechanisms underlying imatinib resistance and evaluates subsequent TKI therapies. Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents—such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib—have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs. Despite progress, long-term efficacy remains limited due to evolving resistance. Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options, especially for rare GIST subtypes. Full article

Rare presentations are surprising and may disturb the day-to-day routine of a medical unit; however, they are expected (not as individual entities, but as a group of “uncommon causes”). While reviewing the literature in relation to three clinical cases of upper gastrointestinal bleeding (UGIB) encountered in our institution—gastric metastases of breast cancer (GMB), pyloric gland adenoma, and gastrointestinal stromal tumor (GIST)—we identified seven and 29 case reports for the first two entities, and over 100 publications addressing GIST. This prompted a shift in focus from novel reporting to diagnostic contextualization. We found it difficult to obtain an overview of the spectrum of UGIB etiologies, as most publications refer to a few individual entities or to a subgroup of rare causes. The narrative review we conducted arose from this particular research methodology. Based on a broad literature search, UGIB etiologies were organized in five categories (lesions of the mucosa, neoplasms, vascular causes, bleeding predisposition, and external sources of bleeding). In the management of patients with UGIB, the underlying etiology deviates from the classic peptic ulcer disease/esophageal varices dyad in approximately half of the cases. This underscores the need for heightened clinical vigilance, particularly in complex scenarios, where endoscopic findings, imaging results, and histopathological interpretations may be unexpected or prone to misinterpretation. As an illustration, we conducted two systematic reviews of case reports of bleeding GMB and PGA. Our findings support a proactive diagnostic and research mindset and advocate for improved awareness of uncommon UGIB etiologies. Full article

Background/Objectives: The present investigation quantifies the striking predisposition for small intestinal GISTs in NF-1 patients, examining both multifocal and solitary tumor patterns while establishing critical epidemiological comparisons with the general population. By elucidating these distinct clinical and biological profiles, the study aims to transform the understanding of NF1-associated tumorigenesis and optimize patient surveillance strategies. Methods: This systematic review and meta-analysis was conducted in strict accordance with PRISMA guidelines, the gold-standard framework for minimizing bias and maximizing reproducibility in evidence synthesis. Prospectively registered in PROSPERO, the study employed a PICO framework to evaluate interventions, outcomes, and comparisons. Results: This systematic review and meta-analysis reveals a profound oncogenic propensity for small intestinal GISTs in NF-1 patients, demonstrating markedly increased prevalence relative to population baselines. The tumors display characteristic presentation and histological profiles, with a distribution of 54% multifocal lesions, 41% solitary SI-GIST, and 5% solitary duodenal GIST cases, demonstrating the diverse clinical manifestations of NF-1-associated tumors. These compelling findings not only redefine the epidemiological landscape of NF1-associated malignancies but also underscore extraordinary disease susceptibility, far surpassing previous estimates and sporadic occurrence rates in the general population. Conclusions: The distinct clinical patterns and high frequency of these tumors among NF-1 patients provide important insights into GIST development while underscoring the need for heightened clinical suspicion, particularly in patients manifesting gastrointestinal hemorrhage. These findings highlight the unique challenges in managing these cases—including diagnostic limitations and therapeutic constraints—underscoring the imperative for multidisciplinary therapeutic frameworks for detection, monitoring and treatment in this high-risk population. Full article

Background/Objectives: Mesenchymal tumors of the gastrointestinal tract are rare and can pose significant diagnostic challenges, particularly when located in atypical sites such as the sigmoid colon. Gastrointestinal stromal tumors (GISTs) are often the primary consideration based on imaging findings; however, other spindle cell neoplasms, such as schwannomas, must also be considered. We present a case of a sigmoid colon schwannoma initially suspected to be a GIST and provide a literature review on the diagnostic and therapeutic challenges associated with these tumors. Methods: A literature review based on articles from 2015 to 2024 was conducted to identify cases of mesenchymal tumors of the colon misdiagnosed as GISTs. The review focused on the role of imaging, endoscopic biopsy, and immunohistochemistry in differentiating these neoplasms. Additionally, treatment approaches, including surgical resection versus targeted therapy, were assessed. Results: The literature review revealed that GISTs and schwannomas share overlapping imaging characteristics, including submucosal location, hyperintensity on T2-weighted MRI, and contrast enhancement. However, immunohistochemical markers remain the gold standard for differentiation. Studies also highlighted the increasing role of minimally invasive diagnostic techniques, such as fine-needle aspiration and molecular profiling, in achieving a definitive preoperative diagnosis. Unlike GISTs, which often require adjuvant therapy with tyrosine kinase inhibitors, schwannomas are typically treated with surgical excision alone, with a low risk of recurrence. Conclusions: Current evidence supports a multimodal diagnostic approach combining imaging, biopsy, and immunohistochemistry to accurately classify mesenchymal tumors of the colon. While imaging can suggest a probable diagnosis, histopathological confirmation is essential before initiating targeted therapy. Full article

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that develop in the gastrointestinal tract; KIT mutations are present in both canine and human GISTs. In this study, genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) sections of 55 canine GIST cases, and mutation searches were performed for exons 8, 9, and 11. The results revealed novel mutations, A434T and F436S, in exon 8. In contrast to the A434T mutation without functional changes, the F436S mutant retained its dimerization ability, but lost its phosphorylation function and attenuated downstream Akt signaling, which is reflected in wound healing and migration activities. A comparison of the subcellular localization of WT KIT and the F436S mutant revealed no differences. In silico simulations indicated that the F436S mutation alters the structure of the near-membrane region and that its effects may extend to the transmembrane and intracellular domains compared to the WT. F436S is a point mutation that affects the entire molecule because co-mutation with the F436S mutation and the known autophosphorylation mutation reduces the autophosphorylation abilities. Full article

Background/Objectives: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal (GI) tract, predominantly driven by KIT or PDGFRα oncogene mutations. Nonspecific symptoms contribute to diagnostic delays, with general practitioners (GPs) playing a pivotal role in early detection. However, studies on GIST-specific primary care pathways are limited. This study examines GP contacts, diagnoses, and prescribed drugs in primary care during the 12 months preceding GIST diagnosis. Methods: This case-control study utilized data from the Netherlands Cancer Registry and Nivel Primary Care Database. It included 294 GIST patients diagnosed between 2010 and 2020 and 576 matched cancer-free controls. GP contacts, diagnoses, and newly prescribed drugs were analyzed across two time intervals: 0–4 and 5–12 months prediagnosis. Statistical comparisons were conducted using the Wilcoxon rank-sum test and descriptive analyses. Results: GIST cases had a median of six GP contacts (IQR 4–11) in the 12 months prediagnosis versus three (IQR 2–6) for controls (p < 0.05). Contacts increased 4 months before diagnosis, peaking 1 month prior. Common diagnoses in the 4-month interval included malignant neoplasms of the stomach (27.9%) and other digestive sites (27.6% and 11.2%), abdominal pain (9.5%), and iron deficiency anemia (9.5%). Newly prescribed drugs included proton pump inhibitors (13.9%) and osmotically acting laxatives (15.0%). Conclusions: This study highlights increased GP visits and specific reasons for these visits before GIST diagnosis. Future research should further examine GP records, not only through coded data but also unstructured data, and incorporate patient and GP perspectives to explore potential improvements in the diagnostic process. Full article

Background/Objectives: Extra-gastrointestinal stromal tumors (EGISTs) are rare mesenchymal tumors arising outside the gastrointestinal tract, making up <5% of all GISTs. Rectovaginal EGISTs are particularly uncommon, with limited available data. This study systematically reviews the clinicopathological features, management, and outcomes of rectovaginal EGISTs. Methods: A systematic review of the English-language literature was conducted for studies on rectovaginal EGISTs (search date: 15 January 2025). Results: Thirty-one studies, including 40 female patients (mean age: 55.2 ± 15.4 years), met the inclusion criteria. Presenting symptoms included vaginal bleeding (24.3%), palpable mass (13.5%), constipation (10.8%), and abdominal pain (8.1%); however, the majority of patients (45.9%) were asymptomatic. Surgical excision was undertaken in 95% of patients, more often via local resection (61.1%). A high-grade mitotic index (>5/50 HPF) was noted in 63.2%. CD117, DOG-1, and vimentin was expressed in all cases, while CD34 was positive in 97.1%. Adjuvant therapy with tyrosine kinase inhibitors (TKIs) was administered in 57.5%, and neoadjuvant therapy was rare (8.6%). Recurrence occurred in 39.4% over a median follow-up of 40 ± 61.5 months, with a median disease-free survival (DFS) of 48 months. One death occurred 13 months postoperatively. Conclusions: Rectovaginal EGISTs are exceedingly rare and often asymptomatic, complicating preoperative diagnosis. Surgical resection remains the cornerstone of treatment, complemented by stage-specific neoadjuvant or adjuvant TKI therapy. The challenging location predisposes to recurrence, underscoring the need for further studies to optimize management and improve outcomes. Full article

Gastrointestinal stromal tumors (GISTs), which usually develop with a significant malignant potential, are a serious challenge in stromal health. With Endoscopic ultrasound (EUS), GISTs can appear similar to other tumors. This study introduces a lightweight convolutional neural network model optimized for the classification of GISTs and leiomyomas using EUS images only. Models are constructed based on a dataset that comprises 13277 augmented grayscale images derived from 703 patients, ensuring a balanced representation between GIST and leiomyoma cases. The optimized model architecture includes seven convolutional units followed by fully connected layers. After being trained and evaluated with a 5-fold cross-validation, the optimized model achieves an average validation accuracy of 96.2%. The model achieved a sensitivity, specificity, positive predictive value, and negative predictive value of 97.7%, 94.7%, 94.6%, and 97.7%, respectively, and significantly outperformed endoscopists’ assessments. The study highlights the model’s robustness and consistency. Our results suggest that instead of using developed deep models with fine-tuning, lightweight models with their simpler designs may grasp the essence and drop speckle noise. A lightweight model as a hypothesis with fewer model parameters is preferable to a deeper model with 10 times the model parameters according to Occam’s razor statement. Full article

Background and Clinical Significance: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract but are exceedingly rare in the appendix, with only 20 cases reported in the literature. Due to their rarity, clinical behavior, histopathologic features, and management of appendiceal GISTs remain poorly understood. Case Presentation: We present the case of a 74-year-old man who underwent a right hemicolectomy for colonic adenocarcinoma, during which an incidental 1.2 cm appendiceal GIST was discovered. Histopathological examination revealed spindle cell morphology with abundant skeinoid fibers (SF), minimal mitotic activity (<1/50 HPF), and no nuclear atypia. Immunohistochemical staining confirmed positivity for CD117, DOG1, and CD34. The tumor was classified as low risk based on its size and mitotic count, and the patient remained recurrence-free at a 4-month follow-up. Conclusions: Our case expands the limited literature on appendiceal GISTs by demonstrating their histopathological and immunohistochemical features, favorable prognostic outcomes, and potential for incidental detection during surgeries for unrelated conditions. However, additional studies are needed to further elucidate their molecular characteristics and overall clinical behavior. Full article

Soft tissue sarcomas [STSs] are rare tumors of mesodermal origin that arise in diverse tissues such as muscles, fat, and nerves. There are over 100 subtypes of STS, each with distinct clinical behaviors and responses to treatment. Recent advances in treatment have moved towards histology-specific approaches, emphasizing the integration of pathological, immunohistochemical, and molecular features to guide treatment. Localized STS is primarily treated with surgery, often supplemented by neoadjuvant or adjuvant radiation and/or chemotherapy. However, about half of patients with localized disease will progress to an advanced stage, which is typically managed with systemic therapies including anthracycline-based chemotherapy such as doxorubicin or epirubicin. Despite these treatments, the survival rates for most subtypes of advanced metastatic STS remain relatively low. While anthracycline-based chemotherapy remains the mainstay of treatment, ongoing research into the biology of STSs is enhancing our understanding and approach to these complex tumors with an expansion beyond chemotherapy to include targeted therapy and immunotherapy to improve response rates and survival outcomes. This review focuses on STS other than gastrointestinal stromal tumors [GISTs], examines the current systemic treatment strategies, highlights recent advances, and explores future directions in the systemic therapy of sarcoma patients. Full article

Background: Neoadjuvant imatinib therapy plays a crucial role in the management of gastrointestinal stromal tumors (GISTs), but its impact across various mutational profiles remains uncertain. Objective: The aim of this study is to describe the clinicopathological features and to assess the response and surgical outcomes of neoadjuvant imatinib in GIST patients exhibiting diverse mutational profiles. Methods: We conducted a retrospective study, extracting data from the Dutch GIST Registry, including patients treated with neoadjuvant imatinib. Response rate was the primary outcome, and secondary outcomes were the time on neoadjuvant treatment and resection margins (R0 vs. R1/R2), respectively. Results: Between 2009 and 2021, 326 patients were treated with neoadjuvant imatinib, of which 264 (80.9%) underwent resection. A total of 197 (74.6%) of them had a KIT-exon 11 mutation, 19 (7.3%) had other KIT mutations, 10 (3.8%) had PDGFRA D842 mutations, 21 (6.8%) had other PDGFRA mutations, 2 (0.7%) had NTRK mutation, 1 (0.4%) had an SDH mutation, and 17 (6.4%) had WT GISTs. Patients with KIT-exon 11 mutations demonstrated a higher rate of partial response to imatinib (60.5% vs. 33.3%; p = 0.00). A positive resection margin (R1 or R2) was observed in 14 (21.2%) patients with a non-KIT exon 11 mutations and in 11 (5.5%) patients with a KIT-exon 11 mutation (p = 0.00). Moreover, non-KIT exon 11 mutation patients had a shorter median duration of neoadjuvant therapy (5.3 months, range 0.5–21.0) compared to patients with a KIT exon 11 mutation (8.8 months, range 0.2–31.3; p < 0.001). Conclusions: Our study highlights the variability in treatment response associated with different GIST mutational profiles. Patients with a KIT-exon-11 mutation tended to respond more favorably to neoadjuvant imatinib in terms of partial response and surgical outcomes. Full article

Endoscopic ultrasound (EUS) effectively diagnoses malignant and pre-malignant gastrointestinal lesions. In the past few years, artificial intelligence (AI) has shown promising results in enhancing EUS sensitivity and accuracy, particularly for subepithelial lesions (SELs) like gastrointestinal stromal tumors (GISTs). Furthermore, AI models have shown high accuracy in predicting malignancy in gastric GISTs and distinguishing between benign and malignant intraductal papillary mucinous neoplasms (IPMNs). The utility of AI has also been applied to existing and emerging technologies involved in the performance and evaluation of EUS-guided biopsies. These advancements may improve training in EUS, allowing trainees to focus on technical skills and image interpretation. This review evaluates the current state of AI in EUS, covering imaging diagnosis, EUS-guided biopsies, and training advancements. It discusses early feasibility studies and recent developments, while also addressing the limitations and challenges. This article aims to review AI applications to EUS and its applications in clinical practice while addressing pitfalls and challenges. Full article

Introduction. Interstitial Cells of Cajal (ICCs) play a critical role in the regulation of gastrointestinal motility and have been implicated in various functional gastrointestinal disorders. Recent research indicates a possible association between ICCs and the tumor risk of Gastrointestinal Stromal Tumors (GISTs). This research aims to examine the clinical, histopathological, and biomolecular characteristics of ICCs and their relevance in assessing GIST risk. Materials and Methods. This study examined fourteen GIST patients who underwent surgical intervention at the Surgery Department of Carol Davila Nephrology Hospital in Bucharest. Parameters including age, gender, tumor location/ dimensions were scrutinized. Immunohistochemistry employing markers CD117, DOG-1, and CD34 was employed to ascertain the presence of ICCs and GISTs. Results. The GIST risk stratification revealed distribution with 35.71% very low-risk, 21.42% low-risk, 14.28% intermediate-risk, and 28.57% high-risk categories. Predominantly, 57.14% of cases fell within the very low-risk and low-risk categories. Positive immunoreactivity for CD117 and DOG-1 was noted in 92.86% of patients, while CD34 exhibited positivity in 85.71% of cases. Gastric GISTs manifested heightened marker expression. Notably, immunohistochemistry unveiled robust positivity for CD117, DOG-1, and CD34, illustrating a positive correlation between elevated ICC levels and high-risk GISTs. Conclusions. The findings propose an association between ICC levels and high-risk GISTs, accentuating the diagnostic utility of CD117, DOG-1, and CD34 markers in GIST assessment. Full article