A diagnostic challenge of KIT p.V559D and BRAF p.G469A mutations in a paragastric mass.

A patient with gastrointestinal stroma tumor (GIST) and KIT p.V559D and BRAF p.G469A alterations was referred to our institutional molecular tumor board (MTB) to discuss therapeutic implications. The patient had been diagnosed with B-cell chronic lymphocytic leukemia (CLL) years prior to the MTB presentation. GIST had been diagnosed 1 month earlier. After structured clinical annotation of the molecular alterations and interdisciplinary discussion, we considered BRAF/KIT co-mutation unlikely in a treatment-naïve GIST. Discordant variant allele frequencies furthermore suggested a second malignancy. NGS of a CLL sample revealed the identical class 2 BRAF alteration, thus supporting admixture of CLL cells in the paragastric mass, leading to the detection of 2 alterations. Following the MTB recommendation, the patient received imatinib and had a radiographic response. Structured annotation and interdisciplinary discussion in specialized tumor boards facilitate the clinical management of complex molecular findings. Coexisting malignancies and clonal hematopoiesis warrant consideration in case of complex and uncommon molecular findings.

A Deep Learning-Based System Trained for Gastrointestinal Stromal Tumor Screening Can Identify Multiple Types of Soft Tissue Tumors.

The accuracy and timeliness of the pathologic diagnosis of soft tissue tumors (STTs) critically affect treatment decision and patient prognosis. Thus, it is crucial to make a preliminary judgement on whether the tumor is benign or malignant with hematoxylin and eosin-stained images. A deep learning-based system, Soft Tissue Tumor Box (STT-BOX), is presented herein, with only hematoxylin and eosin images for malignant STT identification from benign STTs with histopathologic similarity. STT-BOX assumed gastrointestinal stromal tumor as a baseline for malignant STT evaluation, and distinguished gastrointestinal stromal tumor from leiomyoma and schwannoma with 100% area under the curve in patients from three hospitals, which achieved higher accuracy than the interpretation of experienced pathologists. Particularly, this system performed well on six common types of malignant STTs from The Cancer Genome Atlas data set, accurately highlighting the malignant mass lesion. STT-BOX was able to distinguish ovarian malignant sex-cord stromal tumors without any fine-tuning. This study included mesenchymal tumors that originated from the digestive system, bone and soft tissues, and reproductive system, where the high accuracy of migration verification may reveal the morphologic similarity of the nine types of malignant tumors. Further evaluation in a pan-STT setting would be potential and prospective, obviating the overuse of immunohistochemistry and molecular tests, and providing a practical basis for clinical treatment selection in a timely manner.

Deep learning analysis for differential diagnosis and risk classification of gastrointestinal tumors.

OBJECTIVES: Recently, artificial intelligence (AI) has been applied to clinical diagnosis. Although AI has already been developed for gastrointestinal (GI) tract endoscopy, few studies have applied AI to endoscopic ultrasound (EUS) images. In this study, we used a computer-assisted diagnosis (CAD) system with deep learning analysis of EUS images (EUS-CAD) and assessed its ability to differentiate GI stromal tumors (GISTs) from other mesenchymal tumors and their risk classification performance. MATERIALS AND METHODS: A total of 101 pathologically confirmed cases of subepithelial lesions (SELs) arising from the muscularis propria layer, including 69 GISTs, 17 leiomyomas and 15 schwannomas, were examined. A total of 3283 EUS images were used for training and five-fold-cross-validation, and 827 images were independently tested for diagnosing GISTs. For the risk classification of 69 GISTs, including very-low-, low-, intermediate- and high-risk GISTs, 2,784 EUS images were used for training and three-fold-cross-validation. RESULTS: For the differential diagnostic performance of GIST among all SELs, the accuracy, sensitivity, specificity and area under the receiver operating characteristic (ROC) curve were 80.4%, 82.9%, 75.3% and 0.865, respectively, whereas those for intermediate- and high-risk GISTs were 71.8%, 70.2%, 72.0% and 0.771, respectively. CONCLUSIONS: The EUS-CAD system showed a good diagnostic yield in differentiating GISTs from other mesenchymal tumors and successfully demonstrated the GIST risk classification feasibility. This system can determine whether treatment is necessary based on EUS imaging alone without the need for additional invasive examinations.

Endoscopic Ultrasound-Guided Tissue Acquisition Using Fork-Tip Needle for Subepithelial Lesions: A Single-Center Validation Study.

BACKGROUND: The cutoff value for stereomicroscopic on-site evaluation (SOSE) in endoscopic ultrasound-guided tissue acquisition (EUS-TA) has high diagnostic sensitivity when a Franseen needle is employed for upper gastrointestinal subepithelial lesions (SELs) (stereomicroscopically visible white core [SVWC] ≥ 4 mm). AIM: We aimed to determine whether high diagnostic sensitivity could be obtained when EUS-TA was performed using a Fork-tip needle. METHODS: Twenty-one patients were prospectively registered. Patients underwent EUS-TA using a Fork-tip needle for upper gastrointestinal SELs at Kitasato University Hospital between January and November 2022. Punctures were made twice using the needle, and SOSE was conducted for each specimen. Blood and physical examination were performed to assess adverse events. Pathological diagnosis was made using hematoxylin and eosin-stained sections and immunohistochemical staining. Statistical comparisons were completed using Fisher's exact tests. RESULTS: The diagnostic rate of EUS-TA was 100% (21/21 cases). The final diagnosis was gastrointestinal stromal tumor in 17 (81.0%) and leiomyoma in 4 (19.0%) patients. SOSE was conducted on all 42 punctures, and the tissue sampling rate was 100% (42/42 punctures). Specimens with SVWC ≥ 4 mm were collected in 97.6% punctures (41/42 punctures) and the diagnostic sensitivity for these specimens was 100% (41/41 punctures), which is significantly higher (p < 0.0238) compared to the absence of cutoff value (diagnostic sensitivity of 0%). No EUS-TA-related adverse events occurred. CONCLUSIONS: EUS-TA combined with SOSE for upper gastrointestinal SEL using a fork-tip needle had a high diagnostic rate, and the cutoff value of SVWC ≥ 4 mm had high diagnostic sensitivity.

Primary EGIST of the greater omentum - a rare presentation.

Extragastrointestinal stromal tumors (EGISTs) are rare mesenchymal neoplasms, which develop in the retroperitoneum, mesentery, and omentum, lacking continuity to the stomach or intestines. Authors hereby present a female patient with a large heterogeneous abdominal mass as a case of an omental EGIST. A 46-year-old woman was referred to our hospital due to an insidious enlargement and colicky pain in the right iliac fossa. Abdominal palpation revealed a voluminous, freely mobile, and non-pulsatile mesoabdominal bulge expanding to the hypogastrium. On exploratory midline laparotomy, the tumor was densely fused to the greater omentum, not connected to the stomach, without gross involvement of adjacent structures. The large mass was completely excised after adequate mobilization. Immunohistochemical techniques showed strong and diffuse expression of WT1, actin and DOG-1, as well as multifocal c-KIT marking. Mutational study concluded a double mutation of KIT exon 9 and a mutation of PDGFRA exon 18. The patient was submitted to adjuvant treatment with imatinib mesylate 800 mg/day. Despite an extremely diverse presentation, omental EGISTs often remain clinically silent for a long time having enough space to grow before becoming symptomatic. These tumors have a consistent pattern of metastasis that typically spares lymph nodes unlike epithelial gut neoplasms. Surgery remains the preferred treatment for non-metastatic EGISTs of the greater omentum. It is possible that DOG-1 will supplant KIT as the leading marker in the future. The scarcity of knowledge on omental EGISTs implies a close monitoring of these patients to detect local relapse or distant metastasis.

Clinical features and prognosis of malignant small bowel tumors: Experience from a university hospital in Chile.

BACKGROUND: Small bowel tumors (SBT) are infrequent and represent a small proportion of digestive neoplasms. There is scarce information about SBT in Latin America. AIM: To describe the epidemiology, clinical characteristics, diagnostic methods, and survival of malignant SBTs. METHODS: Retrospective observational study of adult patients with histopathological diagnosis of SBT between 2007 and 2021 in a university hospital in Chile. RESULTS: A total of 104 patients [51.9% men; mean age 57 years] with SBT. Histological type: neuroendocrine tumor (NET) (43.7%, n=38), gastrointestinal stromal tumors (GIST) (21.8%, n=19), lymphoma (17.2%, n=15) and adenocarcinoma (AC) (11.5%, n=10). GIST was more frequent in duodenum (50%; n=12) and NET in the ileum (65.8%; n=25). Metastasis was observed in 17 cases, most commonly from colon and melanoma. Nausea and vomiting were significantly more often observed in AC (p=0.035), as well as gastrointestinal bleeding in GIST (p=0.007). The most common diagnostic tools were CT and CT enteroclysis with an elevated diagnostic yield (86% and 94% respectively). The 5-year survival of GIST, NET, lymphoma and AC were 94.7% (95%CI: 68.1-99.2), 82.2% (95%CI: 57.6-93.3), 40.0% (95%CI: 16.5-82.8) and 25.9% (95%CI: 4.5-55.7%), respectively. NET (HR 6.1; 95%CI: 2.1-17.2) and GIST (HR 24.4; 95%CI: 3.0-19.8) were independently associated with higher survival compared to AC, adjusted for age and sex. CONCLUSIONS: Malignant SBT are rare conditions and NETs are the most common histological subtype. Clinical presentation at diagnosis, location or complications may suggest a more probable diagnosis. GIST and NET are associated with better survival compared to other malignant subtypes.

Colonic gastrointestinal stromal tumor (GIST) presenting with colocolonic intussusception: A rare case report.

An 8-year-old spayed female British bulldog was presented with vomiting, hyporexia, and large-bowel diarrhea. Abdominal ultrasound revealed a focal colonic mass with an intussusception located immediately oral to the mass. The intussusception encompassed the ascending and transverse colon and was non-reducible. Colonic resection and anastomosis were completed to include the intussusception and colonic mass. Histopathological examination of the mass demonstrated a spindle cell neoplasm arising within the muscular wall of the intussuscepted segment that obliterated normal architecture. Mild-to-moderate cytoplasmic immunoreactivity of the tumor cell population for CD117 and smooth muscle actin was consistent with a diagnosis of a gastrointestinal stromal tumor. The dog described herein remains alive and free of progressive disease at the time of writing. Key clinical message: The entire gastrointestinal tract should be evaluated in any animal with gastrointestinal symptoms. A gastrointestinal stromal tumor remains a plausible differential diagnosis, regardless of the intestinal segment affected, and tumorassociated intussusception is a rare but urgent clinical finding.

Tumeur stromale gastro-intestinale du côlon (GIST) présentant une invagination colocolique : un rapport de cas rare. Une femelle bouledogue anglais stérilisée de 8 ans a présenté des vomissements, une hyporexie et une diarrhée d'origine du gros intestin. L'échographie abdominale a révélé une masse colique focale avec une invagination située immédiatement oralement à la masse. L'intussusception englobait le côlon ascendant et transverse et était non réductible. La résection colique et l'anastomose ont été réalisées pour inclure l'intussusception et la masse colique. L'examen histopathologique de la masse a révélé un néoplasme à cellules fusiformes apparaissant dans la paroi musculaire du segment invaginé qui a oblitéré l'architecture normale. L'immunoréactivité cytoplasmique légère à modérée de la population de cellules tumorales pour le CD117 et l'actine des muscles lisses étaient compatibles avec un diagnostic de tumeur stromale gastro-intestinale. Le chien décrit ici est toujours vivant et exempt de maladie évolutive au moment de la rédaction.Message clinique clé :L'ensemble du tractus gastro-intestinal doit être évalué chez tout animal présentant des symptômes gastrointestinaux. Une tumeur stromale gastro-intestinale reste un diagnostic différentiel plausible, quel que soit le segment intestinal atteint, et l'intussusception associée à la tumeur est une constatation clinique rare mais urgente.(Traduit par Dr Serge Messier).

[Diagnostic yield and utility of boring biopsy for subepithelial lesions of the stomach and esophagus].

Herein, we aimed to examine the diagnostic yield and utility of boring biopsy for subepithelial lesions (SEL) of the stomach and esophagus. A total of 52 patients with SELs of the stomach or esophagus underwent boring biopsy. The diagnostic yield of boring biopsy for gastric and esophageal SELs was 50% (21/42) and 80% (8/10), and for SELs with a diameter of less than 10mm, the diagnostic yield was 67% (6/9) and 83% (5/6), respectively. Forty-three percent (9/21) of the gastric SELs were diagnosed with gastrointestinal stromal tumor (GIST), while all esophageal SELs (8/8) were leiomyomas. Ten percent (4/42) of boring biopsies for the stomach were accompanied by complications:two cases of perforation and two of bleeding.

[Surgical management of gastrointestinal stromal tumors of gastric origin]. / Prise en charge chirurgicale des tumeurs stromales gastro-intestinales d'origine gastrique.

Gastrointestinal Stromal Tumors (GISTs) account for 1 to 2% of gastrointestinal malignant tumors. They are characterized by overexpression of the tyrosine kinase (KIT). 60% of GISTs originate in the stomach. Managing them remains complex and varies depending on several factors such as location, size, molecular biology, type of clinical presentation, and the risks/benefits of surgical treatment. Surgery remains the only curative treatment, while tyrosine kinase inhibitors have demonstrated their efficacy as systemic treatment in the perioperative context. Risk stratification for recurrence guides the choice of adjuvant treatment, with a recommended duration of 3 years for high-risk patients.

Les tumeurs stromales gastro-intestinales (GIST) constituent entre 1 et 2 % des tumeurs malignes gastro-intestinales. Elles se caractérisent par une surexpression de la tyrosine kinase (KIT). 60 % des GIST sont d'origine gastrique. Leur prise en charge reste complexe et varie selon plusieurs facteurs tels que la localisation, la taille, la biologie moléculaire, le type de manifestation clinique et les risques/bénéfices du traitement chirurgical. La chirurgie demeure le seul traitement curatif, tandis que les inhibiteurs de tyrosine kinase ont démontré leur efficacité comme traitement systémique dans le contexte périopératoire. La stratification du risque de récidive guide le choix du traitement adjuvant, avec une durée recommandée de 3 ans pour les patients à haut risque.

Diagnosis, Treatment, and Prognosis of Patients with Primary Familial Gastrointestinal Stromal Tumor: A Case Report and Literature Review.

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the digestive tract, most of which are sporadic, and familial GISTs with germline mutations are rarely seen. Here, we report a 26-year-old female with a germline p. W557R mutation in exon 11 of the KIT gene. The proband and her father and sister presented with multifocal GIST and pigmented nevi. All 3 patients underwent surgery and imatinib therapy. To date, only 49 kindreds with germline KIT mutations and 6 kindreds with germline PDGFRA mutations have been reported. Summarizing the reported kindreds, the majority of familial GISTs manifest as multiple primary GISTs complicated with special clinical manifestations, including cutaneous hyperpigmentation, dysphagia, mastocytosis, inflammatory fibrous polyps, and large hands. Familial GISTs are generally thought to exhibit TKI sensitivity similar to that of sporadic GISTs with the same mutation.

Circulating tumor DNA analysis of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor treated with avapritinib or regorafenib.

BACKGROUND: The current treatment paradigm of imatinib-resistant metastatic gastrointestinal stromal tumor (GIST) does not incorporate KIT/PDGFRA genotypes in therapeutic drug sequencing, except for PDGFRA exon 18-mutant GIST that is indicated for avapritinib treatment. Here, circulating tumor DNA (ctDNA) sequencing was used to analyze plasma samples prospectively collected in the phase III VOYAGER trial to understand how the KIT/PDGFRA mutational landscape contributes to tyrosine kinase inhibitor (TKI) resistance and to determine its clinical validity and utility. PATIENTS AND METHODS: VOYAGER (N = 476) compared avapritinib with regorafenib in patients with KIT/PDGFRA-mutant GIST previously treated with imatinib and one or two additional TKIs (NCT03465722). KIT/PDGFRA ctDNA mutation profiling of plasma samples at baseline and end of treatment was assessed with 74-gene Guardant360® CDx. Molecular subgroups were determined and correlated with outcomes. RESULTS: A total of 386/476 patients with KIT/PDGFRA-mutant tumors underwent baseline (pre-trial treatment) ctDNA analysis; 196 received avapritinib and 190 received regorafenib. KIT and PDGFRA mutations were detected in 75.1% and 5.4%, respectively. KIT resistance mutations were found in the activation loop (A-loop; 80.4%) and ATP-binding pocket (ATP-BP; 40.8%); 23.4% had both. An average of 2.6 KIT mutations were detected per patient; 17.2% showed 4-14 different KIT resistance mutations. Of all pathogenic KIT variants, 28.0% were novel, including alterations in exons/codons previously unreported. PDGFRA mutations showed similar patterns. ctDNA-detected KIT ATP-BP mutations negatively prognosticated avapritinib activity, with a median progression-free survival (mPFS) of 1.9 versus 5.6 months for regorafenib. mPFS for regorafenib did not vary regardless of the presence or absence of ATP-BP/A-loop mutants and was greater than mPFS with avapritinib in this population. Secondary KIT ATP-BP pocket mutation variants, particularly V654A, were enriched upon disease progression with avapritinib. CONCLUSIONS: ctDNA sequencing efficiently detects KIT/PDGFRA mutations and prognosticates outcomes in patients with TKI-resistant GIST treated with avapritinib. ctDNA analysis can be used to monitor disease progression and provide more personalized treatment.

Long-term outcome after surgical resection of non-high-risk gastrointestinal stromal tumours without adjuvant therapy.

BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most common intra-abdominal sarcoma. Risk classification systems, commonly the modified National Institutes of Health consensus criteria, identify tumour properties relating to patient outcomes. However, owing to limited long-term evidence, most guidelines recommend up to 10-year follow-up for all risk groups except very low-risk GIST. METHODS: This retrospective multicentre study included patients who had complete resection of primary, non-metastatic GIST from three Scandinavian sarcoma centres: Gothenburg (2004-2020), Stockholm (2000-2019), and Oslo (2000-2017). Medical records were reviewed for clinical details regarding diagnosis, treatment, and follow-up, and recurrence-free and disease-specific survival evaluated. RESULTS: The total cohort consisted of 1213 patients with GIST. High-risk patients and those treated with tyrosine kinase inhibitors were excluded. The remaining 649 patients were included in the present analysis: 118 with very low-, 381 with low-, and 150 with intermediate-risk GISTs. Five-year recurrence-free survival rates were 100, 98.5, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.246). Disease-specific survival rates 10 years after surgery were 100, 98.4, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.262). CONCLUSION: Patients with completely resected non-high-risk GISTs have an excellent long-term outcome, irrespective of risk group. Follow-up programmes to detect disease recurrences in these patients are probably not indicated.

Gastrointestinal stromal tumours (GISTs) originate from the muscle layer of the gastrointestinal tract. They are divided into risk groups according to size, location, and how quickly they grow. Patients with GIST, regardless of risk group, have been followed with imaging for several years after their tumour has been successfully removed with an operation. The aim of this study was to evaluate whether follow-up is necessary for patients in the lower-risk groups. Six hundred and forty-nine patients with GISTs from the lower-risk groups were followed for 5 years (median). Only 1.2 per cent of the patients experienced a recurrence of their cancer. It was concluded that patients with GIST in the lower-risk groups do not need follow-up with imaging after a successful operation.

Auxiliary diagnosis of subepithelial lesions by impedance measurement during EUS-guided fine-needle biopsy.

BACKGROUND AND AIMS: EUS-guided FNA/biopsy (EUS-FNA/B) is the citerion standard for diagnosing subepithelial lesions (SELs); however, its diagnostic ability for SELs <20 mm is low. We developed a new diagnostic method to differentiate between GI stromal tumor (GIST) and non-GIST by measuring high-frequency impedance (H-impedance) using an EUS-FNB needle. METHODS: The H-impedance of gastric epithelial neoplasms from 16 cases were measured with a conventional impedance probe to confirm whether H-impedance is clinically useful for assessing cell density (study 1). The H-impedance values of exposed SELs from 25 cases with use of the conventional probe (study 2) and nonexposed SELs from 20 cases with use of the EUS-FNB needle probe (study 3) were measured to determine the diagnostic ability of H-impedance for differentiating GISTs from non-GISTs. RESULTS: H-impedance significantly positively correlated with cell density (P = .030) (study 1). The H-impedance of GIST (99.5) measured with a conventional probe was significantly higher than with those of the muscular layer (82.4) and leiomyoma (89.2) (P < .01) (study 2). The H-impedance of GIST measured with the EUS-FNB needle was also significantly higher than that of leiomyoma (GIST: 80.2 vs leiomyoma, 71.8; P = .015). The diagnostic yield of the impedance method for differentiating GISTs from non-GISTs had 94.4% accuracy, 88.9% sensitivity, 100% specificity, and 0.95 area under the curve. Diagnostic ability was not affected by lesion size (P = .86) (study 3). CONCLUSION: Auxiliary differential diagnosis between gastric GISTs and non-GISTs by the H-impedance measurement during EUS-FNB could be a good option, especially when the lesion is <20 mm.

Gastrointestinal Glomus Tumors: A Single Institution, 20-Year Retrospective Study.

INTRODUCTION: Glomus tumors are rare mesenchymal neoplasms composed of cells resembling those of the thermoregulatory glomus body, typically occurring in the skin and superficial soft tissues. Rarely do they occur in the gastrointestinal tract, in particular the stomach, where they have been the subject of case reports and small series. We present our institutional experience with gastrointestinal glomus tumors. METHODS: A retrospective review of all gastrointestinal glomus tumors was conducted across all three Mayo Clinic sites in Minnesota, Arizona, and Florida from 2001 to 2021. Patient characteristics, pathologic findings, imaging features, operative reports, and clinical outcomes were abstracted. Descriptive statistics were utilized to report outcomes. RESULTS: Nine patients with glomus tumors were identified (five men and four women). The median age was 53 [interquartile range (IQR), 44-69] y. Four patients presented with abdominal discomfort, three had anemia or bleeding, and two tumors were incidentally diagnosed. Computed tomography scans identified masses thought to represent gastrointestinal stromal tumors or neuroendocrine tumors in all patients. The tumors were localized to the stomach in all cases, specifically in the gastric antrum. Seven patients underwent preoperative endoscopy, including five with endoscopic ultrasonography. Endoscopic biopsies were interpreted as glomus tumors (n = 3), neuroendocrine tumors (n = 2), and nondiagnostic (n = 2). All patients underwent open (n = 3) or minimally invasive (n = 6) margin-negative resection by wedge resection (n = 5) or distal gastrectomy (n = 4). No nodal metastases were identified radiographically or on pathologic examination. The median tumor size was 2.5 [IQR 1.3-3.4] cm. All tumors showed at least in part typical glomus tumor morphology and smooth muscle actin expression. Aberrant synaptophysin expression was present in the two tumors initially classified as NET. Using the current WHO criteria, tumors were classified as histologically malignant (n = 1) and of "uncertain malignant potential" (n = 8). At a median follow-up of 15 [IQR 1-56] mo, all patients were asymptomatic and without recurrence. Two patients died of unrelated causes. No patients received adjuvant therapies. CONCLUSIONS: Our 20-year, single institution, 3-site experience with resected gastrointestinal glomus tumors suggests the rarity, predisposition to involve the gastric antrum, and potentially an indolent clinical behavior of many of these tumors. Long-term follow-up is warranted as some previously reported gastric glomus tumors have metastasized, including cases lacking morphologic evidence of malignancy. Surgical resection, with minimally invasive wedge resection alone, is likely sufficient for the management of most gastric glomus tumors.

Prognostic significance of serum CA125 in the overall management for patients with gastrointestinal stromal tumors.

BACKGROUND: Carbohydrate antigen 125 (CA125) is elevated as a tumor marker in many carcinomas, but its association with gastrointestinal stromal tumor (GIST) has received less attention. This study intends to evaluate whether CA125 level can predict tumor progression and overall survival (OS) of GIST patients. METHODS: We retrospectively analyzed the clinical data and follow-up records of GIST patients who underwent surgical resection in Nanjing Drum Tower Hospital from August 2010 to December 2020. All patients were classified according to serum CA125 level. The relationship between CA125 and clinical outcomes was then examined. RESULTS: A total of 406 GIST patients were enrolled in this study, among which 46 patients had preoperative elevated serum CA125 level and 13 patients with high CA125 level both preoperative and postoperative were observed. Preoperative CA125 concentration was significantly related to rupture status, resection style, tumor site, tumor size, mitotic index, NIH risk grade and c-kit exons. According to Kaplan-Meier curve analysis, high expression of postoperative CA125 was significantly correlated with worse progression-free survival (PFS) and OS among patients with preoperative elevated CA125 level. Ultimately, Cox proportional regression model analysis revealed that increase of preoperative and concurrent postoperative CA125 concentration was an independent predictive factor for PFS. CONCLUSIONS: The concurrent abnormality of serum CA125 before and after operation was an independent risk factor for GIST progression, suggesting its significance as a serum biomarker in the overall management of GIST patients.

Progress in the Treatment of Small Intestine Cancer.

OPINION STATEMENT: Small intestine cancer is rare, accounting for approximately 3% of all gastrointestinal malignancies. The most common histological subtypes include adenocarcinoma, neuroendocrine tumours (NETs) and gastrointestinal stromal tumours (GISTs). In localised disease, surgery remains the mainstay of treatment and the best approach to improve survival. Current treatment for small intestine adenocarcinoma (SIA) is extrapolated from small studies and data from colorectal cancer (CRC). There is limited evidence to guide therapy in the adjuvant setting. However, there are small phase II studies in the advanced setting providing evidence for the role of chemotherapy and immunotherapy. There is also limited evidence assessing the efficacy of targeted therapies. Small intestine NETs are rare, with evidence for somatostatin analogue therapy, particularly in the low to intermediate-grade well-differentiated tumours. Poorly differentiated NETs are generally managed with chemotherapy but have worse outcomes compared with well-differentiated NETs. The management of small intestine GISTs is largely targeting KIT mutations with imatinib. Recent trials have provided evidence for effective therapies in imatinib-resistant tumours and the potential role of immunotherapy. The aim of this article was to review the evidence for the current management and recent advances in the management of small intestine adenocarcinoma, NETs and GISTs.

Primary vulvar extragastrointestinal stromal tumor in a 77-year-old woman.

Extragastrointestinal stromal tumors (EGISTs) carry the same morphological, immunohistochemical and molecular features as gastrointestinal stromal tumors (GISTs) and involve extragastrointestinal tract soft tissue. The majority of reported EGIST cases arise from intraabdominal, retroperitoneal, or pelvic soft tissue. A significant subset of such tumors originates from the gastrointestinal muscle layer, grows in an exophytic manner, then loses attachment to the gastrointestinal tract. Consequently, true EGISTs are exceedingly rare. Herein, we are reporting a case of a vulvar EGIST. A 77-year-old woman presented with a painless subcutaneous nodule on the right perineum. An excisional biopsy showed a fairly circumscribed bland spindle cell lesion in the dermis. The tumor cells were positive for CD117 and ANO1/DOG-1 and negative for smooth muscle myosin, smooth muscle actin, STAT6, low- and high-molecular-weight cytokeratins, SOX10, MART-1, CD10, S-100 protein, and estrogen and progesterone receptors. A diagnosis of EGIST was made and complete excision was recommended. Superficial/subcutaneous EGISTs are extremely rare, and it is important for dermatopathologists to be aware of this entity as it can be misdiagnosed as more common spindle cell neoplasms, both benign and malignant, including but not limited to smooth muscle neoplasms (leiomyoma/leiomyosarcoma), spindle cell melanoma, and sarcomatoid squamous cell carcinoma.

Gastrointestinal stromal tumors of the small intestine: the challenge of diagnosis and the outcome of management.

PURPOSES: Gastrointestinal stromal tumor (GIST) is a rare small intestinal tumor. Most patients usually report long-period complaints due to difficult diagnoses. A high grade of suspicion is required for early diagnosis and initiation of the proper management. METHODS: A retrospective study of all patients with small intestinal GIST who were operated in the period between January 2008 and May 2021 at Mansoura University Gastrointestinal Surgical Center (GIST). RESULTS: Thirty-four patients were included in the study with a mean age of 58.15 years (± 12.65) with a male to female ratio of 1.3:1. The mean duration between onset of symptoms and diagnosis was 4.62 years (± 2.34). Diagnosis of a small intestinal lesion was accomplished through abdominal computed tomography (CT) in 19 patients (55.9%). The mean size of the tumor was 8.76 cm (± 7.76) ranging from 1.5 to 35 cm. The lesion was of ileal origin in 20 cases (58.8%) and jejunal in 14 cases (41.2%). During the scheduled follow-up period, tumor recurrence occurred in one patient (2.9%). No mortality was encountered. CONCLUSION: Diagnosis of a small bowel GISTs requires a high grade of suspicion. Implementing new diagnostic techniques like angiography, capsule endoscopy, and enteroscopy should be encouraged when suspecting these lesions. Surgical resection is always associated with an excellent postoperative recovery profile and very low recurrence rates.

Cytopathology of rare gastric mesenchymal neoplasms: A series of 25 cases and review of literature.

BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm arising in the stomach. However, a number of other rare mesenchymal neoplasms do occur at this anatomic site, which often presents a diagnostic challenge for cytopathologists on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Our study aims to selectively present the clinico-radiological and cytopathological characteristics of these rare "non-GIST" neoplasms, as well as their differential diagnoses. MATERIAL AND METHODS: We performed a 20 year retrospective search in the cytopathology database of our two large medical institutions for non-GIST mesenchymal neoplasms arising in the stomach and diagnosed on EUS-FNA. Data regarding the patients' demographics and radiological findings were analysed. All available cytopathology specimens were reviewed. The cytomorphological characteristics and the accompanying immunohistochemical stains, when available, were subsequently analysed. RESULTS: Twenty-five cases of gastric mesenchymal tumours were selectively included in the study after excluding all cases of GIST (n = 113) diagnosed on FNA. These cases included 10 leiomyomas (40%), eight schwannomas (32%), five glomus tumours (20%), one perivascular epithelioid cell neoplasm, and one desmoid tumour. The specimen cellularity was variable and ranged from hypocellular to highly cellular. Most smears were composed of spindle cells with a few showing epithelioid morphology. Cell blocks were available in 20 cases and a range of immunohistochemical ancillary studies were performed. DOG-1, c-KIT, smooth muscle actin (SMA), and S100-protein were the most common immunomarkers done. CONCLUSION: Our study highlights important cytomorphological characteristics of rare mesenchymal neoplasms arising in the stomach. In the appropriate clinical setting and with the help of immunohistochemistry, an accurate diagnosis of these neoplasms can be achieved.

CT features of gastrointestinal spindle cell, epithelial, and round cell tumors in 41 dogs.

There is sparse published information on computed tomographic (CT) characteristics of canine gastrointestinal tumors. The purposes of this multi-center, retrospective, descriptive study were to describe the CT features of histologically-confirmed canine gastrointestinal spindle cell, epithelial, and round cell tumors and, when available, describe the corresponding ultrasound findings. The inclusion criteria were as follows: availability of pre-and post-contrast CT study, and a histopathological diagnosis of the lesions. Recorded parameters were tumor size, location, gastrointestinal wall layers involvement, lesion's growth and enhancement patterns, tumor margination, presence of stenosis, mineralization, ulcerations, lymphadenopathy, or other lesions in the abdomen/thorax. When available, ultrasound images were evaluated. Forty-one dogs met the inclusion criteria and had the following histological diagnoses: 21/41 (51%) spindle cells (7 leiomyomas, 14 leiomyosarcomas/gastrointestinal stromal tumors (GISTs)), 13/41 (32%) epithelial (adenocarcinoma), and 7/41 (17%) round cell (lymphoma) tumors. The growth pattern was concentric, eccentric, and mixed in epithelial, spindle cell, and round cell tumors, respectively. Spindle cell tumors had the largest main volume and involved the outer gastrointestinal layer with an unaffected inner layer. Leiomyosarcomas/GISTs showed irregular margins compared to leiomyomas. Only lymphomas showed multifocal gastrointestinal involvement. Nine carcinomas and six spindle cell tumors caused partial stenosis with secondary sub-obstruction. Mineralizations were more frequent in spindle cell tumors (10/21) and absent in lymphomas. Lymphadenomegaly was widespread in lymphomas, regional in leiomyosarcomas-GISTs and adenocarcinomas, and absent in leiomyomas. The reported CT features may be useful in prioritizing the differential diagnosis between spindle cell, epithelial, and round cell tumors, similar to those reported on ultrasound.