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GIST Gastrico

Gastrointestinal stromal tumors (GISTs) sono i più comuni tumori stromali del tratto Gastrointestinale. Essi possono infatti originare da qualunque porzione dell'apparato digerente in quanto pare originino dalle cellule interstiziali di Cajal  e si presentano pertanto come delle lesioni maligne subepiteliali. I GISTs sono caratterizzati da una mutazione in KIT o PDGFR alfa. La chirurgia rappresenta il trattamento di scelta in caso di GIST.  I GIST gastrici danno luogo raramente ad una sintomatologia eclatante ed è per questo motivo che al momento della diagnosi essi spesso presentano dimensioni considerevoli e hanno già metastatizzato per via ematica. Le metastasi linfatiche sono estremamente rare e rappresentano un segno ulteriore di malignità e di prognosi sfavorevole.

I GIST di dimensioni più contenute ed aggredibili chirurgicamente possono tuttavia presentare una percentuale di metastasi a 5 anni dall'intervento pari al 50%. Considerata la sensibilità dei GISTs all' imatinib, un inbitore delle tirosinkinasi, va sempre considerata una terapia adiuvante anche in caso di piccoli GIST completamente asportati. In caso di voluminosi GISTs o di GISTs metastatici una terapia neoadiuvante con imatinib preoperatoriamente va sempre presa in considerazione.

Di seguito riportiamo un caso riscontrato presso l'ospedale di Senigallia di un voluminoso GIST Gastrico diagnosticato accidentalmente dopo un'ecografia addominale eseguita per trauma.  La paziente era giunta in PS per dolore addominale secondario a caduta a casa ma non presentava alcun sintomo  legato alla lesione gastrica. Il riscontro ecografico di una massa in ipocondrio sinistro e la successiva TAC con mezzo di contrasto hanno consentito di addivenire ad una diagnosi di certezza, suffragata da un agoaspirato ecoendoguidato.  La lesione di 16x10x12 è stata completamente asportata insieme alla metastasi epatica del VII segmento e la paziente è stata dimessa in nona giornata postoperatoria. 

GIST Gastrico immagine TAC

Giant Metastatic Gastric Gist: A case report


Vincenzo Guarino,




Gastrointestinal stromal tumors (GISTs), the most common mesenchymal neoplasms of the gastrointestinal (GI) tract, represent about 1% of the tumors of the digestive tract. GISTs are usually asymptomatic and detected incidentally and for this reason its diagnosys is often  delayed.  Giant GISTs (GG) of the stomach, are not so rare and often they are larger than 10 cm in diameter and associated with distant metastases at the diagnosis. Therapeutic strategies include surgical resection associated with adjuvant imatinib therapy. In case of Giant metastatic Gists, neoadjuvant imatinib therapy is mandatory before surgery to increase probabilities of a complete resection of the tumor and of its metastasis. In anycase a multidisciplinary approach is raccomanded to coordinate surgery and therapy in order to maximize clinical outcomes.

Case Presentation

A 74-year-old-woman was admitted to the emergency unit for abdominal pain after accidentally falling at home. Ultrasound examination detected a voluminous left hypocondrium mass of 95x 67 mm with apparently finely corpuscolar content. Ultrasounds findings, according to the clinical history, were initially suspected for a splenic hematoma. TC scan examination detected, in the left hypocondrium, a voluminous mass of 10x9x10 cm arising from the gastric body. The mass was suspected for a Giant Gist with radiological features of intratumoral central necrosis. TC scan showed moreover a minimal increase in the density of the posterior perigastric wall without infiltrative phenomena. A lesion of  the 8th segment of the liver suspected for metastasis was reported too.  EUS (endoscopic ultrasound) and EUS–guided Fine Needle Aspiration (EUS-FNA) confirmed histologically the diagnosis of GIST. A sub-total gastrectomy with metastasectomy and colecistectomy were performed and the postoperative period ran without complications. Specimen’s histopatological examination confirmed a gastrointestinal stromal tumor and patient underwent adjuvant imatinib therapy.


The aim of this work is to discuss the risk assessment in case of surgical primary treatment for metastatic simptomatic GISTs, completely resectable,  that are not eligible for neoadjuvant therapy and to analyze its impact on patient’s survival. Is neoadjuvant therapy always mandatory? What is the best strategy for those rare symptomatic patients?



Keywords: Giant gastrointestinal stromal tumors, neadjuvant therapy, imatinib therapy.

Abbreviations: Giant metastatic gastrointestinal stromal tumors (GMGISTs). GIST: gastrointestinal stromal tumor. SELs: subepithelial lesions


1. Introduction

Gastrointestinal stromal tumors (GISTs) represent 80% of mesenchymal neoplasms of the gastrointestinal tract with an estimated unadjusted incidence of around 1/100000/year [1][2]. GISTs are characterized by wide variability in biological behaviors and by the difficulty to predict its malignant potential. They appears endoscopically as malignant subepithelial lesions (SELs) of the gastrointestinal tract from the oesophagus to the rectum [3]. GISTs  are thoutghts to originate from the interstitial cells of Cajal [4]. Aproximately 70-80% of sporadic GISTs are caused by oncogenic mutations in the thyrosine Kinase receptor KIT, whereas 5-10% are caused by gene mutations, deletions, or insertions that activate platlet derived growth factor receptor alfa (PDGFRα) [5].  GISTs are considered malignant tumors and they aren’t classified as either benign or malignant but are rather stratified by their clinical risk of malignancy: Very low, low, intermediate or high. [6]. Mietinenn reported that the metastatic risk of GISTs increases according to the tumor size irrespective of the mitotic count. At present, EUS –guided fine needle aspiration (EUS-FNA) is the most accurate, safe and reliable preoperative immunohistological test to secure a preoperative diagnosis of SELs [7]. Surgical resection is the first choice for resectable GISTs without metastasis. Even if a complete (R0) resection can be achieved in up to 85% of patients with primary disease, approximately 50 % of patients develop recurrences or metastases within 5 years from primary resection. [8] Administration of tyrosine Kinase inhibitors such as imatinib is indicated after radical surgery for three years for patients with a significant risk of relapse [9]. Neoadjuvant therapy is the  first approach in case of unresectable metastatic giant GISTs [9-10] and it had been proved as an adjuvant therapy in resectable GISTs  too [11]. Tumor size, mitotic rate and tumor site are considered as the most important prognostic parameters for patients after surgery [12]. Imatinib is the standard treatment for locally advanced inoperable and metastatic disease. [13]. Imatinib is also the standard treatment for patients with metastatic disease who have had all lesion removed surgically, although surgery is not recommended as a primary approach in the metastatic setting. [14] We report our experience of a resectable Giant metastatic sintomatic GIST of the stomach.


2. Case presentation

A 72 year-old-woman was admitted to the emergency unit of our hospital after an accidental fall at home. Physical examination of the abdomen revealed a voluminous mass in the left hypocondrium. The abdomen was distended but no pain or vomiting was referred. The red blood cells count was normal. The ultrasound examination of the abdomen showed a voluminous mass of the left hypocondrium that initially was suspicious for a splenic hematoma. TC scan revealed the presence of a 10x9x10 cm solid mass with peripheral contrast enhancing and a large central area apparently lacking of vascularization that was referred to a voluminous Gastric GIST. (FIG. 3-4) Moreover a suspicious metastasis of the eighth segment of the liver at the TC examination was detected too (FIG. 5). EUS –FNA findings of KIT and CD 117 positive spindle-shaped cells provided a conclusive immunohistochemical diagnosis of GIST.  Our patient showed a rapid worsening of general conditions in a few days after the diagnosis. She became unable to feed and presented an incoercible vomiting (probably due to the location and dimensions of the GIST). After multidisciplinary discussion and according to the high probability (based on the TC features of the mass) to achieve an R0 resection we decided to submit to surgery the patient in a few days.  At the beginning we supposed to perform a laparoscopic sleeve gastrectomy to remove the tumor according to the TC scan findings that seemed to localize the GIST along the great curvature of the stomach. After a laparoscopic partial mobilization of the great curvature of the stomach, we converted the procedure into a bisubcostal laparotomy. The size and the weight of the GIST in fact appeared to increase too much the risk of a peritoneal dissemination due to accidental intraoperative rupture of the GIST. A subtotal gastrectomy, metastasectomy and cholecystectomy was performed with a Roux and Y anastomosis reconstruction (FIG. 1). The postoperative period ran without complications. The patient started oral feeding at the 6th post-operative day after performing a gastrointestinal oral contrast study that confirmed the integrity of the anastomosis. The patient was discharged at the 10th postoperative days. The histopatological examination of the surgical specimen was described as a solid smooth grey and white mass of the greater curvature of 16x11x10 cm (FIG. 2) with a pseudocystic, hemorrhagic, central area. H&E staining showed spindle-shaped cell proliferation. The mitotic index was 5 mitosis / 5mm². The immunohistochemical staining was positive for cKIT, CD117+, DOG1+, CD34+ and Negative for Desmin-. The tumor was categorized as pT4 pN0 pM1 (AJCC VIII ed.). A muation on cKIT was found in exon 9.  According to size, location and mitotic count, the tumor was categorized as high risk GIST. The liver metastasis was completely excised.


3. Discussion

(GISTs) are usually asymptomatic malignant subepithelial lesions of the whole gastrointestinal tract.  [15]. GISTs have no specific symptom, and for this reason it is very difficult an early diagnosis and treatment [16]. The most frequent complaint is abdominal discomfort. Frequently GISTs are diagnosed accidentally and their prognosis is influenced by the size of the tumor, mitotic rate and anatomic site. [12] Mitotic rate was described as a vital indicator for GIST staging and consequential choice of surgical and target therapeutic approach [17]. GISTs usually are characterized by positive immunohistochemical (IHC) staining of KIT (CD117), a trans-membrane tyrosine kinase receptor. DOG1 is a more recent antigen incorporated in the IHC panel when CD 117 results negative. [18] Lympho node metastasis are extremely rare in GISTs and its presence is to considerate a morphological feature associated with malignancy and poor prognosis [19]. GISTs’ classification distinguishes different groups of risk (very low, low, intermediate and high-risk groups) that are obviously related to a different prognosis [20]. To know the evolution and the biological behavior of a GIST is essential to select candidates for adjuvant therapy as well as to determinate the frequency and the intensity of postoperative surveillance. Long term monitoring has shown that surgery alone is usually insufficient to control high-risk diseases. Imatinib has greatly improved the survival of GIST’s patients. Neoadjuvant imatinib is mandatory in recurrent, residual or metastatic GISTs according to guidelines of ESMO 2018 [21]. In our case the surgical approach was the first choice for the patient. She started adjuvant Imatinib therapy after R0 radical surgery. Because of the metastatic setting the treatment with Imatinib has been continued indefinitely.



4. Conclusions

Gastrointestinal stromal tumors (GISTs) are usually not symptomatic and Giant Gists are not so rare. Actually, according to ESMO guidelines 2018, we usually treat metastatic GISTs with neoadjuvant imatinib therapy to improve patients’ outcomes. In some metastatic cases, however, radical surgery is the first choice for the patient. In these cases we usually prefer radical surgery and then adjuvant imatinib therapy to improve overall survival and the quality of life of patients. Anyway, every case should be evaluated by a multidisciplinary team in order to assess the indications for imatinib adjuvant therapy and for close monitoring and follow-up.

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