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EUS-guided aspiration biopsy cytology of recurrent GIST showing clusters of atypical epithelioid and spindle cells (PAP ×400).
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Gastrointestinal stromal tumours (GIST) frequently occur in patients with neurofibromatosis type 1 (NF-1). It has been reported that GIST may co-exist with pancreatic endocrine tumors but this has only been in association with NF-1.
A 76 year old woman presented with a 12 month history of hypoglycaemia symptoms. Abdominal CT scan demonstrated a 13...
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... A high incidence of GISTs has been previously reported in patients with NF1 (19). What's more, coincidence in the development of GISTs and NET has been recognized, especially in patients with NF1 (20). Moreover, KIT and platelet-derived growth factor receptor-alpha (PDGFRA) mutations have been reported to be sporadic events in NF1 GISTs. ...
Background: Patients with Neurofibromatosis type 1 (NF1) have an increased risk of developing neuroendocrine tumors, and the most frequent target organs of periampullary neuroendocrine neoplasms (NENs) in NF1 patients are the duodenum and peri-ampullary region.
Case presentation: A 50-year-old male patient was admitted to our hospital after experiencing progressive skin and scleral yellowing for over six months. An abdominal contrast-enhanced computed tomography (CT) scan showed a tumor in the periampullary region, which measures 1.2×1.4cm in size and showed a progressive enhancement. Magnetic resonance cholangiopancreatography (MRCP) showed the dilation of intra- and extrahepatic bile ducts. The patient was diagnosed with an ampullary tumor with the possibility of malignancy. A Whipple procedure was performed. Microscopically, the duodenum tumor invades the mucosa, sphincter, and muscular layer of the duodenal papilla. Histologic hematoxylin and eosin (HE)stain confirmed the presence of duodenal G1 neuroendocrine tumor (NET). In order to get the whole picture of NENs, a bibliometric analysis was performed, which showed that publications about periampullary NENs increase gradually every year, and most of them focus on the treatment and diagnosis of NENs.
Conclusions: We reported a case of periampullary duodenal NET in a patient with NF1, and carried out a bibliometric analysis on periampullary NENs.
... Previously reported literature review data were used to support this study. ese prior studies (and datasets) are cited at relevant places within the text as references [11][12][13][14][15][16]. ...
Insulinomas are extremely rare pancreatic endocrine tumors. The tumor is characterized by endogenous hypersecretion of insulin and ensuing development of symptoms of neuroglycopenia and the catecholaminergic response. Symptoms may not always be present, particularly in patients compensating appropriately with increased appetites and caloric intake due to low glucose levels. Early localization of the disease is essential to prevent lethal hypoglycemia and timely treatment. This case report and literature review depict the case of a pancreatic insulinoma in an 86-year-old female, an exceptionally rare presentation based on age and absence of clinical symptoms for one or more years prior to hospitalization. Despite its rarity, similar presentations have been reported in the literature and are further outlined with characteristics and treatment plans. This case highlights a unique presentation of insulinoma and suggests the need for clinical vigilance and further study. It also discusses diagnosis, localization, and management of this uncommon disease in patients above the age of seventy-five.
... That can be the result from the fact that 10% of NETs will be associated with an inherited genetic syndromes, such as MEN1 (hyperparathyroidism, pancreatic NETs in up to 75% of cases, and pituitary tumors), Von Hippel-Lindau disease (NF-pancreatic NETs) in 10-20% of patients, cystadenomas, hemangioblastomas and adenocarcinoma, tuberous sclerosis, and NF1 [10]. The coexistence of gastric GIST and pancreatic NETs is extremely a rare condition and there are only three more cases, described in the literature, excluding our case [4,12,13]. Although there are very few cases of NF1-related concurrent GEP NETs and GISTs, there is no evidence that the mutation in the NF1 involved in the pathogenesis of GIST is the same mutation existing in NF1 patients with coexistent GISTs and GEP NETs [12]. ...
... The coexistence of gastric GIST and pancreatic NETs is extremely a rare condition and there are only three more cases, described in the literature, excluding our case [4,12,13]. Although there are very few cases of NF1-related concurrent GEP NETs and GISTs, there is no evidence that the mutation in the NF1 involved in the pathogenesis of GIST is the same mutation existing in NF1 patients with coexistent GISTs and GEP NETs [12]. In the described four cases (with our patient), there was also no family history or clinical findings suggestive of NF-1, so mutations in non-NF1 patients with coexistent GISTs and GEP NETs are still unclear. ...
... In the described four cases (with our patient), there was also no family history or clinical findings suggestive of NF-1, so mutations in non-NF1 patients with coexistent GISTs and GEP NETs are still unclear. Interestingly, in the three cases with synchronous gastric GIST and pancreatic NETs, as in our case, the grade of GIST is low or very low, and the pancreatic NETs are nonfunctional in three of the four cases [4,12,13]. ...
Background
Although gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, they comprise less than 1% of all gastrointestinal tumors. Neuroendocrine tumors (NET) of the gastro-enteropancreatic system are also rare, representing about 2% of all gastrointestinal neoplasms. Pancreatic localization of NET is extremely uncommon—these tumors are only 1–5% of all pancreatic cancers. Case presentationWe describe an unusual case with triple tumor localization—a gastric tumor, a formation in the pancreas, which involves the retroperitoneal space, and a uterine leiomyoma. The exact diagnosis was confirmed with immunohistochemical study after surgical treatment of the patient. Distal pancreatic resection, splenectomy, partial gastrectomy, omentectomy, and hysterectomy were performed. The histological examination proved an epithelioid type of gastric GIST. Immunostaining showed focal positive expression of c-kit and no mitotic figures per 50 HPF. Histology of the pancreatic and retroperitoneal formation proved a well-differentiated NET with origin from the islets of Langerhans. The immunohistochemical study demonstrated co-expression of chromogranin A and synaptophysin. Conclusions
This is the fourth case published so far of a patient with synchronous pancreatic NET and gastric GIST. The main objective of the study is to present a unique case because we have not found any reports for coexistence of the described three types of neoplasm, as in our patient, and we hope that it will be valuable in the future investigations about the genesis, diagnosis, and treatment of these types of tumors.
... in NF-1 patients in whom these tumors are frequent, there are only 9 cases reporting this association. [3] The question raised by the present case is whether this association is a coincidental fi nding or are we actually overlooking the pancreas when assessing GIST patients. A systematic evaluation of the pancreas, when EUS is performed in this setting, could help clarify this question. ...
... In the present case, PNET and GIST occurred synchronously. This is an extremely rare condition, with only four cases, including the present case, having been reported to date (15)(16)(17) (Table). Although PNETs and GISTs arise at a frequency of 0-10% and 11-25%, respectively, in patients with NF-1 (18,19), no such cases have been reported in the literature. ...
We recently encountered the case of a patient with a synchronous duodenal gastrointestinal stromal tumor (GIST) and pancreatic neuroendocrine tumor (PNET). This is the first report of this specific combination of multiple primary tumors, although three cases involving both PNET and gastric GIST have previously been reported. Since the duodenal GIST developed close to the pancreatic uncus in this case, we considered the possibility of multiple PNETs in the differential diagnosis. However, a histopathological examination using endoscopic ultrasonography-guided fine-needle aspiration confirmed the diagnosis of multiple primary lesions, involving PNET and duodenal GIST.
... The concomitant occurrence of a GIST and a neuroendocrine tumor (NET) in the setting of NF1 has been reported in approximately 13 cases, [5] with seven additional NF1-independent cases. [6,7] Moreover, an association between multiple endocrine neoplasia type 1 (MEN1) and stromal tumors has been reported: Four reports described an association between MEN1 and leiomyomas, [8] whereas only one report described an association between a GIST and a gastrinoma in a MEN1 patient. [7] ...
... The coexistence of a GIST and GEP-NET has been described in 20 cases: 13 in the setting of NF1, and the remaining 7 occurring independently of NF1. [5][6][7] MEN1 is an inherited autosomal dominant disorder, and the MEN1 gene has been mapped on chromosome 11q13; high rates of loss of heterozygosity (LOH) in the 11q13 region have been reported in MEN1 classical neuroendocrine tumors, suggesting that the MEN1 gene acts as a recessive tumor suppressor gene and is responsible for the occurrence of multiple neoplasms. [9] GISTs can be sporadic or associated with familial NF1 syndrome at a rate of 4-25%. ...
... [9] GISTs can be sporadic or associated with familial NF1 syndrome at a rate of 4-25%. [6] Approximately, 85% of GISTs harbor activating mutations in KIT or the homologous receptor tyrosine-kinase PDGFRA gene. [1] GISTs have been demonstrated to express synaptic-like microvesicle (SLMV) proteins, ghrelin, and peptide hormone receptors, which are commonly expressed in NETs, suggesting that these stromal tumors might undergo neuroendocrine differentiation, showing a similar phenotype as NETs, with a possible analogous target of genetic mutations. ...
Both multiple endocrine neoplasia type 1 (MEN1)-related gastrinomas and gastrointestinal stromal tumors (GISTs) are rare neoplasms, and their association has been rarely reported. We describe an unusual association between a GIST and a MEN1-related gastrinoma. A 44-year-old man had undergone surgical removal of a pancreatic gastrinoma in 2004 and was then administered long-term somatostatin analogs, and diagnosed as having MEN1 syndrome. Following an uneventful follow-up, in April 2009, an upper gastrointestinal tract endoscopy showed esophageal narrowing, with evidence of a 2-cm solid mass on endoscopic ultrasonography. Histology revealed a tumor composed of elongated cells with plump cytoplasm arranged in a storiform pattern. The immunophenotype of the lesion was CD117 and Platelet Derived Growth Factor (PDGF) positive, whereas alpha-1 muscle actin and S-100 protein were negative. Due to morphological and immunohistochemical results, a final diagnosis of esophageal GIST was made. The association between GISTs and MEN1 could be casual, although a single case of the coexistence of a GIST and a MEN1-related gastrinoma has already been reported. A role of the MEN1 gene in the pathogenesis of GISTs could be hypothesized.
... In addition, GISTs in patients with NF-1 often develop in the small intestine, and multiple occurrence is common, while it is rare in sporadic GISTs [21]. Furthermore, coincidental development of GIST and NET has been recognized, particularly in patients with NF-1 [22]. Recently, Yamamoto et al. [23] reported that KIT and platelet-derived growth factor receptor-alpha (PDGFRA) mutations are very rare events in NF-1 GIST and that activation of the RAS-MAPK pathway associated with inactivation of the NF-1 gene may play an important role in the development of GIST in NF-1 patients. ...
Patients with neurofibromatosis-1 (NF-1) sometime develops neuroendocrine tumors (NET). Although these NETs usually occur in the duodenum or peri-ampullary region, they occasionally grow in the pancreas (PNET). A 62-year-old man with NF-1 had mild liver dysfunction and was admitted to our hospital for further examination. An abdominal contrast enhanced computed tomography scan demonstrated a 30 mm tumor in the head of the pancreas. The scan showed showed an invasion of the tumor into the duodenum, and biopsy under an endoscopic ultrasonography indicated that the tumor was a NET. A subtotal stomach-preserving pancreaticoduodenectomy was performed. Macroscopically, the pancreatic tumor was white and elastic hard. Microscopically, tumor cells were composed of ribbons, cords, and solid nests with acinus-like structure. The tumor was diagnosed as NET G2 according to WHO classification (2010). The product of NF-1 gene, i.e., neurofibromin, was weakly positive in the tumor cells, suggesting that the tumor was induced by a mutation in the NF-1 gene. This is the seventh case of PNET arising in NF-1 patients worldwide.
... The gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract, and have an incidence of about 30/million/ population/year. 1 Stromal tumours represent less than 1% of all of the gastrointestinal tract tumours. GISTs are mesenchymal neoplasms stemming from the interstitial cells of Cajal localised within the wall of the gastrointestinal tract. ...
... There were only nine reports of GISTs associated with neuroendocrine tumour of the pancreas and almost all of these have been diagnosed in patients with NF1. 1 In summary, this is the second case report of a non-NF1 patient that had a pancreatic neuroendocrine tumour coexistent with a gastric GIST. ...
... Available evidence suggests that mutations in the NF1 gene might be involved in the pathogenesis of GIST in NF1 patients. 1 However, it is unknown whether the same mutation exists in NF1 patients with coexistent GISTs and GEP NETs, and more importantly, it is unknown whether there are such mutations in non-NF1 patients with coexistent GISTs and GEP NETs. 1 A meticulous follow-up (along with a well-scheduled initial therapeutic approach) should be performed for all patients suffering from the aforementioned neoplasms so that the devastating consequences of a metastatic disease are avoided. 2 In patients with NF1, NF1 gene mutation occurs and its gene product-neurofibromin-acts as a tumour suppressor. ...
The gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract. These are rare tumours with an incidence of 15 new cases per million per year. The occurrence of neuroendocrine tumours of the pancreas is rare, representing 1-5% of pancreatic cancers, and it is estimated that its incidence does not exceed five to one million. GISTs are common in patients with neurofibromatosis type 1 (NF1); there are few reported cases of synchronous neuroendocrine tumours in these patients and most are pheochromocytomas. The case reports a 64-year-old woman referred to the General Surgery Outpatient for incidental finding of gastric and pancreatic tumours. She underwent a radical subtotal pancreatectomy + partial gastrectomy with jejunal transposition. The pathological examination revealed: gastric GISTs and a well-differentiated neuroendocrine carcinoma of the pancreas. This is the second case published so far of a patient with both tumours and without NF1. Posterior studies must be performed to evaluate if some other genetic disorder is involved in these patients without NF1.
... There are, to the best of our knowledge, only three reported cases of pNET co-existing with GIST [1,12,16] (Table 1). ...
... This case report is, to the best of our knowledge, the fourth report of concomitant pNET and GIST [1,12,16] (Table 1). Among the other three reports, which included one patient with NF-1, none included cytogenetic data. ...
... 11 The rapid recurrence that follows was attributed to removing the inhibition exerted by the primary tumor on its remote metastases via circulating angiostatin. 12,13 Currently, achieving negative surgical margins on frozen section examination is mandatory 14 and this entails segmental resection, at times amounting to subtotal gastrectomy and omentectomy as in perforation, bleeding or when a tumor ruptures. 9,15 Being of no profitable use lymphadenectomy is not required and adjuvant therapy with the KIT tyrosine kinase inhibitor imatinib remains essential for high risk or metastasizing tumors, as it significantly prolongs survival. ...
Though recurrence is high, local excision is the preferred approach for dealing with gastric stromal tumors. Achieving negative margins is mandatory, sometimes requiring subtotal gastrectomy. Adjuvant imatinib is essential for advanced cases and prolonging survival; however, there is not enough data to recommend its use before surgery to increase resectability. The current study aims at investigating this concept in Egyptian patients.
The study included 16 patients (13 males, 3 females, mean age 60 years) presenting with gastrointestinal stromal tumors (GISTs) who were candidates for emergency (n = 3) or elective (n = 13) surgery. Investigations included endoscopy (+biopsy), sonography, and computed tomography (CT). Patients were enrolled in two groups: A (n = 6: projected to planned surgery) and B (n = 7: harboring c-kit +ve tumors). Each B patient received imatinib (400 mg/day) for 6 months before surgery. Clinical and radiological evaluation was at day 100. The Chi-square test was used to check size changes, and p at <0.02535 was considered significant.
All patients had abdominal discomfort, while 62.5% had epigastric pain, and 12.5% had hematemesis. Tumor sizes ranged from 8.4 to 20 cm 2/3 were located in the upper stomach. Five patients (31.3%) harbored lesions with low risk malignancy, eight (50%) with moderate risk and three (18.8%) with high risk. Wedge gastrectomy was the most common operation performed (81.25%) while partial gastrectomy was carried out in the rest, reporting no recurrence for 6 months. Not determined in group A patients, c-kit status was strongly positive in all members of group B; in two of them treatment was suspended due to poor response.
Imatinib has an acceptable safety profile and can be considered as a neoadjuvant therapy in GISTs. Until clear guidelines have been developed, we report that a 6 month intake may noticeably increase their resectability potential and improve prognosis.
