|Year : 2014 | Volume
| Issue : 3 | Page : 92-95
A rare case of pediatric gastrointestinal stromal tumor arising from ileum
Vijay C Pujar, Shirin S Joshi
Department of Pediatric Surgery, KLE University, Belgaum, Karnataka, India
|Date of Web Publication||15-Dec-2014|
Vijay C Pujar
Department of Paediatric Surgery, KLE University, Belgaum, Karnataka
Source of Support: None, Conflict of Interest: None
Malignant tumors arising from ileum are very rare in pediatric age group. Non-Hodgkin's lymphoma is the most common tumor. Gastrointestinal stromal tumors belong to a group of cancers called soft tissue sarcomas seen in adults are being reported even in pediatric age group. We report a rare occurrence of CD 117 marker positive Ileal tumor in a 2 year male child presenting with Abdominal mass associated with malnutrition and anemia.
Keywords: Small intestine, Gastro intestinal stromal tumor, pediatric
|How to cite this article:|
Pujar VC, Joshi SS. A rare case of pediatric gastrointestinal stromal tumor arising from ileum
. Saudi Surg J 2014;2:92-5
| Introduction|| |
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the GI tract. They belong to a group of cancers called soft tissue sarcomas which are common in elderly age group. GISTs having a first occurrence in patients <18 years of age are now described as pediatric GISTs and accounts for about 1-2% of all GIST patients. , Increased recognition of adult GIST has led to better awareness of the existence of this entity in the pediatric population. GIST occurring in pediatric patients has a unique biology and clinical behavior and response to treatment making them a separate group. 
Pediatric GIST is much more common in girls than in boys.  Usually it occurs between the ages of about 6-18 years. The majorities of pediatric GIST patients are female and often present with multi-focal tumors arising from gastric wall and are completely or partly epithelioid in nature. These young patients often have metastatic disease, but still follow a slow course of disease progression as compared to adults.  They appear to lack oncogenic activating tyrosine kinase mutations in both KIT and PDGFRA.  Pediatric GISTs are treated differently than adult GIST. Surgical removal of the tumor (s) has historically been the primary treatment for Pediatric GIST. , Use of drugs has shown success in the treatment of adults with metastatic or inoperable GISTs (in cases where surgery is not possible). Drugs are less effective in pediatric age group as these tumors have different mutations. The genetic defects that cause adult GIST (KIT and PDGFRA mutations) can now be targeted with a drug called Gleevec ® (also known as imatinib (IM) and Glivec ® ). Sunitinib is a small molecule multi-targeted receptor tyrosine kinase (RTK) inhibitor with selectivity against FLT3, KIT, platelet-derived growth factor receptor tyrosine kinase and vascular endothelial growth factor receptor that has been used to treat IM-refractory adult GISTs. ,
| Case Report|| |
A 2-year-old male child was brought to our department with complaints of abdominal pain, loss of appetite and failure to thrive. Mother noticed an abdominal mass incidentally while giving bath about 2 months back. There were no other associated symptoms. On examination the child was malnourished with pallor. Abdominal examination revealed a donut hard mass in the mid abdomen of 5 cm × 4 cm size, which was nontender and freely mobile. His blood parameters were normal except anemia (Hb - 8.2 g/dl, hematocrit - 24.6%) requiring blood transfusion prior to surgery. Ultrasonography and computerized tomography revealed a soft tissue mass arising from the mesentery of small bowel with fine calcification [Figure 1]. Laparotomy revealed a donut shaped tumor with central aperture arising from the wall of ileum [Figure 2]. Tumor was deriving additional blood supply through a large tortuous vessel from greater omentum [Figure 3]. No local lymph node enlargement or hepatic nodules were seen. Complete excision with 6 cm ileal segment was done. Continuity of ileum was established by end to end anastomosis. Postoperative period was uneventful. Histopathology confirmed the features of GIST tumor with predominantly spindle cell variety with positive immunohistochemistry (IHC) for CD117. Child gained weight and had no local recurrences even at 1-year follow-up.
| Discussion|| |
Gastrointestinal stromal tumors are the most frequent mesenchymal tumors of the gastrointestinal tract. GIST has been shown to arise from interstitial cells of Cajal, the pacemaker cells of the gut. GIST term was introduced in 1983. Until the late 1990s, all nonepithelial tumors of the gastrointestinal tract were called "gastrointestinal stromal tumors." Distinct histology and histochemistry helped forming a separate group. In fact, 95% of GIST immunohistologically stain positive for kit (CD117). The exact incidence is not known, but the estimated incidence of GIST in the United States is approximately 5000 cases annually.  An association between pediatric GISTs and Carney triad has been reported.  This syndrome, originally described by Carney in 1977, comprises the triad of GIST, paraganglioma, and pulmonary chondromas. 
Gastrointestinal stromal tumors are predominantly the disease of 50-70 years age group and the incidence is similar in men and women. GISTs occurring below the age of 18 years are grouped as pediatric GISTs and 6-10 years is the most common age group with 2.7 folds higher incidence in girls.
Gastrointestinal stromal tumors can occur anywhere along the gastrointestinal tract, including stomach (70%), small intestine (20-30%), anorectum (7%), colon, and esophagus.  GISTs can also originate in the mesentery and omentum. They typically arising within the muscle wall of the GI tract, small GIST may form solid subserosal, intramural, or, less frequently, polypoid intraluminal masses whereas large tumors form an external mass inseparable from the muscular layer as seen in our case and central necrosis has made the tumor to attain typical donut shape and receive secondary vascular supply from omentum. Predominantly these tumors comprised of spindle cells (70%), epithelloid cells (20%) or mixed. The most commonly used marker for GIST is the CD117 antigen, a marker expressed by IHC. Approximately 95% of GISTs are positive for the CD117 antigen, an epitope of the KIT RTK. 
The first reported KIT mutation in a pediatric GIST was a novel homozygous point mutation in exon 9 that results in an amino acid change at codon 456. 
Molecularly, most pediatric GISTs lack the gain-of-function mutations in the KIT and PDGFRA genes, which are commonly found in adult cases. 5Gene expression analysis showed high expression of PHKA1, FZD2, NLGN4, IGF1R, and ANK3 in the pediatric and young adult versus older adult cases.  The frequency of mutations found in the young adult population appears to be greater than in the pediatric subset,  but lower than in the adult population, again pointing to the mixed nature of this group. A current focus in this field is to search for genetic determinants of GIST pathogenesis, other than KIT or PDGFRA, in order to gain insights into these tumors and to provide additional therapeutic options for these young patients. The genes with significantly different expression in the pediatric group as compared to the adult tumors included FGF4* (fibroblast growth factor 4), BAALC* (brain and acute leukemia, cytoplasmic), IGF1R*, NELL1* (NEL-like 1), CRLF1 cytokine receptor-like factor 1), PLAG1* (pleomorphic adenoma gene 1) and FGF3 (fibroblast growth factor 3). Differential expression for five of these (denoted with*) was confirmed by qPCR. The only common gene to show up in both studies was IGF1R.
Presenting signs and symptoms are variably depending on the size and anatomic location of the tumor and can include abdominal pain, hematemesis, melena and anemia from occult gastrointestinal bleeding. 
Colicky abdominal pain loss of weight causing severe emaciation with anemia was symptoms as tumor was arising from ileum. No risk factors have been identified.  CD117 has become a very important tool in the differentiation of GIST from other GI mesenchymal tumors. , Pathological features of small intestine GISTs are not standardized as these tumors are extremely rare.
Despite the proven success of im and other newer tyrosine-kinase inhibitors in adults, pediatric GIST has poor response to drugs hence not uniformly recommended in the management protocol of pediatric GIST. Surgical resection remains the treatment of choice and offers the only chance for cure from GIST in pediatric age group.  The main operative principle is resection of the tumor with negative microscopic margins. The most appropriate tests and frequency of testing for metastatic or recurrent disease in patients who have undergone GIST resection are ill-defined, since the impact of follow-up strategies on clinical outcomes is not known.
| Conclusion|| |
Gastrointestinal stromal tumor is an uncommon tumor in younger children. CD117 is an important marker to differentiate from other mesenchymal tumor. Complete surgical resection is the treatment of choice.
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[Figure 1], [Figure 2], [Figure 3]