Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract in adults.  These tumors are rare in children.  Approximately 2% of all GIST occur in children and young adults.    In one series, pediatric GIST accounted for 2.5% of all pediatric nonrhabdomyosarcomatous soft tissue sarcomas.  Previously, these tumors were diagnosed as leiomyomas, leiomyosarcomas, and leiomyoblastomas.
Histologically, pediatric gastrointestinal stromal tumors (GIST) have a predominance of epithelioid or epithelioid/spindle cell morphology and, unlike adult GIST, the mitotic rate does not appear to accurately predict clinical behavior.   Most GIST in the pediatric age range have loss of the succinate dehydrogenase (SDH) complex and consequently, lack SDHB expression by immunohistochemistry.   In addition, these tumors have minimal large-scale chromosomal changes and overexpress the insulin-like growth factor 1 receptor.  
Activating mutations of KIT and PDGFA, which are seen in 90% of adult GIST, are present in only a small fraction of pediatric GIST.    The lack of SDHB expression in most pediatric GIST implicates cellular respiration defects in the pathogenesis of this disease and supports the notion that this disease is better categorized as SDH-deficient GIST. Furthermore, about 50% of patients with SDH-deficient GIST have germline mutations of the SDH complex, most commonly involving SDHA,  supporting the notion that SDH-deficient GIST is a cancer predisposition syndrome and testing of affected patients for constitutional mutations for the SDH complex should be considered.  A small percentage of SDH-deficient GIST lack somatic or germline mutations of the SDH complex and are characterized by SDHC promoter hypermethylation and gene silencing and are categorized as SDH-epimutant GIST. 
In an observational study carried out at the National Cancer Institute, 116 patients with presumed wild-type GIST were evaluated, and 95 of these patients had an adequate tumor specimen available for molecular profiling. Among these 95 patients, the investigators identified the following three distinctive subgroups of patients: 
Of the 95 patients that were evaluated at this clinic, 18 patients had syndromic GIST (i.e., Carney triad or Carney-Stratakis syndrome). Among the Carney triad patients, two patients had the complete triad, five patients had SDH mutations, and six patients had epimutant tumors. Seven patients with Carney-Stratakis syndrome had SDH-mutant GIST (n = 6) or SDH-epimutant GIST (n = 1). 
Most pediatric patients with gastrointestinal stromal tumors (GIST) are diagnosed during the second decade of life with anemia-related gastrointestinal bleeding. In addition, pediatric GIST have a high propensity for multifocality (23%) and nodal metastases.    These features may account for the high incidence of local recurrence seen in this patient population. Despite these features, patients have an indolent course characterized by multiple recurrences and long survival. 
Once the diagnosis of pediatric gastrointestinal stromal tumors (GIST) is established, referral to medical centers with expertise in the treatment of GIST should be considered, with all samples evaluated for mutations in KIT (exons 9, 11, 13, 17), PDGFR (exons 12, 14, 18), and BRAF (V600E).  
Treatment options for GIST depend on whether a mutation is detected, as follows:
Responses to imatinib and sunitinib in pediatric patients with SDH-deficient GIST are uncommon and consist mainly of disease stabilization.    In a review of ten patients who were treated with imatinib mesylate, one patient experienced a partial response and three patients had stable disease.  In the phase III SWOG Cancer Research Network intergroup trial S0033 (NCT00009906), 20 tumors from patients who were presumed to be wild-type were resequenced.  Twelve of these tumors were identified as being SDH mutant, and only one patient (8.3%) experienced a partial response to imatinib.  In another study, sunitinib appeared to show more activity, with one partial response and five cases of stable disease in six children with imatinib-resistant GIST.  Unlike the adult recommendations, the use of adjuvant imatinib cannot be recommended in children with SDH-deficient GIST. 
Given the indolent course of the disease in pediatric patients, it is reasonable to avoid extensive initial surgeries and to withhold subsequent resections unless they are needed to address only symptoms such as obstruction or bleeding.  
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following are examples of national and/or institutional clinical trials that are currently being conducted:
Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
Cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975.  Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered for children and adolescents with cancer. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:
(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)
Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.  At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%.  Childhood and adolescent cancer survivors require close monitoring because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.  The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 persons. Therefore, all pediatric cancers are considered rare.
The designation of a rare tumor is not uniform among pediatric and adult groups. Adult rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people, and they are estimated to account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.   Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows:
Most cancers within subgroup XI are either melanomas or thyroid cancer, with the remaining subgroup XI cancer types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.
These rare cancers are extremely challenging to study because of the low incidence of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.
Information about these tumors may also be found in sources relevant to adults with cancer such as the PDQ summary on adult Gastrointestinal Stromal Tumors Treatment.
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This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pediatric gastrointestinal stromal tumors. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
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PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Gastrointestinal Stromal Tumors Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/soft-tissue-sarcoma/hp/child-gist-treatment-pdq. Accessed <MM/DD/YYYY>.
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