Wild-Type Pediatric GIST Management

Background 

A 13-year-old female presents with her mother to her pediatrician’s office for lightheadedness and dizziness after starting her first menstrual period. Her bleeding started 2 weeks ago and lasted for 5 days with some fatigue, light cramps, feelings of bloating, and nausea. She denies any episodes of syncope or vomiting. Endorses continued stomach upset; the patient at first believed this was related to the cramps, however it persisted after her period stopped. Her mother is also concerned about her lack of appetite, which has been particularly noticeable over the last few days.  

The pediatrician orders routine bloodwork, which includes a CBC, CMP, and total iron binding capacity (TIBC). Lab workup finds the patient’s hemoglobin to be 7.2, with a hematocrit of 22.6; CMP and TIBC are within normal limits. The pediatrician then orders an upper endoscopy, which reveals a 3.0 cm mass in the stomach.  

Endoscopic ultrasound biopsy of the stomach mass is positive for spindle cell neoplasm, consistent with gastrointestinal stromal tumor (GIST). No exon or PDGFRA mutation was detected. The patient was referred to a local pediatric oncology group, who recommended that she and her parents proceed with surgical resection, and due to the rarity of the diagnosis, obtain a second opinion at a large academic medical center across the state.  

After discussion with the gastrointestinal oncology team, which included consults with a medical oncologist, radiation oncologist, and surgical oncologist, the patient and her parents elected to proceed with surgical resection. Pathology revealed a 3.1 x 2.4 cm multi-lobulated GIST, 6 mitoses/10 high-power fields, with negative margins. The patient recovered well from surgery and was able to return to her normal activities a few weeks later, with postoperative imaging and a follow-up oncology visit scheduled to monitor for recurrence.  

Discussion 

It is incredibly rare for a pediatric patient to be diagnosed with a GIST; overall they account for up to 2% of all diagnosed GIST cases each year.^1-4As a result, there is little known about this disease in the pediatric population. Much of what is available is based on retrospective data and literature review.^3,4The NCCN guidelines do not make any specific recommendations regarding pediatric GIST management, and there is currently no other known set of guidelines for practitioners to follow.^5,6  

In pediatric patients, GISTs are more likely to be diagnosed in females.² It is most common for these tumors to be found in the stomach; however, there are reports of GISTs appearing in the duodenum.³Unlike their adult counterparts, pediatric GISTs are more likely to be classified as “wild-type,” meaning no KIT, PDGFRA, or other mutations (BRAF, RAS, NF1).^1,3They are also more resistant to TKI therapy.^2,3Additionally, there are two pediatric syndromes, the Carney triad and the Carney-Stratakis syndrome, that are associated with the diagnosis of succinate dehydrogenase (SDH)-deficient GISTs. Although not expressed in this case study, many pediatric GISTs lack the SDH complex.² Advanced practice providers should evaluate their pediatric patients for these syndromes if they are diagnosed with GIST.  

It is important for the advanced practice provider to be aware that, while rare, GISTs can occur in the pediatric population. Pediatric patients usually present similarly to adult patients, with fatigue, pallor, sudden abdominal pain, and/or gastrointestinal bleeding.^2,5,6 In this case, some of the patient’s symptoms overlapped with her menstrual period, which can delay diagnosis. Thorough workup and evaluation of all the differential diagnoses is key. Close follow-up of this patient population is highly recommended, as pediatric GISTs are known to metastasize, commonly to lymph nodes.²  

References 

1. Agaram NP, Laquaglia MP, Ustun B, et al. Molecular characterization of pediatric gastrointestinal stromal tumors. Clin Cancer Res. 2008;14(10):3204-3215. doi:10.1158/1078-0432.CCR-07-1984 
2. National Cancer Institute (2024). Childhood Gastrointestinal Stromal Tumors Treatment (PDQ®)–Health Professional Version. https://www.cancer.gov/types/soft-tissue-sarcoma/hp/child-gist-treatment-pdq 
3. Popoiu TA, Pîrvu CA, Popoiu CM, et al. Gastrointestinal Stromal Tumors (GISTs) in Pediatric Patients: A Case Report and Literature Review. Children (Basel). 2024;11(9):1040. Published 2024 Aug 26. doi:10.3390/children11091040 
4. Quiroz HJ, Willobee BA, Sussman MS, et al. Pediatric gastrointestinal stromal tumors-a review of diagnostic modalities. Transl Gastroenterol Hepatol. 2018;3:54. Published 2018 Aug 8. doi:10.21037/tgh.2018.07.08 
5. Janeway KA, Weldon CB. Pediatric gastrointestinal stromal tumor. Semin Pediatr Surg. 2012;21(1):31-43. doi:10.1053/j.sempedsurg.2011.10.003 
6. NCCN Guidelines: Gastrointestinal stromal tumors. Version 2.2024; July 31, 2024.