Short CommunicationPediatric gastrointestinal stromal tumor: Report of two novel patients harboring germline variants in SDHB and SDHC genes
Introduction
Gastrointestinal stromal tumors (GISTs) are the most common GI mesenchymal neoplasms [1], but rarely occur in pediatric patients, displaying a unique biology and clinical behavior [2]. Activating mutations of KIT or PDGFRA proto-oncogenes are detected in 85–90% of GISTs occurring in adult patients [3], [4], and most of these respond to tyrosine kinase inhibitors such as imatinib or sunitinib [5], [6]. However, 85% of pediatric GISTs and 10–15% of GISTs in adults lack of KIT or PDGFRA mutations [7], [8]. These tumors are termed “wild-type” GISTs and 40% of them present deficiency of succinate dehydrogenase (SDH) complex, a heterotetrametric enzyme involved in both the citric acid cycle and the electron transport chain [9]. Here, we describe two pediatric patients, with multifocal GIST, liver lesions and no history of paraganglioma (PGL), harboring respectively a novel and a previously reported loss-of-function germline variant, in SDHC and SDHB genes.
Section snippets
Patient 1
A 16-year-old boy with unremarkable medical history was referred to our Institution for an abdominal lesion discovered by ultrasound during the clinical work-up of an iron-deficiency anemia. At physical examination an epigastric mass was evident. Combined computed tomography and 18-fluoro-deoxyglucose-positron emission tomography (18FDG-PET CT) scans showed increased metabolic uptake in primary lesion arising from gastric antrum, as well as in perigastric nodes and in multiple sites of hepatic
Discussion
GISTs in pediatric and adolescent patients differ significantly in clinical, histological and genetic characteristics from those in adults with important implications for the medical management of pediatric cases. The percentage of patients younger than 21 years with GISTs is estimated to be 0.5% to 2.7% [10]. Most pediatric GISTs are located in the stomach, usually in the antrum, and show an epithelioid morphology [11]. In comparison, adult GISTs most often have a spindle cell morphology [12].
CRediT authorship contribution statement
Martina Rinelli: Conceptualization, Data curation, Formal analysis, Writing - original draft, Writing - review & editing. Emanuele Agolini: Conceptualization, Data curation, Formal analysis, Writing - original draft, Writing - review & editing. Giuseppe Maria Milano: Conceptualization, Writing - review & editing. Ida Russo: Conceptualization, Writing - review & editing. Alessandro Crocoli: Conceptualization, Writing - review & editing. Rita De Vito: Conceptualization, Data curation, Formal
Declaration of Competing Interest
The authors declare that they have no conflict of interest.
Acknowledgments
We are grateful to the participating families. We are thankful to Technogenetics for its support on NextSeq 550 (Illumina) instrument.
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Both authors contributed equally to this manuscript.