Multiple Gastric Stromal Tumors in a Child without Syndromic Association Lacks Common KIT or PDGFRα Mutations

Abstract

A diagnosis of multiple gastric stromal tumors that were nonmetastatic at presentation was made in an 11-year-old girl who presented with hematemesis. Gastrointestinal stromal tumor (GIST) is a rare diagnosis in childhood and reported multiple lesions are generally seen in the context of familial disease, occasionally with syndromic associations. Although there are no reports of genetic mutation in cases of pediatric GIST, very many cases of multiple GISTs investigated on a molecular level have shown germline KIT or platelet-derived growth factor receptor-alpha mutation; these were familial cases. Despite the negative family history in our patient, the multiplicity of lesions in such a young patient raised concern for a genetic predisposition and prompted extensive molecular workup. Repeat evaluation of distinct aliquots of tumor tissue by polymerase chain amplification followed by sequence analysis of selected coding sequences of KIT and platelet-derived growth factor receptor-alpha previously shown to harbor mutations in GIST, yielded no evidence of even a somatic mutation. This clinically unique case is discussed in the context of a literature review.

Coexistence of gastrointestinal stromal tumors with other neoplasms

“…67 Multiple GISTs may develop in patients with a germline mutation; however, multiple GISTs have been reported in a child with no family history and without any of the common C-KIT and PDGFRA mutations in the tumor tissue. 67 It has not been established whether the coexistence of a GIST with other, unrelated syndromes or tumors is incidental or results from related pathophysiological processes. 21,22,24,[29][30][31]36,48 Coexisting tumors may be favored by a high incidence of tumors among the given population.…”

Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours

“…However, paediatric and Carney triad GISTs occur predominantly in female patients and are associated with gastric location and epithelioid morphology. These tumours lack KIT and PDGFRA mutations, suggesting that other mechanisms of KIT activation or unrelated oncogenic mechanisms are operational 128–133 . A Pro456Ser in KIT exon 9 and nonsense mutation in PDGFRA exon 18 have been reported in two separate paediatric GISTs, 134,135 however, these mutations probably represent random molecular events.…”

Gastrointestinal stromal tumor of the stomach in a child with a 3-year follow-up period—Case report

“…The likelihood of metastatic disease correlates with tumor size and degree of mitotic activity: one mitosis or fewer per 10 (higher power fields (HPF) is considered to be low grade, whereas 2 or more mitoses per 10 HPF is thought to have a greater malignant potential. [3][4][5][6] Surgical resection is considered the current standard of care for GIST, and lymphadenectomy has not been shown to improve survival. 3 Although the response to conventional chemotherapy and radiotherapy is poor, the oral protein kinase inhibitor, imatinib mesylate, has shown promising antiproliferative and apoptotic effects and may be beneficial for patients with GISTs, particularly those with recurrent metastatic disease.…”