Hereditary and non-hereditary syndromic gastointestinal stromal tumours

The majority of gastrointestinal stromal tumours (GISTs) present as solitary gastrointestinal masses in adults aged 50-70 years. A small subset of GISTs (a parts per thousand currency sign5%) occurs in the setting of familial or idiopathic multitumour syndrome. In decreasing order of frequency, neurofibromatosis Recklinghausen (NF-1), Carney triad (gastric GIST, pulmonary chondroma and extra-adrenal paraganglioma), familial GIST syndromes resulting from germline mutations in c-Kit/PDGFRA and the Carney-Stratakis syndrome (hereditary GIST paraganglioma syndrome caused by germline mutations in the mitochondrial tumour suppressor gene pathway involving the succinate dehydrogenase subunits SDHD, SDHC and SDHB) represent the four most important GIST syndromes characterized to date. Since affected patients and their family members require special treatment and/or counseling and follow-up, early diagnosis and precise classification of this likely still underdiagnosed diseases is of the utmost importance. This review summarizes the pertinent clinicopathological and molecular features of the main GIST syndromes to facilitate their diagnosis and distinction from their non-syndromic mimics.