PURPOSE OF REVIEW: Knowledge related to gastrointestinal stromal tumor (GIST) in 
the setting of nonhereditary and hereditary multiple tumor syndromes continues 
to expand. This review describes associations between sporadic GIST and second 
malignancies, as well as new contributions to our knowledge about hereditary 
GIST multiple tumor syndromes.
RECENT FINDINGS: Sporadic GIST patients have increased risk of developing 
synchronous/metachronous cancers, including nonhematologic and hematologic 
malignancies. Data suggest these associations are nonrandom, more prevalent in 
men and increase with age. New adrenal tumors have also been associated with 
nonhereditary Carney's triad. Meanwhile, understanding of the molecular basis of 
heritable GIST syndromes has improved. Several new familial GIST kindreds have 
been reported, including those with germline KIT and PDGFRα mutations. Knowledge 
about succinate dehydrogenase (SDH) deficiency and mutations in hereditary GIST 
syndromes has expanded. It is now known that neurofibromatosis-1-associated 
GISTs are SDHB-positive, whereas Carney-Stratakis syndrome-associated GISTs are 
SDHB-deficient with underlying germline mutations in SDH subunits A-D.
SUMMARY: Recognition and early diagnosis of GIST syndromes allows for improved 
comprehensive medical care. With additional understanding of the molecular 
pathogenesis of GIST multiple tumor syndromes, we can refine our screening 
programs and management of these patients and their families.