Gastrointestinal stromal tumors in the setting of multiple tumor syndromes.

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.