Syndrome | Trigger | Inheritance | Sex predilection | Average age at diagnosis (years) | GIST features | Other manifestations | |||
---|---|---|---|---|---|---|---|---|---|
Sitea | Morphologyb | Immunohistochemistry | |||||||
KIT-mutant | germline KIT mutation | Autosomal dominant, high penetrance | None | 48 | SI, ST > C, R > E | S > M> > E | CD117+ DOG1+ | Skin hyperpigmentation, mast cell disorders, ICCHc, dysphagia | |
PDGFRA-mutant | germline PDGFRA mutation | Autosomal dominant, high penetrance | None | 48 (GIST), 41 (inflammatory fibroid polyp) | ST | E, M | CD117+/− DOG1+/− | Inflammatory fibroid polyps (including GId “fibrous tumors”), GI lipomas, large hands | |
Neurofibromatosis type 1 | Germline NF1 mutation + tumor 2nd hit in WT allele | Autosomal dominant, complete penetrance and variable expression | None | 49 | SI > ST | S > M | CD117+ DOG1+ | Neurofibromas and other signs of Neurofibromatosis type 1, ICCH, dysphagia | |
SDH-deficient syndromes | CTe | epigenetic SDHC promoter hypermethylation in tumors | Nonef | F> > M | 22 (either whatever tumor type or GIST) | ST | E > M, S; plexiform | CD117 + DOG1+ | Paragangliomas/pheocromocytomas, pulmonary chondromas, esophageal leiomyoma, adrenal cortical adenoma |
CSSg | Germline SDHB, C or D mutation + tumor 2nd hit in WT allele | Autosomal dominant, incomplete penetrance. Parent-of-origin if SDHD-mutant | None | 19 (whatever tumor type), 24 (GIST) | ST | E > M, S; plexiform | CD117 + DOG1+ | Paragangliomas/pheocromocytomas |