. 2016 Jul 19;14:15. doi: 10.1186/s13053-016-0055-4

Table 3.

Main features of GIST-predisposing syndromes

Syndrome		Trigger	Inheritance	Sex predilection	Average age at diagnosis (years)	GIST features			Other manifestations
Syndrome		Trigger	Inheritance	Sex predilection	Average age at diagnosis (years)	Site^a	Morphology^b	Immunohistochemistry	Other manifestations
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, ICCH^c, 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 GI^d “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	CT^e	epigenetic SDHC promoter hypermethylation in tumors	None^f	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
SDH-deficient syndromes	CSS^g	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

^a E esophagus, ST stomach, SI small intestine, C colon, R rectum

^b S spindle cell, E epithelioid, M mixed spindle cell and epithelioid

^c Diffuse Intersitial cell of Cajal hyperplasia

^d GI, gastrointestinal

^e Carney’s triad

^f Recently reported 6 germline SDHx-mutant cases, one of which with inherited paragangliomas

^g Carney-Stratakis syndrome