Skip to main content

Table 3 Main features of GIST-predisposing syndromes

From: Syndromic gastrointestinal stromal tumors

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
  1. a E esophagus, ST stomach, SI small intestine, C colon, R rectum
  2. b S spindle cell, E epithelioid, M mixed spindle cell and epithelioid
  3. c Diffuse Intersitial cell of Cajal hyperplasia
  4. d GI, gastrointestinal
  5. e Carney’s triad
  6. f Recently reported 6 germline SDHx-mutant cases, one of which with inherited paragangliomas
  7. g Carney-Stratakis syndrome