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