Remarkable effects of imatinib in a family with young onset gastrointestinal stromal tumors and cutaneous hyperpigmentation associated with a germline KIT-Trp557Arg mutation: case report and literature overview

Fam Cancer. 2018 Apr;17(2):247-253. doi: 10.1007/s10689-017-0024-8.


Gastrointestinal stromal tumors (GISTs) occur mostly sporadically. GISTs associated with a familial syndrome are very rare and are mostly wild type for KIT and platelet-derived growth factor alpha (PDGFRA). To date 35 kindreds and 8 individuals have been described with GISTs associated with germline KIT mutations. This is the third family described with a germline p.Trp557Arg mutation in exon 11 of the KIT gene. The effect of imatinib in patients harboring a germline KIT mutation has been rarely described. Moreover, in some studies imatinib treatment was withheld considering the lack of evidence for efficacy of this treatment in GIST patients harboring a germline KIT mutation. This paper describes a 52-year old patient with a de novo germline p.Trp557Arg mutation with multiple GISTs throughout the gastrointestinal tract and cutaneous hyperpigmentation. Imatinib treatment showed long-term regression of the GISTs and evident pathological response was seen after resection. Remarkably, the hyperpigmentation of the skin also diminished during imatinib treatment. Genetic screening of the family revealed the same mutation in two daughters, both with similar cutaneous hyperpigmentation. One daughter, aged 23, was diagnosed with multiple small intestine GISTs, which were resected. She was treated with adjuvant imatinib which prompted rapid regression of the cutaneous hyperpigmentation. Imatinib treatment in GIST patients harboring a germline KIT mutation shows favorable and long-term responses in both the tumor and the phenotypical hyperpigmentation.

Keywords: GIST; Gastrointestinal stromal tumor; Germline KIT mutation; Imatinib; p.Trp557Arg.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Age of Onset
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Exons / genetics
  • Female
  • Gastrointestinal Stromal Tumors / diagnosis
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / pathology
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Germ-Line Mutation
  • Humans
  • Hyperpigmentation / drug therapy*
  • Hyperpigmentation / genetics
  • Imatinib Mesylate / pharmacology
  • Imatinib Mesylate / therapeutic use*
  • Neoplastic Syndromes, Hereditary / diagnosis
  • Neoplastic Syndromes, Hereditary / drug therapy*
  • Neoplastic Syndromes, Hereditary / genetics
  • Neoplastic Syndromes, Hereditary / pathology
  • Proto-Oncogene Proteins c-kit / antagonists & inhibitors
  • Proto-Oncogene Proteins c-kit / genetics*
  • Rectum / diagnostic imaging
  • Rectum / pathology
  • Skin / drug effects
  • Skin / pathology
  • Stomach / diagnostic imaging
  • Stomach / pathology
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Young Adult


  • Antineoplastic Agents
  • Imatinib Mesylate
  • KIT protein, human
  • Proto-Oncogene Proteins c-kit