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Familial Cancer

, Volume 17, Issue 2, pp 247–253 | Cite as

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

  • S. Farag
  • L. E. van der Kolk
  • H. H. van Boven
  • A. C. J. van Akkooi
  • G. L. Beets
  • J. W. Wilmink
  • N. Steeghs
Short Communication

Abstract

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

Germline KIT mutation GIST Gastrointestinal stromal tumor Imatinib p.Trp557Arg 

Notes

Funding

Dr. N. Steeghs received a grant from Novartis, Bayer and Pfizer.

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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  1. 1.Department of Medical OncologyNetherlands Cancer Institute/Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  2. 2.Department of Clinical GeneticsNetherlands Cancer Institute/Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  3. 3.Department of PathologyNetherlands Cancer Institute/Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  4. 4.Department of Surgical OncologyNetherlands Cancer Institute/Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  5. 5.Department of Medical OncologyAcademic Medical CentreAmsterdamThe Netherlands

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