Familial gastrointestinal stromal tumors, lentigines, and café‐au‐lait macules associated with germline c‐kit mutation treated with imatinib

Abstract

A c-kit mutational test in familial GISTs is indicated before initiation of imatinib therapy, as it can help predict tumor response to treatment.

Cutaneous hyperpigmentation and familial gastrointestinal stromal tumour associated with KIT mutation

“…Mutations in KIT exon 11, which encodes the juxtamembrane domain, are most commonly associated with familial GIST syndromes . Four mutations in KIT exon 11 have been identified in six families with familial GIST, and are associated with cutaneous findings that include hyperpigmentation and urticaria pigmentosa . In one of these families, an individual was treated with imatinib, a tyrosine kinase inhibitor, which resulted in resolution of the hyperpigmentation and stable GI disease .…”

“…2,8 In one of these families, an individual was treated with imatinib, a tyrosine kinase inhibitor, which resulted in resolution of the hyperpigmentation and stable GI disease. 8 Germline mutations involving exons 8, 11, 13 and 17 have also been reported in familial GIST syndromes, with a number of individuals demonstrating cutaneous features such as hyperpigmentation, lentigines, urticarial pigmentosa and naevi. 9 The association of cutaneous hyperpigmentation and GIST tumours is not surprising given the role of c-Kit in development of both melanocytes and interstitial cells of Cajal.…”

Autosomal dominant progressive hyperpigmentation and lentigines in a Japanese pedigree due to a missense mutation near the C-terminus ofKIT

“…The hyperpigmentation phenotype in this family is mild (Fig. ) compared with that in individuals with KIT mutations associated with both hyperpigmentation and GIST . In contrast to somatic mutations, germline mutations of KIT have been found in only a small number of cases of familial mastocytosis and GIST .…”

“…1) compared with that in individuals with KIT mutations associated with both hyperpigmentation and GIST. 5,6 In contrast to somatic mutations, germline mutations of KIT have been found in only a small number of cases of familial mastocytosis and GIST. 3,7 As of 2016, 37 reports described 21 well-sequenced germline mutations in KIT.…”

Novel KIT mutation presenting as marked lentiginosis

“…Early detection is important as surgical resection remains the only curative option. Data surrounding the role of imatinib in familial GIST remain limited, and the response is dependent on the type of mutation and its location within the KIT receptor . Other than GISTs, KIT mutations are also associated with piebald trait (autosomal dominant abnormality of pigmentation characterized by patches of white skin and hair), mast cell disease, urticaria pigmentosa, testicular germ cell tumor, and acute myelogenous leukemia.…”