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Familial gastrointestinal stromal tumors, lentigines, and café‐au‐lait macules associated with germline c‐kit mutation treated with imatinib
Author(s) -
Gupta Divya,
Chandrashekar Laxmisha,
Larizza Lidia,
Colombo Elisa A.,
Fontana Laura,
Gervasini Cristina,
Thappa Devinder M.,
Rajappa Medha,
Rajendiran Kalai Selvi,
Sreenath Gubbi Shamanna,
Kate Vikram
Publication year - 2017
Publication title -
international journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 93
eISSN - 1365-4632
pISSN - 0011-9059
DOI - 10.1111/ijd.13516
Subject(s) - cd117 , medicine , neurofibromatosis , pathology , neurofibroma , familial adenomatous polyposis , germline mutation , stromal tumor , pdgfra , imatinib mesylate , cancer research , cd34 , gist , imatinib , mutation , stromal cell , biology , cancer , genetics , colorectal cancer , stem cell , myeloid leukemia , gene
Background Familial lentiginosis syndromes are characterized by a wide array of manifestations resulting from activation of molecular pathways which control growth, proliferation, and differentiation of a broad range of tissues. Familial gastrointestinal stromal tumors ( GIST s) are often accompanied by additional features like hyperpigmentation, mastocytosis, and dysphagia. They have been described with mutations in c‐kit (most commonly), platelet‐derived growth factor receptor A, neurofibromatosis‐1, and succinate dehydrogenase genes. Materials and Methods We report on molecular characterization and tumor histopathology of two siblings in whom lentigines and café‐au‐lait macules were present along with multifocal GIST . Immuhistochemical analysis of CD 34 and CD 117 was performed on GIST biopsy samples from both siblings, while c‐kit mutational analysis was done by PCR and direct sequencing on DNA from peripheral blood leukocytes of all family members and from paraffin‐embedded gastric biopsy specimens of affected siblings. Results Histopathology revealed positive expression of CD 117 and CD 34. Mutational analysis showed the germline c.1676T>C mutation in c‐kit exon 11, (p.(Val559Ala)), in the peripheral blood of both siblings and a second exon 11 mutation, c.1669T>A (p.(Trp557Arg)) in the tumor biopsy of one of them. Initiation of imatinib treatment resulted in striking resolution of their hyperpigmentation and a stable gastrointestinal disease in one of them. Conclusions A c‐kit mutational test in familial GIST s is indicated before initiation of imatinib therapy, as it can help predict tumor response to treatment.