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- Title
Familial gastrointestinal stromal tumors, lentigines, and café-au-lait macules associated with germline c-kit mutation treated with imatinib.
- Authors
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
- Abstract
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 ( GISTs) 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 CD34 and CD117 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 CD117 and CD34. 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 GISTs is indicated before initiation of imatinib therapy, as it can help predict tumor response to treatment.
- Subjects
LENTIGO; CELL differentiation; GENETIC disorders; GASTROINTESTINAL stromal tumors; DEGLUTITION disorders
- Publication
International Journal of Dermatology, 2017, Vol 56, Issue 2, p195
- ISSN
0011-9059
- Publication type
Article
- DOI
10.1111/ijd.13516