Generalized lentigines associated with familial gastrointestinal stromal tumors dramatically improved by imatinib treatment

Hasegawa, Michiko; Shimizu, Akira; Ieta, Keisuke; Shibusawa, Kyoko; Ishikawa, Osamu; Ishida‐Yamamoto, Akemi; Tamura, Atsushi

doi:10.1111/1346-8138.15321

Cited by 6 publications

(5 citation statements)

References 5 publications

(9 reference statements)

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“… 23 In a case report published by Mara Fornasarig in 2020, in addition to GIST, the index case also developed breast cancer and thyroid papillary carcinoma. 10 In the case reported by Wadt, the patient had breast cancer with a GIST. 24 Whether long-term TKI therapy or frequent imaging would further increase the risk of second malignancy in this population remains to be determined.…”

Section: Discussionmentioning

confidence: 98%

Diagnosis, Treatment, and Prognosis of Patients with Primary Familial Gastrointestinal Stromal Tumor: A Case Report and Literature Review

et al. 2023

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Gastrointestinal stromal tumors are the most common mesenchymal tumors of the digestive tract, most of which are sporadic, and familial GISTs with germline mutations are rarely seen. Here, we report a 26-year-old female with a germline p. W557R mutation in exon 11 of the KIT gene. The proband and her father and sister presented with multifocal GIST and pigmented nevi. All 3 patients underwent surgery and imatinib therapy. To date, only 49 kindreds with germline KIT mutations and 6 kindreds with germline PDGFRA mutations have been reported. Summarizing the reported kindreds, the majority of familial GISTs manifest as multiple primary GISTs complicated with special clinical manifestations, including cutaneous hyperpigmentation, dysphagia, mastocytosis, inflammatory fibrous polyps, and large hands. Familial GISTs are generally thought to exhibit TKI sensitivity similar to that of sporadic GISTs with the same mutation.

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Section: Discussionmentioning

confidence: 98%

Diagnosis, Treatment, and Prognosis of Patients with Primary Familial Gastrointestinal Stromal Tumor: A Case Report and Literature Review

et al. 2023

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“…Familial GIST was first reported by Nishida in 1998[ 10 ]. It is a rare inherited disease and has been reported in 35 different families and eight individuals with germline KIT mutations[ 11 ]. Most affected families, including the members described in our study, have been shown to harbor a germline KIT mutation in exon 11 (encoding the juxtamembrane domain)[ 6 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

Familial gastrointestinal stromal tumors with KIT germline mutation in a Chinese family: A case report

Wang¹,

Wen²,

Lang³

et al. 2022

WJCC

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BACKGROUND Familial gastrointestinal stromal tumors (GISTs) is a rare autosomal dominant disorder characterized by an array of clinical manifestations. Only 35 kindreds with germline KIT mutations and six with germline PDGFRA mutations have been reported so far. It is often characterized by a series of manifestations, such as multiple lesions and hyperpigmentation. However, the effect of imatinib treatment in these patients is still uncertain. CASE SUMMARY Here, we report two patients (father and daughter) in a Chinese family (for the first time) with germline KIT mutation, and described their pathology, genetics and clinical manifestations. A 25-year-old Chinese woman went to hospital because of abdominal pain, and computed tomography showed multiple tumors in the small intestine. Small pigmented spots appeared on the skin within a few months after birth. Her father also had multiple pigmented spots and a history of multifocal GISTs. Multiple GISTs associated with diffuse interstitial Cajal cells (ICCs) hyperplasia were positive for CD117 and DOG-1. Gene sequencing revealed a germline mutation at codon 560 of exon 11 ( p.V560G ) of KIT gene in these two patients. Imatinib therapy showed the long-lasting disease stability after resection. Remarkably, the hypopigmentation of the skin could also be observed. Luckily germline KIT mutation has not been identified yet in the 3-year-old daughter of the female patient. CONCLUSION Diagnosis of familial GISTs depends on combination of diffuse ICCs hyperplasia, germline KIT / PDGFRA mutation, hyperpigmentation and family history.

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“…Apart from somatic mutations of KIT in melanomas, germline KIT mutations are reported to be associated with other pigmented disorders, often accompanied by GIST or mastocytosis ( 1 , 2 , 4 – 7 ). However, two independent groups have recently revealed a new missense mutation of KIT in patients with hyperpigmentation and lentigines without systemic disorders.…”

Section: Discussionmentioning

confidence: 99%

Case Report: A Missense Mutation of KIT in Hyperpigmentation and Lentigines Unassociated With Systemic Disorders: Report of a Chinese Pedigree and a Literature Review

2022

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BackgroundKIT is a proto-oncogene that is involved in the proliferation, survival, and regulation of melanocytes, mast cells, and the interstitial cells of Cajal. Mutations of KIT have been reported to be associated with hyperpigmentation and lentigines, mastocytosis, and gastrointestinal stromal tumors (GISTs). Some hotspot mutations of KIT have been reported to be associated with mastocytosis and GISTs, while the relationship between KIT mutations and hyperpigmentation and lentigines has not been fully elucidated.MethodsIn this study, we presented a three-generation Chinese pedigree with progressive hyperpigmentation and generalized lentigines inherited in an autosomal dominant pattern. High-throughput sequencing was performed to capture genetic variations in peripheral blood samples of the proband. Also, Sanger sequencing was performed to further verify the result. We also reviewed previous literature on KIT mutations with hyperpigmentation and lentigines.ResultsA missense mutation of the KIT gene was identified: c. 2485G > C, which was co-segregated in the proband and his insulted father. Germline KIT mutations presenting as generalized hyperpigmentation and lentigines without systemic disorders are rare, with only two reports of c. 2485G > C mutation associated with this phenotype in previous literature.ConclusionOur pedigree, together with those two reports, indicates a possible phenotype-genotype correlation of this germline KIT mutation, which might be helpful for genetic counseling, further functional segregation of KIT, and design of targeted therapy in the future.

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Generalized lentigines associated with familial gastrointestinal stromal tumors dramatically improved by imatinib treatment

Cited by 6 publications

References 5 publications

Diagnosis, Treatment, and Prognosis of Patients with Primary Familial Gastrointestinal Stromal Tumor: A Case Report and Literature Review

Diagnosis, Treatment, and Prognosis of Patients with Primary Familial Gastrointestinal Stromal Tumor: A Case Report and Literature Review

Familial gastrointestinal stromal tumors with KIT germline mutation in a Chinese family: A case report

Case Report: A Missense Mutation of KIT in Hyperpigmentation and Lentigines Unassociated With Systemic Disorders: Report of a Chinese Pedigree and a Literature Review

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