Case Report
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 26, 2022; 10(15): 4878-4885
Published online May 26, 2022. doi: 10.12998/wjcc.v10.i15.4878
Familial gastrointestinal stromal tumors with KIT germline mutation in a Chinese family: A case report
Wei Yuan, Wen Huang, Lei Ren, Chen Xu, Li-Juan Luan, Jie Huang, An-Wei Xue, Yong Fang, Xiao-Dong Gao, Kun-Tang Shen, Jing-Huan Lv, Ying-Yong Hou
Wei Yuan, Wen Huang, Lei Ren, Chen Xu, Li-Juan Luan, Jie Huang, Ying-Yong Hou, Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
An-Wei Xue, Yong Fang, Xiao-Dong Gao, Kun-Tang Shen, Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Jing-Huan Lv, Department of Pathology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, Jiangsu Province, China
Author contributions: Yuan W participated in the design of this study; Huang W drafted this manuscript; Ren L and Xu C performed literature research and data acquisition; Luan LJ and Huang J provided help for the methodology used; Xue AW, Fang Y and Gao XD analyzed the CT findings; Lv JH collected the background information and contributed to manuscript drafting; Hou YY contributed to funding acquisition; Shen KT and Hou YY reviewed and edited this manuscript; all authors issued final approval for the version to be submitted.
Supported by Shanghai Municipal Key 306 Clinical Specialty, No. shslczdzk01302.
Informed consent statement: Informed consent was obtained from this patient prior to inclusion in the study.
Conflict-of-interest statement: The authors declare that they have no competing interests.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ying-Yong Hou, PhD, Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, China. 980455691@qq.com
Received: May 11, 2021
Peer-review started: May 11, 2021
First decision: October 16, 2021
Revised: October 29, 2021
Accepted: March 25, 2022
Article in press: March 25, 2022
Published online: May 26, 2022
Processing time: 378 Days and 5.5 Hours
Abstract
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.

Keywords: Familial gastrointestinal stromal tumor; Germline KIT mutation; Cutaneous hyperpigmentation; Imatinib therapy; Case report

Core tip: Familial gastrointestinal stromal tumors (GISTs) with a germline KIT oncogene mutation are always accompanied by symptoms, such as cutaneous hyperpigmentation, dysphagia and mastocytosis. We present a novel KIT germline mutation (p.V560G) in a 25-year-old Chinese woman with familial GISTs. The same mutation was detected in the tumor and saliva samples of her father. They both had similar cutaneous hyperpigmentation on their face, body and limbs. Imatinib therapy resulted in a long-term response and generalized hypopigmentation. This case highlights that clinical manifestations, family history, pathological examination and molecular determination should be combined for correct diagnosis. This novel KIT germline mutation may be of therapeutic significance.