Published online May 26, 2022. doi: 10.12998/wjcc.v10.i15.4878
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
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.
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.
Diagnosis of familial GISTs depends on combination of diffuse ICCs hyperplasia, germline KIT/PDGFRA mutation, hyperpigmentation and family history.
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.