Synchronous and metachronous multiple gastrointestinal stromal tumors.
Sporadic multiple gastrointestinal stromal tumors (GISTs) are rare events especially those developed metachronously. This study aimed to investigate the clinico-pathologic and genetic features defining multiple GISTs.



624 cases of GISTs were retrieved for retrospective review. 15 cases were identified as multiple GISTs including 13 synchronous and 2 metachronous ones. 32 tumors and 15 normal tissues were obtained from these cases each containing 2-3 tumor nodules and the genomic DNA was extracted for mutational analysis of KIT and PDGFRA genes. The associated patients were recruited for clinical follow-up studies, including 5 males and 10 females at 49 to 84 years of age.



Multiple GISTs comprised of 2.4% of GIST cases in our consecutive series. Twenty-six tumors showed mutations at KIT gene in exon 11 and one at PDGFRA gene in exon 18. In seven synchronous cases, different tumors from the same patients displayed different genotypes of KIT or PDGFRA, suggesting their polyclonal origin. In the two multiple GISTs occurring metachronously, the tumors from each patient showed different KIT mutations, suggesting that the second tumors were not the relapse or metastasis of the primary GISTs.



Based on types of KIT or PDGFRA mutations and other pathological features, multiple primary GISTs can be differentiated from multiple GISTs resulting from recurrence or metastasis of a single primary tumor. Unlike recurrence or metastasis of GISTs that are malignant, most multiple GISTs are mostly benign and do not require aggressive adjuvant therapy. Therefore, correct diagnosis is critical for proper treatment.
Department of Pathology, Zhongshan Hospital of Fudan University, Shanghai, China.
Chen
C
Xu
Ya-Lan
YL
Liu
Hong-Yu
HY
Yu
Ying-Yong
YY
Hou
Shao-Hua
SH
Lu
Li-Jun
LJ
Zhao
Yang
Y
Zhou
Yuan
Y
Shi
Yun-Shan
YS
Tan
Xiong-Zeng
XZ
Zhu
D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology*; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000235:genetics
D019089:Stem Cell Factor; D020796:Receptor, Platelet-Derived Growth Factor alpha