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The present study investigated multiple extragastrointestinal stromal tumors (EGISTs) occurring in the peritoneum, identified their clinicopathologic and immunohistochemical features, and examined their c-KIT gene mutations, clonal status and clonal relationships. Fifteen different tumors of a multiple EGIST from the same female patient were examined by microscopy and immunohistochemistry, then genomic DNA was isolated from the lesions and, as the control, the surrounding fibrous connective tissues. PCR amplification and sequencing were used to investigate the mutation status of c-KIT gene exons 9, 11, 13 and 17. Finally, a clonality assay was conducted based on X-chromosome inactivation mosaicism in female somatic tissues and polymorphisms of the phosphoglycerate kinase and androgen receptor genes. Immunohistochemical analysis revealed CD117- and CD34-positive reactivity in the tumors. Mutation analysis identified the c-KIT gene mutation in exon 13. The clonality assay revealed a loss of X-chromosome inactivation mosaicism and an identical inactivated allele in all 15 nodules. No similar findings were observed in the surrounding fibrous connective tissues. The c-KIT gene mutation was found in the multiple EGISTs from the patient. The EGIST, like most tumors, was of monoclonal origin. This and the identical inactivated allele found in the nodules indicated a common clonal origin for the tumor.

c-KIT gene mutation and clonal origin of multiple gastrointestinal stromal tumors occurring in the peritoneum