Metachronous Gastrointestinal Stromal Tumors (GISTS) or Relapse of the Primary Tumor? A Challenging Case of Multiple GISTS in an Elderly Patient

Background: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal cancers of the gastrointestinal tract and the majority of them carries pathogenic mutations of KIT and PDGFRA genes. Sporadic Multiple Primary GISTs (MPGs) are a rare entity that could occur in adult patients characterized by multiple synchronous lesions generally located in the same organ and even more rarely by metachronous neoplasms. The differential diagnosis among MPGs and disseminated disease or recurrent primary GIST is critical as it affects clinical management.

Case report: Here, we present a case of an 86-year-old female who underwent emergency surgery in June 2016 for a giant GIST of the stomach occupying most of the left side of the abdomen. After two years, during adjuvant imatinib 400 mg daily, emergency sigmoid resection was performed due to subacute obstruction and a colonic GIST carrying the same KIT mutation (deletion 557-558 at exon 11) of the previous gastric neoplasm was detected. In this case, we hypothesized the primary nature of the two tumors despite being metachronous and occurring in different organs. However, the same mutational pattern suggested a clonal relationship between the two neoplasms. The onset of a third duodenal lesion, that could corroborate the assumption of the primary metachronous nature of the disease, still remains an unsolved question since its malignancy was not confirmed.

Conclusion: Differentiating among metachronous multiple primary GISTs or relapse on imatinib is relevant for staging and choosing the most proper therapeutic approach. Further investigations are surely needed in order to asses a diagnostic tool that may help clinicians to distinguish this rare entity (both synchronous or metachronous) from recurrences. In this scenario, molecular analysis may add essential data to discriminate sporadic MPGs and recurrent or metastatic GISTs.