Multiple Primary Sporadic Gastrointestinal Stromal Tumors in the Adult: An Underestimated Entity

Purpose: Gastrointestinal stromal tumors (GIST) are commonly regarded as solitary tumors.The occurrence of multiple lesions is considered an extraordinary event restricted to pediatric GISTs and rare hereditary conditions.Beyond these well-defined situations, the presentation of multiple synchronous lesions is commonly viewed as the result of the metastatic spreading of a single primary GIST.Based on this axiom, patients with multifocal disease are classified as advanced stage and treated as such.Whether, indeed, the detection of several lesions in sporadic adult GIST patients may be suggestive of phenomena of tumor multiplicity still needs to be clarified. Experimental Design: From a multicentric series of 442 consecutive cases, 26 of which with advanced disease, we selected 5 patients who presented up to three distinct GIST nodules.Five additional cases with similar characteristics were also contributed by two other institutions.The clonal relationship between the synchronous lesions was assessed by comparing KIT/PDGFRA mutation and microsatellite pattern. Results: An independent origin of the synchronous lesions was established in 6 of 10 cases. Notably, in one patient, one lesion arose in the peritoneum, which is ordinarily regarded as a site of metastasis. Conclusions: Our data indicate that a significant fraction of GIST patients with multifocal pre- sentation are actually affected by multiple primary tumors, suggesting that mesenchymal GIST precursor cells of these individuals are somehow primed to transformation.Thus, in the presence of multifocal GIST manifestations, an accurate characterization of the different tumor sites should be undertaken for a proper patient staging and therapy planning. Gastrointestinal stromal tumors (GIST) are mesenchymal tumors most often originating in the muscular wall of the gastrointestinal tract. The estimated annual incidence is 12 to 14 per million, as recently reported in two European studies (1, 2). Stomach and small intestine are the most commonly affected anatomic sites, accounting for about two thirds and one third of the cases, respectively (3 - 5). Rare cases of primary GISTs originating outside the gastrointestinal tract have also been reported, although the actual existence of extragastro- intestinal GISTs is still debated (4, 6 - 9).