Multiple gastrointestinal stromal cell tumors (GIST) in an adult, non-NF1 patient Free

LB-162

The occurrence of multiple, non metastatic GIST has been reported exclusively in children and in NF1 patients. The finding at the presentation of multiple GIST lesions in non-NF1 adult individuals is commonly attributed to metastatic spreading of the disease. However, pathologic examination can hardly distinguish whether these lesions are clonally related each other or represent multiple primary GIST. To shed light on the nature of these lesions 5 cases were selected by virtue of the presentation of syncronous multiple lesions at the diagnosis, all from non-NF1 adult GIST patients. Four patients had a dominant gastrointestinal nodule together with a smaller peritoneal nodule, while one patient had two nodules, in the stomach and small intestine, of comparable size. Mutational analysis of c-KIT (exons 9, 10, 11, 13, 14 and 17) and PDGFRA (exons 12 and 18) was performed on the DNA extracted from paraffin-embedded tissues coming from both nodules of each patient. Mutations were detected in 4 out of 5 cases analyzed. In 3 patients the same c-KIT mutation was detected in the distinct nodules analyzed, corroborating the metastatic nature of the disease. In contrast, 1 case carried different c-KIT mutations in the two synchronous tumors (stomach W557G and del29nt with stop at 480, intestine del555-572), suggesting the occurrence of two independent GIST. Our analysis, although limited, suggests the existence of exceptional cases of multiple primary GIST in adult, non-NF1 patients and indicates that the phenomenon of tumor multiplicity in the context of GIST might be underestimated. Further studies are required to assess the prevalence of this phenomenon. This would be relevant not only for the understanding of the biology of GIST but also for the proper clinical management of the disease.