Challenging differential diagnosis of a wild-type gastrointestinal stromal tumour (GIST) or rare reticular perineurioma of the stomach? The role for mutational analysis

The differential diagnosis of submucosal stomach lesions includes gastrointestinal stromal tumour (GIST), leiomyoma, synovial sarcomas, perineurioma, myxoid chondrosarcoma, myoepithelial tumour and other rare mesenchymal tumours. GISTs are well-defined lesions with distinctive morphologic and histogenetic characteristics that show 95% positive staining for CD117. Differential diagnosis of wild-type GISTs can be challenging. Here, we present two stomach tumours that were operated on in our surgical department. Both presented with positive immunoreactivity for CD117. In one tumour, c-Kit mutation analysis demonstrated positivity of exon 11_c.1674_1676delGGT, thus confirming the diagnosis of a GIST. Mutational analysis of the second stomach lesion demonstrated negativity for all known c-KIT and PDGFRA exons. In situ hybridisation ruled out a synovial sarcoma. An additional immunohistochemical staining for epithelial membrane antigen eventually confirmed the diagnosis of an extremely rare reticular perineurioma in the stomach, so far reported for the second time worldwide. Both patients have not shown any signs of recurrence 2 years after surgery. The presented cases emphasise the benefits of performing a mutational analysis in difficult GISTs, including wt-GISTs, and demonstrates the importance and challenges in differentiating GISTs from other mesenchymal tumours.