Gastrointestinal stromal tumors (GIST) usually form a well-circumscribed mass. However, patients with germline mutations in c-KIT, PDGFRA and NF1 may present with diffuse interstitial cell of Cajal (ICC) hyperplasia along the Auer-bach plexus without forming a discrete mass. To our knowledge, sporadic diffuse ICC hyperplasia replacing the gut wall has not been described previously. We describe herein two such cases. Case 1 was a 59-yr-old woman who presented with signs of ileus and a large mass submitted as Meckel diverticulum. The resection specimen showed a large GIST with diverticulum-like and solid areas. The diverticular component showed a diffuse proliferation of spindle cells extending for several centimetres from the solid tumor replacing the full thickness of the gut wall and lined by intact mucosa. Mutation analysis revealed a combined deletion/insertion in c-KIT exon 11 (V560delEins) in both the solid and the diffuse tumor component. Case 2 was a 66-yr-old man who underwent segmental sigmoid colon resection for adenocarcinoma in a villous adenoma. Random sections from grossly unremarkable colonic wall showed a diffuse proliferation of CD117+/CD34+ spindle cells completely replacing the muscularis propria for a length of 6 mm. Molecular analysis revealed a somatic point mutation/ deletion in exon 11 of c-KIT (Q575L; L576_W582del). Absence of multiple lesions and demonstration of a wild-type sequence for c-KIT in surrounding normal tissue ruled out the possibility of a germline mutation in both cases. This peculiar diffuse form of sporadic ICC hyperplasia results from somatic c-KIT mutations and must be distinguished from syndromic ICC hyperplasia associated with hereditary GIST syndromes.
Keywords: GIST; ICC hyperplasia; KIT mutation; Meckel Diverticulum; hereditary GIST.