Gastrointestinal pacemaker cell tumor: clinicopathological, immunohistochemical, and ultrastructural study with special reference to c-kit receptor antibody

Recent studies indicate that a subgroup of gastrointestinal stromal tumors, including gastrointestinal autonomic nerve tumors (GANTs), originate from stem cells that differentiate toward a pacemaker-cell phenotype. These pace maker cells form a complex network intercalated between the autonomic nerve s and the muscle walls of the gastrointestinal tract and are called interst itial cells of Cajal (ICC). The c-kit receptor (CD117) is a sensitive marke r for ICC. The aim of our study was to support the hypothesis that GANTs sh ow ICC differentiation. Seven GANTs without convincing smooth muscle or neu ral differentiation all showed homogeneous reactivity for the c-kit recepto r. CD34 was positive in three cases. On electron microscopy, the typical fe atures of GANT were present. Six tumors contained skeinoid fibers. Most tum ors were related to the small bowel. They presented as single (two cases) o r multiple (five cases) tumors. The presenting symptoms were abdominal blee ding (2), abdominal mass (2), anemia (1), and small-bowel perforation (1). In two cases, liver metastases developed. Because of the close immunohistoc hemical and electron microscopic similarities of these tumors to the inters titial cells of Cajal, the term gastrointestinal pacemaker cell tumor seems appropriate.