Answer: Gastrointestinal stromal tumor (GIST)

Histology: This tumor has a markedly hypocellular appearance overall, and it had other (unillustrated) large areas of gross necrosis. Focally, there are clusters of spindled cells with amphophilic cytoplasm and perinuclear vacuoles. These cells label for c-kit (CD117), confirming that they are residual GIST cells. The areas of hypocellular fibrosis do not contain c-kit positive spindle cells, indicating that they represent scar replacing areas of treated tumor.

Discussion: A fibromatosis is typically seen in the abdominal mesentery or peritoneum but occasionally can involve the bowel wall. Fibromatosis typically features myofibroblastic cells arranged in intersecting fascicles, with an infiltrative border. Schwannomas in the GI tract typically have a non-circumscribed border and prominent lymphoid aggregates. These lesions are strongly and diffusely immunoreactive for S-100 protein. Leiomyosarcomas are typically immunoreactive for desmin, while GISTs are not.

The importance of correctly identifying GISTs is that these lesions are highly treatable with STI571 (Gleevec), a drug which inhibits the activated c-kit tyrosine kinase within these tumors. The vast majority of GISTs demonstrate activating mutations in the c-kit gene leading to constitutive tyrosine kinase activity that is inhibited by Gleevec. Approximately one-third of the rare c-kit negative GISTs have demonstrated mutations in the PDGFRA gene, another tyrosine kinase which feeds into the same pathways as c-kit does.