Gastrointestinal stromal tumours: pathology and differential diagnosis

Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumours in the digestive tract. Although the GIST diagnosis is facilitated by the existence of several very sensitive immunohistochemical markers the correct diagnosis may be missed due to several reasons: low or only focal expression of the most sensitive marker CD117 (KIT receptor), unusual morphology or uncommon location. Among the morphological subtypes are spindle, epithelioid and mixed cell phenotypes. Often, the phenotype can serve as a first indicator for the genotype and the expected biological behaviour. Immunohistochemistry can also help to identify rare subtypes of GIST without KIT or PDGFRα mutation as for example multiple epithelioid GIST related to loss of function-mutations in the succinate dehydrogenase complex which present with immunohistochemical loss of succinate dehydrogenase B. The related syndrome where germline mutations can be found is called Carney–Stratakis-syndrome which is further characterized by the occurrence of paragangliomas. The most important differential diagnoses to be excluded before diagnosing a GIST in the context of mesenchymal tumors occurring in the gastrointestinal tract are leiomyomatous, vascular, fibroblastic/myofibroblastic, neurogenic tumours and inflammatory fibroid polyps. The criteria for these differential diagnosis are elucidated in this manuscript.