What key feature distinguishes GIST from leiomyoma and leiomyosarcoma?

Gastrointestinal stromal tumors (GISTs) are distinct from leiomyomas and leiomyosarcomas primarily due to the mutation in the c-KIT gene, which is responsible for encoding a receptor tyrosine kinase that is crucial for the proliferation and survival of gastrointestinal interstitial cells of Cajal, the cells from which GISTs arise.

The presence of mutations in the c-KIT gene leads to constitutive activation of the receptor, promoting cell growth and division, which is characteristic of GISTs. This mutation is a fundamental aspect that helps in the accurate diagnosis of GISTs through immunohistochemical staining that typically demonstrates positive c-KIT expression, particularly in the context of gastrointestinal tract tumors.

In contrast, leiomyomas and leiomyosarcomas are tumors of smooth muscle origin and do not typically involve mutations in the c-KIT gene. Instead, these tumors show different expression patterns, including desmin positivity, and arise from smooth muscle cells without the specific genetic alterations seen in GISTs. Therefore, identifying the mutation in c-KIT is critical in differentiating GISTs from smooth muscle tumors such as leiomyomas and leiomyosarcomas.