Molecular and morphological correlation in gastrointestinal stromal tumours (GISTs): an update and primer

Abstract

Gastrointestinal stromal tumours (GISTs) are a commonly encountered tumour in routine practice. In the main, the morphology of spindle, epithelioid or mixed are well recognised along with mutations of c-kit. However, there are other genes that are mutated resulting in characteristic clinicopathological correlations. GISTs harbouring platelet-derived growth factor receptor α (PDGFRα) gene mutations lead to a typical morphological constellation of findings: gastric and omental location, gross tumour that is cystic and haemorrhagic, composed of epithelioid, plasmacytoid cells exhibiting pleomorphism, low mitotic count and containing characteristic giant cells with peripherally placed nuclei. These cells are set in a myxoid stroma containing several mast cells. In addition, perivascular/intratumoural hyalinisation is often seen. These tumours are CD117 and DOG-1 positive. GISTs with SDH mutations are multinodular/bilobed/dumb-bell shape tumour masses with mucosal ulceration and histologically characterised by fibrous bands around and within nodules of epithelioid or mixed epithelioid/spindle cells. Lymphovascular invasion with lymph node metastases are usual. Immunohistochemically, the GISTs are CD117, DOG-1 positive, SDHA negative (if SDHA mutated), SDHA positive (if SDHA intact) and SDHB negative. BRAF and NF-1 mutated GISTs do not have any characteristic morphological features.