Gastrointestinal stromal tumours (GISTs) typically show uniform nuclear morphology, with spindle cell, epithelioid or mixed histology. Risk of progression in GIST is estimated based on anatomical site, tumour size and mitotic index. Pleomorphic GISTs are rare and have not been systematically investigated. We evaluated the prognostic significance of pleomorphism in GIST.

In total, 108 of 2517 (4.3%) GISTs reviewed between 2000 and 2021 were reported to show pleomorphism. Seventeen cases underwent mutational testing. Pleomorphism was noted prior to therapy in 37 GISTs, affecting 18 males and 19 females, with a mean age of 55.4 years. Most tumours arose in the stomach (n = 15) or small intestine (n = 19), with a mean size of 9.2 cm and a median mitotic rate of seven per 5 mm2; the median follow-up was 5.7 years. Immunohistochemistry for KIT was positive in 36 (97.3%) tumours. Mutational testing revealed KIT and PDGFRA mutations in 68.4 and 21.0% of cases, respectively; no SDHX, KIT or PDGFRA alterations were found in two cases (one of which was succinate dehydrogenase-deficient). According to standard risk assessment criteria for progressive disease, 18 tumours were high-risk, five were moderate-risk, four were low-risk, five were very low-risk and one had no risk. Disease progression was exclusive to high-risk tumours (79%; P < 0.001).

Pleomorphism is present prior to therapy in approximately 2% of GISTs and is most prevalent in high-risk gastric and small intestinal GISTs. Pleomorphism appears to have no prognostic significance beyond conventional risk stratification.