The Prognostic Significance of Pleomorphism in Gastrointestinal Stromal Tumors.

Abstract

AIMS\nGastrointestinal stromal tumors (GISTs) typically show uniform nuclear morphology, with spindle cell, epithelioid, or mixed histology. Risk of progression in GIST is estimated based on anatomic site, tumor size, and mitotic index. Pleomorphic GISTs are rare and have not been systemically investigated. We evaluated the prognostic significance of pleomorphism in GIST.\n\n\nMETHODS AND RESULTS\nIn total, 108 of 2517 (4.3%) GISTs reviewed between 2000-2021 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 yrs. Most tumors 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 7 per 5 mm2 ; the median follow-up was 5.7 yrs. Immunohistochemistry for KIT was positive in 36 (97.3%) tumors. 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 tumors were high-risk, 5 were moderate-risk, 4 were low-risk, 5 were very low-risk, and 1 had no risk. Disease progression was exclusive to high-risk tumors (79%; p<0.001).\n\n\nCONCLUSIONS\nPleomorphism 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.