Pathological changes related to Imatinib treatment in a patient with a metastatic gastrointestinal stromal tumour.

Abstract

Gastrointestinal stromal tumors (GISTs) are a distinct tumor type driven by activating mutations in c-kit (detected via CD117 immunohistochemistry) or, less commonly, PDGFRA, leading to constitutive kinase activation that promotes tumor growth. Imatinib mesylate (Gleevec/Glivec), a tyrosine kinase inhibitor targeting c-kit, PDGFRA, and other kinases, has shown remarkable efficacy in advanced GISTs. This report describes a 54-year-old man with metastatic GIST who underwent gastrectomy in 1999 and partial hepatectomy for liver metastases in 2001. In 2003, a new hepatic metastasis was treated with imatinib (600 mg daily) for 24 weeks, followed by resection. Post-treatment histology revealed dramatic changes: marked reduction in tumor cell density, replacement by myxohyaline stroma, absence of mitoses, necrosis, or inflammation. Only rare residual cells were CD117-positive, with no Ki-67 (MIB-1) proliferation marker expression—contrasting sharply with pre-treatment high-density, proliferative tumor. These findings align with broader evidence from clinical trials (e.g., partial responses in ~54% of patients, stable disease in ~28%) and other reports, where imatinib induces hypocellular myxoid/sclerohyaline stroma, variable hemorrhage/necrosis/cystic changes, reduced CD117 expression, and lowered proliferative index—sometimes achieving near-complete histological remission. The morphological spectrum underscores imatinib's effectiveness in inhibiting the c-kit pathway, offering a promising targeted therapy for advanced/metastatic GISTs.