Related Experiment Video
Updated: Aug 18, 2026
Robotic Duodenal Sleeve Resection for Gastrointestinal Stromal Tumor with Rare Exon 8 KIT Mutation Following Neoadjuvant Imatinib
Published on: April 3, 2026
Epithelioid gastrointestinal stromal tumor with PDGFRA activating mutation and immunoreactivity
Eunhee S Yi1, Curtis R Strong, Zhe Piao
1Department of Pathology, University of California San Diego, School of Medicine, San Diego, CA 92103-8720, USA. jeyi@ucsd.edu
Abstract:
The authors report a unique case of an intra-abdominal, epithelioid mesenchymal tumor that had an activating mutation of PDGFRA and a strong PDGFRA immunoreactivity but lacked both c-kit mutation and c-kit protein (CD117) expression. IHC study showed that the tumor cells were diffusely and strongly positive for PDGFRA, vimentin, CD34, and Bcl-2 but completely negative for CD117 as well as for muscle, epithelial, endothelial, endocrine, mesothelial, neural, and melanocytic cell markers. Molecular study revealed a mutation at the juxtamembrane domain of exon 12 in PDGFRA gene with GTC to GAC transition at codon 561 (V561D), as shown in the previous mutational studies on gastrointestinal stromal tumor (GIST). This case likely represents an example of GIST with PDGFRA activating mutation and PDGFRA immunoreactivity without CD117 positivity, which has not been documented in the literature. STI 571 (imatinib mesylate [Gleevec]) might be an effective therapy in this case, since Gleevec targets both PDGFRA and c-kit oncoproteins.
Insights
This study describes a rare intra-abdominal tumor with a PDGFRA mutation but no CD117 expression, a unique finding in gastrointestinal stromal tumors (GIST). This case suggests potential efficacy of imatinib mesylate therapy for such PDGFRA-mutated GIST.
Area of Science:
- Oncology
- Molecular Pathology
- Gastrointestinal Pathology
Background:
- Gastrointestinal stromal tumors (GIST) are typically characterized by mutations in KIT or PDGFRA.
- CD117 expression is a common diagnostic marker for GIST, although exceptions exist.
Observation:
- A unique intra-abdominal epithelioid mesenchymal tumor presented with strong PDGFRA immunoreactivity and an activating PDGFRA mutation (V561D in exon 12).
- Crucially, this tumor lacked both KIT mutation and CD117 protein expression, differentiating it from typical GIST cases.
Findings:
- Immunohistochemistry confirmed diffuse positivity for PDGFRA, vimentin, CD34, and Bcl-2, while being negative for CD117 and other lineage markers.
- Molecular analysis identified a specific missense mutation in the PDGFRA juxtamembrane domain, consistent with activating mutations found in some GISTs.
Implications:
- This case expands the understanding of GIST heterogeneity, highlighting a subset of tumors driven by PDGFRA mutations without CD117 expression.
- The findings suggest that targeted therapy with imatinib mesylate (Gleevec), which inhibits both PDGFRA and KIT, could be a viable treatment option for this specific GIST subtype.
