Golgi-Pattern PDGFRA Immunoreactivity Correlates With PDGFRA Mutation Status in Gastric Epithelioid and Mixed-Type Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumors (GISTs) with PDGFRA mutations represent a distinct subset with characteristic clinicopathological features and important therapeutic implications. The diagnostic performance of PDGFRA immunohistochemistry (IHC) as a phenotypic correlate of PDGFRA mutation status requires further evaluation. This study aimed to assess the diagnostic performance and reproducibility of PDGFRA IHC against PDGFRA mutation status as the reference standard. A total of 117 tumors were analyzed (19 PDGFRA-mutant, 40 non-PDGFRA, 49 GISTs of undetermined genotype, 9 non-GIST mimics). IHC for KIT, DOG1, CD34, and PDGFRA was performed on full sections and tissue microarrays, and 3 pathologists independently scored intensity, extent, and Golgi-pattern accentuation. PDGFRA-mutant GISTs were predominantly gastric with epithelioid or mixed morphology. Sixteen carried D842V, whereas 3 had exon 18 deletion or exon 12 mutations. KIT expression was reduced (47.4%) compared with non-PDGFRA-mutant GISTs (85%), while DOG1 remained consistently positive. Overall, PDGFRA expression was observed in 94.7% of PDGFRA-mutants compared with 32.5% of non-PDGFRA-mutants (P<0.001), and Golgi-pattern accentuation was present in 89.5% (17/19) of PDGFRA-mutants versus 7.5% (3/40) of molecularly confirmed non-PDGFRA-mutants (P<0.001). Among non-GIST mimics, only a monophasic synovial sarcoma showed diffuse PDGFRA positivity. Interobserver agreement for PDGFRA was substantial (κ=0.691). PDGFRA IHC showed 95% sensitivity and 78% specificity but did not distinguish D842V from non-D842V variants. PDGFRA IHC correlates with PDGFRA-mutant genotype when diffuse Golgi-type staining is observed in a gastric epithelioid or mixed tumor showing reduced KIT expression. However, therapeutic selection-particularly for avapritinib-requires precise detection of D842V variants, which mandates molecular sequencing.