Peak Uptake Value on Positron Emission Mammography Addresses Biopsy Sampling Limitations in Stratifying Proliferative Activity of Malignant Non-Mass Enhancement

OBJECTIVES: To evaluate peak uptake value (PUVmax) derived from positron emission mammography (PEM) as a functional biomarker for identifying high-risk/high-proliferation phenotypes and addressing biopsy sampling limitations in malignant non-mass enhancement (NME). METHODS: This prospective study included patients with MRI-detected BI-RADS 4-5 NME between March 2023 and March 2025. Of 246 patients assessed, 92 were excluded because of benign pathology, planned neoadjuvant therapy, incomplete histopathological data, or unavailable surgical outcomes, leaving 154 patients with histologically confirmed malignancy and surgical pathology. All underwent ultrasound-guided core-needle biopsy followed by surgical excision. PEM was performed before biopsy (n = 91) or at least 2 weeks afterward (n = 63). PUVmax was measured, with ≥4.1 defining a high-risk biological phenotype. Interobserver agreement was assessed using the intraclass correlation coefficient (ICC). ROC, multivariable logistic regression, and reclassification analyses were performed. RESULTS: Interobserver agreement was excellent (ICC=0.94). Biopsy-surgical discordance occurred in 26/154 cases (16.9%), mainly upgrades (24/26). PEM identified 20/24 upgrades (83.3%). Concordance between PEM and surgical pathology was 97.4%, with four false-negative cases (2.6%) and no false positives. PUVmax was significantly associated with high-risk/high-proliferation phenotype (OR = 2.89, 95% CI: 1.95-4.28; p < 0.001; AUC=0.86). CONCLUSION: PEM-derived PUVmax shows high concordance with surgical pathology and may provide a reliable whole-lesion functional biomarker of high-risk biology in malignant NME. ADVANCES IN KNOWLEDGE: A PUVmax threshold ≥4.1 distinguished low- from high-risk disease across invasive carcinoma and ductal carcinoma in situ. PEM correctly reclassified 84.6% of biopsy-surgical discordant cases, potentially reducing underestimation caused by limited biopsy sampling of biologically heterogeneous lesions.