Background:Last-generation ultra high-resolution ultrasound (UHFUS) transducers, producing frequencies up to 70 MHz and achieving tissue resolution up to 30 μm, are opening up new possibilities for the study of labial salivary glands (LSG) in patients clinically suspected with primary Sjögren’s syndrome (pSS).Objectives:To explore the value of LSG-UHFUS as a predictor of the intensity of the histological inflammation in LSG biopsy in an inception cohort of patients with sicca symptoms derived from daily clinical practice.Methods:Consecutive patients undergoing a LSG for clinically suspected pSS were included in this study from January 2018 to October 2020. UHFUS of LSG was performed by using VEVO MD, equipped with a 70 MHz probe, scanning first the central compartment of the inferior lip, and then both peripheral compartments. Parenchymal homogeneity was graded on a scale of 0 (normal) to 3 (evident). UHFUS imaging was used to locate the LSG for the US-guided biopsy. For each of the LSG specimens the area of the glandular tissue, the presence and number of foci and the focus score (FS) were assessed. Immunostaining for CD21 was performed to evaluate the presence of follicular dendritic cells (FDC) in foci.Results:We included a total of 171 patients with suspected pSS: out of them, 83 (48.5%) received a diagnosis of pSS (ACR 2016 criteria) and 88 (51.5 %) were diagnosed as no-SS sicca controls. Out of the 171 LSG biopsies, 73/171 (42.7%) were characterized by a nonspecific chronic sialadenitis (NSCS) whereas a focal lymphocytic sialadenitis (FLS) was described in the remaining 98/171 (57.3%). UHFUS-LSG scores were differently distributed in pSS patients with respect to no-SS sicca controls: a score 0 was detected in 16/88 no-SS sicca controls and in none of the 83 pSS patients, whereas a score 3 was detected in 12/83 pSS and in none of no-SS sicca controls. (p<0.001). The higher was the UHFUS grading, the higher was the number of foci (from a mean (S.D) = 0.38 (0.72) in UHFUS-score 0 to 4.58 (3.11) in UHFUS-score 3, p<0.001) and the focus score (from 0.17 (0.32) in UHFUS-score 0 to 1.88 (0.90) in UHFUS-score 3, p<0.001) of the samples. Overall, out of the 16 no-SS controls with LSG-UHFUS score 0, only 4/16 showed histological features of focal lymphocytic infiltrate; however, the mean FS of those 4/16 samples was 0.17 (0.32). In fact, considering a FS≥1, negative UHFUS-LSG was highly predictive of a negative histology (100 %). By contrast, out of the 12 pSS patients with the highest score at LSG-UHFUS (score 3), 10/12 presented FDC networks in their biopsies, with a positive predictive value of 83% of the severity of the infiltrate.Conclusion:UHFUS of LSG appeared feasible and sensitive in pSS; due to its striking negative predictive value this novel tool can help to identify negative patients on subsequent lip biopsy, thus avoiding invasive procedures in selected cases. Besides its diagnostic role, considering the association with the presence of FDC networks, UHFUS-LGS may also have a role in patients prognostic stratification.Disclosure of Interests:None declared