Histopathological Evaluation of Minor Salivary Gland Biopsies in Patients With Primary Sjögren's Syndrome: A Comparative Analysis of Diagnostic and Nondiagnostic Features

ABSTRACT Background Minor salivary gland (MSG) biopsy is a key diagnostic tool for primary Sjögren's disease (pSjD), primarily for determining the focus score (FS). However, a wide range of additional histopathological features is frequently encountered, and their diagnostic and biological relevance remains to be elucidated. To comprehensively evaluate histopathological features in MSG biopsies from patients with pSjD compared with non‐Sjögren sicca (NSS) controls and to assess their associations with clinical, serological, and demographic variables. Materials and Methods This retrospective cross‐sectional study included 90 patients with pSjD (defined by the 2016 ACR/EULAR classification criteria) and 28 NSS controls who underwent MSG biopsy between 2011 and 2018. Hematoxylin and eosin‐stained sections were reassessed for FS and several ancillary histopathological features, including lymphoepithelial lesions (LEL), acinar atrophy, ductal dilatation, fibrosis, and adipose tissue replacement. Associations with demographic data, autoantibodies (SSA, SSB, and Ro52), inflammatory markers (CRP and ESR), and ocular/oral test results were analyzed using appropriate statistical tests and Spearman correlation. Results Among the 118 patients who underwent MSG biopsy, 90 met the 2016 American College of Rheumatology/European League Against Rheumatism criteria for pSjD, while 28 were classified as NSS controls. FS ≥ 1 was observed in 82.2% of patients with pSjD and in none of the controls ( p < 0.001). Lymphoepithelial lesions (20.0%), giant foci (14.4%), and extrafocal inflammation (70.0%) were significantly more common in the pSjD group ( p < 0.05). No association was found between FS and clinical or serological parameters. Ductal dilatation and adipose replacement > 5% were more frequent in patients aged > 50 years ( p = 0.01 and p = 0.001, respectively). Adipose tissue replacement correlated with age and biopsy area but not with FS. Patients who were SSA‐positive were less likely to exhibit > 5% fat infiltration ( p = 0.001). Spearman correlation revealed two distinct histological clusters: an inflammatory axis (FS, LEL, and plasma cell foci) and a remodeling axis (atrophy, fibrosis, and adiposity), supporting histological heterogeneity in pSjD. Conclusion MSG histopathology in pSjD extends beyond FS and encompasses distinct inflammatory and structural changes. LEL and extrafocal inflammation are observed more frequently in pSjD biopsies. Age‐related features, such as adipose infiltration, should be interpreted cautiously. A multiparametric histopathological approach may enhance diagnostic precision and provide insights into disease heterogeneity in pSjD.