Ultrasonographic scores and histopathology correlations in primary Sjögren’s syndrome

Title: Ultrasonographic scores and histopathology correlations in primary Sjögren’s syndrome Introduction: Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by exocrine glands involvement, leading to sicca symptoms. The glandular damage exposes pSS patients to an increased risk of lymphoproliferative disease. The diagnostic approach relies on a set of clinical, laboratory, imaging and histopathological features, and salivary gland biopsy is considered the gold standard tool, playing a key role in the classification criteria for pSS. Even if not included in the pSS classification criteria, salivary gland ultrasonography is emerging as a valuable complement tool to histopathology, allowing the identification of alterations suspicious for pSS disease and for lymphoma. However, the correlation between histopathological and ultrasonographic features remains incompletely elucidated in the literature. Aim of the study is to analyze the correlation between the ultrasonographic and histological features of major salivary glands in terms of inflammatory infiltrate, fibrosis, and presence of adipose tissue. Methods: Adult patients with pSS and a clinical indication for major salivary gland biopsy between September 2018 and October 2023 were selected for this study. All patients underwent major salivary gland ultrasonography and performed a major salivary gland biopsy. For each histopathological sample, the evaluation included the presence of lymphoepithelial lesions (LELs), germinal centers (GCs), adipose replacement area and focus score, as well as the presence of Multiple Focal Lymphocytic Sialadenitis/ Lymphoepithelial Sialadenitis (MESA/LESA). Each ultrasound image is assessed according to the Hocevar and OMERACT scoring method. Results: 63 patients were included in this study. Correlations between ultrasonography and histopathological features were registered. The 0-48 Hocevar score was correlated to the presence of GCs (p=0.009). Aiming at a direct comparison between histopathological findings and the ultrasonographic score of the same major salivary gland, we compare the ultrasonographic score of the biopsied gland with the histopathological results. The gland specific Hocevar score and the OMERACT score both showed correlation with the presence of LELs and GCs (p=0.004 and p<0.001, respectively). Focusing on patients without pSS complication (i.e. lymphoma patients), we reported significant correlation between Hocevar score and LELs and MESA/LESA (p=0.05). Analysing in this cohort the direct comparison between histopathological findings and ultrasonographic score (Hocevar and OMERACT score) of the same salivary gland, we reported associations with LELs and GCs in both scoring system. Conclusion: The ultrasonographic scores of patients with pSS correlate with histopathological features, notably LELs and GCs, which are typical characteristics of pSS. This study suggests the potential utility of SGUS as an alternative for histopathological examination.