Minor Salivary Gland Biopsy in the Differential Diagnosis of Sicca Syndrome: A Monocentric Cohort Analysis

Abstract

Sicca syndrome is a common condition that draws the attention of rheumatologists, and is frequently related to Sjögren's disease (SjD). This study analyzed 164 patients with sicca syndrome (clinically suspected for SjD) who underwent minor salivary gland biopsy (mSGB). Patients completed the Xerostomia Inventory (XI) and Standard Patient Evaluation of Eye Dryness (SPEED) questionnaires to assess Patient-Reported Outcome Measures (PROMs), and biopsies were graded using the Chisholm and Mason system. Patients were classified as seropositive (SSA, SSB, Ro52, Ro60 positive) or seronegative, and also divided into three groups by age. Positive biopsies (60.37%) were more common in older patients (61-80) and associated with confirmed SjD, more severe xerostomia, and stronger lymphocytic infiltrates. Among these, 37.37% were seropositive, showing higher disease activity, hypergammaglobulinemia, and elevated IgG. Seronegative patients had a heavier symptom burden, confirmed by the PROMs, and more fibrosis and fatty replacement in biopsies. Age-stratified analysis showed younger patients (18-40) were more affected by ocular dryness, while older patients had worse xerostomia and more severe histological and ultrasound changes. Younger individuals had higher IgG/IgA, more anemia, and reduced C3. Hydroxychloroquine was used more in younger and seropositive groups; older patients used more topical therapies. These results highlight mSGB's diagnostic value, especially in seronegative cases, and stress the importance of combining clinical, histological, imaging, and patient-reported outcomes for optimal care.

Keywords: Sjögren’s disease; minor salivary gland biopsy; patient-reported outcomes.

Figure 1

Procedure for performing minor salivary gland biopsy. Original images, acquired with the patient’s consent: (A): lidocaine anesthesia; (B): incision using an 18G needle tip; (C): exposure of the minor salivary glands; (D): lifting of the glands with forceps for removal; (E): placement of gauze for hemostasis; (F): sample in formalin. Arrows indicate the 3 excised glands.

Figure 2

Minor salivary glands in H&E staining, C&M classification. (A) (100×): grade 0; (B) (100×): grade 1–2; (C) (100×): grade 3; (D) (25×): grade 4. Black arrows indicate lymphocytic foci.