Background: Enumeration of lymphocytic foci is a key component of minor salivary gland biopsy (MSGB) interpretation in Sjögren’s disease (SjD). However, this task is not straightforward, given the need to determine whether there are 50 or more mononuclear cells, tight cellular aggregation, a predominance of lymphocytes, and location adjacent to normal-appearing mucus-secreting acinar tissue. Misinterpretation of the labial gland biopsy is common in SjD and can lead to potential overdiagnosis of seronegative SjD where a positive biopsy is essential.

Objectives: We sought to determine whether focus score enumeration was influenced by glandular surface area and serologic status and thus impact the diagnosis of seronegative SjD.

Methods: We utilized data on 3297 participants of the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry with suspected or established SjD for whom there were complete data on the five objective criteria for SjD (as defined by the ACR/EULAR classification criteria). Each labial gland biopsy in SICCA was interpreted independently by two pathologists, blinded with respect to the phenotypic features of the participant. Differences in interpretation were resolved by consensus between the two, or with a third pathologist.

Results: 1890 biopsies had focal lymphocytic sialadenitis (i.e. focus score >0) and a mean surface area of 14.6 ± 7.7 mm ² . with the surface area <8 mm ² in 345 subjects. A focus score of ≥1 was present in 261/345 (75.7%) biopsies with a surface area <8 mm ² compared to 1013/1545 (65/6%) with a surface area ≥8 mm ² (p=0.0003). This difference was dependent on the SSA antibody reactivity of the participant (Table 1). Thus, the prevalence of a focus score ≥1 was equivalent among SSA-positive subjects with a surface area ≥8 mm ² and those with surface area <8 mm ² (85.4% vs 84.1%) but significantly lower among SSA-negative subjects with a surface area ≥8 mm ² compared to those with surface area <8 mm ² (45.1% vs 65.4%; p<0.0012). It was also dependent on known phenotypic correlates of SSA reactivity, including rheumatoid factor, hyperglobulinemia, and low saliva and tear flow, but not leucopenia. Age of the subject had no influence.

Conclusion: The prevalence of a focus score ≥1 in labial gland biopsies in the SICCA registry was significantly higher among those with a glandular surface area of <8 mm ² compared to those with higher surface areas. This difference was dependent on SSA antibody reactivity and its known correlates. We hypothesize that pathologists are prone to counting “borderline” foci as positive in biopsies with a glandular surface area <8 mm ² , given their inability to bolster their interpretation with examination of more tissue. The result of this bias is to overdiagnose seronegative SjD in participants with small gland biopsies.

REFERENCES: NIL.

Acknowledgements: Data and specimens used in this abstract are from the Sjögren’s International Collaborative Clinical Alliance (SICCA) Next Generation Studies, funded under contract #1U01DE028891-01A1 (and previously under N01 DE-32636 and #HHSN26S201300057C) by the National Institute of Dental and Craniofacial Research. This abstract was prepared using a publicly available SICCA data set and does not necessarily reflect the opinions or views of the SICCA investigators, the NIH or NIDCR.

Disclosure of Interests: Alan Baer Bristol-Myers Squibb; iCell Gene Therapeutics, Priya Patel: None declared, Stephen Shiboski: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.