Associations between salivary gland histopathologic diagnoses and phenotypic features of Sjögren's syndrome among 1,726 registry participants

Abstract

Objective: To examine associations between labial salivary gland (LSG) histopathology and other phenotypic features of Sjögren's syndrome (SS).

Methods: The database of the Sjögren's International Collaborative Clinical Alliance (SICCA), a registry of patients with symptoms of possible SS as well as those with obvious disease, was used for the present study. LSG biopsy specimens from SICCA participants were subjected to protocol-directed histopathologic assessments. Among the 1,726 LSG specimens exhibiting any pattern of sialadenitis, we compared biopsy diagnoses against concurrent salivary, ocular, and serologic features.

Results: LSG specimens included 61% with focal lymphocytic sialadenitis (FLS; 69% of which had focus scores of ≥1 per 4 mm²) and 37% with nonspecific or sclerosing chronic sialadenitis (NS/SCS). Focus scores of ≥1 were strongly associated with serum anti-SSA/SSB positivity, rheumatoid factor, and the ocular component of SS, but not with symptoms of dry mouth or dry eyes. Those with positive anti-SSA/SSB were 9 times (95% confidence interval [95% CI] 7.4-11.9) more likely to have a focus score of ≥1 than were those without anti-SSA/SSB, and those with an unstimulated whole salivary flow rate of <0.1 ml/minute were 2 times (95% CI 1.7-2.8) more likely to have a focus score of ≥1 than were those with a higher flow rate, after controlling for other phenotypic features of SS.

Conclusion: Distinguishing FLS from NS/SCS is essential in assessing LSG biopsies, before determining focus score. A diagnosis of FLS with a focus score of ≥1 per 4 mm², as compared to FLS with a focus score of <1 or NS/SCS, is strongly associated with the ocular and serologic components of SS and reflects SS autoimmunity.

Figure 1

Five hematoxylin and eosin stained labial salivary glands exhibit focal lymphocytic sialadenitis in all glands. About 10 focal lymphocytic infiltrates can be seen in this image. In the microscope, there is a total glandular area of 24 mm² giving a focus score of 2 foci per 4 mm². Original magnification ×2.

Figure 2

Labial salivary glands (LSG) stained with hematoxylin and eosin exhibiting focal lymphocytic sialadenitis (FLS): A. One LSG with a small lymphocytic aggregate that is minimally sized (> 50 cells) for inclusion in a focus score calculation. Original magnification X100. B. One LSG with four variously sized lymphocytic foci. Note normal appearing acini immediately adjacent to the lymphocyte aggregates, a characteristic feature of FLS. The entire specimen has a focus score of 3 foci per 4 mm². Original magnification ×16. C. FLS with two prominent lymphocytic germinal centers and ductal hyperplasia with lymphocytic infiltration. Original magnification ×40.

Figure 3

Labial salivary glands (LSG) stained with hematoxylin and eosin exhibiting non-specific chronic sialadenitis (NSCS) or sclerosing chronic sialadenitis (SCS). These patterns do not represent the salivary component of Sjögren’s syndrome and all of these specimens are from participants with negative: anti-SS-A, anti-SS-B antibodies and rheumatoid factor: A. SCS in a LSG exhibiting scattered lymphocytes and plasma cells with prominent interstitial fibrosis. Original magnification ×100. B. SCS in a LSG with duct dilation, interstitial fibrosis and a prominent lymphocytic infiltrate, but without adjacent normal-appearing acini. Original magnification ×50. C. SCS with severe interstitial fibrosis, a lymphocytic aggregate, many duct-like structures and no normal-appearing acini. Original magnification ×50.