Digital image analysis of intraepithelial B-lymphocytes to assess lymphoepithelial lesions in salivary glands of Sjögren's syndrome patients

Martha S van Ginkel; Tineke van der Sluis; Marian L C Bulthuis; Henk J Buikema; Erlin A Haacke; Suzanne Arends; Stine Harder; Fred K L Spijkervet; Hendrika Bootsma; Arjan Vissink; Frans G M Kroese; Bert van der Vegt

doi:10.1093/rheumatology/keac212

Digital image analysis of intraepithelial B-lymphocytes to assess lymphoepithelial lesions in salivary glands of Sjögren's syndrome patients

Rheumatology (Oxford). 2022 Dec 23;62(1):428-438. doi: 10.1093/rheumatology/keac212.

Affiliations

¹ Department of Rheumatology and Clinical Immunology.
² Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
³ Visiopharm A/S, Hørsholm, Denmark.
⁴ Department of Oral and Maxillofacial Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.

Abstract

Objective: Salivary glands of primary SS (pSS) patients characteristically harbour periductal infiltrates, in which lymphoepithelial lesions (LELs) can develop. LELs are composed of hyperplastic ductal epithelium with infiltrating lymphocytes and may assist in the challenging diagnostic process of pSS. As manual identification of LELs remains difficult, we aimed to identify LELs by using an objective digital image analysis (DIA) algorithm that detects intraepithelial lymphocytes.

Methods: A virtual triple-staining technique developed for this study was used to count intraepithelial lymphocytes in consecutive slides stained for CD3 (T-lymphocytes), high-molecular-weight cytokeratin (hmwCK) (striated ducts) and CD20 (B-lymphocytes) in labial and parotid gland biopsies in a diagnostic cohort of 109 sicca patients. Patients were classified as having pSS or non-SS according to the ACR-EULAR classification criteria.

Results: T-lymphocytes were detected in almost all analysed ducts of pSS and non-SS sicca patients, whereas intraepithelial B-lymphocytes were present in 59-68% of labial and parotid gland biopsies of pSS patients, against only 2-3% of patients classified as non-SS. Intraepithelial B-lymphocytes were found in almost all striated ducts with hyperplasia (LELs). Remarkably, ∼25% of analysed striated ducts without hyperplasia of pSS patients also contained B-lymphocytes (precursor-LELs). Furthermore, presence of intraepithelial B-lymphocytes was associated with clinical parameters of pSS (i.e. serology).

Conclusion: The presence of intraepithelial B-lymphocytes in salivary gland biopsies of sicca patients is a clear indicator of pSS and can be used as an objective alternative to LEL scoring. Therefore, identification of B-lymphocyte-containing ducts should be added to the diagnostic histopathological work-up of patients suspected of pSS.

Keywords: SS; histopathology; labial gland; lymphoepithelial lesions; parotid gland; salivary gland.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

B-Lymphocytes
Humans
Hyperplasia / pathology
Intraepithelial Lymphocytes* / pathology
Salivary Glands / pathology
Sjogren's Syndrome*