Histopathology, salivary flow and ultrasonography of the parotid gland: three complementary measurements in primary Sjögren’s syndrome

Abstract

Objective The involvement of salivary glands in primary Sjögren’s syndrome (pSS) can be assessed in different ways: histopathology, salivary flow and ultrasonography. To understand the relative value of these different approaches, it is crucial to understand the relationship between them. As we routinely perform these three modalities in the parotid gland for disease evaluation, our aim was to investigate the construct validity between these modalities in one and the same gland. Methods Consecutive sicca patients underwent a multidisciplinary diagnostic work-up including parotid gland biopsy, collection of parotid gland-specific saliva and parotid gland ultrasonography. Patients who were classified as pSS according to the ACR-EULAR criteria were included. Construct validity was assessed using Spearman’s correlation coefficients. Results The 41 included pSS patients completed a full work-up within mean time interval of 2.6 months. Correlations between histopathological features and stimulated parotid salivary flow were fair (ρ=-0.123 for focus score, and ρ=-0.259 for percentage of CD45+ infiltrate). Likewise, poor correlations were observed between stimulated parotid salivary flow and parotid ultrasonography (ρ=-0.196). Moderate to good associations were found between the histopathological items focus score and percentage of CD45+ infiltrate, with parotid ultrasound scores (total ultrasound score: ρ = 0.510 and ρ = 0.560; highest for homogeneity: ρ = 0.574 and ρ = 0.633). Conclusion Although pSS associated ultrasonographic findings did correlate with histopathological features, the three modalities that evaluate salivary gland involvement assess different (or at best partly related) constructs. Therefore, histopathology, salivary flow and ultrasonography are complementary measurements and cannot directly replace each other in the work-up of pSS.

Can salivary gland ultrasonography replace salivary gland biopsy in the diagnosis of Sjögren's syndrome?

“…However, they also showed that a FS ≥1 is not always reflected by the presence of hypoechogenic areas in the parotid gland, and the presence of hypoechogenic areas is not always reflected by a positive FS, indicating that parotid gland histopathology and parotid gland ultrasonography assess only partly related constructs in pSS. (42). Similar correlations between FS and ultrasound scores were found in a study comparing labial gland ultrasound with histopathology of the labial gland (43).…”

Lymphoepithelial lesions in the salivary glands of primary Sjögren's syndrome patients: the perfect storm?

“…Thus, the presence of LELs is indicative of more severe serological abnormalities and glandular disease and could be employed to identify pSS patients with pronounced (pathogenic) B cell involvement. Patients with LELs also demonstrate significantly higher presence of hypoechoic regions of the parotid SG as identified by ultrasound (10). Considering the size of LELs however (in the µm range), compared to the very large, macroscopic nature of hypoechoic regions, LELs are unlikely to be the sole source of hypoechoic regions in the SG in pSS.…”

The lacrimal gland in Sjögren's syndrome: can we unravel its mystery using ultrasound?

“…The relationship between LGUS features and LG pathology, and indeed tear production still needs to be further explored. We have recently shown in the salivary gland of pSS patients that ultrasound, histology and function are 3 independent measures, depicting apparently distinct pathological events in pSS (5). If this also applies to the LG with relation to Schirmer's tests or the OSS test remains to be investigated, as indeed does that between SGUS and LGUS of the same patient.…”

“…The pathology of the salivary gland in Sjögren's syndrome The volume of both 'whole mouth' saliva, that is the combination of saliva produced by all SGs working in concert, and that of saliva specific to particular salivary glands, is decreased in pSS patients, compared to sicca controls (1)(2)(3)(4). Lymphocytic infiltration invades the SGs, but the extent of this infiltration appears poorly correlated with the degree of salivary gland function (5,6). Lymphocytic infiltration invades the major and minor SGs in pSS patients congregating in 'foci' around the SG striated ducts.…”

“…in the classification of pSS(12). Mossel et al, on the other hand, argue that the histology, salivary flow, and ultrasonography assess separate structures, and that the 3 measures cannot be used interchangeably in the diagnosis of pSS(5). In summary, although strides have been made towards the standard employment of ultrasound in evaluating SG pathology in pSS, consensus over exactly what we are measuring is still wanting.Ultrasound scoring systems for the salivary glands in Sjögren's syndromeA recent meta-analysis has identified 33 different scoring systems used to evaluate the major SGs in patients with SS.…”