**3. Histologic criteria for diagnosis of SS on labial salivary gland biopsies**

Labial salivary gland biopsy is an objective test of SS and plays a significant role in the diagnostic process. In fact, the presence of either anti-SSA/SSB seropositivity or a positive lip biopsy is a requirement for an individual to be classified as having SS. The microscopic confirmation of SS is based on the presence of focal lymphocytic sialadenitis (FLS) with a focus score ≥ 1 per 4 mm<sup>2</sup> of glandular tissue. According to the revised American-European Consensus Group's (AECG) classification criteria and the ACR classification criteria for SS, an LSGB is considered positive if minor salivary glands demonstrate FLS, with a focus score of 1 or more, as evaluated by an expert histopathologist. A lymphocytic focus is defined as a dense aggregate of 50 or more lymphocytes adjacent to normal-appearing mucous acini in salivary gland lobules that lacked ductal dilatation. Focal lymphocytic sialadenitis is applied to specimens that show the presence of 1 or more foci of lymphocytes located in periductal and perivascular locations. The foci can contain plasma cells, but these must be a minority constituent of the inflammatory infiltrate. The focus score can be calculated for those specimens showing the histopathologic appearance of FLS. The number of lymphocytic foci is then determined for all the gland lobules in a single tissue section. The focus score is then calculated as the number of foci per square millimeter of glandular tissue multiplied by four, which then yields foci/4mm<sup>2</sup> . A focus score of 1 equates to 1 focus/4 mm<sup>2</sup> . To determine the focus, a calibrated eyepiece grid or image analysis software with a closed polygon tool is used. FLS has to be distinguished from nonspecific chronic sialadenitis. The symptoms of nonspecific sialadenitis are mild to moderate acinar atrophy, interstitial fibrosis, and ductal dilatation, with lymphocytes and macrophages often scattered in the parenchyma, but not forming dense aggregates of 50 or more lymphocytes immediately adjacent to normal-appearing acini. In addition to the focus score (FS), two scoring systems for salivary glands are in use for the diagnosis and classification of SS. These systems are based on the presence of foci [7]. Grading according to Tarpley's system involves destruction of acinar tissue and fibrosis (**Table 1**). Grading according to the Chisholm and Mason system is based on the presence of infiltrates from slight to one or more foci (**Table 2**) [16, 17].

Focus: a cluster of 50 or more lymphocytes and histiocytes. Aggregate: approximately 50 cells (lymphocytes, plasma cells, or histiocytes).


#### **Table 1.**

*Grading systems for salivary gland biopsies of Tarpley.*


**Table 2.**

*Grading systems for salivary gland biopsies of Chisholm and Mason.*
