Do Labial Minor Salivary Gland Biopsies Maintain Diagnostic Sensitivity and Specificity for Sj\xf6gren\u2019s Disease \u2013 An Institutional Study

BackgroundThe Focus Score (FS) ≥ 1 in minor labial salivary gland (LSG) biopsies is one of the 2 main items (with anti-SSA positivity) to establish the diagnosis of Primary Sjögren...

(1) Background: The aim of this study was to analyze labial minor salivary gland biopsy (MSGB) findings of a large sicca cohort and to examine their associations with Sjogren’s syndrome (SS)-associated laboratory markers, phenotypic characteristics and systemic manifestations. Moreover, we sought to explore the ability of MSGB to identify SS patients among subjects with pre-diagnosed fibromyalgia (FM). (2) Methods: Included were all patients of three rheumatology departments having undergone a diagnostic MSGB within 9 years. Next to the examination of histological and immunohistochemical findings, we focused on activity and chronicity parameters of the underlying disease, autoantibodies, presence of systemic and hematologic involvement, as well as chronic pain and SS comorbidities. (3) Results: Among the 678 included patients, 306 (45.1%) had a positive focus score (FS). The remaining patients (n = 372) served as control subjects. There were significant correlations between FS and hypergammaglobulinemia (p < 0.001), ANA and rheumatoid factor positivity (both; p < 0.001), a weak significant correlation with erythrocyte sedimentation rate (rho = 0.235; p < 0.001) and a negative correlation with nicotine use (p = 0.002). Within the primary SS subgroup, FS was associated significantly with glandular enlargement (p = 0.007) and systemic hematologic manifestations (p = 0.002). Next to FS, CD20 cell staining showed an excellent diagnostic performance in the diagnosis of SS by an area under the curve of 0.822 (95%CI 0.780–0.864; p < 0.001). Interestingly, 42.1% of all patients with fibromyalgia (FM) having received an MSGB could be diagnosed with SS. (4) Conclusion: By examining one of the largest cohorts in the literature, we could show that MSGB histological and immunohistochemical findings not only play a key role in the classification and diagnosis of SS but could also provide important information regarding SS phenotype and systemic manifestations. Furthermore, MSGB may help differentiate patients with FM from patients with subclinical SS who suffer primarily from chronic pain.

SAT0217 Diagnostic value of labial minor salivary gland biopsy for primary sjögren’s syndrome: A systematic review

Introduction: Sjögren’s syndrome (SS) is an autoimmune disease characterized predominantly by exocrine gland inflammation, leading to xerostomia and/or xerophthalmia, along with systemic manifestations. Minor salivary gland biopsy is an important technique that has been used for [Formula: see text]50 years to assess for focal lymphocytic sialadenitis in patients suspected to have SS. Labial salivary gland with focal lymphocytic sialadenitis and a focus score of [Formula: see text] 1 has been attributed a score of 3 points in the EULAR/ACR Criteria for the Classification of Primary Sjögren Syndrome. This study aimed to assess various histo-pathological findings seen in patients with suspected Sjogren’s syndrome; and assess its clinical correlation. Methods: Consecutive patients presenting to rheumatology OPD with sicca symptoms were referred for minor salivary gland biopsy from June 2023 to March 2024. A total of 67 patients were enrolled in the study after informed written consent. All biopsies were obtained from the lower lip. The mucosal surface of the lip was examined, and a site halfway between the free edge of the lip and gingivolabial sulcus, in the paramedian position, was selected and anesthetized by submucosal injection of lidocaine and epinephrine. A 5-10 mm mucosal incision was made sharply, and gentle submucosal dissection was performed. At least 6 lobules of minor salivary gland tissue were removed. Histo-pathological examination of the specimen was done by trained immuno-histopathologist. Also, data regarding clinical symptoms, auto-antibodies, medications, Schirmer’s test, whole sialometry were recorded. Results: Among 67 patients, 95.5% (64) were female. Pre-existing rheumatic diseases were present in 28% (16). Around 25% (17) had focal lymphocytic sialadenitis with a focus score (FS) of [Formula: see text] 1, and 9.1% (5) had FS of [Formula: see text] 3. Around 40 (58.8%) had non-specific chronic sialadenitis. A significant correlation was found between FS[Formula: see text] 1 and auto-antibodies (anti Ro/anti La) positivity (p 0.001). No significant difference was noted in age (p 0.904), Schirmers test (p 0.058) and salivary flow rate (p 0.490) between the patients with FS&lt; 1 or FS [Formula: see text] 1. No significant correlation was noted between FS and symptoms like rash, fatigue, paresthesia or fibromyalgia. Conclusions: Labial salivary gland biopsy plays an important role in diagnosis of Sjogrens syndrome, especially in cases with negative autoantibodies. It also helps in exclusion of the diagnosis.

Objectives:To examine the performance of the minor salivary gland biopsy (MSGB) to diagnose Sjögren’s syndrome (SS) and to identify predictive factors for MSGB’s positivity in Tunisian SS-suspected patients.Methods:In a retrospective study, histopathological evaluation of MSGB from SS suspected- patients were examined. The classifications of the American-European Consensus Group (AECG, 2002) and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR, 2016) have been applied. We classified a positive MSGB when a focus score ≥ 1 and/or Chisholm and Mason grading ≥ 3 were observed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MSGB were assessed, and the area under the ROC curve was performed to evaluate its diagnostic accuracy.Results:One hundred and two MSGBs were examined. They were positive in 48 patients (47%). For the positive diagnosis of SS, MSGB had 77,6% sensitivity, 93,2% specificity, 93,8% PPV and 75,9% NPV. With an air under the curve (AUC) of 0.854, MSGB was considered an excellent discriminating test in SS diagnosis. Keratoconjunctivitis sicca (p=0.04), elevated erythrocyte sedimentation rate (p=0.036), leukopenia (p=0.025), positive antibodies: anti-Ro/SSA (p=0.029), anti-Ro/SSA, anti-La/SSB (p=0.037), antinuclear (p=0.01), anti-extractable nuclear antigen (p=0.04), positive rheumatoid factor (p=0.032), positive elevated IgG levels (p=0.03) and abnormal unstimulated whole salivary flow rate (p=0.002) were predictive of a positive MSGB.Conclusion:In cases of suspected SS, a predictive scoring system incorporating these clinical and biological factors will streamline MSGB indications and serve as a diagnostic tool for positive SS diagnosis in research studies.

The aim of this study was to find out the correlation and evaluate the accuracy of labial minor salivary gland biopsy as a diagnostic tool in the multidisciplinary management of patients with Sjögren syndrome. Patients, referred to our outpatient office between January 2014 and December 2018 from a rheumatologist for biopsy examination, as part of the complex diagnostic plan for suspected Sjögren syndrome, were included in the current study. Each specimen was examined histomorphometrically by the pathologist to calculate the focus score describing the degree of salivary gland inflammatory infiltration. Fifty patients met the inclusion criteria. From the total number of patients, 39 presented with an established Sjögren syndrome by fulfilling the revised American-European criteria. From those, 27 had a positive lip biopsy. The remaining 12 patients from the total group, who were diagnosed with Sjögren syndrome based on the same criteria, had a negative lip biopsy. The labial minor salivary gland biopsy is a valuable diagnostic tool to establish the diagnosis of Sjögren syndrome. However, a positive biopsy result must always be correlated with all the other diagnostic criteria to prove the exact diagnosis (Tab. 1, Fig. 4, Ref. 49). Text in PDF www.elis.sk Keywords: Sjögren syndrome, keratoconjunctivitis sicca, xerostomia, labial minor salivary glands, biopsy, focal lymphocytic infiltration, focus score.

SP0098 Etiology of SICCA Syndrome: the Forgotten Causes

Diagnostic value of labial minor salivary gland biopsy for Sjögren's syndrome: A systematic review

ObjectivesTo characterize the clinical features and outcomes of childhood-onset primary Sjögren’s syndrome (pSS).MethodsPatients less than 18 years old who were diagnosed with pSS by paediatric rheumatologists were included, and all patients were applied the 2002 American-European Consensus Group (ACEG) criteria, the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for pSS, or the 1999 proposed juvenile pSS criteria. The electronic medical records of patients with pSS from 2013 to 2020 were collected and analysed.ResultsThirty-nine patients were included. Of them, 27 (69.2%), 38 (97.4%) and 35 (89.7%) patients fulfilled the AECG criteria, ACR/EULAR criteria and proposed juvenile pSS criteria, respectively. The female:male ratio was 3.9:1. The median ages at first signs or symptoms and at diagnosis were 9.2 (4.7, 14.5) years and 10.9 (6.3, 15.0) years, respectively. The main clinical manifestations were rash or purpura (20, 51.3%), followed by fever (12, 30.8%), glandular enlargement/recurrent parotitis (10, 25.6%), and dry mouth and/or dry eyes (9, 23.1%). Twenty-eight (56.4%) patients had systemic damage, the most common of which was haematological involvement (14, 35.9%), followed by hepatic (13, 33.3%) and renal involvement (8, 20.5%). Thirty-eight (97.4%) patients underwent labial minor salivary gland biopsy, and all exhibited focal lymphocytic sialadenitis. All patients had a global ESSDAI score ≥ 1 at diagnosis, and the median total score at diagnosis was 8 (2, 31). Thirty-six (92.3%) patients were followed up for a median time of 23.6 (7.9, 79.5) months, and three patients developed systemic lupus erythematosus (SLE) at follow-up times of 13.3, 38.8 and 63.8 months.ConclusionsThe presentation of childhood-onset pSS is atypical, and extraglandular manifestations and systemic involvement are more common than in adult-onset pSS. Labial salivary gland biopsy is vital for patients with probable pSS. Some patients may develop SLE over time.

Sjogren's syndrome (SjS) is an autoimmune disease characterized clinically by dry eyes and dry mouth, and histopathologically by lymphocytic infiltrates in the salivary glands. Labial minor salivary gland biopsy (MSGB) is a major diagnostic test for SjS, deemed positive by a focus score of ≥1, meaning that ≥50 lymphocytes were found in 4mm2 tissue on hematoxylin and eosin (H&E)-stained slides. The diagnosis can be challenging, and the above diagnostic criteria has low and variable sensitivity. We performed a retrospective study on MSGBs done for possible SjS. We compared the percent of MSGBs which met the histologic criteria by H&E stain alone and that with the addition of CD45, CD3, and CD20 immunohistochemical (IHC) staining for these patients. A total of 45 cases with complete data were analyzed. Thirty-five of the 45 patients had the diagnosis of Sjogren's syndrome (SjS+) based on ACR criteria. However, based on H&E staining alone, only 22/35 cases (63%) met the histologic criteria. After adding IHC staining with CD45, CD3, and CD20 to MSGBs of SjS+patients, 29/35 (83%) cases met the histological criteria for SjS. All MSGBs from patients without SjS had no significant lymphocyte infiltrate on either H&E or IHC stains. Immunohistochemical better identifies lymphocytic infiltrates in MSGB and increases diagnostic certainty. Due to high cost, their use should be restricted to cases where there is high clinical suspicion of SjS and negative H&E evaluation alone, or if the diagnosis is uncertain.

Oral and maxillofacial symptoms of patients with IgG4-related disease: The meaning of a labial minor salivary gland biopsy

Purpose. The goal of this paper is to find out the correlation, and evaluate the accuracy of labial minor salivary gland biopsy as a diagnostic tool in the multidisciplinary management of patients with Sjögren’s syndrome. Patients and Methods. Thirty seven patients referred to our outpatient office between January 2016 and December 2017 from a rheumatologist for biopsy examination, as part of the complex diagnostic plan for suspected Sjögren syndrome were included in the current study. Each specimen was examined histomorphometrically by the pathologist to calculate the focus score describing the degree of salivary gland inflammatory infiltration. Results. From the total number of patients, 25 presented with an established Sjögren syndrome diagnosis by fulfilling the revised American-European criteria. From those 15 had a positive lip biopsy. The rest 10 patients from the total group who were diagnosed with Sjögren syndrome based on the same criteria had a negative lip biopsy. Conclusion. The labial minor salivary gland biopsy is a valuable diagnostic tool to establish the diagnosis of Sjögren syndrome. However, a positive biopsy result must always be correlated with all the other diagnostic criteria to prove the exact diagnosis.

Sjogren's syndrome (SjS) is an auto-immune disease with a chronic inflammation causing dysfunction of salivary and lacrimal glands, leading to dry eyes and dry mouth. Focal lymphocytic sialadenitis (FLS) and focus score (FS) are significant diagnostic criteria in SjS. To evaluate the FLS and FS and quantify FS in H&E sections of normal salivary gland, inflammatory conditions, and SjS group. A total of 60 cases were included and divided equally among the groups - SjS, inflammatory conditions, and normal salivary gland. The clinical symptoms, associated disease, and serological tests (ANA, SSA, SSB, RF) were obtained from the records of the patient. Immunohistochemistry (IHC) staining was done (anti-CD20 monoclonal antibody). All the H&E and IHC slides were assessed by independent observers and were taken up for evaluation. In H&E sections, FLS and FS were found only in the SjS patients and not in normal and inflammatory conditions. CD20 expression was found to be positive in 55% of SjS cases but negative in the normal and inflammatory groups. FS had been upgraded in IHC CD20 staining. FLS and FSs should be strictly evaluated according to the criteria. It was found only in SjS patients and not in normal and inflammatory conditions. Furthermore, CD20 can be used as an adjunct marker to decide the theranostic and prognostic markers of SjS. The results showed that criteria for scoring FS should be strictly followed and CD20 IHC can be used as a prognostic marker.

Objectives: Labial minor salivary gland biopsy (MSGB) is a procedure in which complications such as bleeding, hematoma, numbness, wetness can be seen after the procedure. It is not known whether these complications have changed in patients with primary Sjögren's syndrome (PSS). The aim of this study is to investigate the frequency of complications after the labial MSGB and to investigate whether these complications has changed in PSS. Methods: Participants with a preliminary diagnosis of PSS who underwent a labial MSGB without any suture were included in the study. One month after the procedure, the complication screening questionnaire was administered face-to-face interview or by telephone. All complications were compared between PSS and non-PPS groups. Results: Complications screening questionnaire was applied to 99 participants (face to face with 79 participants and by telephone with 20 participants). After the procedure, 17.2% of the participants had uncomfortable bleeding, 2.0% had persistent numbness which continues more than 1 week and 1.0% had wetness and hematoma. Bleeding duration was more than 1 hour in 11.1% of the participants. Complications were not different between PSS and non-PSS groups (p &amp;gt; 0.05). Conclusions: After the labial MSGB procedure without suturing, uncomfortable bleeding is frequent and the duration of bleeding is long, but complications other than bleeding are rare. The incidence of complications after labial MSGB procedure was not different in participants with PSS than in those without PSS.

To determine the sialendoscopy findings associated with positive findings on minor salivary gland biopsy. Single-center retrospective study. Patients ≥18 years old who underwent sialendoscopy from 2016 to 2022 and were evaluated for SS via labial minor salivary gland biopsy. Biopsy positive and negative patients were compared on the primary outcome measure of sialendoscopy findings. Data were abstracted from the sialendoscopy operative notes and included involved gland, location of ductal pathology, and the presence of scarring, stenosis, mucus plugs, webs, and dilations. Additional characteristics included demographics, presenting symptoms, caffeine or tobacco, use of drying medications, and need for additional treatments. The final cohorts included 22 biopsy positive and 21 biopsy negative patients with a total of 42 glands in the biopsy positive and 37 glands in the biopsy negative groups. Biopsy positive patients were found to require dilation at the hilum and distal duct at significantly higher rates than biopsy negative patients (p < 0.0001). However, there was no statistical difference in scarring, stenosis severity, mucus, webs, or dilations between each group. The outcomes of this study suggest that there are no distinct sialendoscopy findings associated with biopsy positive patients. The presence of significant distal stenosis on sialendoscopy may be associated with positive minor salivary biopsy. Other endoscopic parameters are likely more consistent with non-specific chronic sialadenitis. 3 Laryngoscope, 134:1183-1189, 2024.