Minor salivary gland involvement in Sjögren's syndrome

doi:10.1016/0030-4220(74)90160-1

Oral Surgery, Oral Medicine, Oral Pathology

Volume 37, Issue 1, January 1974, Pages 64-74

Oral Surgery, Oral M...

https://doi.org/10.1016/0030-4220(74)90160-1 Get rights and content

Abstract

This article presents a histologic evaluation of ninety-six minor labial salivary gland biopsies performed at the Clinical Center of the National Institutes of Health from patients with a suspected diagnosis of Sjögren's syndrome. A proposed system of grading, utilizing a 1+ to 4+ scale, is offered on the basis of histologic criteria.

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Cited by (208)

Frequency of Sjögren's syndrome in patients with dry symptoms using two histopathological methods
2024, Revista Colombiana de Reumatologia
Los criterios de clasificación del síndrome de Sjögren (SS) (ACR/EULAR-2016) incluyen la biopsia de glándula salival menor (BGSM), la cual utiliza el puntaje de focos (Focus Score [FS]), pero en algunos casos sigue basándose en Chisholm y Mason (CM). Nuestro objetivo fue evaluar la frecuencia de SS en pacientes con síntomas secos, mediante el uso de FS y CM y el grado de concordancia inter- e intraobservador de la lectura por ambos métodos.
Estudio transversal. Se incluyeron todos los pacientes con síntomas secos y estudios para realizar los criterios de clasificación SS (2016). Dos lectores hicieron la evaluación independiente. Se utilizó estadística descriptiva para el cálculo de la frecuencia de SS. Se analizó la concordancia interobservadores e intraobservadores (kappa de Cohen) (STATA) para cada prueba (CM y FS). Se obtuvo aprobación ética.
Se incluyeron 92 pacientes. Se clasificó SS en el 26,1% de los pacientes en quienes se empleó FS y en el 34,8% en quienes se empleó CM. El grado de concordancia intraobservador fue perfecto y moderado-alto para los observadores. La concordancia interobservador fue sustancial, con valores de kappa de 0,77 FS y 0,75 CM.
El método FS es una puntuación más detallada y específica que facilita una correcta clasificación. El uso de CM como método de clasificación histopatológica para SS incluye más pacientes en comparación con FS. Estos resultados son relevantes para unificar la lectura de la BGSM en los servicios que atienden pacientes con SS.
The criteria for Sjögren's syndrome (SS) classification (ACR/EULAR 2016), include labial salivary gland (LSG) biopsy using the focus score (FS). But, in some cases it continues to be based on Chisholm and Mason (CM). Our objective was to evaluate the frequency of SS in patients with dry symptoms using FS and CM and to evaluate the degree of inter and intra-observer concordance of the histopathological reading by both methods.
Cross-sectional study design. All patients with dry symptoms and studies to perform the SS classification criteria (2016) were included. The samples were independently evaluated by two readers. Descriptive statistics was used for the calculation of SS frequency. Agreement (Cohen's kappa coefficient) was analysed (STATA) for each test (CM and FS). Ethics approval was obtained.
92 patients were included. According to the 2016 criteria, SS was reported in 26.1% patients in whom FS was used and in 34.8% patients in whom CM was used. The degree of intra-observer concordance for the diagnosis of FLS was perfect and moderate-high for observers. Inter-observer agreement was substantial, with kappa values of .77 FS and .75 CM.
FS method is a more detailed and specific score that facilitates correct classification. The use of CM as a histopathological classificatory method for SS includes more patients when compared with FS. These results are of relevance to standardise the reading of LSG biopsy in specialized services attending SS patients.
Bedside labial salivary gland biopsy (LSGBx: Lip biopsy): An update for rheumatologists
2023, Best Practice and Research: Clinical Rheumatology
Retrieval of minor salivary glands from a labial submucosal site through a minimally invasive bedside procedure was first described nearly 60 years ago and remains an attractive alternative to more invasive surgical procedures to obtain salivary gland tissue for pathologic examination. Examination of glands for features of Sjögren's has constituted the primary use of this procedure but other systemic disorders can affect minor salivary glands and their diagnoses can be supported by biopsy. Performance of the procedure does not require specialized training in head and neck surgery or dentistry, only simple wound closure skills. Skill in performing the procedure enables the clinician to acquire potentially diagnostic material without the need for referral while offering immediate expert feedback to the patient being biopsied. Material obtained at biopsy can also be the focus of research investigations.
High-content multimodal analysis supports the IL-7/IL-7 receptor axis as a relevant therapeutic target in primary Sjögren's syndrome
2023, Journal of Autoimmunity
While the involvement of IL-7/IL-7R axis in pSS has been described in relation to T cells, little is known about the contribution of this pathway in relationship with other immune cells, and its implication in autoimmunity. Using high-content multiomics data, we aimed at characterizing IL-7R expressing cells and the involvement of IL-7/IL-7R pathway in pSS pathophysiology.
An IL-7 signature established using RNA-sequencing of human PBMCs incubated with IL-7 was applied to 304 pSS patients, and on RNA-Seq datasets from tissue biopsies. High-content immunophenotyping using flow and imaging mass cytometry was developed to characterize peripheral and in situ IL-7R expression.
We identified a blood 4-gene IL-7 module (IKZF4, KIAA0040, PGAP1 and SOS1) associated with anti-SSA/Ro positiveness in patients as well as disease activity, and a tissue 5-gene IL-7 module (IL7R, PCED1B, TNFSF8, ADAM19, MYBL1) associated with infiltration severity. We confirmed expression of IL-7R on T cells subsets, and further observed upregulation of IL-7R on double-negative (DN) B cells, and especially DN2 B cells. IL-7R expression was increased in pSS compared to sicca patients with variations seen according to the degree of infiltration. When expressed, IL-7R was mainly found on epithelial cells, CD4⁺ and CD8⁺ T cells, switched memory B cells, DN B cells and M1 macrophages.
This exhaustive characterization of the IL-7/IL-7R pathway in pSS pathophysiology established that two IL-7 gene modules discriminate pSS patients with a high IL-7 axis involvement. Their use could guide the implementation of an anti-IL-7R targeted therapy in a precision medicine approach.
A biomarker for lymphoma development in Sjogren's syndrome: Salivary gland focus score
2021, Journal of Autoimmunity
The aim of this study is to explore the role of labial minor salivary gland (LMSG) focus score (FS) in stratifying Sjögren's Syndrome (SS) patients, lymphoma development prediction and to facilitate early lymphoma diagnosis. Ιn an integrated cohort of 1997 patients, 618 patients with FS ≥ 1 and at least one-year elapsing time interval from SS diagnosis to lymphoma diagnosis or last follow up were identified. Clinical, laboratory and serological features were recorded. A data driven logistic regression model was applied to identify independent lymphoma associated risk factors. Furthermore, a FS threshold maximizing the difference of time interval from SS until lymphoma diagnosis between high and low FS lymphoma subgroups was investigated, to develop a follow up strategy for early lymphoma diagnosis. Of the 618 patients, 560 were non-lymphoma SS patients while the other 58 had SS and lymphoma. FS, cryoglobulinemia and salivary gland enlargement (SGE) were proven to be independent lymphoma associated risk factors. Lymphoma patients with FS ≥ 4 had a statistically significant shorter time interval from SS to lymphoma diagnosis, compared to those with FS < 4 (4 vs 9 years, respectively, p = 0,008). SS patients with FS ≥ 4 had more frequently B cell originated manifestations and lymphoma, while in patients with FS < 4, autoimmune thyroiditis was more prevalent. In the latter group SGE was the only lymphoma independent risk factor. A second LMSG biopsy is patients with a FS ≥ 4, 4 years after SS diagnosis and in those with FS < 4 and a history of SGE, at 9-years, may contribute to an early lymphoma diagnosis. Based on our results we conclude that LMSG FS, evaluated at the time of SS diagnosis, is an independent lymphoma associated risk factor and may serve as a predictive biomarker for the early diagnosis of SS-associated lymphomas.
Minor salivary gland biopsy: Its role in the classification and prognosis of Sjögren's syndrome
2020, Autoimmunity Reviews
Citation Excerpt :
It also established the concept of FLS, defined as an FS ≥ 1. The third one, also described in 1974 [14], introduces the concepts of acinar destruction and fibrosis (Table 2). Although the classification systems differ according to the pathologist's criteria, there are no reports that compare the sensitivity and specificity of these scoring systems.
Sjögren's syndrome (SS) is an autoimmune disorder characterized by mononuclear cell infiltration in the exocrine glands, which leads to sicca syndrome (xerostomia and xerophthalmia). The etiology of SS is unknown, but multiple environmental factors (infectious, hormonal and stress-related), as well as genetic factors, may play a role in its pathogenesis. The diagnosis of SS is complex considering its clinical and paraclinical parameters may not be very specific. The minor salivary gland biopsy (MSGB) has undoubtedly become crucial for classifying and determining the prognosis of SS. The three main different classification systems for its interpretation have been described by Chisholm and Mason, Greenspan and Daniels, and Tarpley. However, this invasive procedure has variable sensitivity and specificity as well as low reproducibility. The use of additional methods, such as skin biopsy, imaging techniques, and serum/salivary biomarkers, may be combined with current methods to develop a bioscore that could increase diagnostic performance. In this review, we summarized the main pathological findings in SS and the prognosis of patients with SS according to the biopsy results.
Relationships between increased circulating YKL-40, IL-6 and TNF-α levels and phenotypes and disease activity of primary Sjögren's syndrome
2020, International Immunopharmacology
There is now no single score or marker useful for evaluating disease activity of primary Sjögren's syndrome (pSS). This study was designed to explore the associations of circulating YKL-40, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) with systemic activity and phenotypes of pSS.
This study included 58 pSS patients and 30 healthy controls (HC). The sera were measured by multiplex immunoassay for YKL-40, IL-6 and TNF-α concentrations. The disease activity of pSS patients was evaluated by European league against rheumatism (EULAR) SS disease activity index (ESSDAI). Local severity was assessed in accordance with the Tarpley score.
Serum YKL-40, IL-6 and TNF-α levels significantly elevated in pSS patients compared with those in HC (all P < 0.001). These cytokines correlated with ESSDAI, ESR, CRP, and IgG (all P < 0.05). Serum YKL-40 level correlated markedly with age (r = 0.405, P = 0.002), neutrophil count (r = 0.399, P = 0.002) and neutrophil-to-lymphocyte ratio (NLR) (r = 0.401, P = 0.002), while IL-6 did weakly with NLR (r = 0.296, P = 0.024) and C3 (r = 0.288, 0.036). Serum levels of all three cytokines were substantially lower in patients with eye/mouth dryness vs. those without (all P < 0.05). Additionally, patients with pulmonary, renal involvement or anemia had remarkably higher concentrations of YKL-40 (all P < 0.05), while those with leukocytopenia had lower levels (P = 0.01). Fever or anemia patients showed higher serum concentrations of IL-6 (both P < 0.05), while serum levels of TNF-α were much higher in patients with presence of ANA, anti-SSA or anti-SSB antibodies (All P < 0.05). Serum IL-6 level correlated strongly with YKL-40 (r = 0.452, P < 0.001) and TNF-α (r = 0.743, P < 0.001) in pSS patients. A significant correlation was also found between YKL-40 and TNF-α (r = 0.308, P = 0.022) .
The circulating YKL-40, IL-6 and TNF-α levels increase in pSS, and all of them are significantly correlated with indicators (ESSDAI, ESR, CRP, and IgG) for systemic inflammation of pSS. Each cytokine is separately associated with specific pSS phenotype.

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^∗: Presently with Robert B. Brigham Hospital, Boston, Mass.

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Minor salivary gland involvement in Sjögren's syndrome

Abstract

Oral Surg

Am. J. Med

Sjögren's Syndrome: A Clinical, Pathological, and Serological Study of Sixty-two Cases

Medicine

Hebeden Oration: A Broader Spectrum of Sjögren's Syndrome and Its Pathogenic Implications

Ann. Rheum. Dis

Labial Salivary Gland Biopsy in Sjögren's Disease

J. Clin. Pathol

Immunoglobulin Synthesis by Salivary Gland Lymphoid Cells in Sjögren's Syndrome

J. Clin. Invest

Xerostomia in Sjögren's Syndrome; Evaluation by Sequential Salivary Scintigraphy

J. A. M. A

1958 Revision of Diagnostic Criteria for Rheumatoid Arthritis

Bull. Rheum. Dis

Secretory Sialography in Disease of the Major Salivary Glands

Radium Ther. Nucl. Med

A Specific Antibody Against the Epithelium of the Salivary Ducts in Sera From Patients With Sjögren's Syndrome

Acta Allergol

Occurrence of Antibody to Salivary Duct Epithelium in Sjögren's Disease, Rheumatoid Arthritis and Other Arthritides: A Clinical and Laboratory Study

Ann. Rheum. Dis

Antibodies to Salivary Duct Cells and Other Autoantibodies in Patients With Sjögren's Syndrome and Other Idiopathic Autoimmune Diseases

Clin. Exp. Immunol

Salivary Duct Autoantibody in Sjögren's Syndrome: Correlation With Focal Sialadenitis in the Labial Mucosa

Clin. Exp. Immunol

Sjögren's Syndrome and Its Relation to Connective Tissue Diseases

J. Chron. Dis

Post-mortem Prevalence of Focal Lymphocytic Adenitis of the Submandibular Salivary Gland

J. Pathol. Bacteriol