舍格伦综合征患者唇腺组织中骨桥蛋白的表达

目的：研究原发性舍格伦综合征（Primary SS）和继发性舍格伦综合征（Secondary SS）患者唇腺组织中骨桥蛋白（OPN）的表达。方法：经病理学检查确诊的SS患者40例,其中原发性SS患者15例,继发性SS患者25例,应用免疫组织化学方法检测患者唇腺组织中的OPN表达量,20例健康志愿者作为正常对照。结果：舍格伦综合征（SS）患者唇腺组织中OPN表达较正常健康人增强。SS患者唇腺组织中,OPN染色阳性率为65.38%,其中,原发性SS阳性率为73.3%,继发性SS阳性率为60.0%,与正常对照的10%比较,差异均有统计学意义（P〈0.05）,但SS二类型之间比较无统计学意义（P〉0.05）。结论：OPN表达在SS患者唇腺组织中均明显增加,提示OPN可能参与了SS疾病的发生和发展过程。     

The diagnostic utility of biopsies from the submandibular and labial salivary glands in IgG4-related dacryoadenitis and sialoadenitis,so-called Mikulicz's disease

IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) is characterized by serum IgG4 elevation and the infiltration of IgG4-positive plasma cells in glandular tissues. For definitive diagnosis of IgG4-DS, biopsies of local lesions are recommended to exclude Sjögren's syndrome (SS), malignant tumours, and similar disorders. In this study, we examined the diagnostic utility of submandibular gland (SMG) and labial salivary gland (LSG) biopsies in IgG4-DS. Fourteen patients presenting with swelling of the SMG (eight females and six males) underwent both SMG and LSG biopsies. The sensitivity, specificity, and accuracy of SMG biopsies were all 100.0%. In contrast, those of LSG biopsies were 69.2%, 100.0%, and 71.4%, respectively. Thirty-three out of 61 LSG biopsies (54.1%) from all 14 patients were positive for the diagnostic criteria of IgG4-DS (IgG4-positive/IgG-positive plasma cells >0.4). None of the patients experienced complications such as facial nerve palsy, sialocele, or hyposalivation. The IgG4/IgG ratio showed no significant correlation between the LSG and SMG. The final diagnosis was IgG4-DS in 13 patients and marginal zone B-cell lymphoma (MZL) in one. These results suggest that incisional biopsy of the SMG is useful and appropriate for the definitive diagnosis of IgG4-DS, while diagnosis by LSG biopsy alone requires more caution.     

Oral pilocarpine HCl stimulates labial (minor) salivary gland flow in patients with Sjögren's syndrome

Pilocarpine HCl has been shown to stimulate parotid and submandibular gland salivary flow. The purpose of this study was to determine whether this cholinergic-muscarinic drug also stimulates labial (minor) salivary gland (LSG) flow and to relate that with whole unstimulated salivary (WUS) flow rateS. Subjects diagnosed with primary Sjögren's syndrome (SS-1; n = 9) or secondary Sjögren's syndrome (SS-2; n = 9) were enrolled in this study after meeting stringent enrollment criteria. An age-gender matched control group was also enrolled. The labial saliva was collected in a standardized manner on Per-iopaper® for 5 min and the volume was analysed by the Periotron®.Whole unstimulated salivary samples were collected for 5 min by the method of Mandel and Wot-man (1976).Each subject was dosed with pilocarpine HCl (5 mg; tablets; p.o.).After 60 min the LSG flow as well as the WUS flow was determined again as previously. The results indicated a significant (>180%) increase in both labial salivary gland flow as well as whole salivary flow in the SS-1 and SS-2 subjects (mean ± S. e.m.): [SS-1: WUS = 0.1080 ± 0.03 vs 0.2242 ± 0.03 ml per 5 min; LSG = 93.1 ± 22.2 vs 167.8 ± 15.9 μl/5 min; P < 0.001; SS-2: WUS = 0.1384 ± 0.02 vs 0.2775 ± 0.09 ml per 5 min; LSG = 97.7 ± 20.2 vs 182.8 ± 17.9 μl per 5 min; P < 0.001]. These results indicate a significant increase in labial salivary gland flow as well as whole salivary flow as stimulated by pilocarpine HCI in Sjögren's syndrome patients.     

The accuracy of fine needle aspiration cytology in the clinical diagnosis of minor salivary gland tumours

The objective of this study was to investigate the accuracy of fine needle aspiration cytology (FNAC) and biopsy for the clinical diagnosis of minor salivary gland tumours (MSGTs). This retrospective study of 32 MSGT cases was conducted over a 5-year period. Clinical features including age, sex, and location of the tumour were obtained from the patient clinical records. All cases were also assessed histologically according to the 2017 World Health Organization Classification of Head and Neck Tumours. The results of FNAC and biopsy were correlated with those of histopathology, and their sensitivity, specificity, and diagnostic efficacy were calculated using histopathology as the gold standard. Eighteen malignant MSGTs (56.3%) and 14 benign MSGTs (43.8%) were diagnosed by pathological diagnosis. The most common malignant tumour was mucoepidermoid carcinoma (seven cases, 38.9%). Most benign cases were pleomorphic adenomas (13 cases, 92.9%). FNAC was performed for 23 cases and biopsy for 13 cases. The sensitivity and specificity of FNAC were 66.7% and 91.0%, respectively, while those of biopsy were 90.0% and 100.0%, respectively. Although FNAC is a minimally invasive and cost-effective procedure, it is less accurate than biopsy in the assessment of MSGTs. Repeated FNAC or biopsy should be considered in negative and unsatisfactory FNAC cases.     

Relative frequency of intra-oral minor salivary gland tumors: a study of 380 cases from northern California and comparison to reports from other parts of the world

BACKGROUND: The relative frequency of individual intra-oral minor salivary gland tumors (IMSGT) is not well documented in the literature. The aim of this study was to determine the relative frequency and distribution of IMSGT in an oral pathology biopsy service and to compare the data with similar studies from different parts of the world. METHODS: Files from the Pacific Oral and Maxillofacial Pathology Laboratory of the University of the Pacific, San Francisco, California served as a source of material for this study. Files were systematically searched for all cases of IMSGT during a 20-year period. Tumors were classified according to the 2005 WHO classification of salivary gland tumors. RESULTS: IMSGT were identified in 380 (0.4%) cases of 92 860 accessed. This is the largest series of IMSGT from one source reported in recent years. Of the 380 tumors, 224 (59%) were benign and 156 (41%) were malignant. Of the benign tumors, pleomorphic adenoma (PA) was the most common (39.2%), followed by cystadenoma (6.3%), canalicular adenoma (6.1%), ductal papillomas (4.4%), basal cell adenoma (1.6%), and myoepithelioma (1.3%). Of the malignant tumors, mucoepidermoid carcinoma was the most common (21.8%), followed by polymorphous low-grade adenocarcinoma (7.1%), adenoid cystic carcinoma (6.3%), adenocarcinoma, not otherwise specified (NOS; 2.1%), acinic cell carcinoma (1.6%), clear cell carcinoma, NOS (1.0%), and carcinoma ex PA (0.5%). CONCLUSIONS: Studies related to the relative frequency of individual IMSGTs from different parts of the world are difficult to compare because many studies are outdated, the number of cases is small, the list of tumors is limited, and new entities are not included. To determine the true relative frequency, more studies should be conducted, on a large number of cases from one source, by experienced pathologists in the field of salivary gland tumors.     

Localization of antimicrobial peptides human β-defensins in minor salivary glands with Sjögren's syndrome

Sjögren's syndrome is a common systemic autoimmune disease associated with inflammatory cells that infiltrate exocrine glands. The antimicrobial peptides human β-defensin-1, human β-defensin-2, and human β-defensin-3 are expressed in various human epithelial cells and in normal salivary glands. Antimicrobial peptides provide local protection against infection and participate in inflammatory responses. Because of the presence of inflammation, we hypothesized that human β-defensin expression in minor salivary glands may be increased in subjects with Sjögren's syndrome. However, the expression of human β-defensins 1 and 2 was decreased in salivary glands affected by Sjögren's syndrome in comparison with the human β-defensin expression patterns in salivary glands from normal subjects. In addition, the reduction in expression of human β-defensin-2 was greater than the reduction in expression of human β-defensin-1. The aforementioned result suggests that the reduction in expression of human β-defensin-2 may occur earlier than the reduction in expression of human β-defensin-1, which may lead to a greater decrease in human β-defensin-2 than in human β-defensin-1 during disease progression.     

The minor salivary gland proteome in Sjögren's syndrome

Objective:  To identify the global protein expression (the proteome) in the minor salivary glands from primary Sjögren's syndrome (pSS) patients and non-SS controls.
Materials and methods:  Minor labial salivary glands were obtained from six pSS patients and from six age-matched non-SS controls, lysed in SDS buffer and pooled into two groups, respectively. The lysates were analysed by liquid chromatography electrospray ionization combined with tandem mass spectrometry. Also, the proteins were separated by two-dimensional polyacrylamide gel electrophoresis and protein spots were subjected to mass spectrometry.
Results:  Heat shock proteins, mucins, carbonic anhydrases, enolase, vimentin and cyclophilin B were among the proteins identified. The differences in the proteomes of minor salivary glands from pSS patients and non-SS controls were mainly related to ribosomal proteins, immunity and stress. Alpha-defensin-1 and calmodulin were among six proteins exclusively identified in pSS patients.
Conclusion:  We have identified several minor salivary gland proteins that may have implications for clarifying the SS pathophysiology. This experiment adds to the knowledge of proteins produced in salivary glands in health and disease, and may form the basis of further studies on biomarkers of prognostic and diagnostic value.     

Sicca symptom in a patient with hemochromatosis: minor salivary gland biopsy for differential diagnosis

This paper reports a case of hemochromatosis with sicca symptom. The patient was a 59-year-old female who had been received a series of intravenous iron injections and blood transfusions because of anemia owing to side-effects of a chemotherapeutic agent. She complained of dry mouth and dry eyes in addition to symptoms of hemochromatosis. The histological appearance of the labial salivary gland, with heavy deposition of iron in acinar and duct epithelial cells and absence of focal lymphoid cell infiltration, did not support a diagnosis of Sj?gren's syndrome but suggested functional damage of the salivary glands related to iron. The patient was given desferrioxamine, and clinical symptoms improved; re-examined labial salivary gland biopsy showed no iron deposition in any parenchymal cells after the treatment.     

A histopathological study of lymphoepithelial island formation in labial salivary glands in patients with primary Sjögren's syndrome

Abstract: The proliferative status of lymphoepithelial islands in the labial salivary glands of primary Sjögren’s syndrome (pSS) patients was investigated by counting the number of argyrophilic nucleolar organizer regions (AgNORs) in epithelial cells constituting the islands. The islands were classified into four groups and evaluated in terms of total area and three discrete zones of the islands. In each pSS group, the mean AgNOR number per total island epithelial cell nucleus was significantly higher than in control ductal epithelial cells. The zonal AgNOR number fluctuated during the process of island formation but became more uniform as the islands developed. Furthermore, statistically significant trends among the four pSS groups were observed in the ratio of T lymphocytes, B lymphocytes and plasma cells surrounding the islands. The results indicated that the islands are highly proliferative once island formation begins and that zonal island cell proliferation may be associated with the inflammatory cells.     

Primary Sjögren's syndrome (pSS): subjective symptoms and salivary findings

We studied the relationship between dry mouth, general health and objective findings in 16 patients having primary Sjogren's syndrome (pSS) according to the 1993 European classification criteria as well as in healthy controls. Serum autoantibody to SSA/SSB (AB) was correlated to unstimulated whole saliva flow (UWS) and labial salivary gland focus score (FS). All patients had dry mouth symptoms and UWS ≦ 0.10 ml/min, but patients with UWS < 0.05 ml/min and AB had more complaints of oral and ocular dryness. These patients also tended to have more exocrine and non-exocrine manifestations, and oral dryness had a greater impact on their self-reported general health than in patients with UWS ≧ 0.05 ml/min. Accordingly, we consider rating of oral dryness by visual analogue scales or categorised questionnaires to be valuable for the evaluation of oral involvement in pSS.     

Anti-cytoplasmic autoantibodies reactive with epithelial cells of the salivary gland in sera from patients with Sjögren's syndrome: their disease- and organ-specificities

To test whether the autoantibodies reactive with epithelial cells of the salivary gland in sera from Sjögren's syndrome (SS) patients are specific for the organ and the disease, tissue reactivities of serum IgG obtained from the patients with SS and oral lichen planus (OLP), another immune-mediated oral mucosal disease, were examined by immunohistochemistry and Western blotting. IgG purified from the sera of SS patients specifically localized not only on the nuclei but also on the cytoplasm of the salivary gland epithelial cells. On the other hand, no convincing staining of the epithelial cells was observed when IgG purified from the sera of OLP patients or those from healthy controls were used for immunohistochemistry. No cytoplasmic staining was observed when sections of kidneys and pancreas were stained with SS patients'IgG. In Western blotting performed by using lysates of a submandibular gland as antigens, all the IgG prepared from the SS patients reacted prominently with several protein bands, including those specific for the disease and the organ. These results suggest that production of autoantibodies reacting with the cytoplasm of salivary gland epithelial cells is a characteristic of SS, and may play a role in the pathogenesis of the sialadenitis.     

Salivary gland scintigraphy with 99mTc-pertechnetate in Sjögren's syndrome: relationship to clinicopathologic features of salivary and lacrimal glands

Salivary gland scintigraphy was performed on 52 patients who were suspected of having Sjögren's syndrome (SS). and the results were compared with clinicopathologic features of the salivary and lacrimal glands. The time-activity curves which were obtained from computer-assisted analysis of ^99mTc-pertechnetate (^99mTc) scintigraphy were classified into four types (normal, median, flat and sloped types). The stimulated parotid flow rate decreased and the incidence of SS-related sialographic and histopathologic findings increased significantly as the scintigraphic abnormality advanced. In addition, the lacrimal gland function decreased and the proportion of patients diagnosed as having keratoconjunctivitis sicca (KCS) increased significantly as the scintigraphic abnormality advanced. These results indicate that the results of scintigraphy are related not only to the clinicopathologic features of the salivary glands but also to the lacrimal gland function in SS.     

Inverted ductal papilloma arising from the buccal minor salivary gland: A case report and immunohistochemical study

Oral inverted ductal papilloma is a rare, benign epithelial tumor that exhibits an endophytic growth pattern and is found almost exclusively in the minor salivary glands. We report on a case of inverted ductal papilloma in the buccal mucosa. We also performed an immunohistochemical study. The tumor cells were positive for cytokeratin and epithelial membrane antigen, while negative for calponin, S-100 protein, α-SMA, vimentin, and desmin. This result indicated that the lesion arises from the excretory duct near the oral mucosal surface but not the myoepithelial cells. In addition, Ki-67 labeling index of 3.96% indicated the low level of proliferation.