Retrograde access of antigens to the minor salivary glands in the monkey Macaca fascicularis

Several authors have postulated that the ducts of minor salivary glands may provide pathways for the presentation of oral antigens to cells involved in a local immune response. This would imply a retrograde passage of oral antigens into the minor salivary glands. Various sites of the oral mucosa of anaesthesized M. fascicularis monkeys were labelled topically with a multiple tracer consisting of horseradish peroxidase (HRP), ferritin and Indian ink for a continuous period of 4-5 h. Serial cryosectioning of labelled lips and soft palates revealed retrograde passage of this tracer deep into some of the corresponding minor salivary glands. Minor salivary gland ducts can therefore serve as "portal of entry" for oral antigens, at least in the M. fascicularis monkey.     

Morphological features of the minor salivary glands

The minor salivary, glands are important components of the oral cavity, present in most parts of the mouth, and their secretions directly bathe the tissues. Individual glands are usually in the submucosa or between muscle fibres, and consist of groups of secretory endpieces made up of mucous acinar cells and serous or seromucous demilune cells. The ductal systems comprise intercalated ducts, intralobular ducts usually lacking basal striations, and excretory ducts opening directly through the mucosa. Minor glands secrete highly glycosylated mucins, containing blood group determinants, and probably active in tissue lubrication and bacterial aggregation. They also secrete several antimicrobial proteins and immunoglobulins, and the lingual serous (van Ebner's) glands secrete digestive enzymes and proteins with possible taste perception functions. Minor gland morphology and function can conveniently be studied in the rat. There are substantial differences between major and minor salivary glands, as well as among the minor glands, in the nature and composition of their mucous and serous secretory products. The role of minor salivary glands in the function and defence of the oral cavity may be better understood as a result of new physiological and molecular methods applicable to samples of limited size and availability.     

Trefoil factor family 3 expression in the oral cavity

This study examined the expression, in oral keratinocytes and in the major and minor salivary glands, of Trefoil factor family 3 (TFF3) peptide. Trefoil factor family 3 messenger RNA (mRNA) and peptide were detected in cultures of normal oral keratinocytes by quantitative real‐time polymerase chain reaction (PCR) and western blotting, respectively. Trefoil factor family 3 was found, by immunohistochemical analyses, to be expressed in the basal layers of the oral mucosal epithelium. In salivary glands, immunohistochemical staining showed that TFF3 peptide expression was strongest in the mucous acini of the submandibular and the small salivary glands. Serous cells in the same glands showed weak staining. In the parotid gland, many serous acini showed weak positive staining, while other areas did not. In all glands examined, the intercalated, striated, and collecting ducts were moderately TFF3‐positive. Double immunostaining confirmed that mucous (MUC5B positive) cells were moderately or strongly positive for TFF3 and that some serous (MUC7 positive) cells showed restricted TFF3 expression, mostly in a granular pattern. The prevalence of the TFF3 peptide in the salivary secretions of healthy volunteers was detected by western blotting of saliva from minor salivary glands (four of five) and the parotid gland (one of five) and of mixed submandibular/sublingual saliva (five of five). In conclusion, the submandibular and small salivary glands appear to be the major producers of oral TFF3, but duct cells of all glands and keratinocytes of the oral mucosa may also contribute as sources of TFF3 in the oral cavity.     

HLA-DR antigens in normal, inflammatory, and neoplastic salivary glands

A monoclonal antibody to HLA-DR antigens that is reactive in formalin-fixed tissues was used with the immunoperoxidase method to evaluate 212 salivary gland lesions (normal, nonspecific, and autoimmune inflammatory, benign, and malignant tumors). Results of immunostaining showed that (1) intercalated ducts, myoepithelial cells, and acinous cells of normal salivary glands express HLA-DR antigens, (2) autoimmune salivary gland disease results in greater HLA-DR expression than that seen in nonspecific inflammatory lesions or normal glands, (3) stromal cells associated with benign and malignant salivary gland tumors express HLA-DR antigens, and (4) numerous benign and malignant salivary gland tumors express HLA-DR antigens. It was of interest that lymphocyte-rich Warthin's tumors displayed epithelial immunoreactivity, whereas oncocytomas devoid of a lymphocytic component were invariably negative. This suggests a lymphocyte-mediated role in salivary epithelial HLA-DR expression. It appears that HLA-DR expression is both a normal and an inducible phenomenon in salivary glands, salivary gland neoplasia, and the desmoplastic host response. There is no discriminatory role in the immunologic detection of HLA-DR for differential diagnosis of salivary gland tumors.     

Sebaceous adenoma of the parotid gland

Tumors of the salivary glands constitute an important field of oral and maxillofacial pathology. The majority of salivary gland neoplasms are benign, with malignant salivary tumors accounting for 15 to 32 percent. The most common site for salivary gland tumors is the parotid gland, accounting up to 80 percent of all cases. This article reports the pathologic picture in a case of sebaceous adenoma of the parotid gland. The tumor was composed of epithelial cells lining ducts and closely associated with broad areas of sebaceous differentiation. The growth pattern was predominantly cystic, with cavities filled with sebaceous material. Areas of oncocytic metaplasia were also seen. The presence of sebaceous glands in salivary neoplasms is frequent, however, and in spite of this, salivary neoplasms constituted partially or entirely of these cells are rarely observed. To the surgeon and pathologist, the major problem in dealing with sebaceous adenoma is the recognition of this rare entity, avoiding confusing with other more aggressive neoplasms. The treatment involves surgical excision. The addition of the current case to the previously published data brings the total number of parotid sebaceous adenoma to seven.     

Expression of cytokeratins in Warthin's tumour (adenolymphoma) of parotid glands: Specific detection of individual cytokeratin types by monoclonal antibodies

This study evaluated the distribution of cytokeratins detected by monoclonal antibodies directed against individual keratin proteins in normal human salivary glands and epithelial tumour cells of Warthin's tumour arising in parotid glands to determine a more precise mapping of their cellular distribution. The normal salivary ducts showed the presence of cytokeratins 7, 8, 18 and 19 in the intercalated, striated and excretory ducts, the primary keratins of stratified and simple epithelia with a profile very similar to the non-cornified epithelium of the oral mucosa. The basally located cells of salivary gland ducts other than myoepithelial cells were reactive for keratins 7 and 19 suggesting a close similarity in profile of keratin in the basal cells of the oral epithelium. In Warthin's tumour, keratins 7, 8, 18 and 19 were consistently detected in the epithelial cells of the tumour, a profile with a tendency to mimic the same in normal ductal epithelium. The distribution, however, was diverse and a heterogeneity was observed in the basal and luminal cells of Warthin's tumour which differed even in different areas of the same tumour specimen.     

Keratin proteins identified in epithelial fragments of salivary mucoceles

Immunohistochemically detected keratin proteins in mucoceles of oral mucosa were used to served as markers to identify epithelial-derived cells of minor salivary glands. Normal ducts of minor salivary glands showed an intense keratin staining. Epithelial lining and or epithelial fragments in cystic walls of mucoceles displayed a strong reaction to keratin proteins too, whereas granulation tissue or connective tissue fibers of the walls were not seen. Foamy macrophages present in cystic cavities signify higher staining with the use of keratin proteins. Mucoceles in oral minor salivary glands are probably caused by ductal obstructions leading to continuous mucous secretion. Keratin proteins were used as an epithelial marker of ductal segments.     

Immunohistochemistry and ultrastructure of myoepithelium and modified myoepithelium of the ducts of human major salivary glands: histogenetic implications for salivary gland tumors

The organization of salivary gland ducts, especially the presence or absence of myoepithelial cells, is central to histogenetic approaches to the classification of salivary gland tumors. Striated and excretory ducts are reported to be devoid of myoepithelial cells but do contain basal cells. To investigate the nature of such basal cells, tissue sections of normal human salivary glands were examined by means of immunohistochemical, ultrastructural, and fluorescent microscopic techniques. With the use of a mouse monoclonal anticytokeratin antibody (3 12C8-1) that, in salivary glands, is specific for myoepithelial cells, these cells associated with acini and intercalated ducts were strongly stained, as were the basal cells of striated and excretory ducts in each case. Ultrastructurally, some basal cells of both striated and excretory ducts had narrow, elongated cellular processes or the main portion of the cell containing parallel arrays of microfilaments with linear densities and micropinocytotic vesicles, whereas in other basal cells tonofilament bundles predominated. A similar range of cytoplasmic features existed in myoepithelial cells associated with acinar and intercalated duct cells. In addition, some duct basal cells have a complement of actin filaments similar to classic myoepithelium of acini and intercalated ducts. Striated and excretory ducts of human salivary glands, therefore, contain fully differentiated and modified myoepithelial cells, both of which express a specific cytokeratin polypeptide that is absent from duct luminal and acinar cells. Differentiation patterns in the intralobular and interlobular ducts suggest that these regions of salivary gland parenchyma cannot be excluded as histogenetic sites for the induction of salivary gland tumors in which neoplastic myoepithelial cells have been shown to have a major role.     

Nucleolar organizing regions (NORs) in pleomorphic adenomas of the salivary glands

The number of nucleolar organizing regions (NORs) can be used to reveal the degree of cell activity or metabolism in histopathology specimens. Forty-one cases of pleomorphic adenomas of the salivary glands were studied with a silver nitrate colloid staining method to demonstrate the NORs in the cells of the solid and duct pattern areas and in chondroid areas. Acinic and intercalated ducts cells of the surrounding normal salivary glands were also examined. The data was analyzed statistically and it was found that the cells in the solid/ductal areas had a higher cellular activity than the chondroid cells. This difference is probably directly related with the possibility of malignant transformation and the incidence of the different types of malignant pleomorphic adenomas. Furthermore, it is concluded that the number of NORs in pleomorphic adenomas to define malignancy should be done discriminating between the different histologic patterns because of their different metabolic activities.     

涎腺膜性基底细胞腺瘤的组织发生学研究

目的 探讨涎腺膜性基底细胞瘤的组织发生和发展过程。方法 对１２例涎腺膜性基底细胞腺瘤患者进行组织病理学和免疫组织化学研究。结果 ４例患者均可见肿瘤周围的腺体和组织中有多灶性纹和纹管增殖，其最早期的改变为纹管基底细胞增殖，持续不断的导管增殖导致了微小腺瘤的形成。结论 纹管基底细胞的殖明显参与涎 腺膜性基底细胞腺瘤的形成，并在其中起主要作用。这一观点丰富了涎腺肿瘤组织发生的多细胞学说。     

Lipofuscin in salivary glands in health and disease.

Lipofuscin granules were observed in normal salivary glands (parotid, submandibular, and minor salivary glands). The pigment was confined mainly to the epithelial cells of the intralobular ducts, but isolated granules were also found in acinar cells and myoepithelial cells. In chronic sialadenitis pigment granules were found in the intralobular epithelial cells and in macrophages in the surrounding ionnective tissue. In benign epithelial tumors pigment granules were observed within neoplastic epithelial cells and in macrophages in the stroma, while malignant tumors displayed pigmented granules only in macrophages in the stroma.     

A review of the proliferative capacity of major salivary glands and the relationship to current concepts of neoplasia in salivary glands

The classification of salivary gland tumors relies heavily on histogenetic postulates. One of these, the semipluripotential reserve cell theory, suggests that certain reserve cells in specific segments of the duct system of major and minor salivary glands are critical to the development of neoplasms in these glands. However, direct evidence in support of this hypothesis is unavailable. This survey of proliferative capacity in normal salivary gland is based on a review of data in the literature, our observations of DNA synthetic and mitotic activity in developing rat and human salivary gland, and autoradiographic studies of induced cell proliferation in rat salivary gland. Autoradiography of neonatal rat salivary gland after tritiated thymidine administration, and electron microscopy of these tissues, reveals that as well as duct basal cells, luminal cells at all levels of the duct system and even acinar cells are capable of DNA synthesis and mitosis. Indeed, in such studies, more luminal than basal cells are seen in mitosis. In adult rat salivary gland induced to undergo hyperplasia, more acinar cells than intercalated duct cells are in the S phase of the cell cycle. However, cycling cells were observed even in striated ducts and, importantly, both basal and luminal cells of major interlobular excretory ducts are also labeled. Similar findings are present in fetal and adult human salivary glands. From such observations, it is evident that dividing cells are not limited to basal cells of excretory ducts and luminal cells of intercalated ducts, so that there is no support for the semipluripotential bicellular reserve cell hypothesis. However, there is considerable evidence for a multicellular theory of tumor histogenesis; that is, any of the multiplicity of cell types in normal salivary gland have the potential to give use to any of the various types of tumor occurring in this organ.     

Ultrastructural study of the histogenesis of salivary gland mucoepidermoid carcinoma

This electronmicroscope study of the histogenesis of mucoepidermoid carcinoma is based on 15 cases from the major and minor salivary glands. Six major cell types were identified: undifferentiated (cuboid) stem cells, intermediate (columnar) cells, serous/mucoid secretory cells, mucus-producing goblet cells, squamous/epidermoid cells and myoepithelium. It is proposed that undifferentiated stem cells serve as pluripotential reserves which give rise to the various cell types seen in mucoepidermoid carcinoma. Reserve cells in the acinar-intercalated duct components of the salivary glands appeared to give rise to the serous/mucoid and myoepithelial cell populations of mucoepidermoid carcinoma. Reserve cells in the proximal ducts system (intra/extralobular striated ducts and excretory ducts) differentiated into myoepithelium, intermediate (columnar) cells, squamous/epidermoid and mucus-producing goblet cell lines. It is proposed that neoplastic reserve cells give rise to different tumor types in the salivary glands. These types result from varying admixtures and arrangements of tumor cells at different stages of their structural and functional cytodifferentiation from reserve cells. It is further proposed that neoplastic reserve cells differentiate along similar cell lines as the embryonic "stem cells" in the development of normal salivary glands.     

Expression of podoplanin in the mouse salivary glands

OBJECTIVE: Podoplanin is one of the most highly expressed lymphatic-specific genes. Here, we report the distribution of cells expressing podoplanin in mouse salivary glands. DESIGN: We immunohistochemically investigated the distribution of cells expressing podoplanin in mouse major salivary glands by laser-scanning microscopy. The expression of endothelial cell marker PECAM-1 was tested to discriminate lymphatic endothelium from salivary gland cells, and myoepithelial cells were identified by an antibody for P-cadherin. RESULTS: The podoplanin expression was rarely found in acini of the parotid gland but clearly found at the basal portion of acini in the submandibular and sublingual glands. The number of portion reacted with anti-podoplanin is greater in the sublingual gland than in the submandibular gland. The expression was also found at the basal portion of ducts in all major salivary glands. The P-cadherin expression was rarely found in acini of the parotid gland but found in acini of the sublingual gland and on ducts in parotid and sublingual glands, corresponding to the area of podoplanin expression. CONCLUSIONS: It was suggested that the acinar and myoepithelial cells in the salivary glands have the ability to express podoplanin, and that the expression may be concerned with the mucous saliva excretion.     

In vitro evaluation of the suppressor potential of conditioned medium from benign myoepithelial cells from pleomorphic adenoma in malignant cell invasion

J Oral Pathol Med (2012) 41 : 610–614 Tumoral invasion process is the result of a complex interaction between the tumor cells and microenvironment which plays an important role in modulating the growth and invasion of the cancer. The myoepithelial cells, present in glandular organs such as the breast and salivary glands, seem to exert paracrine effects on the glandular epithelium, acting as natural tumor suppressors. To verify the influence of the benign myoepithelial cells in the invasion of malignant cells, simulating an in situ carcinoma ex pleomorphic adenoma, we have cultured three different high‐potential invasive malignant tumors (breast ductal adenocarcinoma, melanoma and oral squamous cell carcinoma) in conditioned medium of myoepithelial cells from salivary gland pleomorphic adenomas using transwell chambers with 8‐μm pores membrane coated with matrigel. After 96 h, quantitative analyses of the results were performed by calculating the invasion index (number of cells that invaded in relation to the total number of cells). The results showed that there was a reduction of the invasion index mean for the three different malignant tumors. This study supports a tumoral suppressor function of the myoepithelial cells from pleomorphic adenoma in in vitro invasion process.     

Distribution of MUC1 in the normal human oral cavity is localized to the ducts of minor salivary glands

The change in expression of MUC1 from health to disease forms the basis of its use as a potential disease marker. Previous attempts at isolating MUC1 from normal, healthy human oral mucosa have, however, drawn conflicting conclusions as to its presence. Furthermore, when MUC1 was detected in the oral glycocalyx, it was not clear which cells were synthesising it. We examined human oral glycocalyx using pooled buccal smears from 50 normal individuals. Following isopycnic density centrifugation and membrane extraction with octyl glucoside and saponin, MUC1 was detected with the polyclonal antibody CT1. Immunohistochemistry using antibodies CT1 and BC2 was performed on sections from eight labial, seven palatal, four buccal, three retromolar pad, three dorsum of tongue and two ventral surface of tongue biopsies. In-situ hybridisation using MUC1 and cytoplasmic tail oligoprobes on sections from four palatal, seven labial and two retromolar pad biopsies was also carried out. MUC1 mRNA could only be detected in the minor salivary mucous glands. MUC1 has already been identified in the ducts of normal parotid and submandibular gland, and our findings demonstrate a similar distribution in minor salivary glands. We conclude that when present in the normal oral glycocalyx, the only oral source of MUC1 is from cell membranes of the minor salivary glands.     

Irradiation effect of low-energy laser on rat submandibular salivary gland

Histopathological studies of rat submandibular salivary glands following low-energy laser irradiation using gallium-arsenide semi-conductor laser were conducted. The mitoses of duct epithelial cells without atypia increased between 1 and 24 h after irradiation, reaching a maximum of greater than 5 times control values by 24 h. Mitoses of duct epithelial cells had a tendency to be more frequent in granular ducts, less in striated ducts, and still less in intercalated ducts. Qualitative differences in the effect of low-energy lasers on salivary gland epithelia were also noted. This is the first experimental study of the effect of low-energy laser on salivary glands.     

涎腺恶性肿瘤治疗方法的研究进展

在口腔颌面部恶性肿瘤中,涎腺恶性肿瘤是一类较常见、发生率较高的恶性肿瘤.任何年龄都可发生涎腺恶性肿瘤,且性别发生率无显著差异.涎腺恶性肿瘤多为涎腺上皮组织来源的恶性肿瘤,可发生于大涎腺如腮腺、领下腺和舌下腺,也可发生于小涎腺如腭腺等,具有组织分型多、细胞成分复杂等特点.近年来国内外针对涎腺恶性肿瘤在诊断治疗方面取得了一些进展,本文就涎腺恶性肿瘤的手术治疗、放射治疗、化学药物治疗、生物治疗等手段作一.     

Irradiation effect of low-energy laser on rat submandibular salivary gland

Histopathological studies of rat submandibular salivary glands following low-energy laser irradiation using gallium-arsenide semi-conductor laser were conducted. The mitoses of duct epithelial cells without atypia increased between 1 and 24 h after irradiation, reaching a maximum of greater than 5 times control values by 24 h. Mitoses of duct epithelial cells had a tendency to be more frequent in granular ducts, less in striated ducts, and still less in intercalated ducts. Qualitative differences in the effect of low-energy lasers on salivary gland epithelia were also noted. This is the first experimental study of the effect of low-energy laser on salivary glands.