Interlobular excretory ducts of mammalian salivary glands: structural and histochemical review

In the major salivary glands of mammals, excretory ducts (EDs) succeed striated ducts. They are for the most part interlobular in position, although their proximal portions sometimes are on the periphery of a lobule, where they occasionally retain some of the structural features of striated ducts. Based on a survey of a broad range of mammalian species and glands, the predominant tissue type that composes EDs is pseudostratified epithelium. In some species, there is a progression of epithelial types: the proximal EDs are composed of simple cuboidal or columnar epithelium that, in the excurrent direction, usually gives way to the pseudostratified variety. Secretory granules are visible in the apical cytoplasm of the principal cells of the EDs of only a few species, but histochemistry has shown the presence of a variety of glycoproteins in these cells in a spectrum of species. Moreover, the latter methodology has revealed the presence of a variety of oxidative, acid hydrolytic, and transport enzymes in the EDs, showing that, rather than simply acting as a conduit for saliva, these ducts play a metabolically active role in gland function. It is difficult to describe a "typical" mammalian ED because it can vary along its length and interspecific variation does not follow a phylogenetic pattern. Moreover, in contrast to intercalated and striated ducts, ED cellular features do not exhibit a relationship to diet.     

Intralobular ducts of human major salivary glands contain leptin and its receptor

Leptin, a 16-kDa hormone, plays an important role in the control of food intake and in energy homeostasis both in rodents and in man. Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode. In addition, a leptin receptor has been detected in taste cells of mouse circumvallate papillae and in rat intestinal epithelium. These data prompted us to carry out a detailed study of human salivary glands as potential leptin-producing organs. Biopsies of salivary glands (submandibular and parotid) obtained from male and female patients during surgery for different clinical indications were subjected to immunohistochemical study for the presence of leptin, its functional receptor, insulin and glucagon. The presence and cellular distribution of glucocorticoid receptor in leptin-secreting cells were also investigated. Double immunohistochemical staining (silver-gold intensification and avidin-biotin-peroxidase) was used for the visualization of glucocorticoid receptor and leptin labelling, respectively. The results show that intralobular duct cells of submandibular and parotid glands are immunoreactive for leptin, leptin receptor and glucagon but not for insulin. Leptin was also detected in some microglobules in whole saliva obtained from four healthy volunteers. Co-localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands.     

Histological and functional changes in the salivary glands in thalassaemia major

Oral salivary secretion and oral histology in 15 multi-transfused adult thalassaemia homozygotes was studied. Iron stores of minor salivary glands were also histochemically determined. Salivary secretion in multi-transfused thalassaemia patients was subclinically decreased, but no clear correlation was evident between salivary secretion impairment and salivary gland destruction by iron deposition, lymphocyte infiltration and fibrosis. The underlying mechanism remains to be determined.     

Histogenesis of acinic cell carcinoma of the major and minor salivary glands. An ultrastructural study

This study describes the light microscopic, histochemical and electron-microscopic findings of 10 acinic cell carcinomas from the major and minor salivary glands. Ultrastructurally, four cell types were identified: secretory acinar cells, intercalated duct-like cells, pluripotential reserve/stem cells and myoepithelial cells. This cellular composition suggests that the tumours are derived from neoplastic proliferation, cytodifferentiation and functional maturation of pluripotential reserve/stem cells which normally reside at the acinar-intercalated duct junctions and/or in the intercalated ducts proper of adult salivary glands. This study further supports the concept that different salivary gland tumours recapitulate various developmental stages in the normal embryogenesis of the salivary glands.     

Effect of ultrasound on major salivary glands in rats: Dynamics of their functional state

The effect of ultrasound irradiation focused onto the gonial angle of the mandibular bone (5–10 sessions) on salivary function of the major salivary glands was examined on laboratory rats. Repeated sonication modified the character of salivary secretion cycle. In addition, it qualitatively changed ionic composition of the saliva. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 12, pp. 621–623, December, 2007     

Histochemical and ultrastructural study of the chicken salivary palatine glands

Salivary glands are a good model to investigate the relationship between cell secretion and glandular structure. Most studies of this organ deal with mammals, but we are interested in a morphofunctional characterization of these glands in poultry in relation with particular feeding habits. For this purpose, conventional and lectin histochemical methods as well as ultrastructural methods have been applied to the chicken lateral and medial palatine salivary glands. It was found that periodic acid-Schiff (PAS)-positive, alcianophilic, and metachromatic or orthochromatic cells were present with a more homogeneous distribution pattern in lateral glands than in medial palatine glands. Lectin staining depended on the lectin type that was applied, but also on the glandular part both in lateral and medial glands. Ultrastructural studies showed cytoplasmic membranous structures with a scattered granular or filamentous content depending on the secretory cell. In conclusion, morphofunctional characteristics of salivary glands of chicken suggest that their products are involved in lubrication and humidification of food ingested, and probably in protection of the oral surface, as has been previously described for other animals showing similar histochemical staining patterns.     

Metabolic remodeling triggered by salivation and diabetes in major salivary glands

The metabolic profile of major salivary glands was evaluated by ¹³C nuclear magnetic resonance isotopomer analysis (¹³C NMR‐IA) following the infusion of [U‐¹³C]glucose in order to define the true metabolic character of submandibular (SM) and parotid (PA) glands at rest and during salivary stimulation, and to determine the metabolic remodeling driven by diabetes. In healthy conditions, the SM gland is characterized at rest by a glycolytic metabolic profile and extensive pyruvate cycling. On the contrary, the PA gland, although also dominated by glycolysis, also possesses significant Krebs’ cycle activity and does not sustain extensive pyruvate cycling. Under stimulation, both glands increase their glycolytic and Krebs’ cycle fluxes, but the metabolic coupling between the two pathways is further compromised to account for the much increased biosynthetic anaplerotic fluxes. In diabetes, the responsiveness of the PA gland to a salivary stimulus is seriously hindered, mostly as a result of the incapacity to burst glycolytic activity and also an inability to improve the Krebs’ cycle flux to compensate. The Krebs’ cycle activity in the SM gland is also consistently compromised, but the glycolytic flux in this gland is more resilient. This diabetes‐induced metabolic remodeling in SM and PA salivary glands illustrates the metabolic need to sustain adequate saliva production, and identifies glycolytic and oxidative pathways as key players in the metabolic dynamism of salivary glands.     

Agenesis or hypoplasia of major salivary and lacrimal glands

We described a young man with almost total absence of the parotid glands, hypoplasia of both lacrimal glands, marked hypofunction of both submandibular glands, and left nasolacrimal duct atresia. Lack of tearing, severe dental caries, and conjunctival scarring following chronic xerophthalmia and conjunctivitis serve to alert pediatricians to this autosomal dominant disorder with considerable variation in expressivity.     

Low-grade mucoepidermoid carcinoma of salivary glands: characteristic immunohistochemical profile and evidence of striated duct differentiation

The purpose of the present study is to determine the presence and distribution of epithelial and myoepithelial cells in mucoepidermoid carcinoma (MEC) of salivary glands and to compare them with normal salivary gland tissue and other primary carcinomas. This is in order to establish novel diagnostic criteria and to better understand MEC histogenesis. Formalin-fixed paraffin-embedded tissues from ten well-differentiated MECs, three adenoid cystic carcinomas (ACC), four acinic cell carcinomas (AC), and three epithelial-myoepithelial carcinomas (EMCC) of salivary glands were studied with immunohistochemistry using antibodies that recognise antigens indicative of epithelial and myoepithelial cell differentiation. An anti-mitochondrial antibody was also employed. Normal salivary tissue was present for comparative study in non-tumorous areas of the same section from 12 cases. MEC contained numerous keratin-positive cells. Anti mitochondrial antibody was diffusely positive in all ten of these tumours. Smooth muscle actin, h-caldesmon, and smooth muscle heavy chain myosin, which are indicative of myoepithelial cell differentiation, were negative. Rare cells in only one case were stained by calponin. Cytokeratin 14 (CK14) and anti mitochondrial antibody stained cells located mainly at the periphery of neoplastic nests and cystic spaces, while CK7 was mainly present in cells bordering gland lumina (zoning pattern). The immunohistochemical cell profile was similar to that seen in striated normal ducts. All others tumours studied showed a different immunohistochemical pattern, mostly consisting of a lack of mitochondrion-rich cells and the presence of myoepithelial cells in ACC and EMCC. Immunoreactivity in MEC for CK7, CK14 and mitochondrial antibodies appears as a peculiar pattern of staining, different from that of other salivary gland tumors; this seems helpful for diagnostic purposes. In addition, a differentiation of the "striated duct phenotype" is suggested.     

Morphological and functional state of major salivary glands under conditions of aluminum chloride excess in drinking water

Morphology and function of the major salivary glands were studied in 50 albino rats drinking water supplemented with aluminum chloride for 2 weeks. Against the background of normal gland appearance, the salivation function and the composition of the saliva were changed: the concentrations of sodium and calcium ions and α-amylase activity were reduced. In parallel, cholesterol content was increased by 54%.     

Atypical plasmacytoid monomorphic adenoma of salivary glands of the tongue: Cytologic,histologic, immunohistochemical,and ultrastructural findings

We describe the case of an 11‐yr‐old boy with a 2.5‐cm‐diameter soft tumor superficially located at the dorsal aspect of the tongue. Fine‐needle aspiration cytology smears showed plump epithelioid cells with round to mildly oval nuclei and open chromatin. One or two nucleoli of intermediate size were noticed in each nucleus. These cells appeared singly or in small groups. The findings were interpreted as containing plasmacytoid cells coming from an adenoma of salivary gland origin. The histologic examination of the surgical specimen revealed noncohesive, pleomorphic polygonal cells combining plasmacytoid/rhabdoid cytoplasmic features, with mild to moderate nuclear pleomorphism. One mitotic figure was observed per 10 high‐power fields. Immunoreactivity was strongly positive for vimentin and S‐100 protein, less intense for the cytokeratins, and negative for smooth muscle actin, muscle‐specific actin, myoglobin, and GFAP. No ultrastructural evidences of myogenous differentiation were found. We propose that this case represents an unusual atypical variant of plasmacytoid monomorphic adenoma. Diagn. Cytopathol. 1999;20:29–33. © 1999 Wiley‐Liss, Inc.     

Probiotics and autoimmunity: an evolutionary perspective

Probiotics are microorganisms that have demonstrated beneficial effects on human health. Probiotics are usually isolated from the commensal microflora that inhabits the skin and mucosas. We propose that probiotics represent the species of microorganisms that have established a symbiotic relationship with humans for the longest time. Cultural practices of ancient human societies used to favor that symbiosis and the transmission of probiotics from generation to generation. New practices, introduced as a result of industrialization, such as childbirth by surgical delivery, ingestion of pasteurized and synthetic compounds-supplemented food, cleaner homes, indiscriminate use of antibiotics and so on, have led in recent years to the replacement of probiotics by other microorganisms that are not as well adapted to the microenvironments of the human body. These newly settled microorganisms lack many of the beneficial effects of probiotics. Our hypothesis is that the sudden change (from an evolutive perspective) in human intestinal microflora may importantly contribute to the rise in the incidence of autoimmune diseases, observed in the last half a century.     

Immunohistochemical study of carbonic anhydrase in mixed tumours from major salivary glands and skin

Summary Immunohistochemical distribution of carbonic anhydrase isoenzyme I and II was studied in mixed tumours of major salivary glands and skin. The normal salivary glands displayed strong carbonic anhydrase activity in both ductal epithelium and serous acinar cells and the serous demilune cells in the submandibular glands, including the eccrine ducts. Pleomorphic adenoma salivary gland origin exhibited positive staining in the innerlayer of epithelial cells of tubular, duct-like and glandular structures. No enzymatic staining was noted in the outer layer of tumour cells in these structures. Spindle tumour cells or the fibroblast-like cells with long cytoplasmic processes identified in the adjacent hyalin and myxomatous stroma were rarely positive, while chondroidal and osteo-chondroidal cells were highly reactive. Mixed tumours of eccrine gland origin showed the most reactive staining cells scattered throughout neoplastic epithelium in all tissues examined. Immunohistochemical stainability was usually higher for carbonic anhydrase II than I for both normal and tumour tissues. The biological roles of the distribution profiles of carbonic anhydrase are discussed.This investigation was supported partially from Miyata Research fund     

Polymorphous low-grade adenocarcinoma of the major salivary glands: report of three cases in an unusual location

AIMS: Polymorphous low-grade adenocarcinoma (PLGA) is the second most common type of malignant neoplasm in minor salivary glands. Its origin in major salivary glands is considered exceedingly rare. Herein, we present three cases of de novo PLGA arising in major salivary glands. METHODS AND RESULTS: Three cases of PLGA were identified in a large series of primary tumours of major salivary glands. We investigated their clinicopathological profiles, including immunohistochemical features. The three patients (two men and one woman) were 51, 65, and 79 years old. The tumours were 20-30 mm large; two were in the parotid gland and one in the submandibular gland. Histologically, all the tumours had a polymorphous architectural pattern showing predominantly solid, tubular, and cribriform features and invasive growth. Papillary areas were observed focally in two tumours and an 'Indian-file' array in one. The tumour cells had a bland cytological appearance and low mitotic count. Two tumours showed perineural invasion. No preexisting pleomorphic adenoma component was identified. In all cases, tumour cells were positive for epithelial markers, S100 protein, and vimentin but negative for alpha-smooth muscle actin, muscle-specific actin, and glial fibrillary acidic protein. Proliferative activities assessed with the Ki67 labelling index were 4.3%, 7.1%, and 7.6%; no p53 overexpression was observed. Two patients had local recurrence, but none had metastasis or died of tumour. CONCLUSIONS: PLGAs arising in major salivary glands and those in minor salivary glands have similar clinicopathological and immunohistochemical characteristics. It is important to recognize that PLGA can occur ab initio in the major salivary glands, although it is extremely rare.