Carcinomas of intraoral salivary glands

Of 44 intraoral salivary gland tumours received by the Department of Pathology, Dental Faculty, University of Oslo over the last 20 years, 21 (approx. 48%) were classified as carcinomas. Of these, the adenocarcinomas constituted the largest group, but because some of them bore a certain likeness to adenoid cystic carcinomas and to mucoepidermoid tumours, we believe that transitions exist between these groups of neoplasms. The material is thought to reflect the daily practice of oral surgeons and general dental practitioners, and we think it important to emphasize that approximately every second tumour in this series was malignant.     

Disruption of tight junctions contributes to hyposalivation of salivary glands in a mouse model of type 2 diabetes

Tight junction (TJ) plays an important role in regulating paracellular fluid transport in salivary glands; however, little is known about the involvement of TJs in diabetes salivary glands. This study aimed to investigate the alterations of TJs and their possible contribution in diabetes-induced hyposalivation. Here, we observed that the morphologies of submandibular glands (SMGs) were impaired, characterized by enlarged acini accumulation with giant secretory granules, which were significantly reduced in atrophic ducts in SMGs of db/db mice, a spontaneous model of type-2 diabetes. However, the secretory granules were increased and scattered in the acini of diabetes parotid glands (PGs). Other ultrastructural damages including swollen mitochondria, expansive endoplasmic reticulum, and autophagosomes were observed in the diabetes group. The levels of TJ proteins including claudin-1 (Cldn1) and claudin-3 (Cldn3) were increased, whereas those of claudin-4 (Cldn4), occludin (Ocln), and zonula occludens-1 (ZO-1) were decreased in SMGs of db/db mice. Higher Cldn1 and Cldn3 and lower claudin-10 (Cldn10) and Ocln levels were observed in PGs of diabetes mice. Taken together, the structures of SMGs and PGs were impaired in diabetes mice, and the disruption of TJ integrity in both SMGs and PGs may contribute to diabetes-induced hyposalivation.     

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.     

Effects of duct ligation on choline acetyltransferase activity in salivary glands of rats

Duct ligation was found to cause a decrease in the weights of submaxillary and parotid glands examined 3 weeks postoperatively. Choline acetyltransferase activity in ligated glands was compared with that in unligated contralateral glands. The enzyme activity was also measured in the glands from both sides of unoperated control animals. Interference in the assay of choline acetyltransferase by other acetylated compounds was avoided by introducing suitable control incubations. Ligated submaxillary glands showed a small decrease in the activity of choline acetyltransferase both when compared with contralateral glands and with glands of control rats. In parotid glands the enzyme activity was found to be lower only when ligated and contralateral glands were compared. Structural changes in the nerves and reduced traffic of impulses in them may have to be considered as explanations for the reduction in enzyme activity in duct–ligated glands.     

Parameters of the systemic hemodynamics in conscious rats with acute streptozotocin diabetes

Laboratory of Pathophysiology, Research Institute of Pediatrics, Academy of Medical Sciences of the USSR, Moscow. Department of Human and Animal Physiology, Faculty of Biology, Moscow State University. (Presented by Academician of the Academy of Medical Sciences of the USSR I. P. Ashmarin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 3, pp. 250–252, March, 1992.     

Functional morphology of the submaxillary salivary glands during age involution in albino rats

A quantitative study was made of the morphological and functional characteristics of different parts of the submaxillary salivary glands of albino rats in different stages of involution of the neuroendocrine system. During aging the salivary gland function of rats is preserved, and just as in young animals, clear cyclic fluctuations are observed depending on the phases of the estrous cycle, although the basal level of proteins and mucopolysaccharides is reduced, to correspond on average to the minimal found in young animals. Meanwhile activation of the enzymes responsible for energy and transport processes in the cell is observed and relations between the enzymes are altered. The results prove that the salivary glands are connected with the endocrine system and they confirm the view that in early age involution what occurs is not so much a change of function as a disturbance of relations between the different indices of functional activity of the organ.Department of Pathological Anatomy, I. P. Pavlov First Leningrad Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. K. Kulagin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 736–739, December, 1979.     

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     

Effect of ultrasound on major salivary glands. Dynamic of morphological changes in rat salivary glands

Morphology of rat submandibular salivary glands was examined before and after 10 sessions of ultrasonic treatment focused onto the gonial angle of the mandibular bone. The employed ultrasound protocol induced adaptive reactions and induced no degenerative and inflammatory processes. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 11, pp. 586–589, November, 2007     

糖尿病大鼠下颌下腺内肥大细胞的形态学观察

目的观察糖尿病大鼠下颌下腺内肥大细胞形态和数量变化。方法SD雄性大鼠30只,随机分为实验组12只(4周、12周各6只)、治疗组12只(4周、12周各6只)及对照组6只,用链脲佐菌素复制糖尿病动物模型,应用HE和甲苯胺蓝(Toluidineblue,TB)染色观察并记数肥大细胞。结果对照组大鼠下颌下腺内肥大细胞呈圆形。卵圆形及不规则形,细胞内颗粒密集,平均肥大细胞数为(6.55±4.02)个/HP。实验组大部分肥大细胞胞内颗粒稀疏,有脱颗粒现象。4周平均肥大细胞数为(15.44±5.92)个/HP,12周为(46.67±7.78)个/HP,差异有统计学意义(P<0.01),而治疗组肥大细胞形态结构与对照组比较无明显区别,4周平均肥大细胞数为(12.33±1.67)个/HP,12周为(21.71±6.25)个/HP。结论糖尿病可导致下颌下腺内肥大细胞脱颗粒活跃、数量增多,提示肥大细胞可能参与糖尿病发生与发展病理过程。     

Quantitative histoenzymologic characteristics of the submaxillary salivary glands during the ovarian cycle in albino rats

To study the connection between the salivary and endocrine glands and also the degree of participation of individual components of the salivary glands with different functions in endocrine regulation, the ovarian cycle was used. The concentrations of proteins, mucopolysaccharides, DNA, and RNA, and activity of NAD- and NADP-diaphorases, alkaline phosphatase, malate and isocitrate dehydrogenases, and -leucine-aminopeptidase in the submaxillary salivary glands were investigated. It was shown by cytospectrophotometric analysis that, depending on the phases of the ovarian cycle, synchronous changes in the activity of the enzymes studied took place in all parts of the salivary glands. Of the four consecutive phases of the sex cycle the greatest activity of the enzymes and concentration of proteins and mucopolysaccharides were observed in proestrus and metestrus. The metabolic processes in the salivary tubules were rather different from those in other parts of the glands, and this may be attributable to differences in the pattern of secretion production and also, possibly, hormone formation.Department of Pathological Anatomy, Academician I. P. Pavlov First Leningrad Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Smol'yannikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 6, pp. 736–739, June, 1978.     

Basaloid carcinomas of salivary glands

Three cases of carcinoma of major salivary glands with basaloid morphology are presented. One case was a clear example of a basal cell adenocarcinoma, an uncommon and infrequently recognized, low-grade tumour of major salivary glands. The remaining two cases showed a higher cytological grade of malignancy but shared some features of basal cell adenocarcinoma. Common features included the architectural pattern and myoepithelial cell differentiation, as demonstrated by smooth muscle-specific actin positivity, in cells associated with the deposition of extracellular basal lamina-like material. The relationship between these cases and adenoid cystic carcinoma is discussed.     

Basal cell adenocarcinoma in minor salivary glands

Basal cell adenocarcinoma is a rare and relatively recently characterized malignant salivary gland tumour, the malignant counterpart of basal cell adenoma. Diagnosis depends on finding features similar to adenoma but with an infiltrative growth pattern and exclusion of adenoid cystic carcinoma, sialoblastoma and basaloid squamous carcinoma. Basal cell adenocarcinoma is very rarely reported in minor salivary glands. We report three cases of basal cell adenocarcinoma affecting the labial, buccal and palatal minor salivary glands. One recurred following complete removal but with lesional disruption and further local wide excision appeared curative. A further lesion failed to recur in 5 years' follow-up despite marginal excision and a third after 3 years' follow-up. Basal cell adenocarcinoma is considered a low-grade malignancy, and in the minor glands wide excision and radiotherapy are recommended. However, the reported lesions appear to have a more indolent behaviour than previously reported lesions in minor glands.     

Development of human minor salivary glands: expression of mucins according to stage of morphogenesis

The formation of salivary glands entails the proliferation of epithelial cells from the stomatodeum into the underlying ectomesenchyme, culminating in a complex network of ducts and acinar bulbs. The extent to which mucins regulate this process is unknown, but they appear to mediate luminal space formation and maturation. Our aim was to examine mucin expression patterns during the morphogenesis of human salivary glands. Mucin expression - MUC1, 2, 3, 4, 5AC, 5B, 6, and 16 - was analyzed in specimens of developing human salivary glands, obtained from fetuses at 4-24 weeks' gestation, and fully developed salivary glands by immunohistochemistry. Expression patterns were analyzed qualitatively according to the development stage of the salivary glands. Mucins 1, 3, 4, 5B, and 16 were expressed during salivary gland development - being stronger in all ductal segments by the final phases of branching morphogenesis and in mature glands. Acinar cells were negative for most mucins, including MUC1 in mature salivary glands. Mucins 2, 5AC, and 6 were not expressed. Mucins MUC1, 3, 4, 5B, and 16 are expressed in developing human salivary glands and in mature glands, suggesting important roles in the maturation and maintenance of the ductal network.     

Clear cell carcinoma of minor salivary glands

Two cases of carcinoma of the minor salivary glands are presented in which most cells had clear cytoplasm. Both patients had clinical histories in excess of 10 years and, in the one case with adequate follow-up, no recurrence had occurred after a further 11 years. Both tumours were locally invasive. The clear cells contained small amounts of glycogen, but no intracytoplasmic mucin. Immunohistochemical and ultrastructural studies showed epithelial features, with no evidence of myoepithelial differentiation. These tumours were very similar to the small number of previously reported cases, which were all considered to be low-grade carcinomas. Amongst the differential diagnoses, the most important is metastatic clear cell carcinoma of the kidney and this can only be confidently excluded clinically or by the use of imaging techniques. In summary, we consider intraoral clear cell carcinoma to be a distinct tumour of low malignant potential.     

Melatonin ultrastructural localization in mitochondria of human salivary glands

The hormone melatonin was initially believed to be synthesized exclusively by the pineal gland and the enterochromaffin cells, but nowadays its production and distribution were observed in several other tissues and organs. Among others, the ultrastructural localization of melatonin and its receptors has been reported in human salivary glands. In these glands, the fine localization of melatonin in intracellular organelles, above all in mitochondria, remains to be explored comprehensively. Bioptic samples of parotid and submandibular glands were treated to search for melatonin using the immunogold staining method by transmission electron microscopy. Morphometric analysis was applied to micrographs. The results indicated that, both in parotid and submandibular glands mitochondria, a certain melatonin positivity was present. Within glandular cells, melatonin was less retrieved in mitochondria than in secretory granules; however, its presence in this organelle was clearly evident. Inside striated duct cells, melatonin staining in mitochondria was more prominent than in glandular cells. Our data provide an ultrastructural report on the presence of melatonin in mitochondria of human major salivary glands and represent a fundamental prerequisite for a better understanding of the melatonin role in this organelle.     

Solitary fibrous tumour of the major salivary glands

We report four cases of solitary fibrous tumours which involved the parotid (two cases), submandibular, and sublingual glands of two men and two women ranging in age from 46 to 81, mean 66 years. The tumours presented as painless, firm masses which involved the substance of the salivary gland in each case. All have had an uneventful clinical course after local excision. Awareness of this entity is important to avoid confusion with haemangiopericytoma.     

Polymorphous low-grade adenocarcinoma of the salivary glands with transformation to high-grade carcinoma

AIMS: Polymorphous low-grade adenocarcinoma of the minor salivary glands is an infiltrative neoplasm characterized by bland-looking tumour cells arranged in diverse architectural patterns. It is considered to be of low-grade malignant potential in that nodal metastases are seen in only a minority, and distant spread is rare. Even more unusual is the transformation of polymorphous low-grade adenocarcinoma to a histologically high-grade carcinoma, i.e. dedifferentiation. In this paper, we describe the clinicopathological and immunohistochemical findings in two further examples. METHODS AND RESULTS: Two patients presented each with a tumour of the palate. Histopathological examination showed the typical morphological, cytological and immunohistochemical features of a polymorphous low-grade adenocarcinoma. In one case there was a second component of high-grade carcinoma showing nuclear atypia, markedly increased mitotic activity and MIB1 index, as well as prominent zones of necrosis. It expressed epithelial markers and androgen receptors, and thus resembled salivary duct carcinoma. Similar tumour tissue was observed in one of the cervical nodal metastases, which was biopsied at the same time as the palate. In the second patient, a high-grade component was discovered when the tumour recurred in the palate 13 years after the initial biopsy. Whilst morphologically similar to that in first case, there were significant immunohistochemical differences such as retention of some of the polymorphous low-grade adenocarcinoma profile and absence of androgen receptor expression. CONCLUSIONS: Polymorphous low-grade adenocarcinoma was first described relatively recently, and as experience with it continues to accumulate, it is becoming clear that late recurrences and metastases, whilst still infrequent, may not be quite as rare as previously thought. Reports of histological transformation are even scarcer, and most occurred at least 13 years after the polymorphous low-grade adenocarcinoma was initially recognized. It is a real possibility that this phenomenon, like clinical progression, may also be encountered more often as time passes. Therefore, we believe that, whilst polymorphous low-grade adenocarcinoma is certainly far less aggressive than, for example, adenoid cystic carcinoma, it nevertheless remains a true malignancy with a potential to prove fatal in a minority of patients.     

Diagnostic difficulties in lesions of the minor salivary glands

A wide range of lesions arise from the intra-oral salivary glands, and often present a diagnostic challenge to specialists and generalists alike. Of the salivary neoplasms, pleomorphic adenoma is the most common, but its morphological diversity may bring several other entities to mind, notably polymorphous adenocarcinoma, particularly in a small incisional biopsy. Polymorphous adenocarcinoma in turn shares features with adenoid cystic carcinoma. Immunohistochemistry and molecular cytogenetic studies can assist diagnosis in the face of overlapping morphology. The other salivary neoplasms most likely to be encountered in the oral cavity are canalicular adenoma, mucoepidermoid carcinoma, secretory carcinoma and acinic cell carcinoma. Of the non-neoplastic conditions, necrotising sialometaplasia is most likely to be misdiagnosed as neoplastic on both clinical and histological grounds. However, careful consideration of the clinicopathological features of an adequate tissue specimen will enable correct diagnosis.