Bilateral multiple oncocytic cysts of the parotid gland in type 2 diabetes patients.

AIMS: The hallmarks of type 2 diabetes (T2D) are hyperglycaemia and insulin resistance. These factors, at the cellular level, are associated with mitochondrial dysfunction and increased glucose uptake. Such events are poorly explored in the context of the salivary glands. In this study, we present a series of eight cases of a distinct salivary gland lesion characterised by multiple oncocytic cysts, and we provide new pathological insights regarding its pathogenesis. METHODS AND RESULTS: Seven patients (87.5%) had confirmed T2D, and obesity was identified in five (62.5%) patients. Clinically, the patients showed bilateral parotid gland swelling with recurrent episodes of pain and enlargement. Imaging examination revealed multiple cystic lesions in both parotid glands. Microscopically, the parotid glands showed multiple cysts of different sizes, lined by oncocytic epithelial cells. Intraluminally, strongly eosinophilic glass-like crystalloid material was observed. Immunohistochemical studies were performed, and the most notable finding was glucose transporter 1 (GLUT1) overexpression in the oncocytic cysts which is not observed in any other oncocytic lesion of patients without T2D. In addition, high expressions of mitochondrial antigen, fission 1 protein and mitofusin-2 were observed in the oncocytic epithelium of the cysts. Furthermore, most of the oncocytic cysts showed a pattern of cytokeratin expression consistent with striated ducts. CONCLUSIONS: These results strongly suggest that T2D is associated with alterations in GLUT1 expression in the cells of striated ducts with mitochondrial dysfunction, causing a hyperplastic process characterised by multiple oncocytic cysts. For this lesion, the designation of 'diabetes-associated-bilateral multiple oncocytic cysts of the parotid gland' is proposed.

Adipose Mesenchymal Stem Cell Secretome Modulated in Hypoxia for Remodeling of Radiation-Induced Salivary Gland Damage.

BACKGROUND AND PURPOSE: This study was conducted to determine whether a secretome from mesenchymal stem cells (MSC) modulated by hypoxic conditions to contain therapeutic factors contributes to salivary gland (SG) tissue remodeling and has the potential to improve irradiation (IR)-induced salivary hypofunction in a mouse model. MATERIALS AND METHODS: Human adipose mesenchymal stem cells (hAdMSC) were isolated, expanded, and exposed to hypoxic conditions (O2 < 5%). The hypoxia-conditioned medium was then filtered to a high molecular weight fraction and prepared as a hAdMSC secretome. The hAdMSC secretome was subsequently infused into the tail vein of C3H mice immediately after local IR once a day for seven consecutive days. The control group received equal volume (500 µL) of vehicle (PBS) only. SG function and structural tissue remodeling by the hAdMSC secretome were investigated. Human parotid epithelial cells (HPEC) were obtained, expanded in vitro, and then irradiated and treated with either the hypoxia-conditioned medium or a normoxic control medium. Cell proliferation and IR-induced cell death were examined to determine the mechanism by which the hAdMSC secretome exerted its effects. RESULTS: The conditioned hAdMSC secretome contained high levels of GM-CSF, VEGF, IL-6, and IGF-1. Repeated systemic infusion with the hAdMSC secretome resulted in improved salivation capacity and increased levels of salivary proteins, including amylase and EGF, relative to the PBS group. The microscopic structural integrity of SG was maintained and salivary epithelial (AQP-5), endothelial (CD31), myoepithelial (α-SMA) and SG progenitor cells (c-Kit) were successfully protected from radiation damage and remodeled. The hAdMSC secretome strongly induced proliferation of HPEC and led to a significant decrease in cell death in vivo and in vitro. Moreover, the anti-apoptotic effects of the hAdMSC secretome were found to be promoted after hypoxia-preconditioning relative to normoxia-cultured hAdMSC secretome. CONCLUSION: These results show that the hAdMSC secretome from hypoxic-conditioned medium may provide radioprotection and tissue remodeling via release of paracrine mediators.

Microliths in the parotid of ferret investigated by electron microscopy and microanalysis.

The present investigation is an attempt to determine the occurrence, elemental composition and formation of microliths in the parotid of ferret. Parotids from four normal ferrets were examined by electron microscopy and X-ray microanalysis. Crystalline microliths were found in phagosomes of acinar cells, which occasionally contained secretory material, and in phagosomes situated between mitochondria of striated ductal cells. Crystalline microliths and microliths that consisted of granular material either without crystals or mixed with a component of crystals were found in lumina, where they were often associated with cellular debris. The crystals contained calcium and phosphorus. Phagy and stagnation related to pockets of inefficient secretory activity have been previously found to be features of the parotid of ferret. Thus, possibly persistent degradation of redundant cellular material, particularly secretory granules, in phagosomes results in accumulation of calcium and leads to calcified microliths, whereas consolidation of stagnant debris extracellularly does not involve such accumulation and leads to non-calcified or mixed microliths.

HIV-unrelated benign lymphoepithelial cyst of the parotid glands containing lymphoepithelial lesion--like structures: a report of 3 cases.

Benign lymphoepithelial cyst (BLC) of the salivary gland is uncommon. Among report of these lesions, there were no previous cases of lymphoepithelial lesion (LeL) in human immunodeficiency virus type-1 (HIV-1) unrelated BLC. This study reports 3 cases of HIV-unrelated BLC containing LeL-like structures. Pathologically, 3 lesions were characterized by cuboidal epithelial-lined, cystic spaces, numerous lymphoid follicles, and dense lymphoplasmacytoid infiltrate. Moreover, small lymphocytes invaded the epithelial clusters forming LeL-like structures. Histological findings of 3 lesions resembled marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. However, staining with CD3, CD5, and CD20 demonstrated the mixed nature of small lymphocytes invading the epithelial clusters (LeLlike structures). Moreover, there were no CD43+ B-lymphocytes in any of the cases. The polytypic nature of B-lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. The 3 cases indicate that HIV-unrelated BLC should be added to the differential diagnosis of MALT-type lymphoma involving the parotid glands.

Induction of salivary polypeptides associated with parotid hypertrophy by gallotannins administered topically into the mouse mouth.

Isoproterenol-induced salivary polypeptides (IISP), a group of proline-rich proteins synthesized by mouse parotids, have been considered as markers for isoproterenol-induced parotid hypertrophy. Rodents fed diets containing high-tannin cereals (sorghum), also develop parotid hypertrophy. To test whether tannins are directly involved in provoking sialotrophic growth, we studied the effect of intraperitoneal and topical oral administrations of tannic acid (TA) on the induction of IISP polypeptides in endogamic mice (A/Snell). TA was characterized by HPLC chromatography and spectral analysis and shown to be composed solely of gallotannins, a complex family of glucose and gallic acid esters. IISP polypeptides were monitored in saliva by SDS-polyacrylamide gel electrophoresis during 36 h after ending TA stimulation. Single daily intraperitoneal administrations of TA for 3 consecutive days (0.033 mg/g bw/day), at variance of parallel administrations of isoproterenol (0.042 mg/g bw/day) failed to induce IISP polypeptides. However, repeated topical applications of TA into the mouse mouths (1.21 mg/g bw divided into three equal doses given at 4-h intervals within a single day) resulted in unequivocal induction of IISP polypeptides. That response was clearly intensified by increasing the stimulation frequency to eight equivalent doses given at 1.5-h intervals within a single day (corresponding to 3.23 mg/g bw) and even further by repeating this protocol for 3 days. Under these productive schemes of stimulations by TA, electrophoretic fractionation of parotid homogenates showed new polypeptide bands migrating in parallel to salivary IISP. These results suggest that topically administered gallotannins are effective inducers of trophic growth in mouse parotids.

Histological and histochemical observations on salivary microliths in ferret.

The fortuitous observation of salivary microliths in ferret was pursued in the present investigation. Major salivary glands obtained post-mortem from mature ferrets of either sex were examined with the use of histology and light microscopical histochemistry for calcium, protein, amino acids, mucosubstances and hydrolytic enzymes. Microliths were detected in most parotids, but were absent from submandibular and sublingual glands. The microliths were usually seen in lumens, and occasionally in parenchyma and interstices. They were variably stained for calcium, tryptophan, and neutral and acidic mucosubstances, similarly to acinar or ductal secretory granules. Unlike secretory granules, microliths showed autofluorescence, high levels of tyrosine and a low concentration of -SS- groups. Acid phosphatase and beta-glucuronidase reaction surrounded non-luminal microliths. The present data establish ferret as a new model for the investigation of salivary microliths and do not support the notion of microliths being almost absent from the parotid. Probably there is secretory inactivity in ferret parotid and this fosters the formation and accumulation of microliths containing calcium and disintegrated secretory material.

Oxidative stress in alcohol-induced rat parotid sialadenosis.

This study evaluated the effect of chronic ethanol consumption on the oxidative status of rat parotid and submandibular glands. To identify the endogenous response to ethanol ingestion, the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined. In addition, the antioxidant alpha-tocopherol was supplied to the animals in order to estimate its action in ethanol-associated glandular damage. The thiobarbituric acid reactive substances (TBARS), and the protein carbonyl (PC) content, both markers of cellular oxidative stress on lipid and protein structures, respectively, were recorded. Animals subjected to alcohol ingestion showed a low body growth rate with concomitant enlargement of absolute and relative parotid wet weight, compared with pair-fed calorie-controlled rats. Parotid glands of ethanol-treated animals showed increased SOD and GPx activity, and alpha-tocopherol was able to reduce their activities to the control levels. TBARS and PC were enhanced after chronic ethanol treatment in rat parotids. Supplemental alpha-tocopherol suppressed the oxidative ethanol-induced damage in lipid without affecting induced protein oxidation. Submandibular glands revealed no alterations in the weight, enzymatic and oxidative parameters tested due to ethanol and/or alpha-tocopherol ingestion. These findings indicate the involvement of oxidative stress in parotid gland sialadenosis due to ethanol consumption and the capability of alpha-tocopherol to halt lipid damage, although this low-molecular antioxidant compound leads to neither increased glandular weight nor protein oxidation in ethanol-induced parotid alterations.

Re-distribution of tenascin-C in the parotid acinar cells. An early marker of radiation-induced damage of salivary glands?

PURPOSE: In order to investigate the early changes in the expression of tenascin-C, following irradiation and the associated functional impairment of salivary glands. MATERIALS AND METHODS: Fifteen rabbits were used for the study. Five provided control parotid gland tissue and a further 10 rabbits were scintigraphically examined prior to and 24 h after 15/30 Gy. Glands were studied histologically using HE-staining and tenascin-C antibodies. RESULTS: Reduction in the salivary ejection fraction (SEF) was observed in all irradiated glands. Simultaneously, a marked re-distribution of tenascin-C expression was noticed. Reactivity detected in the intercalated, secretory ducts and perineurinal regions prior to radiation was noticed intracellularly after 24 h. Furthermore, nerves showed tenascin-C expression in the Schwann cells, but no longer perineurinally. Myofibroblasts were also observed in the stroma. CONCLUSION: This study proves the ability to predict functional disorders of salivary function as early as 24 h after radiation and provides evidence of the participation of tenascin-C in the pathological process of radiation-induced damage in salivary glands.

Inflammatory pseudotumor of the parotid gland: report of a case with fine needle aspiration cytology.

BACKGROUND: Inflammatory pseudotumor is a rare lesion of the parotid gland. It usually presents as a mass lesion; thus, the clinical and radiologicfeatures often suggest malignancy. To the best of our knowledge, fine needle aspiration cytologic findings in parotid inflammatory pseudotumor have not been reported previously. CASE: A 59-year-old male presented with a palpable right parotid mass. Computed tomography revealed a mass measuring 2.5 cm in diameter. Fine needle aspiration cytology showed inflammatory cells, foamy histiocytes and groups of spindle-shaped cells without cytologic atypia. A diagnosis of inflammatory pseudotumor was suggested and was confirmed on histology. CONCLUSION: In the presence of a clinically evident mass in the parotid gland and fine needle aspiration cytologic features of inflammatory cells with sheets of spindle cells, the diagnosis of inflammatory pseudotumor should be suspected. The differential diagnosis of this unusual parotid gland lesion principally includes sialadenitis and myoepithelioma.

Sclerosing polycystic adenosis of the left parotid gland: report of a case with fine needle aspiration cytology.

BACKGROUND: Sclerosing polycystic adenosis (SPCA) of major salivary glands is a rare recently described entity. We report a case of SPCA of the left parotid gland, including the cytologic and histopathologic findings. CASE: A 20-year-old man presented with a left parotid mass that had been growing slowly for 3 years. Fine needle aspiration cytology showed many syncytial cell clusters of variable size and some ductal structures with an inflammatory background. The cells forming syncytial clusters were large and polygonal, with abundant, eosinophilic, granular or lacelike cytoplasm. Apocrine differentiation with decapitation secretion was commonly seen. The ductal cells had a relatively high nuclear/cytoplasmic ratio, with granular cytoplasm. Grossly, the 5-cm lesion was a discrete, pale, cystic nodule embedded within the parotid gland parenchyma. Microscopically, the lesion was a nonencapsulated, circumscribed mass of sclerotic and hyalinized, collagenous tissue with lymphoplasmacytic infiltration. Sclerosing adenosis and cystic ducts with frequent apocrinelike cells were commonly seen. Some acinar cells contained eosinophilic, intracytoplasmic granules of various sizes. CONCLUSION: The presence of syncytial clusters with apocrine metaplasia and ductal structures in a lymphoplasmacytic background should suggest a diagnosis of SPCA of a major salivary gland.

Diagnosis and therapeutic management of iatrogenic parotid sialocele.

Salivary gland sialoceles are relatively common and may be a complication of trauma with a penetrating salivary gland injury or may be a complication of salivary gland surgery. The development of new diagnostic tools such as magnetic resonance sialography and endoscopic techniques has led to further improvements in the clinical and diagnostic assessment of this condition, and botulinum toxin therapy has recently been described in the management of parotid sialoceles. We here report the case of a 41-year-old patient with an unusually complicated parotid sialocele following an unsuccessful attempt to remove a stone located in the distal third of Stensen's duct. Magnetic resonance sialography and sialoendoscopy were used in order to obtain an adequate diagnostic assessment. The patient underwent extracorporeal lithotripsy that led to partial symptom regression. After the development of a parotid abscess, he received antibiotics and a botulinum toxin type A injection that induced spontaneous drainage and disappearance of the symptoms. Magnetic resonance sialography and sialoendoscopy are promising new diagnostic techniques for better noninvasive management of iatrogenic sialoceles.

Amylase crystalloids in salivary gland lesions: report of a case with a review of the literature.

Several types of crystalloids may be found in fine-needle aspiration cytology of salivary gland lesions. Amylase crystalloids (sometimes referred to as nontyrosine crystalloids) are tabular structures with frequent pointed ends that have received little attention until recent years. We report on a parotid cyst containing the latter type of crystalloids in a 51-yr-old white woman. The cytologic and radiologic findings were diagnostic of sialolithiasis. To the best of our knowledge, amylase crystalloids have been observed only in benign salivary gland lesions. Although this statement may be helpful in the diagnostic workup of patients presenting with parotid lumps, we do not recommend rendering a specific diagnosis based on the presence of such crystalloids. Good clinical and radiological correlation, as well as close follow-up, is mandatory in this setting.

Lymphoepithelial duct lesions in Sjögren-type sialadenitis.

It is not clear, whether the so-called basal cells of the salivary striated ducts are an independent cell-type distinct from myoepithelial cells, making characterization of the cell proliferation typical of the duct lesions in Sjögren-type sialadenitis/benign lymphoepithelial lesion (BLEL) difficult. An immunohistochemical investigation including different cytokeratin subtypes, alpha-actin, Ki-67 and Bcl-2 was directed at the epithelial cytoskeleton in normal parotid parenchyma (n=8), BLEL (n=12), HIV-associated lymphoepithelial cysts (n=8) and palatine tonsils (n=8). There are profound morphological and functional differences between basal and myoepithelial cells in the normal salivary duct. Development of duct lesions in BLEL arises from basal cell hyperplasia of striated ducts with aberrant differentiation into a multi-layered and reticulated epithelium, characterized by profound alteration of the cytokeratin pattern. This functionally inferior, metaplastic epithelium is similar to the lymphoepithelial crypt epithelium of palatine tonsils. The often postulated participation of myoepithelial cells in duct lesions of Sjögren disease/BLEL cannot be supported. We regard the designations lymphoepithelial lesion and lymphoepithelial metaplasia as the most appropriate.

[Juvenile xanthogranuloma localized in the parotid gland]. / Xanthogranulome juvénile de localisation parotidienne.

Juvenile xanthogranuloma of parotid gland is reported in a 9-year-old boy. This kind of tumor is thought to be very rare in salivary glands. Histological, immunohistochemical and ultrastructural data showed characteristic features and excluded a Langerhans cell histiocytosis. Follow-up was uneventful after 18 months.

The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in human benign and malignant epithelial lesions of the parotid gland.

Immunoreactivity of proliferating cell nuclear antigen (PCNA) was assessed in formalin-fixed, paraffin-embedded sections from human normal parotid gland (N; n = 12), chronic sialadenitis (CS; n = 8), Warthin's tumour (W; n = 10), benign pleomorphic adenoma (BPA; n = 11), mucoepidermoid carcinoma (MEC; n = 14), carcinoma in pleomorphic adenoma (CPA; n = 10) and adenoid cystic carcinoma (ACC; n = 12) of the parotid gland, using the monoclonal antibody PC 10. The morphometric parameters measured comprised PCNA labelling induces (PI = the numerical percentage of PCNA positive nuclei) and volume densities of PCNA positive nuclei(VV, PEP = the relative volume of positive nuclei per unit volume of reference epithelium). All parameters were expressed in relation to total positive, as well as to strongly- and weakly-positive nuclei. In general, the values of PCNA parameters increased progressively in benign lesions in comparison with the N group, and in malignant neoplasms in comparison with non-neoplastic groups and benign lesions. The strongly-positive parameters showed more statistically significant differences than weakly-positive ones, suggesting that weakly-stained nuclei may include some non-cycling cells and, therefore, that weakly-positive parameters may not be reliable proliferation markers. Values for all parameters in CPA were significantly higher than those in BPA, suggesting that these parameters may be used as diagnostic discriminators. Spearman rank correlation analysis showed a highly positive correlation between the morphometric parameters and the severity of the lesions. Furthermore, the mean values of PISP were significantly higher in patients who died of the malignant tumours than in those patients who survived. Our results indicate that PCNA indices might be useful markers for discriminating between benign (BPA) and malignant tumours of the parotid gland and that the parameter PISP may have prognostic applications.

[Salivary calculi. Apropos of 41 cases]. / Lithiases salivaires. A propos de 41 cas.

This retrospective study presents a clinical analysis of 41 patients with salivary gland calculi. Epidemiological, clinical, radiological, mineralogical and therapeutical aspects are presented and discussed. Surgical treatment is the most used but new technics of lithotripsy and/or ultrafine fibroscopy, which are more comfortable and less invasive, may reduce the surgical indications.

Tyrosine crystals in benign parotid gland cysts: report of two cases diagnosed by fine-needle aspiration biopsy with ultrastructural and histochemical evaluation.

Two cases were encountered in which tyrosine crystals were identified by fine-needle aspiration biopsy in nonneoplastic, retention cysts of the parotid. Tyrosine crystals occasionally have been described in parotid neoplasms, but have not been reported in benign retention cysts. To study the frequency and significance of tyrosine crystals in parotid gland cysts, the authors reviewed parotid cytology specimens collected at Loyola University Medical Center from 1985-1993. Among 97 patients, 8.2% (n = 8) had benign retention cysts. No other patients had tyrosine crystals. The presence of tyrosine crystals in benign retention cysts is largely enigmatic. However, because tyrosine crystals previously have been associated with parotid gland neoplasms, awareness of the fact that these unusual structures may be found in benign retention cysts is useful to avoid the erroneous interpretation of tyrosine crystals as an indication of neoplasia, particularly in aspirated material.

Asteroid bodies and calcium oxalate crystals: two infrequent findings in fine-needle aspirates of parotid sarcoidosis.

We have studied 3 cases of sarcoidosis involving the parotid gland by means of fine-needle aspiration cytology (FNAC). The main findings were noncaseating granulomas, multinucleated giant cells (MGCs), and lymphocytes. In one case MGCs contained asteroid bodies and in another case we observed calcium oxalate crystals (COCs) over both stromal fragments and MGCs. Although nonpathognomonic for sarcoidosis, these 2 findings may help in the diagnosis of this condition. However, both are easily overlooked and must be borne in mind when viewing noncaseating granulomas. Sarcoid granulomas displaying COC must be differentiated from foreign-body granulomas. The aforementioned cytological findings must be assessed in conjunction with clinical findings. Nevertheless, in most cases the diagnosis of sarcoidosis is made by exclusion.

An investigation of parotid gland function and histopathology in autoimmune disease-prone mice of different age groups.

This work aimed to characterize parotid gland function in autoimmune disease-prone murine strains (MRL/n, MRL/l and NZB/W) in relation to increasing age and to relate the extent of functional impairment to the intensity of histopathologic changes observed at the different ages. Pilocarpine-stimulated parotid saliva was collected to assess salivary flow rate and composition. Parotid tissue was then removed for histopathologic assessment. Parotid flow rates were not significantly reduced in autoimmune strains compared to controls but were reduced with age in NZB/W mice and in males of the C57 (control) strain. Age-related salivary compositional changes were present in MRL/l mice and in male NZB/W mice. Focal lymphocytic adenitis increased with age in prevalence and intensity in both sexes. The functional and histopathologic changes were not closely correlated. These results suggest that the parotid gland of autoimmune disease-prone mice provides only a poor replication of the salivary changes in human Sjögren's syndrome. Nevertheless, both the functional and histopathological changes developing in these strains, even though of limited extent, are significantly influenced by age.

On stages of postdenervational disturbances in functioning of the human salivary parotid gland (a concise report).

The author presents an original classification of the muscarinic cholinoreceptor subpopulations in the human salivary parotid gland in normal condition or following parasympathetic denervation. The criteria characterizing each stage of the postdenervational syndrome and the general scheme of their occurrence and restoration both reflect the stages of evolutionary transformations in cholinergic receptors. Assessment of salivation rate and volume, observed as the effect of vegetotropic agents, and of electrolyte contents in saliva provide the above scheme of 3 stages of the postdenervational syndrome.