Focal lymphocytic infiltration in aging human palatal salivary glands: a comparative study with labial salivary glands

Investigation of age-related prevalence of various types of focal lymphocytic infiltration (FLI) and degrees of histomorphologic changes was conducted on 120 biopsies of palatal and labial salivary glands (PSG and LSG, respectively) obtained from autopsy subjects free of salivary gland tumors/diseases. Biopsies were divided into young (<30 years, n=30), adult (30-60 years, n=45) and old (>60 years, n=45) age groups. A modified Chisholm & Mason grading system was used to record grades of FLI and a modified Greenspan et al. system was used to evaluate the severity of histomorphologic changes. The prevalence of FLI in PSG increased significantly from 10% in the young group to 46.6% in the old group (P=0.0012). No significant changes were found with aging in LSG. FLI was significantly more prevalent in the adult and old age groups in PSG as compared with LSG (P=0.015 and P=0.003, respectively). Both glands demonstrated significant histomorphologic changes among age groups (p<0.0001); however, these changes were significantly less common in the old age group in PSG as compared to LSG (P=0.003). In cases showing severe histomorphologic changes, FLI was not present. Therefore, FLI should not be considered as part of the deteriorating histomorphologic changes that are usually encountered in salivary glands with aging. The immunologic profile of these infiltrates should be further clarified to understand their role, both in physiologic and pathologic conditions.     

Anorexia/bulimia-related sialadenosis of palatal minor salivary glands

In patients affected by alimentary disorders sialadenosis is frequently observed. This non-inflammatory condition is described to affect major salivary glands, leading to the characteristic parotid and/or submandibular swelling. Thus fine-needle aspiration cytology or parotid open biopsy are generally required to diagnose histologically the disorder. We report the case of a 28-year-old patient affected by bulimia/anorexia nervosa who presented, in addition to parotid enlargement, a bilateral symmetric painless soft swelling of the hard palate. The lesion was biopsied and histopathological examination showed the classical features of sialadenosis. To our knowledge, this is the first case of sialadenosis affecting palatal minor salivary glands. It underlines that when sialadenosis is clinically suspected, clinicians could check also patients' oral cavity for minor salivary glands involvement, in order to potentially avoid invasive extra-oral procedures and to easily confirm diagnosis with an intra-oral biopsy.     

Cell culture and characterization of human minor salivary gland duct cells

In order to facilitate studies on human salivary glands, a method was developed for the culture of minor salivary gland duct cells from tissues obtained from oral surgery protocols. Minor salivary glands were isolated from such tissues, and a serum-free growth medium was developed which supported the growth of the ductal component of these glands. The ductal origin of these cells was confirmed through immunohistochemical localization of replicating nuclei through incorporation of BrdU. The presence of epidermal keratin in replicating cells and the absence of smooth muscle myosin further substantiated the ductal origin of cells. Using normal growth medium calcium concentrations (1.05 mM), these cells produced a keratinized multilayer of cells unable to undergo routine subculture procedures. A reduction in calcium ion concentration to 0.1 mM resulted in a cell monolayer, without evidence of terminal keratinization, which could undergo at least eight serial passages (1:3 ratio) under cell culture conditions. It is advanced that these minor salivary gland duct cell cultures will be of use to those studying diseases and disorders of the salivary glands.     

Stimulation of minor salivary glands by intraoral treatment with the cholinesterase inhibitor physostigmine in man

A large number of the population, especially the elderly, suffers from dry mouth. The aim of the present investigation was to stimulate the minor salivary glands by the topical application of the cholinesterase inhibitor physostigmine. In eight healthy subjects, 100 µl of the substance, in the concentration interval 2–8 mg/ml, was applied locally to the inside of the lower lip for 1 min. In a separate study comprising 12 dry-mouth patients, 10 ml of 0.4–1.6 mg/ml physostigmine was administered as a mouth rinse solution for 2 min. Secretion from the labial glands, assessed using the Periotron^® method, increased in a dose-dependent manner in response to physostigmine in both groups. Average peak secretion exceeded baseline by more than 50% throughout the 30- to 45-min observation period; from 1.71 to 2.62 µl cm⁻² min⁻¹ among the healthy subjects and from 1.17 to 1.84 µl cm⁻² min⁻¹ among the dry mouth patients. No systemic effects were registered as reflected by ECG, heart rate or blood pressure. It is assumed that intraorally applied physostigmine diffuses through the oral mucosa and acts by preserving acetylcholine released from the cholinergic, parasympathetic nerves that innervate the minor salivary glands. The topical application of physostigmine to the oral mucosa may, therefore, be an interesting approach for the treatment of dry mouth.     

A clinicopathologic study of 196 intraoral minor salivary gland tumours

We present a retrospective study of 196 patients with intraoral minor salivary gland tumours, 128 malignant and 68 benign, diagnosed from 1954 to 1993 in the A.C. Camargo Hospital, São Paulo, Brazil. Sixty-five percent of the cases occurred in the palate, followed by tongue (9.7%) and retromolar area (6.1%). Pleomorphic adenoma was the most common benign tumour, and mucoepidermoid carcinoma was predominant among the malignant tumours. Surgery was the main treatment method and postoperative radiotherapy and radiotherapy alone were used in 40 and 15 patients, respectively. Local recurrence was observed in two patients with pleomorphic adenoma and in eight patients with malignant tumours. Regional lymph node metastases occurred in four cases and distant metastases in five. Forty-six of 47 patients with benigh tumours who were followed up from 1 to 7 years were alive without disease. Twenty-four of 79 patients with malignant tumours who were followed up for at least 5 years died due to the tumour and 47 were alive without disease.     

Mucoepidermoid carcinoma of minor salivary glands: a clinical study of 16 cases and review of the literature

OBJECTIVE: Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of salivary glands with a widely diverse biologic behavior that is correlated with the histological grade of the tumor. The purpose of this study was to evaluate the clinical outcomes of MEC of minor salivary glands in a group of 16 patients, who were treated in our clinic, and to discuss the management of this carcinoma. MATERIALS AND METHODS: Between 1985 and 2000, 16 patients with MEC of minor salivary glands were treated in the Clinic of Oral and Maxillofacial Surgery of the 'G. Papanikolaou' General Hospital, in Thessaloniki. The age range was 16-65 years. The distribution of the primary sites was: hard plate (one), soft palate (two), hard and soft palate (three), hard and soft palate with spread in paranasal sinus and nasal cavity (one), buccal mucosa (three), hard palate, alveolar process and buccal mucosa (two), and retromolar triangle (our). The tumors were clinically staged according to the tumor nodes metastase (TNM) system (Seifert, 1991). All patients were treated radically with surgery. The surgery was combined with radiotherapy in nine patients. Radiotherapy was delivered using Co-60. Doses ranged from 50 to 60 Gy and the duration of the therapy ranged from 25 to 35 days. Immunohistochemical assay of the expression of the Ki-67 antigen was performed on a subset of 15 cases. RESULTS: The mean follow-up range was 4-14 years. From the 16 patients with MECs 10 (62.5%) were alive and five (35.6%) had died from the disease. Four patients were free of the disease for more than 5 years (range 8-14), five patients were free of the disease for 5 years and one patient was free of the disease for 4 years. One patient lived more than 10 years and died from another cause. Local recurrence developed in one patient 10 years after the initial treatment. Lymph node metastases occurred in one patient within the first year after the initial surgical treatment. Distant metastases (two in bones and one in lungs) occurred in three patients within 2 years after completing the treatment. The Pearson chi-square statistical analysis was used for comparing the Ki-67 values in correlation with histological grade of the tumors. The Ki-67 expression was only 1% in low-grade MECs, while in intermediate-grade tumors it was estimated between 3 and 4%. The high-grade tumors had increased expression (10%) of tumor cells. CONCLUSION: Complete surgical excision is the treatment of choice for MECs. Adequate excision is important in all grades of tumors. Prognosis of MECs is a function of the histological grade, adequacy of excision and clinical staging. The immunohistochemical study of Ki-67 expression may provide additional prognostic information for this tumor.     

Histologic assessment of the submandibular glands in autoimmune-disease-prone mice

Submandibular glands were examined from three autoimmune-disease-prone strains of mice (NZB/W, MRL/l and MRL/n) and controls (C57BL/6J). Focal lymphocytic adenitis was more prevalent and more severe in autoimmune-disease-prone strains than controls and in females than males. Lymphocytic foci were more frequent in older age groups, but female MRL/1 mice exhibited high levels of focal lymphocytic adenitis irrespective of age. Salivary parenchyma was generally well preserved. In the strain-age groups with the highest focal lymphocytic scores proportional acinar volumes were significantly less than in controls. However, the proportion of acinar tissue showed no consistent relation to the severity of focal lymphocytic adenitis across all strains and age groups of either sex. Sexual dimorphism in granular duct prominence was weakened in NZB/W and MRL/l strains compared to controls.     

Histochemical study of lectin binding in the human fetal minor salivary glands

The emerging synthesis of glycoconjugates containing specific oligosaccharides in developing human fetal labial and lingual salivary glands has been investigated by lectin histochemistry. An avidin-biotin technique was used to study the binding of lectins from Ulex europeus I (UEA-I), Dolichos biflorus (DBA), Glycine maximus (SBA), Helix pomatia (HPA), Arachis hypogaea (PNA) and Triticum vulgare (WGA) to specific sugars on sections of tissue from labial glands, glands of Blandin and Nuhn, glands of von Ebner and the dorsoposterior lingual salivary glands. Incipient synthesis of glycoconjugates in early glands and their presence in the cells and ducts of the later glands was shown. The study also showed a time-related increase in both staining intensity and binding sites of serous acinar cells from all glands and for all lectins used. For mucous cells, peak intensity of staining was reached by the middle phase of development. During later gland development this intensity was maintained in dorsoposterior lingual glands but tended to decline in labial glands. The various lectins showed different degrees of binding but UEA-I lectin generally bound the L-fucose sugar group in all salivary glands at all gestational ages. The results showed that lectins appear to bind to the oligosaccharides on epithelial cell surfaces of fetal salivary glands at all stages of development. The degree of change depends upon the stage of differentiation and maturation of the glands.     

Effects of tobacco and diuretics on human palatal salivary glands

The prevalence of macrophotographically documented sialadenitis in the palatal mucosa of 184 probands, aged 23 yr or older, was studied in the Koster Health project. A total of 75 (mean age 58.9) revealed inflammatory changes around the duct orifices of the palatal glands. In 10, biopsies were performed for histomorphologic analyses to confirm the diagnosis of sialadenitis. Statistics with matched pairs showed a significantly higher ratio of tobacco use among individuals with sialadenitis than among those with clinically unchanged palatal gland orifices. A relationship between the use of diuretics and sialadenitis was also statistically significant. It can be concluded that tobacco use and diuretics may induce inflammatory changes in the palatal glands and that macrophotography of the palatal mucosa may serve as a valuable, non-invasive method for scoring sialadenitis.     

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.     

Expression of cytoskeletal proteins in developing human minor salivary glands

The presence of an epithelium at different stages of proliferation and differentiation raises interesting questions concerning the histogenesis, cell turnover and differentiation of normal salivary glands. In order to expand knowledge of these aspects, we investigated the expression of cytokeratins (CKs) 7,8,10,13,14,16,18 and 19, vimentin (VIM), and smooth muscle actin (SMA) in developing human minor salivary glands using monoclonal antibodies. Labial, buccal, palatine, and lingual salivary glands and those from the floor of the mouth were obtained from human fetuses (forensic postmortem) ranging in age from gestational weeks 10 to 29. Serial sections, 3 microm thick, were immunostained using a strepto-avidin-biotin technique. Reactivity for all antibodies was negative in the salivary gland epithelium during the developmental stages of bud formation, cord growth, and branching of cord. During canalization and cytodifferentiation, the glandular epithelial cells showed a positive reaction to some CKs and SMA. Cytokeratins 7, 8, 18, and 19 showed strong labeling in luminal duct cells that exhibited some degree of morphological differentiation. Myoepithelial cellc were recognized by antibodies to SMA. Cytoskeletal protein expression changes according to the cell type, degree of differentiation, and stage of morphological development of the glandular structure. These changes occur independently of the localization of the gland.     

Marginal zone B-cell lymphoma of minor salivary gland representing tumor-forming amyloidosis of the oral cavity. A case report

We report here a case of mucosa-associated lymphoid tissue (MALT)-type lymphoma arising from the minor salivary gland of the oral cavity exhibiting tumor-forming amyloidosis. The patient was a 64-year-old Japanese woman who presented with 4-year history of a left soft palate mass. Despite multiple and multifocal recurrences including the lip, soft palate, tongue, oral base and vocal code and soft palate, the tumor remained localized in the upper aerodigestive tract, and the patient did not develop multiple myeloma during the course of disease. Histologically, the majority of the lesion was occupied by amyloid deposition. Only the periphery of the lesion contained numerous plasmacytoid cells, along with occasional centrocyte-like cells. In addition, lymphoepithelial lesion and follicular colonization were noted. The present case indicates that primary minor salivary gland MALT-type lymphoma appears to be the cause of tumor-forming amyloidosis of the upper aerodigestive tract including the larynx.     

Enumeration of T cell subsets with monoclonal antibodies in minor salivary glands of patients with rheumatoid arthritis

Abstract – Labial salivary glands of 51 patients with rheumatoid arthritis and those of 25 control patients were examined by the ANAE (acid α-naphthyl acetate esterase) technique to determine the percentages of B- and T-lymphocytes and mononuclear phagocytes (MPS cells). Using monoclonal antibodies (OKT3 for all T cells, OKT4 for helper/inducer T cells, OKT6 for thymocytes, and OKT8 for suppressor/cytotoxic T cells) T cell subsets were enumerated. B- lymphocytes predominated in both series of salivary glands, and the percentages of B and T cells were equal in both series. The absolute cell counts in the salivary glands of rheumatics were significantly higher (P<0.001) than in those of healthy controls. The number of OKT4⁺ cells was increased in rheumatics, leading to an elevated OKT4⁺/OKT8⁺ ratio when compared with that in controls (P<0.01). The results suggest that the basic phenomenon behind the B cell hyperactivity noticed in rheumatics might be due to increased activity of T helper cells rather than reduced number of T suppressor cells, which were shown to remain almost unaffected in the salivary glands of patients with rheumatoid arthritis.     

增殖细胞核抗原在涎腺腺癌中的表达及其临床意义

目的探讨增殖细胞核抗原(PCNA)在涎腺腺癌中的表达及临床意义。方法选择47例涎腺腺癌石蜡标本,用免疫组化方法(SABC)测定PCNA表达。结果PCNA在涎腺腺癌中的表达阳性率为(76.12±19.24)%,表达呈异质性。PCNA指数与口腔癌的肿瘤大小、分化程度、淋巴结转移相关,与TNM分期无关。结论PCNA可作为判断涎腺腺癌恶性程度及预后的有效指标。     

Clear cell carcinoma of the minor salivary glands. Report of a case

Clear cell carcinoma is an extremely rare form of malignant salivary gland tumour. A case of clear cell carcinoma arising in the minor salivary glands is reported.     

Outcomes of patients with adenoid cystic carcinoma of the minor salivary glands

Adenoid cystic carcinoma is a tumour of glandular cells responsible for 10% of salivary gland neoplasms. It has a high rate of perineural spread but limited involvement of regional lymphatics even in late stage disease. Early survival is typically good (60-90%) although long term survival is poor with spread to distant sites in 40-60% of cases. The authors performed a retrospective review of clinical and pathological records for 24 patients managed by their institution over a 22-year period. The overall 5, 10 and 20-year survival rates in this study were 92%, 72% and 54%, respectively. Perineural invasion was seen in 63% and close or positive margins seen in 64% of all primary resection specimens although survival was not associated with any clinical factor other than the initial size of lesion. Most patients presented complaining of a lump, whilst a burning neuralgia-type pain was the second most common symptom. The study confirms the conclusion of previous studies that tumour size at diagnosis is the most important predictor of outcome.     

Analysis of the clinicopathological characteristics and prognosis of adenoid cystic carcinoma of the intraoral minor salivary glands: a retrospective study of 40 cases

The clinicopathological aspects and prognostic factors of 40 patients with adenoid cystic carcinoma (ACC) of the intraoral minor salivary glands, treated between 2007 and 2017 at a single institution, were evaluated retrospectively. Twenty-six were female and 14 were male, and they ranged in age from 26 to 81 years (median 55 years). ACC occurred mainly in the palate, with 54.8% of cases presenting T3–T4 lesions. Curative surgery was performed in all patients, and 62.5% of patients were treated with postoperative adjuvant radiotherapy. In the final analysis, positive surgical margins were noted in 57.5% of cases and perineural invasion in 70%. Follow-up was at least 13 months (range 13–141 months, median 59 months). Nineteen patients (47.5%) developed recurrent disease after initial surgery and nine patients had died at the end of follow-up. The 5- and 10-year overall survival rates were 88.3% and 25.6%, respectively. The 5- and 10-year disease-free survival rates were 75.6% and 34.0%, respectively. Patients with a tumour size >4 cm and those with positive surgical margins showed a significantly higher risk of local recurrence. Elective neck dissection is suggested for patients with clinically positive lymph nodes or a locally advanced tumour, especially those undergoing microvascular reconstruction. The survival analysis results are similar to those reported previously in the literature.     

Expression of two drug-metabolizing cytochrome P450-enzymes in human salivary glands

Objective:  The oral cavity is constantly lubricated by saliva and even small amounts of xenobiotics and / or their metabolites in the saliva may affect the oral mucosa. Our aim was therefore to clarify if xenobiotic metabolizing enzymes CYP1A2 and CYP3A4 are expressed in salivary glands.
Methods:  Formalin-fixed paraffin-embedded specimens from parotid (10), submandibular (7) and labial (10) salivary glands were examined immunohistochemically and by in situ hybridization for expression of CYP1A2 and CYP3A4 protein and mRNA.
Results:  CYP1A2 and CYP3A4 protein and mRNA were detected in ductal and seromucous / serous acinar cells in all gland types although to a varying degree and intensity. Mucous acinar cells were positive to a lesser extent.
Conclusion:  The results indicate a xenobiotic metabolizing capability of salivary glands. This may have implications for development of oral mucosal disease as a result of mucosal exposure to metabolites originating from internal sources (blood) as well as from saliva.     

Inverted ductal papilloma of minor salivary glands

Inverted ductal papillomas are rare tumours of minor salivary glands. A case is reported on the lower lip of a 50–year-old man. The tumour showed a characteristic endophytic growth pattern and was composed of bulbous papillary projections of basaloid cells dilating and filling the superficial portion of the excretory duct. Histologically, inverted ductal papillomas resemble the inverted papilloma of the nose and paranasal sinuses, but are completely benign and are not associated with malignant change.