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Human kallikrein 13 expression in salivary gland tumors.

The human kallikrein 13 protein (hK13) is expressed in many normal tissues. Petraki et al have previously described presence of hK13 in salivary gland tissue, localized to duct epithelia and some acinar cells. The aim of this study was to determine whether hK13 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas (PA), adenoid cystic carcinomas (ACC), polymorphous low grade adenocarcinomas (PLGA), acinic cell carcinomas (ACI), mucoepidermoid carcinomas (MEC) and adenocarcinomas not otherwise specified (ANOS) of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors show high levels of expression of hK13. Overall, staining in PA was significantly less than that seen in normal salivary gland tissue. PLGA, ACC and ANOS each stained significantly more than normal salivary gland tissue while MEC and ACI did not. Ductal cells and cells lining duct-like structures showed a higher intensity of staining than non-ductal cells in most tumors. Tumors which exhibited only non-ductal cells also exhibited cytoplasmic staining. In conclusion, we demonstrate the high expression of hK13 in several common salivary gland tumors.

Adenocarcinoma↗

Immunohistochemical localization of estradiol, progesterone, and progesterone receptor in human salivary glands and salivary adenoid cystic carcinomas.

Immunohistochemical analyses of estradiol, progesterone and progesterone receptor were carried out in human salivary gland and salivary adenoid cystic carcinoma. Immunoreactivity to estradiol and progesterone was found in cytoplasm of the cells of the excretory duct system within normal salivary glands, whereas the progesterone receptor was restricted to nuclei of the cells where both sex steroids were positive. In addition, we demonstrated the presence of both sex steroids and the receptor for progesterone in salivary adenoid cystic carcinomas. These data indicate that the human salivary gland is one of the target tissues of estrogen. This also suggests the good possibility that tumors which express progesterone receptors will respond to endocrine therapy.

Adult↗

Adenoid cystic carcinoma of the tongue.

Malignant tumours of the salivary glands in children are extremely rare. We present here a 12-year-old girl initially diagnosed as pleomorphic adenoma on fine needle aspiration biopsy, and adenoid cystic carcinoma (ACC) after the lesion was excised and examined by histopathology. A wide resection of the lesion and bilateral supraomyohyoid neck dissection was performed. To our knowledge this is one of the youngest patients with ACC of the minor salivary glands. Due to its benign histological appearance, the biological agressiveness of ACC is usually underestimated. Although fine needle aspiration cytology (FNAC) is very valuable in diagnosis, cytological variations of pleomorphic adenoma must be considered. ACC of the tongue in a young age group should be treated with wide resection and selective neck dissection if the tumour is localized in places where the risk of metastasis is increased and if there is a clinically palpable lymph node. In such cases the clinician should not avoid radical operations even in a young patient.

Adenoma, Pleomorphic↗

Presence of endothelin-1 in human salivary glands and tumors.

To elucidate the presence and distribution of Endothelin-1 (ET-1) in tissues of human salivary glands, we performed an immunohistochemical analysis of ET-1 in 15 normal salivary glands, 8 adenolymphomas, 13 pleomorphic adenomas and 5 carcinomas, using the mouse monoclonal antibody against human ET-1. In normal glands, immunoreactivity for ET-1 was observed in the striated duct cells. In adenolymphomas, the columnar cells of the granular epithelium showed strong intracytoplasmic immunoreactivity. In carcinomas, moderate or strong immunoreactivity was observed in the tumor cells, whereas in pleomorphic adenomas, weak immunoreactivity was observed. A good relation was detected between the size of pleomorphic adenoma and ET-1 immunoreactivity, as well as between the duration of tumor in carcinoma and ET-1 immunoreactivity. The presence and distribution of ET-1 in salivary glands and salivary gland tumors suggests a possible role for ET-1 in the regulation of electrolytes and water transport in salivary glands, and as a growth-promoting factor for tumors.

Adenolymphoma↗

Aspiration cytology of salivary gland tumors: diagnostic experience from six years of routine laboratory work.

Fine-needle aspiration cytology has been used as a routine diagnostic instrument in patients with salivary gland lesions during 1966-1972. A retrospective analysis of the primary cytologic reports correlated with the revised final diagnoses in 461 patients where a pathologic report is available, shows exact agreement in 63 percent, good and not misleading agreement in a further 18 percent, while false reports were initially given in 8 percent, and unsatisfactory specimens were obtained in 11 percent of the patients. On revision of the false reports it is found that with the present experience acquired over several years these can be reduced to under 5 percent. This analysis has also given indications upon which types of specimens are likely to cause diagnostic difficulties.

Adenolymphoma↗

Sequenced scintigraphy: a morphological and functional study of the salivary glands.

The use of scintigraphy in sequenced registration shows that there are three fundamental stages in the intraglandular turnover of the radionuclide: 1. At very early stage (between 3 min. and 15 min.), the major salivary glands could be clearly distinguished; 2. At the stage immediately following (between 20 min. and 35 min.), both the parotid and submaxillary glands were already less well defined; while in the mouth projection zone, quite intense radioactivity, connected with a progressive accumulation of the radionuclide in the minor salivary glands, was seen; 3. Within an hour after injection, maximum captation took place in the minor salivary glands, while both the parotid and the submaxillary glands were hardly distinct. These three stages are strictly related to the three phases of behavior of the radionuclide in each salivary gland; arrival, accumulation, dismissal. Then, each documented variation from the normal pattern will indicate a determined functional anomaly related to defined disease of the salivary glands. The sequenced scintigrraphy offers a functional study of the salivary glands from which it is possible to obtain many elements of practical clinical utility.

Humans↗

Necrotizing sialometaplasia.

Necrotizing sialometaplasia of salivary gland tissue is a benign, self-limiting disease usually confined to the minor salivary glands. To date only 49 cases have been reported. The clinical and histologic appearance may simulate squamous cell carcinoma, and unnecessary mutilating surgery may be performed if an erroneous diagnosis is made. The otolaryngologist must recognize this disease entity since it heals spontaneously and requires no treatment. Necrotizing sialometaplasia has no known premalignant potential.

Adult↗

Tissue effects of salivary gland fine-needle aspiration. Does this procedure preclude accurate histologic diagnosis?

Recent reports have alluded to various tissue effects secondary to fine-needle aspiration (FNA), particularly infarction observed in resected salivary gland masses, precluding accurate histologic diagnosis. Our experience with the use of 25-gauge needles indicates otherwise. We retrospectively reviewed 94 resected salivary gland masses previously sampled by FNA, looking for infarction, hemorrhage, needle track tumor seeding, and fibrosis. We assessed the significance of these complications and their impact on the histologic diagnosis. The median interval from FNA to excision was 25 days. Variable degrees of infarction and hemorrhage were present in 7 cases (7%) and 9 cases (10%), respectively. Infarction ranged from 5% to 80% (average, 20%), while hemorrhage averaged less than 20% of the material on the tissue sections. Significant infarction was present in acinic cell carcinomas (3/7), but histologic diagnosis was not compromised, and tissue alterations were absent. We conclude that FNA of salivary gland lesions using 25-gauge needles is safe and does not significantly alter the histologic diagnosis. The tissue effects observed did not preclude accurate diagnostic interpretation in any case.

Biopsy, Needle↗

Human kallikrein 6 expression in salivary gland tumors.

Human kallikrein 6 (hK6), also known as zyme/protease M/neurosin), is expressed in many normal glandular tissues. The aim of this study was to determine whether hK6 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), using an immunohistochemical method. Pleomorphic adenomas (PA), adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas, and adenocarcinomas not otherwise specified of both minor and major salivary glands were examined. Cells lining duct-like structures and non-duct-like cells were scored. Only in PA of minor salivary gland origin was overall staining higher in duct-like than in non-duct-like cells. In all other tumors exhibiting both types of cells, hK6 staining was similar in both duct-like and non-duct-like cells. Tumors that exhibited non-duct-like cells only also exhibited cytoplasmic staining. Results of this study show that salivary gland tumors express hK6, apparently downregulated in comparison with normal salivary gland tissue, and that this expression is not specific for any of the tumors studied.

Down-Regulation↗

Loss of heterozygosity occurs predominantly, but not exclusively, in the epithelial compartment of pleomorphic adenoma.

Pleomorphic adenoma (PA), being the most common benign tumor of the salivary glands, is composed of epithelial and mesenchymal compartments. In this study, we analyzed 19 microsatellite markers from chromosomal arms 6q, 8q, 9p, 12q, and 17p in 31 PAs and 3 carcinoma ex pleomorphic adenomas (CXPAs) as well as 11 other non-PA-related carcinomas of the salivary gland for comparison. In our analysis, we differentiated between epithelial and mesenchymal tissues. Loss of heterozygosity (LOH) in PAs was most often found in 8q (32%) and 12q (29%). Two of the three CXPAs displayed allelic loss at all chromosomal arms investigated, whereas the results of the non-PA-related carcinomas were rather heterogeneous. LOH could not only be detected in the epithelial, but also in the mesenchymal, compartments of a subset of PAs, especially at chromosomal arm 8q. Concerning the CXPAs, we were able to demonstrate allelic losses not only in the malignant epithelial compartment, but also in the residual adenoma parts. Our data give further evidence that alterations in 8q may be an early event in PA tumorigenesis, whereas LOH in 12q may characterize cells with the potential to transform in CXPAs.

Adenoma, Pleomorphic↗

Immunohistochemical demonstration of alpha 1-antichymotrypsin and alpha 1-antitrypsin in salivary gland pleomorphic adenomas of children.

Twenty-five benign pleomorphic adenomas of salivary glands in children were studied with immunohistochemical techniques in order to characterize the cell types comprising the epithelial and so-called "mesenchymal" regions of the tumors. The antisera against alpha 1-antichymotrypsin (alpha 1-ACT) and alpha 1-antitrypsin (alpha 1-AT) were used to stain in normal salivary gland tissue as well as in pleomorphic adenoma. In normal salivary glands, alpha 1-ACT was localized to the intercalated duct and serous acinar cells. On the other hand, there was positive staining for alpha 1-AT in the intercalated and striated duct cells. Twenty-five cases (100%) of pleomorphic adenomas in children displayed positivity to alpha 1-ACT staining and 22 cases (88%) showed a positive staining for alpha 1-AT. alpha 1-ACT staining was particularly intense in chondrocyte-like cells of 20 cases (80%), in inner tubular cells of 16 (64%) and cyst-lining cells of 12 (52%). The limited number of tumor cells which were called plasmatoid or hyaline cells and squamous epithelial cells, were positive for alpha 1-ACT. None of the outer tubular cells and hyalinous material was positively stained for alpha 1-ACT. A strong positive reaction for alpha 1-AT was observed in chondrocyte-like cells of 15 cases (60%). Inner tubular cells were positive for alpha 1-AT in 12 cases (48%), plasmatoid or hyaline cells in 10 (40%) and cyst-lining cells in 8 (35%). Squamous epithelial cells, clear cells, secretory product and hyalinous material were positive for alpha 1-AT in some cases. Chondroid matrix and myxoid stroma had no reaction with both antibodies. The biological role of alpha 1-ACT and alpha 1-AT with a wide immunohistochemical distribution in pleomorphic adenomas of children may be associated with a self regulating mechanism which inhibits degradation by tissue proteinases.

Adenoma↗

Salivary gland-sparing prophylactic pilocarpine treatment has no effect on tumor regrowth after irradiation.

Radiotherapy of head and neck cancer frequently damages the salivary glands. Prophylactic administration of the muscarinic receptor agonist pilocarpine reduces subsequent radiation damage to the salivary glands in rats, but its effects on tumor cell radiosensitivity and tumor regrowth after irradiation had not been assessed. In the current study, we first tested the effect of pilocarpine on clonogenic cell survival in vitro. No effect of pilocarpine on radiosensitivity was observed in a panel of cell lines either with or without expression of muscarinic receptors. Second, a single dose of pilocarpine known to protect salivary gland tissue from radiation damage was given to rats transplanted with subcutaneously growing rhabdomyosarcomas 1 h prior to irradiation with a single dose of 35 Gy. No alterations in growth delay were detected (26 +/- 2 days for controls compared to 26 +/- 2 days for pilocarpine treatment). Our data indicate that pilocarpine pretreatment, which has been shown previously to protect salivary glands from radiation, does not protect tumor cells or tumors. Use of this drug therefore may lead to therapeutic gain in the treatment of head and neck cancer.

Animals↗

Adenomatoid hyperplasia of mucous salivary glands. Report of two cases.

Adenomatoid hyperplasia of the mucous salivary glands is an uncommon benign tumor of the oral cavity. Two cases of palatal involvement are presented. Since clinical differentiation between benign and malignant growth of the palate cannot be established, microscopic examination is necessary. The palate is the most common location of this lesion, and as such it is useful for the periodontist to be aware of this tumor.

Adult↗

Color Doppler sonography of salivary glands.

OBJECTIVE: We used color Doppler sonography to evaluate the vascular anatomy of the salivary glands and to analyze physiologic changes that occur during salivary stimulation in normal subjects and the flow alterations that occur in diseased glands. SUBJECTS AND METHODS: The vascular appearance of the three major salivary glands was examined in healthy volunteers (n = 24); in patients with chronic autoimmune diseases, including Sjögren's syndrome (n = 23) and salivary sarcoidosis (n = 2); and in a variety of benign (n = 49) and malignant (n = 13) nodules. Physiologic changes were assessed in healthy volunteers by means of a stimulation test with lemon and were quantified with color images and spectral analysis. Tumor vascularity was graded on a four-step analog scale of 0 to (+3) and classified as either peripheral or hilar, depending on the distribution of vessels. RESULTS: In the control subjects, color Doppler imaging accurately reflected the complex vascular anatomy of the salivary glands and showed dramatic changes occurring in parenchymal vessels during lemon stimulation as a result of the intense hyperemia associated with the secretion of saliva. Sjögren's syndrome and sarcoidosis showed a diffuse hypervascular pattern when morphologic changes of salivary parenchyma were seen on gray-scale sonograms. Benign tumors showed a lower grade of vascularity than did malignant tumors. All but one of the hypovascular nodules graded as 0 (n = 8) and + (n = 23) were benign. Conversely, eight of 11 nodules labeled with the highest grade of tumor vascularity (+3) were malignant. When the pattern of tumor flow signals was peripheral, it could be considered specific enough to aid in diagnosing pleomorphic adenoma. Peak systolic velocities greater than 60 cm/sec were never detected in benign tumors and were seen in only 44% of malignant tumors. CONCLUSION: Color Doppler sonography is a promising technique for analyzing the vascularity of the salivary glands and for characterizing some pathologic conditions. Our experience suggests that color Doppler sonography can provide additional diagnostic information in patients with chronic inflammatory diseases or suspected malignant tumors and can help in differentiating pleomorphic adenomas from other salivary gland tumors.

Adult↗