Proliferative activity by cell type in the developing rat parotid gland

Background: In contrast to the considerable amount of research that has been done on the proliferative activity of the several types of parenchymal cells in the developing submandibular glands of rodents, systematic studies of cellular proliferation in the developing parotid gland have been confined to the acinar cells. The purpose of the present study was to attempt to fill this knowledge gap. Methods: Tritiated thymidine was parenterally administered to Sprague-Dawley rats at ages representative of the pre- and postnatal development of the parotid gland, and glands were harvested for autoradiography 90 min after injection. Mitotic activity among all cell types was verified by electron microscopy. Results: At all ages, the % labeled cells was much greater among the acini than any other cell type, including well-differentiated cells at 25 and 40 days. However, there were only small alterations in the proportions of cells comprised by the major cell types. Conclusions: Current theories on the histogenesis of salivary glands and their neoplasms are based on the renewing population model, in which both normal differentiated cells and neoplastic cells arise from undifferentiated stem cells in the ducts. However, these results suggest that most of the migration and redifferentiation in the developing rat parotid gland must be in the opposite direction, i.e., the acinar cells redifferentiate into ductal cells. They also indicate that until there are precise data on the rates of cell death among the several cell types, it remains more appropriate for salivary glands to be categorized as an expanding, rather than renewing, population. © 1995 Wiley-Liss, Inc.     

Sebaceous carcinoma of the parotid gland

Summary Sebaceous carcinoma of salivary gland origin is extremely rare and, because of its rarity, the clinicopathological characteristics and the histogenesis are not fully understood. We present a case of sebaceous carcinoma of the parotid gland which brings the total number of reported cases to 22.The tumor showed epithelial cell nests which were mainly composed of sebaceous cells with marked cellular atypia. In most of the nests, glandular spaces lined by ductal epithelium were present. Scattered mucous cells and flattened eosinophilic cells at the periphery of the nests were also seen. Ultrastructural and immunohistochemical observations of the tumour revealed coexistence of sebaceous and glandular differentiations in some tumour cells. Tumour cells with lipid granules often participated in the formation of glandular structures or exhibited intracytoplasmic lumina, and immunohistochemical localization of lactoferrin and secretory component, the functional markers of ductal epithelium of salivary gland, was demonstrated not only in duct-forming tumour cells but also in many sebaceous tumour cells.It seems likely that sebaceous carcinoma originates from pluripotential duct cells which can differentiate into sebaceous, ductal and mucous cells.     

Perineurioma of the parotid gland: first case report

SUMMARY: Neurogenic neoplasms account for approximately 1% of salivary gland tumors. A 45-year-old woman presented with a slowly growing unilateral parotid gland mass that was excised completely by lateral parotidectomy. No recurrence was detectable 6 months after surgery. The resection specimen contained a 1.7 × 1.2 × 1-cm whitish nodular lesion that was firm, well circumscribed, and completely surrounded by compressed normal glandular tissue. The tumor was composed of spindle cells with bipolar tapering, wavy nuclei, and palely stained cytoplasm. The tumor cells were arranged in storiform, lamellar, and whorled patterns. Nuclear atypia, necrosis, and significant mitotic activity were absent. Immunohistochemistry showed expression of epithelial membrane antigen, glucose transporter 1, claudin-1, and collagen IV. All other lineage-specific markers including protein S100 were negative in the tumor cells. To our knowledge, this case represents the first report of soft tissue perineurioma in the salivary gland. Lack of previous reports suggests underrecognition of this tumor entity at this unusual anatomical site.     

Changes in the number and distribution of myoepithelial cells in the rat parotid gland during postnatal development

The mature rat parotid gland shows hardly any cell bodies of myoepithelial cells around the acini, only a few cell processes being visible. However, in the early postnatal period, the rat parotid gland shows many myoepithelial cell bodies around the acini, including the intercalated ducts. In order to clarify the reason for the disappearance of myoepithelial cells from the area around the acinus during postnatal development, changes in the number and distribution of myoepithelial cells in the rat parotid gland were examined histochemically and chronologically, with particular reference to cell proliferation and cell death. From day 7 to day 14, many myoepithelial cells showing a positive reaction with anti-actin antiserum were found around the acini and intercalated ducts, but thereafter the number of such cells decreased gradually, particularly around the acini, and had almost disappeared after day 35. BrdU/PCNA-positive myoepithelial cells surrounding the acini were easily detected on day 14, but disappeared by day 21, whereas BrdU/PCNA-positive acinar cells remained numerous even after day 21. TUNEL/ISEL staining showed no positive myoepithelial cells throughout the observation period. Transmission electron microscopy also demonstrated no myoepithelial cells with chromatin condensation characteristic of apoptosis through the observation period. These findings suggest that the main reason for the disappearance of myoepithelial cells from the area around the acinus during postnatal development is the large difference between the number of myoepithelial cells and that of acinar cells, because the acinar cells retain their proliferative activity even after myoepithelial cells have become quiescent.     

Effects of continuous light on rat parotid gland structure and reactivity

Summary The effects of continuous light on ultrastructural organization and sympathetic secretory responses of the rat parotid gland are reported.After 50 days of continuous light exposure, the fine structure of the parotid gland exhibited features of enhanced secretory activity as judged by the striking development of rough endoplasmic reticulum and Golgi complexes, the depletion of secretory granules and the increased turnover of secretory cells. The secretory responses of parotid gland to isoproterenol revealed that continuous light induced a 30% increase in amylase release. This secretory hyperactivity appears to be related to a postsynaptic supersensitivity of sympathetic fibers of the autonomic nervous system.     

Oncocytic lipoadenoma of the parotid gland with sebaceous differentiation. Study of its keratin profile

Oncocytic lipoadenomas of salivary gland are extremely rare tumors with only two previously reported cases. In this paper, we describe an additional example of oncocytic lipoadenoma showing sebaceous differentiation, a hitherto unreported occurrence. The tumor was encapsulated and measured 3 × 2.5 × 2 cm. Microscopically, the tumor comprised a mixture of oncocytes with “light” and “dark” cells intimately associated with mature adipose tissue. The oncocytes were positive for low molecular keratin, epithelial membrane antigen (EMA), and keratin 7, with only a small subgroup of cells expressing high-molecular-weight keratin, keratin 5/6, keratin 19, and p63. Terminally differentiated sebaceous cells were positive for EMA and keratin 14 only. Calponin and actins were negative, indicating a lack of myoepithelial cells in the tumor. The keratin profile and p63 expression of this oncocytic lipoadenoma suggest the presence of a dual cell population somewhat similar to the dual cell population described in some ultrastructural studies of pure salivary gland oncocytomas and may represent partial basal-cell differentiation. The presence and nature of a dual cell population in oncocytic neoplasms of salivary glands merit further investigation to confirm these observations.     

Crystalloids in salivary duct cysts of the human parotid gland

Summary Crystalloids found in salivary duct cysts of the human parotid gland were examined by scanning electron microscopical observations with electron probe X-ray microanalysis. The cystic spaces were filled with numerous crystalloids which had a variety of forms with slight eosinophilic and glassy appearance. Scanning electron microscopically, crystalloids were hexagonal and rhombohedral in shape, and cutting the surface showed a polycyclic structure or regular parallel lamination. By electron probe X-ray microanalysis, sulphur was the only detected element. The present study suggests that crystalloids resulted from deposition from supersaturated saliva containing sulphur containing compounds into the cystic lumen or into epithelial cytoplasm.     

Calcium redistribution,calcification and stone formation in the parotid gland during experimental stimulation and hypercalcaemia

Summary Distribution and redistribution of intra- and pericellular calcium was investigated in the parotid gland of rats under secretory stimulation and hypercalcaemia. The effects of hypercalcaemia and secretory stimulation and of the combination of both were compared. Calcium content was determined by atomic absorption spectrometry. Calcium distribution within the tissue was demonstrated by light microscopical (GBHA) staining and electron microscopical (pyroantimonate method) cytochemistry in combination with X-ray microanalysis. Typical calcium depot sites were the basal and cellular membranes, the calcium buffer organelles (i.e. mitochondria) the secretory granules and the acinar lumina. After stimulation (by isoprenalin) a decrease of calcium-enriched secretory granules and a depletion of intracellular calcium buffer organelles occurred. During hypercalcaemia (induced by dihydrotachysterol), a calcium overloading of the cell membrane and intracellular buffer organelles without calcification was observed. Combined stimulation and hypercalcaemia induced an excessive calcium overloading of all intra-and extracellular calcium depots with excessive calcium release into the acinar lumina resulting in calcium phosphate aggregates and stone formation. Secretory stimulation and simultaneous hypercalcaemia exert potentiating effects on intracellular and intraluminal calcification proposing an importance for pathogenesis of human sialolithiasis.Supported by Sonderforschungsbereich 34 Endokrinologie     

An ultrastructural study of oncocytoma and oncocytic carcinoma of the parotid gland

One case of oncocytoma and another of oncocytic carcinoma of the parotid gland are reported with ultrastructural studies. The incidence of oncocytoma varies from 0.1% to 1.4% of all parotid gland tumors, while oncocytic carcinoma is extremely rate. The oncocytoma was composed of polyhedral cells with fine eosinophilic granular cytoplasm and a rounded nucleus. The tumor cell clusters were surrounded by basement membrane. The tumor cells of the oncocytic carcinoma were also characterized by eosinophilic cytoplasm, but cellular atypia and mitotic figures were found. Electron microscopically, the cytoplasm of the oncocytoma was packed with abundant mitochondria. They were oval or elongated in shape with stacked cristae. Although the tumor cells of the oncocytic carcinoma also contained many mitochondria, their number was less than that of the benign case, and stacked cristae were very few. Basement membrane was not seen. The ultrastructural characteristics of oncocytoma and oncocytic carcinoma of the parotid gland are discussed with reference to previous reports.     

Menkes protein localization in rat parotid acinar cells

The aim was to study the subcellular localization of the Menkes protein (MNK; ATP7A) in the rat parotid acinar cell. MNK protein is a copper transporting P-type ATPase whose absence or dysfunction causes a fatal neurodegenerative disorder, MNK disease. Rat parotid glands were fixed and low-temperature embedded in Lowicryl K4M resin, and ultrathin sections were prepared for immunocytochemical analysis. Immunolocalization of MNK was demonstrated mainly over the trans Golgi network (TGN) area. Immature and mature secretory granules were also labelled, indicating that MNK protein could be involved here in copper secretion from acinar cells into saliva, consistent with a proposed cariostatic role for copper.     

Intermediate-sized filament proteins (prekeratin,vimentin, desmin) in the normal parotid gland and parotid gland tumours

Summary Antibodies to different intermediate-sized filament proteins can distinguish cells and tissues of epithelial, mesenchymal, muscle, astrocytic and neural origin. Antibodies to prekeratin, vimentin and desmin have been used to distinguish cells of epithelial, mesenchymal and muscle origin in the normal human parotid gland, and in addition to study some common tumors of this gland. Prekeratin-positive and vimentin-positive cells are found among the tumor cells in the pleomorphic adenomas. In contrast the tumor cells of the mucoepidermoid tumors and squamous cell carcinomas are prekeratin-positive but vimentin-negative.Supported by the Deutsche Forschungsgemeinschaft (Ca 93/1-1) and by the Hamburger Stiftung zur Förderung der Krebsbekämpfung     

Lactoferrin and lysozyme in carcinomas of the parotid gland

Summary Lactoferriin and lysozyme, parts of the non-specific defense system, were studied in normal and diseased parotid glands, using the immunohistochemical PAP-method. 31 normal and inflamed glands were investigated. The presence of lactoferrin and lysozyme was demonstrated in the acinar cells and some duct cells. The amount of these substances was increased in obstructive parotitis. The 52 carcinomas showed a distinct distribution pattern for lactoferrin (positive cases: adenocarcinomas 5 of 8; cystadenocarcinomas: 3 of 5; adenoid cystic carcinomas 2 of 4; salivary duct carcinomas 2 of 3). Some of the carcinomas in pleomorphic adenomas were positive for lactoferrin. Squamous cell carcinomas and anaplastic carcinomas were constantly negative.All carcinomas were negative for lysozyme. These observations are discussed with respect to their physiological and pathological significance.Supported by the Deutsche Forschungsgemeinschaft and by the Hamburger Stiftung zur Förderung der KrebsbekämpfungDedicated to Prof. Dr. F.H. Caselitz (Bakteriologische Abteilung des Allgemeinen Krankenhauses Altona) on occasion of his 60th birthday     

Sclerosing rhabdomyosarcoma of the parotid gland in an adult

Primary rhabdomyosarcoma of salivary glands is an extremely rare neoplasm, mostly seen in children. A newly described subtype of rhabdomyosarcoma, sclerosing rhabdomyosarcoma, has not yet been reported in this location. We report on a parotid gland tumor characterized by infiltrative growth of primitive type of neoplastic cells showing strong and diffuse nuclear positivity for MyoD1 and myogenin and by prominent hyalinized/chondroid matrix with some myxoid foci. The tumor recurred several times, and in recurrent tumors, differentiation into strap myoid cells appeared. There were no distant metastases during the 5-year follow-up.Sclerosing rhabdomyosarcoma may cause differential diagnostic problems because it could be confounded for osteosarcoma, chondrosarcoma, and some other types of sarcoma, and as in our case, for myxofibrosarcoma and myoepithelial carcinoma. Its location in the head and neck is of special interest because 6 of 14 previously described adult cases of sclerosing rhabdomyosarcoma and 7 of 18 pediatric cases also occurred in this region. To our knowledge, this is the first reported case of primary sclerosing rhabdomyosarcoma of the parotid gland.     

Myoepithelial cell ultrastructure in the submandibular gland of man

Summary In human submandibular glands, two types of myoepithelial cells can be distinguished in serial, ultrathin sections. The dark myoepithelial cell type was stellate in shape and exhibited a pronouneced electron density due to numerous myofilaments with focal densities. Dark cell types accounted for the greater part (76%) of the myoepithelial cells and furthermore showed adenosine triphosphatase activity. This type of myoepithelial cell is considered to be that previously observed in mammalian salivary glands. Occasionally, desmosomes could be found between the processes of adjacent dark myoepithelial cell types, which is appropriate with respect to the strong compression of acinar or intercalated duct cells. The light myoepithelial cell type was large and ellipsoid with a few short-thick processes, and was characterized by an electron lucent cytoplasm which included scant and unevenly distributed myofilaments. Light cell types showed positive adenosine triphosphatase activity and accounted for only a small part (17%) of the myoepithelial cell number. Transitional forms between these two types were also observed. The light myoepithelial cell type may mature into the dark myoepithelial cell type by means of the transitional form. In addition, clear cells were sometimes encountered between the myoepithelial cell and the acinar or intercalated duct cells.     

Intercalated duct cells in the rat parotid gland may behave as tissue stem cells

This study was conducted to determine whether intercalated duct cells in the rat parotid gland have the properties of tissue stem cells. After induction of cellular proliferation by repeated administration of isoproterenol (IPR), a β-adrenergic agonist, proliferation activity in acinar, intralobular, and intercalated ductal cells was quantified using Ki-67 immunohistochemistry. The total number of each type of component cell in a gland was also estimated in the course of IPR treatment. IPR was found to induce proliferation of acinar and intercalated duct cells, but not intralobular duct cells. The total number of acinar cells in a gland on day 5 of IPR treatment was 1.6 times of that at day 0 (baseline). In contrast, the total numbers of intercalated and intralobular duct cells did not change from baseline, indicating a high possibility that the proliferated intercalated duct cells differentiated into acinar cells. On days 2 to 3 of IPR treatment, intercalated duct cells with amylase-positive secretory granules were recognized in a region very close to the acini, and were suspected of being transitional cells from intercalated duct to acinar cells. This quantitative study indicates that intercalated duct cells may have the properties of tissue stem cells upon IPR stimulation.     

Ultrastructural observations on luminal structures of pleomorphic adenoma of parotid and submandibular salivary glands of man

Summary Luminal structures found in salivary pleomorphic adenomas consisted of lumina surrounded by epithelial cells that varied from being packed together to being widely separated except at the luminal margin. Communication between lumina and the surrounding stroma was occasionally seen. Secretory material and cellular debris were seen in lumina, invaginations of the luminal surfaces of periluminal cells, associated vesicles, and vacuoles. Secretory granules, lysosomes and lipofuscin were seen in periluminal cells. Secretory material and debris from necrotic periluminal cells appear to accumulate in lumina, and to be endocytosed and degraded lysosomally by periluminal cells. The finding of communications between lumina and the surrounding stroma suggests that the stromalization of the epithelium includes the luminal structures. The present investigation supports the hypothesis that many of the cellular features of the pleomorphic adenoma relate to the microenvironment.     

Origin and characterization of atrial natriuretic peptide in the rat parotid gland

Summary The heart atria represent the major site of synthesis for atrial natriuretic peptide (ANP) which exerts potent natriuretic, diuretic and vasoactive functions. Recently, ANP-immunoreactivity has been detected in extracardial organs involved in water and electrolyte homeostasis, such as the intestine and certain exocrine glands. The present study investigates ANP in the parotid gland. It was found by immunohistochemical techniques that the peptide is localized in ductal cells of the gland. An analysis of the immunoreactive material by high-pressure liquid chromatography and radioimmunoassay revealed the prohormone of ANP (ANP 1-126) and the biologically active fragment (ANP 99-126). Furthermore, Northern blot hybridization disclosed the presence of mRNA coding for ANP. It is suggested that ANP is synthesized and released from the parotid gland and functions in the control of saliva production.     

Recepto-secretory mechanism in histamine-stimulated amylase release from rat parotid gland

The recepto-secretory mechanism in histamine-stimulated amylase release from rat parotid slices was studied using blockers of receptors and inhibitors of the intracellular messenger systems. Amylase release stimulated by histamine was inhibited by pyrilamine, an H₁-receptor blocker, but not by cimetidine, an H₂-receptor blocker. Atropine, prazosin and yohimbine had no effect on the release. Histamine-stimulated amylase release was inhibited by W-7, ML-9 and H-7, inhibitors of a calmodulin, a myosin light chain kinase (MLCK) and protein kinase C, respectively, while H-8, an inhibitor of protein kinase A, did not inhibit the release. These results suggest that histamine stimulation evokes amylase release via H₁-receptors, followed by the Ca²⁺-dependent systems involving calmodulin, MLCK and protein kinase C.     

Hamartoma of the parotid gland: A case report with immunohistochemical and electron microscopic study

Summary A case of a solid parotid tumour in a 16-year-old boy is presented. Histologically, the tumour demonstrated some peculiar findings. An acinar pattern was predominant although every component seen in the normal salivary gland was present, namely, serous and mucous gland acini, ducts, myoepithelial cells, adipose and lymphoid tissue. Large eosinophilic granules were abundant in the large acinar cell cytoplasm. Immunohistochemically, the tumour demonstrated the proteins which are present in the normal parotid gland, for example, amylase, lactoferrin and lysozyme. Electron microscopic features were quite similar to those of normal parotid tissue except for accumulation of a large number of cytoplasmic granules in the acinar cells. There has been no previous report of a tumour with the same features as seen in this case. Our pathological diagnosis is hamartoma, although the possibility of hyperplasia or neoplasia can not be excluded.     

Oncocytic lipoadenoma of the parotid gland: Immunohistochemical and cytogenetic analysis

Salivary gland oncocytic lipoadenoma is an exceptional benign tumor composed of mature adipose tissue associated with a mixture of oncocytes. We report a case of oncocytic lipoadenoma showing sebaceous differentiation, and provide a cytogenetic analysis, which has not yet been described. A 64-year-old male developed a left parotid gland, well-encapsulated tumor measuring 3.5×3 cm², showing mature fat cells associated with oncocytic changes of epithelial components. Immunohistochemistry showed a dual epithelial population with ductal (positivity for AE1/AE3, CK19, CK7 antibodies) and basal-cell (positivity for p63, CK14, CK5,6 antibodies) differentiation in oncocytic areas. Moreover, oncocytic cells were stained with anti-alpha-1 antichymotrypsin antibody and phosphotungstic acid–hematoxylin staining. Molecular cytogenetic analysis showed a translocation t(12;14), resulting in structural rearrangement of the region framing the HMGA2 gene at 12q14.3. Such alterations in HMGA2 have been described in both lipomas and pleomorphic adenomas of the salivary glands.