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.     

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.     

Chronology of peroxidase activity in the developing rat parotid gland

The course of development of salivary peroxidase, an enzyme that has an important role in oral defense mechanisms, has been well documented in rat submandibular glands. However, the only report on salivary peroxidase activity in the other major salivary glands of the rat has been a cytochemical study of the adult parotid gland. In the present investigation, the accumulation of salivary peroxidase activity in developing parotid glands of rats was followed both biochemically and cytochemically. Specific activity (units per mg protein) attributable to salivary peroxidase began at 1 day after birth, then rose rapidly but unevenly, with peaks at 21 and 70 days, and no difference between the sexes at any age. Activity per gland increased progressively to 42 days in both sexes and was significantly higher in males at 70 days. The cytochemical observations on peroxidase activity localized to the rough endoplasmic reticulum and secretory granules of the developing acini were well correlated with the biochemical findings. Peroxidase-negative cells occurred in immature acini at 1 and 7 days, but only in the intercalated ducts thereafter. This observation suggests that the acini are a source of some of the ductal cells, at least during early postnatal development. The developmental pattern of specific activity differed from those of other rat parotid secretory enzymes, indicating that control of their synthesis during development is noncoordinate. The patterns of specific activity of the parotid and submandibular glands were complementary, suggesting that their combined secretions may supply biologically significant peroxidase activity to the oral cavities of rats throughout postnatal development. © 1993 Wiley-Liss, Inc.     

Characteristics of stimulated parotid gland secretion in the aging rat

The production of pilocarpine-stimulated parotid saliva was evaluated in young adult and aged male and female rats. Parotid salivary flow rate was about 50% lower in aged animals of both sexes. Saliva of aged animals had the same Na+ concentration as that of young rats but contained about 40% more protein. Salivary K+ concentration was similar in young and aged males but not females.     

Immunoelectron microscopy of amylase in the human parotid gland

Summary Specimens of the human parotid gland were studied by immuno-electron microscopy for the presence of amylase. Both the protein A-gold technique and the biotin-avidin-gold technique were used on the same specimens. Different fixations were tried. Amylase was detected in the zymogen granules in high amounts. This enzyme could even be seen in glutaraldehyde fixed and routinely embedded material. The subcellular localization of this enzyme opens a new field of functional morphological studies and studies in special tumours including acinic cell carcinomas.Supported by the Deutsche Forschungsgemeinschaft and by the Hamburger Stiftung zur Förderung der KrebsbekämpfungDedicated to Prof Dr. med. Dres. h.c. Wilhelm Doerr, Heidelberg, in honour of his 70th birthday     

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.     

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.     

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.     

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.     

Non-specific secretory supersensitivity in rat parotid gland following neonatal sympathetic denervation

Newborn rats were surgically sympathectomized by extirpation of the left superior cervical ganglion. After 9 weeks the parotid glands of both sides were used for secretory studies. Isoprenaline, dopamine, and the dibutyryl analogue of cAMP (DBcAMP) caused an increase in amylase release, which was significantly higher in the denervated glands. Also carbamylcholine was more effective in the denervated gland; the concentration-response curve was shifted to the left, and the maximal output of amylase was increased. Neonatal sympathetic denervation induces supersensitivity for both adrenergic and cholinergic agonists as well as for DBcAMP. This may be due to compensatory mechanisms involving both up-regulation of receptors as well as amplification of the intracellular mediation.     

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     

Cell deletion by apoptosis during regression of rat parotid sialadenosis

Enlargement of the rat parotid salivary glands was induced by repeated administration of isoproterenol. Mean wet weights of the treated glands increased steadily to 240% of control values. Following withdrawal of the drug, quantitative histological techniques were used to investigate the balance between hypertrophy, hyperplasia and apoptosis. The volume occupied by acinar cells relative to the total gland volume together with cytoplasmic|:|nuclear area ratios as measures of hypertrophy increased during the early experimental period. Similarly, serous acinar cell mitotic counts increased, indicating that hyperplasia had occurred. Apoptosis was demonstrated at light microscopical level to be the main mechanism for cell deletion as the glands returned to normal size and weight. The results indicate that hypertrophy and hyperplasia of serous acinar cells contribute to isoproterenol-induced sialadenosis. The experimental animal model demonstrates that these proliferative changes are completed by 48 h and thereafter are balanced by apoptosis as the glands recover their normal size and weight.     

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.     

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.     

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.     

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     

Encepalomyocarditis virus-induced apoptosis and ultrastructural changes in the lacrimal and parotid glands of mice

Development of acinar cell apoptosis and ultrastructural changes in the exorbital lacrimal and parotid glands was examined in DBA/2 mice infected with 10(2) PFU/mouse of EMC-D virus. Pyknotic acinar cells, most of which were positive for TUNEL and cleaved caspase-3 and had ultrastructural characteristics of apoptotic cells, developed earlier and were more frequently observed in the parotid gland than in the exorbital lacrimal gland, while the total damage of acinar cells and interstitial infiltration of macrophages were more prominent in the latter than in the former. These findings indicate that EMC-D virus induces acinar cell apoptosis in these glands. In addition, corresponding to the results of the detection of viral RNA signals by in situ hybridization, small aggregates of virus-like particles having typical size and structure of EMC virus were frequently observed in both the cytoplasm and the nucleus of acinar cells in the exorbital lacrimal gland, while they were found only in the cytoplasm of a few acinar cells in the parotid gland. In conclusion, between the exorbital lacrimal and parotid glands, there was a reverse relationship observed between the development of acinar cell apoptosis and that of total damage of acinar cells.     

The embryonal carcinoma of the parotid gland

Summary Embryonal tumors are a neoplastic proliferation of cells of organ rudiments. Morphologically, these tumors are similar to the developmental stages of these organ rudiments. Embryonal tumors of the salivary glands have not been previously described. In the salivary gland register, reviewing the years 1965–1982 (n=8043), we diagnosed 2,878 tumors of the salivary glands, of these 73 were tumors in children. One case was a malignant epithelial tumor in a 12-year-old boy, which showed the criteria of an embryonal carcinoma in light- and electron microscopy. The tumor revealed solid undifferentiated areas, epidermoid structures with keratinization and acinic structures. Immunhistochemically, the better differentiated epidermoid cells reacted positively with anti-CEA and anti-keratin, the acinic cells were positive with anti-amylase. The ultrastructure was characterized by primitive ductular epithelial cells and acinic cells with their typical morphological features. The embryonal carcinoma has to be distinguished from undifferentiated carcinomas of the salivary glands, which consist of primitive ductular structures only. The failure to detect other tumor markers (lactoferrin, tissue polypeptide antigen) indicates that poorly and well differentiated areas can exist simultaneously in embryonal carcinomas.Dedicated to Prof. Dr. W. Doerr, Heidelberg on the occasion of his 70th birthday.Supported by Hamburger Stiftung zur Förderung der Krebsbekämpfung