Pleomorphic Adenoma Cells Research Articles

Squamous cell carcinoma arising in a dentigerous cyst

Odontogenic cysts can give rise to a variety of neoplasms, including the odontogenic adenomatoid tumor, pleomorphic adenoma, mucoepidermoid carcinoma, and squamous cell carcinoma, as well as serve as a precursor of an ameloblastoma.1 Carcinoma arising in a dentigerous cyst is extremely rare,2-4 with a review of literature showing fewer than 20 cases.2-16 This report describes a case of squamous cell carcinoma arising in a dentigerous cyst that was initially diagnosed as a dentigerous cyst and discusses its clinical course, the diagnostic problems, and therapeutic regimen.

Keratin 14 immunoreactive cells in pleomorphic adenomas and adenoid cystic carcinomas of salivary glands.

Our recent study of developing myoepithelial cells (MECs) in rat salivary glands demonstrated that developing MECs begin to express alpha-smooth muscle actin (alphaSMA) first and, thereafter, keratin 14. Therefore, it is unlikely that duct basal cells expressing keratin 14 alone are immature or undifferentiated MECs. In this study we carried out immunohistochemistry of pleomorphic adenomas and adenoid cystic carcinomas including normal salivary glands using monoclonal antibodies to keratin 14, smooth muscle proteins and keratin 19. The smooth muscle proteins examined included alphaSMA, h-caldesmon and h1-calponin; h1-calponin was observed in keratinocytes and nerve fibers, indicating that the protein is not specific to smooth muscle, whereas alphaSMA and h-caldesmon turned out to be highly specific markers for smooth muscle cells in normal tissues. In normal glands, MECs were positive for both keratin 14 and smooth muscle proteins (alphaSMA and h-caldesmon). Non-MEC cells were essentially devoid of smooth muscle proteins. Non-MEC duct basal cells expressed keratin 14 with or without keratin 19, and luminal cells keratin 19 with or without keratin 14. This suggests that the keratin 14-positive, smooth muscle proteins-negative duct basal cells are luminal cell progenitors. Luminal cells in tubular structures of both tumors were positive for keratin 19 with or without keratin 14. Nonluminal peripheral cells of pleomorphic adenomas were mostly positive for keratin 14, and a small fraction of them expressed smooth muscle proteins. Conversely, peripheral cells of adenoid cystic carcinomas were mostly positive for smooth muscle proteins, and some of them expressed keratin 14. These results strongly suggest (1) that the luminal cell progenitors transform into major constituents of pleomorphic adenoma cells with keratin 14 but not smooth muscle proteins, and (2) that the peripheral cells of adenoid cystic carcinoma are derived from undifferentiated MECs. Solid structures of pleomorphic adenomas were formed by proliferation of the peripheral cells. MECs were observed only occasionally in the periphery. Solid and cribriform structures of adenoid cystic carcinomas were formed by proliferation of the luminal cells. MECs were observed in the periphery and around the pseudocyst.

Molecular evidence that the stromal andepithelial cells in pleomorphic adenomas of salivary gland arise from the same origin: clonal analysis using Human Androgen Receptor Gene (HUMARA) Assay

Salivary gland pleomorphic adenomas are characterized by abiphasic growth of “epithelial” and “stromal” regions. The “epithelial” region is a compactly organized mixture of both luminal and nonluminal cells, whereas the stromal region is composed predominantly of the nonluminal cells. Using the polymerase chain reaction (PCR)-based HUMARA assay on DNA from formalin-fixed, paraffin embedded tissues from pleomorphic adnomas of female patients, we intend to clarify the clonal relation between the luminal and nonluminal cells and the clonal nature of the morphologically diverse nonluminal cells in this tumor. HUMARA, the human androgen receptor gene, is located on the X chromosome and contains a segment of polymorphic CAG tandem repeats in exon 1. Several methylationsensitive HhaI restriction sites are located 5' to these CAG repeats. It is an ideal tool to study clonality of female tissues by examining the methylation pattern. Of the 13 cases analyzed, 3 were homozygous at the HUMARA locus and therefore noninformative. The remaining 10 cases were informative. All 10 cases showed a monoclonal pattern in the stromal area, indicating that the morphologically diverse nonluminal cells are monoclonal. Eight of the 10 cases showed monoclonality in the “epithelial” areas, suggesting a common clonality between luminal and nonluminal cells. Of the remaining 2 samples, 1 was polyclonal for the “epithelial” region, and the other was not amplifiable. Our data provide the first molecular evidence that the luminal and nonluminal cells in pleomorphic adenomas arise from the same clone in most cases, and the morphologically diverse nonluminal cells are monoclonal. Preliminary results of this work have been presented in theAnnual Meeting of the Association for Molecular Pathology, Crystal City, VA, November 1998.

An immunohistochemical study of bizarre neoplastic cells in pleomorphic adenoma: its cytological nature and proliferative activity.

The cytological nature and proliferative activity of bizarre neoplastic cells, widely scattered in pleomorphic adenomas of salivary gland origin were studied. Pleomorphic adenomas containing numerous bizarre neoplastic cells were found in four cases, and were equal to 2.9% of all pleomorphic adenomas examined. All four cases presented as well-circumscribed, firm masses measuring less than 1.5 cm in size, located in the palate, and were of 7 months to 4 years duration. Histopathologically, these pleomorphic adenomas were cell rich type, and were well demarcated from surrounding tissues, although their fibrous capsules were partially defective. In addition to characteristic histopathological findings of pleomorphic adenoma, numerous neoplastic cells with bizarre appearance were scattered throughout the lesion, excepting for tubuloductal structures. These bizarre neoplastic cells had irregular-shaped and large nuclei with or without hyperchromatism, although their nucleoli were small and mitotic figures were few. Furthermore, there were many multinucleated giant cells, some of which showed multilobulated nuclei. Neither necrosis nor infarct was seen in the tumors. Immunohistochemically, bizarre neoplastic cells scattered in solid-proliferating areas and myxoid areas were neoplastic myoepithelial cells in nature. There was no statistical significance of MIB-1 labeling indices between pleomorphic adenomas with bizarre neoplastic cells and usual pleomorphic adenomas. The p53 labeling indices were quite low. Although the benign nature of pleomorphic adenomas with numerous bizarre neoplastic cells and hypercellularity, distinguishing such pleomorphic adenomas from various stages of malignant transformation in pleomorphic adenomas and other carcinomas should be made by histological section of submitted biopsy specimen or aspirated content for cytological diagnosis. The present paper suggests that the term 'bizarre cell pleomorphic adenoma' is an appropriate name for this neoplasm, in that it is distinguished from the usual benign pleomorphic adenoma which is easily diagnosed by routinely prepared histological or cytological stainings.

Effect of calcium and vitamin D on pleomorphic adenoma cells in vitro

Effect of calcium and vitamin D on pleomorphic adenoma cells in vitro

Oncocytic myoepithelioma and pleomorphic adenoma of the salivary glands.

Twenty oncocytic myoepitheliomas (MEs) and pleomorphic adenomas (PAs) were composed of interlacing fascicles of swollen spindle-shaped or/and epithelioid oncocytic myoepithelial cells showing intense finely granular immunoreactivity with anti-mitochondrial antibody. Focal vacuolation of the cytoplasm of oncocytic myoepithelial cells and their gradual transition into sebaceous metaplasia were observed in 3 cases. Another unusual feature found in 5 cases was the presence of slit-like adenomatoid spaces lined with double-layered oncocytic myoepithelium closely resembling Warthin's tumour. The nuclei of oncocytic cells were characterized by enlargement, hyperchromasia and polymorphism, which should not be confused with malignancy. Oncocytic change in myoepithelial cells in MEs and PAs can cause pitfalls in the differential diagnosis of salivary gland tumours. We describe some unusual histological features associated with onococytic metaplasia in benign myoepithelial cell-derived salivary gland tumours, hoping to help to avoid the overdiagnosis of malignancy.

Reconstruction of pleomorphic adenoma of the salivary glands in three-dimensional collagen gel matrix culture.

The morphogenesis of salivary gland pleomorphic adenoma was examined in vitro using three-dimensional (3-D) collagen gel culture. Pleomorphic adenoma cells were isolated from three parotid gland tumours and cultured as monolayers, after which they were subcultured in floating-collagen gel sandwiches. Cells cultured in both conditions were immunohistochemically characterized and compared using antibodies against various proteins representative of each histological component of salivary glands. Monolayers had myoepithelial characteristics, being positive for vimentin and alpha-smooth muscle actin. In collagen gels, however, the cells assembled in epithelial nests, showing an architecture similar to that of pleomorphic adenoma. The nests were composed of duct-lining epithelial cells that were positive for epithelial markers, surrounded by myoepithelial cells. Collagen gel culture induces multidirectional differentiation of adenoma cells, suggesting that pleomorphic adenomas originate from stem or reserve cells.

Malignant Plasmacytoid Myoepithelioma of the Palate: Histological Observations Compared to Benign Predominant Plasmacytoid Myoepithelial Cells in Pleomorphic Adenoma of the Palate

Predominant benign plasmacytoid myoepithelial cells in pleomorphic adenoma and malignant plasmacytoid myoepithelioma cells were investigated morphologically. The cells of both tumors were plasmacytoid in appearance and sheet-like. Immunohistochemically, they were positive for keratin, vimen-tin, and S-100 protein, and negative for a-smooth muscle ac-tin. In the malignant cells, large nuclei with irregular nuclear membranes and distinct nucleoi and occasional intranuclear inclusions and nuclear grooves were seen. Ultrastructural findings showed that the benign cells were richer in intermediate filaments and had fewer mitochondria. The intranuclear inclusions and nuclear grooves of the malignant cells were caused by invagination of the irregular nuclear membranes. Taken in their entirety, the above light microscopical nuclear findings may be useful as an adjunct for distinguishing malignant from benign plasmacytoid neoplastic myoepithelial cells of the salivary gland.

Expression of pancreatic digestive enzymes in normal and pathologic epithelial cells of the human gastrointestinal system.

Pancreatic digestive enzymes have rarely been reported in human nonpancreatic organs. We examined their expression in the epithelial cells of the nonpancreatic gastrointestinal organs, looking for pancreatic alpha-amylase, trypsin, chymotrypsin and pancreatic lipase. Western blotting, enzyme assay and pancreatic alpha-amylase mRNA were also used in selected specimens. In normal tissues, immunoreactivity of one or more of these enzymes was frequently noted in cells of the salivary glands, stomach, duodenum, large pancreatic ducts, extrahepatic bile ducts and gall bladder. The epithelium of the normal oesophagus, small intestine and colon were consistently negative for these enzymes. In pathologic tissues, immunoreactivity for one or more enzymes was present in epithelial cells of pleomorphic adenomas of the salivary glands, oesophageal squamous cell carcinoma, gastric adenoma and adenocarcinoma, pancreatic adenocarcinoma, cholecystitis, adenocarcinoma of the gall bladder and extrahepatic bile duct, and colon adenoma and adenocarcinoma. Western blotting showed a specific band of each enzyme in some specimens of normal stomach. In situ hybridization for pancreatic alpha-amylase mRNA showed specific signals in the normal stomach, but not in the normal colon. Reverse transcriptase polymerase chain reaction analysis for pancreatic alpha-amylase mRNA revealed specific signals in the normal stomach. Enzyme assay revealed that the stomach and gall bladder showed these activities. The data suggest that pancreatic digestive enzymes are produced by several epithelial cell types of the nonpancreatic gastrointestinal organs, that the organs positive for pancreatic enzyme have a common cell lineage, and that neoplasms continue to express or neoexpress these enzymes after neoplastic transformation.

RGD Peptides Inhibit the Adhesion of a Recurrent Pleomorphic Adenoma Cell Line to a Variety of Extracellular Matrix Proteins

Otolaryngology–Head and Neck SurgeryVolume 117, Issue 2 p. P132-P133 Article RGD Peptides Inhibit the Adhesion of a Recurrent Pleomorphic Adenoma Cell Line to a Variety of Extracellular Matrix Proteins Melissa G. Steiner PhD, Melissa G. Steiner PhD (presenter) New York, N.Y.Search for more papers by this authorDavid B. Rosenberg MD, David B. Rosenberg MD New York, N.Y.Search for more papers by this authorWilliam I. Kuhel MD, William I. Kuhel MD New York, N.Y.Search for more papers by this authorW. Shain Schley MD, W. Shain Schley MD New York, N.Y.Search for more papers by this author Melissa G. Steiner PhD, Melissa G. Steiner PhD (presenter) New York, N.Y.Search for more papers by this authorDavid B. Rosenberg MD, David B. Rosenberg MD New York, N.Y.Search for more papers by this authorWilliam I. Kuhel MD, William I. Kuhel MD New York, N.Y.Search for more papers by this authorW. Shain Schley MD, W. Shain Schley MD New York, N.Y.Search for more papers by this author First published: 01 August 1997 https://doi.org/10.1016/S0194-59989780243-4Read the full textAboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume117, Issue2August 1997Pages P132-P133 RelatedInformation

Expression of VIA (β1) Integrins in a Recurrent Pleomorphic Adenoma Cell Line

Expression of VIA (β1) Integrins in a Recurrent Pleomorphic Adenoma Cell Line

RGD peptides inhibit the adhesion of a recurrent pleomorphic adenoma cell line to a variety of extracelular matrix proteins

RGD peptides inhibit the adhesion of a recurrent pleomorphic adenoma cell line to a variety of extracelular matrix proteins

Effect of spatial arrangement of the basement membrane on cultured pleomorphic adenoma cells. Study by immunocytochemistry and electron and confocal microscopy.

In a cell line from human pleomorphic adenoma (AP2 cells) we studied the response of these cells to basement membrane proteins. The culture was characterized as myoepithelial-like by transmission electron microscopy and immunocytochemistry. AP2 cells were grown in contact with a reconstituted basement membrane (Matrigel). Cells grown on Matrigel showed conspicuous phenotypic alterations, depending on how the substrate was applied. Cells grown on the top of Matrigel developed a dendritic phenotype, exhibiting thin, long and intercommunicating cytoplasmic extensions resembling normal myoepithelial cells. Cells grown inside Matrigel formed multi-layered clusters. Light, confocal and transmission electron microscopy showed that these clusters were formed by double-layered epithelioid cells delimiting luminal spaces. The cells facing the lumen were cuboidal, showing microvilli at the apical plasmalemmal and junctional complexes. The spatial arrangement of basement membrane is a key modulator of morphogenetic changes and cytodifferentiation of tumour myoepithelial cell lineage in culture.

Quantitation and localization of cycling tumor cells in pleomorphic adenomas and myoepitheliomas: an immunohistochemical analysis.

Previous investigations have suggested that in certain salivary gland tumors only nonluminal (myoepithelial-like) tumor cells proliferate and that this may have histogenetic implications; however, no quantitative assessment of the cycling component is available. We decided, therefore, to enumerate the cycling luminal and nonluminal cells in 15 pleomorphic adenomas and six myoepitheliomas by using an antibody to proliferating cell nuclear antigen. The mean percentages of cycling luminal and nonluminal cells in pleomorphic adenomas were 2.3 +/- 1.4 and 2.4 +/- 2.3, respectively, and 2.1 +/- 0.7 of the tumor cells in myoepitheliomas. Even though duct-like structures in pleomorphic adenomas are considerably separated by more numerous nonluminal cells and, therefore, cycling cells may seem fewer, both cell types proliferate at similar rates. The results indicate that nonluminal cells are not the sole proliferative component in salivary gland tumors.

唾液腺多形腺腫にみられる筋上皮細胞の細胞像

唾液腺多形腺腫にみられる筋上皮細胞の細胞像

Effects of Acidic and Basic Fibroblast Growth Factors on Cell Proliferation in Pleomorphic Adenoma of the Parotid Gland

Localization and biochemical characteristics of acidic and basic fibroblast growth factor (aFGF and bFGF) were studied in the normal parotid gland (NPG) and in pleomorphic adenoma (PA). In addition, the effects of these factors on proliferation activity were investigated in cultured PA cells. aFGF and bFGF were detected immunohistochemically in 62% and 58% of NPG and 44% and 58% of PA, respectively, and they were localized in the cytoplasm of the ductal segments of the NPG, and of the tubular, trabecular and squamous components of PA. Both aFGF and bFGF, each with a molecular weight of 18 kDa, were identified in PA using heparin-sepharose chromatography and Western blot analysis. Both recombinant human aFGF and bFGF stimulated [3H]-thymidine incorporation by cultured PA cells. These results indicated that aFGF and bFGF, probably produced by neoplastic cells, play important roles in the proliferation of PA of the parotid gland.

RGD peptide inhibits adhesion of pleomorphic adenoma cell lines to fibronectin in a dose-dependent manner

RGD peptide inhibits adhesion of pleomorphic adenoma cell lines to fibronectin in a dose-dependent manner

Immunohistochemical study on sebaceous adenoma and sebaceous carcinoma arising in parotid gland

The present study presents two cases of parotid mass diagnosed as sebaceous adenoma and sebaceous carcinoma in which immunohistochemical staining was performed for cytokeratins, vimentin, S-100 proteins, lactoferrin, lysozyme, alpha 1-antichymotrypsin, alpha 1-antitrypsin, and proliferating cell nuclear antigen to evaluate the characteristics of tumor cells and to distinguish these lesions from their counterparts in the skin. Sebaceous adenoma had circumscribed lobules containing sebaceous cell nests with well differentiated sebaceous cells surrounded by basaloid cells and a population of transitional cells. Sebaceous carcinoma had cellular pleomorphism and nuclear atypia and a population of cells resembling neoplastic myoepithelial cells of pleomorphic adenoma. The profile of markers used in the present study when compared with studies on sebaceous tumors of skin and the characteristics of other salivary neoplasms reasonably allowed us to conclude that the sebaceous differentiation and sebaceous tumors in salivary glands may differ from that of their counterparts in skin. The histogenesis of salivary sebaceous neoplasms may be attributable to the process of sebaceous metaplasia in the salivary tissues and based on our finding of similar immunohistochemical profile of sebaceous cells in sebaceous carcinoma with that of neoplastic myoepithelial cells in pleomorphic adenoma as reported earlier, sebaceous neoplasms may have a common histogenetic origin with other salivary neoplasms. However, their origin from the sebaceous glands normally present in the salivary tissues could not be excluded.

Parathyroid Hormone-related Peptide: Immunolocalisation in Normal Salivary Glands and in Pleomorphic Adenomas

Parathyroid hormone-related peptide (PTHrP) has been shown to be produced as an early step in the differentiation sequence and is considered to be a marker of some progenitor cells. We investigated the presence and distribution of PTHrP in 7 normal parotid glands and in 18 salivary pleomorphic adenomas (PA). Localisation of PTHrP was studied by immunohistochemistry with a three-step unlabelled peroxidase-antiperoxidase method. In the normal glands PTHrP is found mainly in the basal and dark cells, and to a lesser extent in the light cells of the ducts. In PA the inner layer of tubulo-ductal structures and all cells of the cyst-like structures show strong positivity for PTHrP. Scattered cells in the dense clusters also stain strongly. Virtually all tumour cells in myxoid and chondroid areas are devoid of staining. In clusters of squamous metaplasia, most cells are slightly positive and scattered cells are stained strongly. PTHrP contributes to cellular differentiation and is also related to keratinisation. We suggest that the PTHrP-positive inner layer cells in pleomorphic adenomas represent a step in the squamous differentiation and in the further elaboration of the tubulo-ductal structures.

Diagnostic criteria for neoplastic myoepithelial cells in pleomorphic adenomas and myoepitheliomas: Immunocytochemical detection of muscle-specific actin, cytokeratin 14, vimentin, and glial fibrillary acidic protein

Markers for normal salivary gland myoepithelium were used to determine the extent of their expression in the neoplastic myoepithelial (nonluminal) cells of pleomorphic adenomas and then in the tumor cells in myoepitheliomas and to gather information necessary to establish diagnostic criteria, especially muscle actin expression, for myoepitheliomas. Methanol/acetic acid-fixed and paraffin-embedded tissue was used to immunohistochemically study expression of intermediate and smooth-muscle actin filaments in nonluminal cells in 14 pleomorphic adenomas and to compare this to their expression in five myoepitheliomas. In routine histologic sections, the morphologic variants of nonluminal tumor cells--spindle, stellate, polygonal, angular, and plasmacytoid--in pleomorphic adenoma mirror the spectrum of tumor cells in myoepitheliomas. Immunocytochemical similarities are also apparent. Two specific markers for myoepithelial cells in the normal salivary gland, muscle-specific actin and cytokeratin 14, were both variably, independently, and never uniformly expressed in nonluminal cells of pleomorphic adenoma and tumor cells in myoepitheliomas regardless of their morphology. Cytokeratin 14 in addition labels basal cells of excretory ducts. Both muscle-specific actin and cytokeratin 14 preferentially localized to single layers of periductal cells in pleomorphic adenomas, angular, polygonal, and plasmacytoid cells preferentially expressed cytokeratin 14. Similar patterns were noted in the three myoepitheliomas with reasonable expression of the two markers. Only isolated single cells or small groups of plasmacytoid cells in four pleomorphic adenomas with a significant component of these cells and the two plasmacytoid myoepitheliomas immunostained for muscle-specific actin and cytokeratin 14. In both tumor types, vimentin was nearly uniformly expressed in nonluminal tumor cells of all morphologic types, including plasmacytoid cells. The range and transition of morphology of nonluminal cells in pleomorphic adenomas is reflected in myoepitheliomas. Incomplete or absent expression of the myoepithelial/basal cell markers, muscle-specific actin, and cytokeratin 14, and the general expression of vimentin is common to both tumors. Because these findings apply to the majority of plasmacytoid cells in pleomorphic adenomas, tumor cells with a similar morphology and immunoprofile are to be expected in myoepitheliomas; the term plasmacytoid myoepitheliomas is thus appropriate regardless of the presence or absence of muscle-specific actin.