Abstract
To determine the cellular origin of plasmacytoid cells in salivary gland adenomas, immunohistochemistry was performed on sections from 12 pleomorphic adenomas rich in these cells. In normal salivary glands included in these sections, the myoepithelial cells (MECs) expressed α-smooth muscle actin (αSMA) and smooth muscle myosin heavy chain (SMMHC), whereas the duct luminal cells expressed keratins 19, 18 and 8. Some of the salivary duct basal cells expressed these keratins, and the acinar cells expressed keratins 18 and 8. The expression profile was similar in rat salivary glands not only after but also during development. The immature MECs never expressed the keratins nor did the immature duct cells express αSMA. In seven cases, up to 60% of the plasmacytoid cells expressed keratin 19. In three of these cases, about 10% of the plasmacytoid cells expressed keratin 18. No plasmacytoid cells expressed αSMA, SMMHC or keratin 8. These results indicate that plasmacytoid cells originate from luminal cells and not from MECs. Furthermore, in addition to the luminal tumor cells, the non-luminal cells could express keratins 19, 18 and 8. Therefore, it is necessary to re-evaluate the prevailing notion that non-luminal cells are modified MECs. Keratin 14, basic calponin, vimentin and p63 were bi-specific for the MECs and the duct cells. Therefore, expression of these proteins by significant numbers of the non-luminal tumor cells and the plasmacytoid cells never denied the above notion.
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Achstätter T, Moll R, Anderson A, Kuhn C, Pitz S, Schwechheimer K, Franke WW (1986) Expression of glial filament protein (GFP) in nerve sheaths and non-neural cells re-examined using monoclonal antibodies, with special emphasis on the co-expression of GFP and cytokeratins in epithelial cells of human salivary gland and pleomorphic adenomas. Differentiation 31:206–227
Araújo VC, Araújo NS (1990) Vimentin as a marker of myoepithelial cells in salivary gland tumors. Eur Arch Otorhinolaryngol 247:252–255
Araújo VC, Carvalho YR, Araújo NS (1994) Actin versus vimentin in myoepithelial cells of salivary gland tumors. A comparative study. Oral Surg Oral Med Oral Pathol 77:387–391
Batsakis JG, El-Naggar AK (1999) Myoepithelium in salivary and mammary neoplasms is host-friendly. Adv Anat Pathol 6:218–226
Bilal H, Handra-Luca A, Bertrand JC, Fouret PJ (2003) p63 is expressed in basal and myoepithelial cells of human normal and tumor salivary gland tissues. J Histochem Cytochem 51:133–139
Born IA, Schwechheimer K, Maier H, Otto HF (1987) Cytokeratin expression in normal salivary glands and in cystadenolymphomas demonstrated by monoclonal antibodies against selective cytokeratin polypeptides. Virchows Arch 411:583–589
Bouwens L (1998) Cytokeratins and cell differentiation in the pancreas. J Pathol 184:234–239
Buchner A, David R, Hansen LS (1981) "Hyaline cells" in pleomorphic adenoma of salivary gland origin. Oral Surg Oral Med Oral Pathol 52:506–512
Dardick I, van Nostrand AWP, Jeans MTD, Rippstein P, Edwards V (1983) Pleomorphic adenoma, I: ultrastructural organization of "epithelial" regions. Hum Pathol 14:780–797
Dardick I, van Nostrand AWP, Jeans MTD, Rippstein P, Edwards V (1983) Pleomorphic adenoma, II: ultrastructural organization of "stromal" regions. Hum Pathol 14:798–809
Dardick I, Rippstein P, Skimming L, Boivin M, Parks WR, Dairkee SH (1987) Immunohistochemistry and ultrastructure of myoepithelium and modified myoepithelium of the ducts of human major salivary glands: histogenetic implications for salivary gland tumors. Oral Surg Oral Med Oral Pathol 64:703–715
Dardick I, Parks WR, Little J, Brown DL (1988) Characterization of cytoskeletal proteins in basal cells of human parotid salivary gland ducts. Virchows Arch 412:525–532
Dardick I, Thomas MJ, van Nostrand AWP (1989) Myoepithelioma-new concepts of histology and classification: a light and electron microscopic study. Ultrastruct Pathol 13:187–224
Dardick I, Cavell S, Boivin M, Hoppe D, Parks WR, Stinson J, Yamada S, Burns BF (1989) Salivary gland myoepithelioma variants. Histological, ultrastructural, and immunocytological features. Virchows Arch 416:25–42
Dardick I, Stratis M, Parks WR, DeNardi FG, Kahn HJ (1991) S-100 protein antibodies do not label normal salivary gland myoepithelium. Histogenetic implications for salivary gland tumors. Am J Pathol 138:619–628
Denny PC, Ball WD, Redman RS. (1997) Salivary glands: a paradigm for diversity of gland development. Crit Rev Oral Biol Med 8:51–75
Di Palma S, Guzzo M (1998) Myoepithelial carcinoma with predominance of plasmacytoid cells arising in a pleomorphic adenoma of the parotid gland. Histopathology 33:485
Draeger A, Nathrath WBJ, Lane EB, Sundström BE, Stigbrand TI (1991) Cytokeratins, smooth muscle actin and vimentin in human normal salivary gland and pleomorphic adenomas. Immunohistochemical studies with particular reference to myoepithelial and basal cells. APMIS 99:405–415
Eckert F, de Viragh PA, Schmid U (1994) Coexpression of cytokeratin and vimentin intermediate filaments in benign and malignant sweat gland tumors. J Cutan Pathol 21:140–150
Ellis GL, Auclair PL (1996) Tumors of the salivary glands. Atlas of tumor pathology, 3rd series, fascicle 17. Armed Forces Institute of Pathology, Washington, DC
Franquemont DW, Mills SE (1993) Plasmacytoid monomorphic adenoma of salivary glands. Absence of myogenous differentiation and comparison to spindle cell myoepithelioma. Am J Surg Pathol 17:146–153
Gilles C, Polette M, Zahm JM, Tournier JM, Volders L, Foidart JM, Birembaut P (1999) Vimentin contributes to human mammary epithelial cell migration. J Cell Sci 112:4615–4625
Gould VE, Koukoulis GK, Jansson DS, Nagle RB, Franke WW, Moll R (1990) Coexpression patterns of vimentin and glial filament protein with cytokeratins in the normal, hyperplastic, and neoplastic breast. Am J Pathol 137:1143–1155
Gustafsson H, Kjörell U, Eriksson A, Virtanen I, Thornell L-E (1988) Distribution of intermediate filament proteins in developing and adult salivary glands in man. Anat Embryol 178:243–251
Hirano T, Gluckman JL, deVries EJ (1990) The expression of a vascular smooth-muscle actin in salivary gland tumors. Arch Otolaryngol Head Neck Surg 116:692–696
Ihrler S, Zietz C, Sendelhofert A, Lang S, Blasenbreu-Vogt S, Löhrs U (2002) A morphogenetic concept of salivary duct regeneration and metaplasia. Virchows Arch 440:519–526
Kahn LB, Schoub L (1973) Myoepithelioma of the palate. Histochemical and ultrastructural observations. Arch Pathol 95:209–212
Leoncini P, Cintorino M, Vindigni C, Leoncini L, Armellini D, Bugnoli M, Skalli O, Gabbiani G (1988) Distribution of cytoskeletal and contractile proteins in normal and tumour bearing salivary and lacrimal glands. Virchows Arch 412:329–337
Lomax-Smith JD, Azzopardi JG (1978) The hyaline cell: a distinctive feature of "mixed" salivary tumours. Histopathology 2:77–92
Moll R, Franke WW, Schiller DL, Geiger B, Krepler R (1982) The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24
Moll R, Dhouailly D, Sun T-T (1989) Expression of keratin 5 as a distinctive feature of epithelial and biphasic mesotheliomas. An immunohistochemical study using monoclonal antibody AE14. Virchows Arch 58:129–145
Mori M, Ninomiya T, Okada Y, Tsukitani K (1989) Myoepitheliomas and myoepithelial adenomas of salivary gland origin. Immunohistochemical evaluation of filament proteins, S-100α and β, glial fibrillary acidic protein, neuron specific enolase, and lactoferrin. Pathol Res Pract 184:168–178
Morinaga S, Nakajima T, Shimosato Y (1987) Normal and neoplastic myoepithelial cells in salivary glands: an immunohistochemical study. Hum Pathol 18:1218–1226
Nakazato Y, Ishizeki J, Takahashi K, Yamaguchi H, Kamei T, Mori T (1982) Localization of S-100 protein and glial fibrillary acidic protein-related antigen in pleomorphic adenoma of the salivary glands. Lab Invest 46:621–626
Ninomiya T, Naito R, Okada Y, Kobayashi K, Mori M, Tsukitani K (1989) Immunohistochemical localization of the α and β subunits of S-100 protein in pleomorphic adenoma of the salivary glands. Virchows Arch 57:63–75
Nguyen M, Lee MC, Wang JL, Tomlinson JS, Shao Z-M, Alpaugh ML, Barsky SH (2000) The human myoepithelial cell displays a multifaceted anti-angiogenic phenotype. Oncogene 19:3449–3459
Ogawa Y, Yamauchi S, Ohnishi A, Ito R, Ijuhin N (1999) Immunohistochemistry of myoepithelial cells during development of the rat salivary glands. Anat Embryol 200:215–228
Ogawa Y, Toyosawa S, Ishida T, Ijuhin N (2000) Keratin 14 immunoreactive cells in pleomorphic adenomas and adenoid cystic carcinomas of salivary glands. Virchows Arch 437:58–68
Ogawa Y (2003) Immunocytochemistry of myoepithelial cells in the salivary glands. Prog Histochem Cytochem (in press)
Savera AT, Gown AM, Zarbo RJ (1997) Immunolocalization of three novel smooth muscle-specific proteins in salivary gland pleomorphic adenoma: assessment of the morphogenetic role of myoepithelium. Mod Pathol 10:1093–1100
Savera AT, Sloman A, Huvos AG, Klimstra DS (2000) Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 25 patients. Am J Surg Pathol 24:761–774
Sciubba JJ, Goldstein BH (1976) Myoepithelioma. Review of the literature and report of a case with ultrastructural confirmation. Oral Surg Oral Med Oral Pathol 42:328–338
Sciubba JJ, Brannon RB (1982) Myoepithelioma of salivary glands: report of 23 cases. Cancer 49:562–572
Seifert G, Sobin LH (1991) Histological typing of salivary gland tumors. World Health Organization international classification of tumors, 2nd ed. Springer Verlag, Berlin Heidelberg New York
Simpson RH, Jones H, Beasley P (1995) Benign myoepithelioma of the salivary glands: a true entity? Histopathology 27:1–9
Sternlicht MD, Barsky SH (1997) The myoepithelial defense: a host defense against cancer. Med Hypotheses 48:37–46
Sternlicht MD, Safarians S, Rivera SP, Barsky SH (1996) Characterizations of the extracellular matrix and proteinase inhibitor content of human myoepithelial tumors. Lab Invest 74:781–796
Sternlicht MD, Kedeshian P, Shao Z-M, Safarians S, Barsky SH (1997) The human myoepithelial cell is a natural tumor suppressor. Clin Cancer Res 3:1949–1958
Suzuki H, Inoue K, Fujioka Y, Ishikura H, Furuta Y, Fukuda S (1998) Myoepithelial carcinoma with predominance of plasmacytoid cells arising in a pleomorphic adenoma of the parotid gland. Histopathology 32:86–87
Wayne Stromeyer F, Haggitt RC, Nelson JF, Hardman JM (1975) Myoepithelioma of minor salivary gland origin. Light and electron microscopical study. Arch Pathol 99:242–245
Weber A, Langhanki L, Schutz A, Gerstner, A, Bootz F, Wittekind C, Tannapfel A (2002) Expression profiles of p53, p63, and p73 in benign salivary gland tumors. Virchows Arch 441:428–436
Zarbo RJ, Regezi JA, Hatfield JS, Maisel H, Trojanowski JQ, Batsakis JG, Crissman JD (1988) Immunoreactive glial fibrillary acidic protein in normal and neoplastic salivary glands: a combined immunohistochemical and immunoblot study. Surg Pathol 1:55–63
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The authors thank Dr. Ross T. Fernley for his critical reading of the manuscript.
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Ogawa, Y., Kishino, M., Atsumi, Y. et al. Plasmacytoid cells in salivary-gland pleomorphic adenomas: evidence of luminal cell differentiation. Virchows Arch 443, 625–634 (2003). https://doi.org/10.1007/s00428-003-0890-3
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DOI: https://doi.org/10.1007/s00428-003-0890-3