Abstract
Lysozyme is an enzymatic marker of acinar and intercalated duct cells of normal salivary glands. The aim of this study was to verify whether lysozyme expression could be useful to distinguish acinic cell carcinoma (ACC) from its main mimic, mammary analog secretory carcinoma (MASC). For comparison, DOG1 expression was analyzed as well. Seventeen cases of ACC, 15 MASC, and 125 other salivary tumors were studied. Lysozyme expression was found in tumor cells as well as in secreted material of MASC (86.6 % of cases) and in ductal cells of epithelial–myoepithelial carcinoma (EMC-53.8 %), pleomorphic adenoma (PA-29.1 %) and polymorphous low-grade adenocarcinoma (PLGA-23.8 %). However, in ACC, lysozyme was not expressed. Three patterns of DOG1 staining were seen: apical–luminal, cytoplasmic, and mixed cytoplasmic/membranous. The apical–luminal pattern was detected in ductal cells of ACC (58.8 % of cases), EMC (38.4 %), adenoid-cystic carcinoma (AdCC-35.3 %), PA (8.3 %), and PLGA (4.8 %). These tumors also showed mixed membranous/cytoplasmic staining for DOG1. MASC, mucoepidermoid, and salivary duct carcinomas exhibited only DOG1 cytoplasmic staining. In conclusion, lysozyme cannot be used as a marker of acinar differentiation in salivary tumors. However, lysozyme expression can be helpful to distinguish MASC from ACC due to its high frequency in the former and absence in ACC. It is likely that in MASC, lysozyme expression may reflect a lactational-like secretory differentiation since lysozyme belongs to breast milk proteins. Regarding DOG1 expression, the apical–luminal pattern is related to acinar and intercalated duct differentiation whereas the cytoplasmic staining does not seem to be associated with a specific cellular phenotype.
Similar content being viewed by others
References
Pinto A, Nosé V, Rojas C, Fan YS, Gomez-Fernandez C. Searching for mammary analogue [corrected] secretory carcinoma of salivary gland among its mimics. Mod Pathol. 2014;27:30–7.
Bishop JA. Unmasking MASC: bringing to light the unique morphologic, immunohistochemical and genetic features of the newly recognized mammary analogue secretory carcinoma of salivary glands. Head Neck Pathol. 2013;7:35–9.
Urano M, Nagao T, Miyabe S, Ishibashi K, Higuchi K, Kuroda M. Characterization of mammary analogue secretory carcinoma of the salivary gland: discrimination from its mimics by the presence of the ETV6–NTRK3 translocation and novel surrogate markers. Hum Pathol. 2015;46:94–103.
Chiosea SI, Griffith C, Assaad A, Seethala RR. The profile of acinic cell carcinoma after recognition of mammary analog secretory carcinoma. Am J Surg Pathol. 2012;36:343–50.
Griffith C, Seethala R, Chiosea SI. Mammary analogue secretory carcinoma: a new twist to the diagnostic dilemma of zymogen granule poor acinic cell carcinoma. Virchows Arch. 2011;459:117–8.
Chiosea SI, Griffith C, Assaad A, Seethala RR. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. Histopathology. 2012;61:387–94.
Skálová A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, et al. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6–NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol. 2010;34:599–608.
Connor A, Perez-Ordoñez B, Shago M, Skálová A, Weinreb I. Mammary analog secretory carcinoma of salivary gland origin with the ETV6 gene rearrangement by FISH: expanded morphologic and immunohistochemical spectrum of a recently described entity. Am J Surg Pathol. 2012;36:27–34.
Jung MJ, Song JS, Kim SY, Nam SY, Roh JL, Choi SH, et al. Finding and characterizing mammary analogue secretory carcinoma of the salivary gland. Korean J Pathol. 2013;47:36–43.
Stenman G. Fusion oncogenes in salivary gland tumors:molecular and clinical consequences. Head Neck Pathol. 2013;7:12–9.
Skálová A. Mammary analogue secretory carcinoma of salivar gland origin: an update and expanded morphologic and immunohistochemical spectrum of recently described entity. Head Neck. 2013;7(Suppl 1):S30–36.
Bishop JA, Yonescu R, Batista D, Begum S, Eisele DW, Westra WH. Utility of mammaglobin immunohistochemistry as a proxy marker for the ETV6–NTRK3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma. Hum Pathol. 2013;44:1982–8.
Chênevert J, Duvvuri U, Chiosea S, Dacic S, Cieply K, Kim J, et al. DOG1: a novel marker of salivary acinar and intercalated duct differentiation. Mod Pathol. 2012;25:919–29.
Simpson RH, Skálová A, Di Palma S, Leivo I. Recent advances in the diagnostic pathology of salivary carcinomas. Virchows Arch. 2014;465:371–84.
Mariano FV, dos Santos HT, Azañero WD, da Cunha IW, Coutinho-Camilo CM, de Almeida OP, et al. Mammary analogue secretory carcinoma of salivar glands is a lipid-rich tumour, and adipophilin can be valuable in its identification. Histopathology. 2013;63:558–67.
Hsieh MS, Chou YH, Yeh SJ, Chang YL. Papillary cystic pattern in characteristic in mammary analogue secretory carcinomas but is rarely observed in acinic cell carcinomas of the salivary gland. Virchows Arch. 2015;467:145–53.
Caselitz J, Jaup T, Seifert G. Lactoferrin and lysozyme in carcinomas of the parotid gland: a comparative immunocytochemical study with the occurrence in normal and inflammated tissue. Virchows Arch. 1981;394:61–73.
Korsrud FR, Brandtzaeg P. Characterization of epithelial elements in human major salivary glands by functional markers: localization of amylase, lactoferrin, lysozyme, secretory component and secretory immunoglobulins by paired immunofluorescence staining. J Histochem Cytochem. 1982;30:657–66.
Habata I, Yasui T, Fujimori O, Tsukise A. Immunohistochemical aspects of anti-microbial properties in goat submandibular glands. Anat Histol Embryol. 2012;41:54–9.
Weinreb I, Seethala RR, Hunt JL, Chetty R, Dardick I, Perez-Ordoñez B. Intercalated duct lesions of salivary gland: a morphologic spectrum from hyperplasia to adenoma. Am J Surg Pathol. 2009;33:1322–9.
Montalli VA, Martinez E, Tincani A, Martins A, Abreu Mdo C, Neves C, et al. Tubular variant of basal cell adenoma shares immunophenotypical features with normal intercalated ducts and s closely related to intercalated duct lesions of salivary gland. Histopathology. 2014;64:880–9.
Chow BD, Reardon JL, Perry EO, Laforce-Nesbitt SS, Tucker R, Bliss JM. Host defense proteins in breast milk and neonatal yeast colonization. J Hum Lact. 2016;32:168–73.
Vizoso F, Plaza E, Vázquez J, Serra C, Lamelas ML, González LO, et al. Lysozyme expression by breast carcinomas, correlation with clinicopathologic parameters, and prognostic significance. Ann Surg Oncol. 2001;8:667–74.
Yang YD, Cho H, Koo JY, Tak MH, Cho Y, Shim WS, et al. TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature. 2008;455:1210–5.
Galietta LJ. The TMEM16 protein family: a new class of chloride channels? Biophys J. 2009;16(97):3047–53.
Stevens TM, Kovalovsky AO, Velosa C, Shi Q, Dai Q, Owen RP, et al. Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study. Mod Pathol. 2015;28:1084–100.
Hemminger J, Iwenofu OH. Discovered on gastrointestinal stromal tumors 1 (DOG1) expression in non-gastrointestinal stromal tumor (GIST) neoplasms. Histopathology. 2012;61:170–7.
Chan JK. Newly available antibodies with practical applications in surgical pathology. Int J Surg Pathol. 2013;21:553–72.
Qu Z, Yao W, Yao R, Liu X, Yu K, Hartzell C. The Ca(2+) -activated Cl(−) channel, ANO1 (TMEM16A), is a double-edged sword in cell proliferation and tumorigenesis. Cancer Med. 2014;3:453–61.
Raboh NM, Hakim SA. Diagnostic role of DOG1 and p63 immunohistochemistry in salivary gland carcinomas. In J Clin Exp Pathol. 2015;8:9214–22.
Thompson LD, Aslam MN, Stall JN, Udager AM, Chiosea S, McHugh JB. Clinicopathologic and immunophenotypic characterization of 25 cases of Acinic Cell Carcinoma with high-grade transformation. Head Neck Pathol. 2016;10:152–60.
Author information
Authors and Affiliations
Corresponding author
Additional information
Fernanda Viviane Mariano and Camila Andrea Concha Gómez have contributed equally to this study, and should be considered as first authors.
Rights and permissions
About this article
Cite this article
Mariano, F.V., Gómez, C.A.C., de Souza do Nascimento, J. et al. Lysozyme Expression Can be Useful to Distinguish Mammary Analog Secretory Carcinoma from Acinic Cell Carcinoma of Salivary Glands. Head and Neck Pathol 10, 429–436 (2016). https://doi.org/10.1007/s12105-016-0718-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12105-016-0718-5