Abstract
Pleomorphic adenoma (PA) is the most common biphasic type of salivary gland tumour to arise in adults. It is a biphasic tumour composed of both luminal (ductal) cells and abluminal (basal and myoepithelial) cells. Other biphasic salivary gland type tumours, both benign and malignant, can mimic PA, especially on small biopsies. Previous studies have shown that glial fibrillary acidic protein (GFAP) is preferentially expressed in PA and can be useful in the distinction from other salivary gland tumours. However, most of these studies were performed on a small subset of tumour types at a time when the classification of salivary gland type tumours was less refined. The purpose of this study was to assess the expression of glial fibrillary acidic protein (GFAP) in a broad group of both benign and malignant salivary gland tumours. The expression of GFAP was assessed in 99 tumours including 54 PAs, 5 basal cell adenomas, 1 myoepitheliomas, 5 adenoid cystic carcinomas, 6 epithelial-myoepithelial carcinomas (EMCA), 6 mucoepidermoid carcinomas, 7 salivary duct carcinomas, 1 adenocarcinomas NOS, 2 myoepithelial carcinomas, 4 basal cell adenocarcinomas, 5 acinic cell carcinomas and 3 polymorphous adenocarcinomas. Of the malignant cases, 8 were classified as carcinomas ex PA. GFAP was also assessed in 19 concurrent biopsy specimens. GFAP was expressed in the resections of 51 PAs examined (94%). Expression was predominantly strong and diffusely seen in myoepithelial cells. Strong and diffuse GFAP expression was also seen in two EMCAs (33%) and one myoepithelial carcinoma (50%). On biopsy specimens, 100% of PAs and basal cell adenomas expressed GFAP. GFAP was also seen in 1 out of 3 carcinomas ex PAs on biopsies. Almost all PAs show strong and diffuse expression of GFAP. In contrast, most malignant neoplasms that can mimic PA on biopsies show only rare, focal expression. Other benign tumours composed of abluminal/myoepithelial cells also show focal expression of GFAP, highlighting the spectrum these tumours share with PA. Overall, the presence of strong and diffuse GFAP expression can favour a benign neoplasm, specifically a PA, on limited biopsy specimens.
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Nagao T, Sato E, Inoue R, et al. Immunohistochemical analysis of salivary gland tumors: application for surgical pathology practice. Acta Histochem Cytochem. 2012;45(5):269–82. https://doi.org/10.1267/ahc.12019.
Tarakji B, Baroudi K, Hanouneh S, Kharma MY, Nassani MZ, Azzeghaiby SN. Extensive review in the detection of the malignant transformation of pleomorphic adenoma. Gulf J Oncolog. 2013;1(13):67–82.
Francesco G, Emanuele C, Gabriele M, Valeria M, Angelo S, Antonio T. Myoepithelial carcinoma ex pleomorphic adenoma of the maxillary sinus: a case report and review of literature. Head Neck Pathol. 2021;15(4):1345–9. https://doi.org/10.1007/s12105-020-01282-5.
Toluie S, Thompson LD. Sinonasal tract adenoid cystic carcinoma ex-pleomorphic adenoma: a clinicopathologic and immunophenotypic study of 9 cases combined with a comprehensive review of the literature. Head Neck Pathol. 2012;6(4):409–21. https://doi.org/10.1007/s12105-012-0381-4.
Altunpulluk MD, Karabulut MH, Kır G, Şahin Ş. Pleomorphic adenoma of the larynx. North Clin Istanb. 2016;3(1):67–70. https://doi.org/10.14744/nci.2015.47965.
Cantley RL. Fine-needle aspiration cytology of cellular basaloid neoplasms of the salivary gland. Arch Pathol Lab Med. 2019;143(11):1338–45. https://doi.org/10.5858/arpa.2019-0327-RA.
Zaib N, Mushtaq S, Mamoon N, Akhter N, Ayaz B. Immunohistochemical pattern of pleomorphic adenoma, polymorphous low grade adenocarcinoma and adenoid cystic carcinoma in minor salivary glands. J Dent (Tehran). 2014;11(1):38–46.
Curran AE, Allen CM, Beck FM, Damm DD, Murrah VA. Distinctive pattern of glial fibrillary acidic protein immunoreactivity useful in distinguishing fragmented pleomorphic adenoma, canalicular adenoma and polymorphous low grade adenocarcinoma of minor salivary glands. Head Neck Pathol. 2007;1(1):27–32. https://doi.org/10.1007/s12105-007-0003-8.
Yang Z, Wang KK. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci. 2015;38(6):364–74. https://doi.org/10.1016/j.tins.2015.04.003.
Ostrzega N, Cheng L, Layfield L. Glial fibrillary acid protein immunoreactivity in fine-needle aspiration of salivary gland lesions: a useful adjunct for the differential diagnosis of salivary gland neoplasms. Diagn Cytopathol. 1989;5(2):145–9. https://doi.org/10.1002/dc.2840050207.
Stead RH, Qizilbash AH, Kontozoglou T, Daya AD, Riddell RH. An immunohistochemical study of pleomorphic adenomas of the salivary gland: glial fibrillary acidic protein-like immunoreactivity identifies a major myoepithelial component. Hum Pathol. 1988;19(1):32–40. https://doi.org/10.1016/s0046-8177(88)80313-7.
Nishimura T, Furukawa M, Kawahara E, Miwa A. Differential diagnosis of pleomorphic adenoma by immunohistochemical means. J Laryngol Otol. 1991;105(12):1057–60. https://doi.org/10.1017/s0022215100118183.
Ianez RF, Buim ME, Coutinho-Camillo CM, Schultz R, Soares FA, Lourenço SV. Human salivary gland morphogenesis: myoepithelial cell maturation assessed by immunohistochemical markers. Histopathology. 2010;57(3):410–7. https://doi.org/10.1111/j.1365-2559.2010.03645.x.
Acharya S, Padmini S, Koneru A, Krishnapillai R. Intraoral salivary duct carcinoma: a case report and a brief review. J Oral Maxillofac Pathol. 2014;18(Suppl 1):121–7. https://doi.org/10.4103/0973-029X.141353.
Xie S, Yang H, Bredell M, et al. Salivary duct carcinoma of the parotid gland: a case report and review of the literature. Oncol Lett. 2015;9(1):371–4. https://doi.org/10.3892/ol.2014.2655.
Seethala RR. Basaloid/blue salivary gland tumors. Mod Pathol. 2017;30(s1):84–95. https://doi.org/10.1038/modpathol.2016.190.
Seethala RR, Stenman G. Update from the 4th edition of the world health organization classification of head and neck tumours: tumors of the salivary gland. Head Neck Pathol. 2017;11(1):55–67. https://doi.org/10.1007/s12105-017-0795-0.
Wilson TC, Robinson RA. Basal cell adenocarcinoma and basal cell adenoma of the salivary glands: a clinicopathological review of seventy tumors with comparison of morphologic features and growth control indices. Head Neck Pathol. 2015;9(2):205–13. https://doi.org/10.1007/s12105-014-0562-4.
Griffith CC, Siddiqui MT, Schmitt AC. Ancillary testing strategies in salivary gland aspiration cytology: a practical pattern-based approach. Diagn Cytopathol. 2017;45(9):808–19. https://doi.org/10.1002/dc.23715.
Griffith CC, Pai RK, Schneider F, et al. Salivary gland tumor fine-needle aspiration cytology: a proposal for a risk stratification classification. Am J Clin Pathol. 2015;143(6):839–53. https://doi.org/10.1309/AJCPMII6OSD2HSJA.
Xu B, Mneimneh W, Torrence DE, et al. Misinterpreted myoepithelial carcinoma of salivary gland: a challenging and potentially significant pitfall. Am J Surg Pathol. 2019;43(5):601–9. https://doi.org/10.1097/PAS.0000000000001218.
Wang C, Zhang Z, Ge Y, et al. Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 29 patients. J Oral Maxillofac Surg. 2015;73(10):1938–45. https://doi.org/10.1016/j.joms.2015.03.054.
Xu B, Katabi N. Myoepithelial carcinoma. Surg Pathol Clin. 2021;14(1):67–73. https://doi.org/10.1016/j.path.2020.09.008.
Chowsilpa S, An D, Maleki Z. Adenoid cystic carcinoma cytology: salivary gland and nonsalivary gland. Diagn Cytopathol. 2020;48(12):1282–9. https://doi.org/10.1002/dc.24573.
Jain R, Gupta R, Kudesia M, Singh S. Fine needle aspiration cytology in diagnosis of salivary gland lesions: a study with histologic comparison. Cytojournal. 2013;10:5. https://doi.org/10.4103/1742-6413.109547.
Zhu S, Schuerch C, Hunt J. Review and updates of immunohistochemistry in selected salivary gland and head and neck tumors. Arch Pathol Lab Med. 2015;139(1):55–66. https://doi.org/10.5858/arpa.2014-0167-RA.
Vázquez A, Patel TD, D’Aguillo CM, et al. Epithelial-myoepithelial carcinoma of the salivary glands: an analysis of 246 cases. Otolaryngol Head Neck Surg. 2015;153(4):569–74. https://doi.org/10.1177/0194599815594788.
El Hallani S, Udager AM, Bell D, et al. Epithelial-myoepithelial carcinoma: frequent morphologic and molecular evidence of preexisting pleomorphic adenoma, common HRAS mutations in PLAG1-intact and HMGA2-intact cases, and occasional TP53, FBXW7, and SMARCB1 alterations in high-grade cases. Am J Surg Pathol. 2018;42(1):18–27. https://doi.org/10.1097/PAS.0000000000000933.
Kusafuka K, Yamashita M, Muramatsu A, Arai K, Suzuki M. Epithelial-myoepithelial carcinoma ex-pleomorphic adenoma of the parotid gland: report of a rare case with immunohistochemical and genetic analyses. Med Mol Morphol. 2021;54(2):173–80. https://doi.org/10.1007/s00795-020-00262-6.
Russo D, Di Crescenzo RM, Varricchio S, et al. Low-grade intraductal carcinoma of the parotid gland: a case report and literature review. Head Neck Pathol. 2021;15(4):1359–71. https://doi.org/10.1007/s12105-021-01290-z.
Kuo YJ, Weinreb I, Perez-Ordonez B. Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature. Head Neck Pathol. 2013;7(Suppl 1):59–67. https://doi.org/10.1007/s12105-013-0460-1.
Okano K, Ishida M, Sandoh K, Fujisawa T, Iwai H, Tsuta K. Cytological features of carcinoma ex pleomorphic adenoma of the salivary glands: a diagnostic challenge. Diagn Cytopathol. 2020;48(2):149–53. https://doi.org/10.1002/dc.24333.
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Gorski, Z., Purgina, B. & Wasserman, J.K. Glial Fibrillary Acidic Protein Expression Helps Distinguish Pleomorphic Adenoma from Histologic Mimics. Head and Neck Pathol 16, 695–702 (2022). https://doi.org/10.1007/s12105-021-01409-2
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DOI: https://doi.org/10.1007/s12105-021-01409-2