Objective: Fine-needle aspiration (FNA) diagnosis of salivary gland neoplasms is often challenging. Differentiating between pleomorphic adenomas (PA) and other basaloid neoplasms, especially basal cell adenoma (BCA) and adenoid cystic carcinoma (AdCC), can be difficult in cellular aspirates. PLAG1 (PA gene 1) is a proto-oncogene, which is frequently rearranged in PAs, leading to the aberrant expression of its protein. PLAG1 IHC expression has been reported to be positive in most PAs. The aim of this study was to evaluate the sensitivity and specificity of PLAG1 to differentiate PA from other basaloid neoplasms. Study Design: Immunohistochemical evaluation of PLAG1 was performed on 125 cases (52 FNAs and 73 surgical excisions). Nuclear staining of tumor cells was scored by the intensity and percentage of positive tumor cells. A combined score of >5 was defined as positive. Results and Conclusion: The sensitivity (55%) and specificity (75%) of PLAG1 in diagnosing PA in FNAs is relatively modest thus limiting its diagnostic utility. BCAs and AdCCs showed PLAG1 false positivity, in surgical excision specimens and less so in FNAs. This may be due to limited sampling or tumor heterogeneity. Hence, PLAG1 is a modest marker for PAs in FNAs.

1.
Stewart CJ, MacKenzie K, McGarry GW, Mowat A: Fine-needle aspiration cytology of salivary gland: a review of 341 cases. Diagn Cytopathol 2000;22:139-146.
2.
Schindler S, Nayar R, Dutra J, Bedrossian CW: Diagnostic challenges in aspiration cytology of the salivary glands. Semin Diagn Pathol 2001;18:124-146.
3.
Hughes JH, Volk EE, Wilbur DC: Pitfalls in salivary gland fine-needle aspiration cytology - lessons from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology. Arch Pathol Lab Med 2005;129:26-31.
4.
Martins C, Fonseca I, Roque L, et al: PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry. Mod Pathol 2005;18:1048-1055.
5.
Voz ML, Agten NS, Van de Ven WJ, Kas K: PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II. Cancer Res 2000;60:106-113.
6.
Rotellini M, Palomba A, Baroni G, Franchi A: Diagnostic utility of PLAG1 immunohistochemical determination in salivary gland tumors. Appl Immunohistochem Mol Morphol 2014;22:390-394.
7.
El-Naggar AK, Huvos AG: Tumours of the salivary glands; in: Barnes L, Eveson JW, Reichart P, Sidransky D (eds): World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours. Lyon, IARC Press, 2005, pp 209-281.
8.
Pusztaszeri MP, García JJ, Faquin WC: Salivary gland FNA: new markers and new opportunities for improved diagnosis. Cancer Cytopathol 2016;124:307-316.
9.
Pusztaszeri MP, Faquin WC: Update in salivary gland cytopathology: recent molecular advances and diagnostic applications. Semin Diagn Pathol 2015;32:264-274.
10.
Katabi N, Ghossein R, Ho A, Dogan S, Zhang L, Sung YS, Antonescu CR: Consistent PLAG1 and HMGA2 abnormalities distinguish carcinoma ex-pleomorphic adenoma from its de novo counterparts. Hum Pathol 2015;46:26-33.
11.
Bahrami A, Dalton JD, Shivakumar B, Krane JF: PLAG1 alteration in carcinoma ex pleomorphic adenoma: immunohistochemical and fluorescence in situ hybridization studies of 22 Cases. Head Neck Pathol 2012;6:328-335.
12.
Bahrami A, Dalton JD, Krane JF, Fletcher CD: A subset of cutaneous and soft tissue mixed tumors are genetically linked to their salivary gland counterpart. Genes Chromosomes Cancer 2012;51:140-148.
13.
Matsuyama A, Hisaoka M, Nagao Y, Hashimoto H: Aberrant PLAG1 expression in pleomorphic adenomas of the salivary gland: a molecular genetic and immunohistochemical study. Virchows Arch 2011;458:583-592.
14.
Pusztaszeri MP, Sadow PM, Ushiku A, Bordignon P, McKee TA, Faquin WC: MYB immunostaining is a useful ancillary test for distinguishing adenoid cystic carcinoma from pleomorphic adenoma in fine-needle aspiration biopsy specimens. Cancer Cytopathol 2014;122:257-265.
15.
West RB, Kong C, Clarke N, et al: MYB expression and translocation in adenoid cystic carcinomas and other salivary gland tumors with clinicopathologic correlation. Am J Surg Pathol 2011;35:92-99.
16.
Brill LB, Kanner WA, Fehr A, et al: Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms. Mod Pathol 2011;24:1169-1176.
17.
Foo W, Jo V, Krane JF: Usefulness of translocation-associated immunohistochemical stains in the fine needle aspiration diagnosis of salivary gland neoplasms. Cancer Cytopathol 2016;124:397-405.
18.
Voz ML, Aström A-K, Kas K, Mark J, Stenman G, Van de Ven WJ: The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in upregulation of PLAG1 gene expression under control of the LIFR promoter. Oncogene 1998;16:1409-1416.
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