Oncocytoid Salivary Tumors: Differential Diagnosis and Utility of Newly Described Immunohistochemistry

Overview

Journal Head Neck Pathol

Specialties Oncology
Pathology

Date 2024 Mar 19

PMID 38502259

Authors

Nora Katabi

Affiliations

Soon will be listed here.

Abstract

Background: Oncocytoid salivary tumors include several entities such as oncocytoma, Warthin tumor, secretory carcinoma (SC), salivary duct carcinoma (SDC), acinic cell carcinoma (AciCC), oncocytic mucoepidermoid carcinoma (OMEC), intraductal carcinoma, and epithelial myoepithelial carcinoma (EMC). This review investigates the differential diagnosis of oncocytoid salivary tumors and explore the role of newly described immunostains as valuable tools for their diagnosing and potentially guiding treatment options.

Methods: We assess the utility of incorporating new immunohistochemical markers in routine practice to aid in diagnosing oncocytoid salivary tumors and potentially provide treatment options.

Results: In SDC, AR and Her2 immunostains are utilized as diagnostic tools and biomarkers for selecting patients who might benefit from Androgen-deprivation therapy (ADT) and HER2-targeted therapy. Furthermore, nuclear Pan-Trk immunostaining can aid in diagnosing SC. Additionally, NR4A3 immunostaining has been shown high sensitivity and specificity in identifying AciCC in both surgical and cytologic specimens. Similarly, RAS Q61R mutant-specific immunostaining, detected in EMC, may offer a cost-effective diagnostic marker for this tumor. Although further studies are required to evaluate the role of BSND, this marker has been reported to be positive in Warthin tumor and oncocytoma, aiding in differentiating them from other oncocytoid tumors, particularly OMEC. In addition, BRAFV600E mutant-specific immunostaining can serve as a diagnostic and potentially therapeutic marker for oncocytic intraductal carcinoma in mutation positive cases.

Conclusion: Oncocytoid salivary tumors may have overlapping morphologies, posing diagnostic challenges for pathologists. Recently described immunohistochemical markers may offer valuable tools for diagnosing and potentially guiding treatment options for these tumors.

Citing Articles

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The Utility of BSND Immunohistochemistry in the Differential Diagnosis of Oncocytic and Warthin-like Mucoepidermoid Carcinoma of Salivary Gland.

Xu B, Jungbluth A, Frosina D, Alabkaa A, Serrette R, Qin H Head Neck Pathol. 2024; 18(1):123.

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References

Haller F, Bieg M, Will R, Korner C, Weichenhan D, Bott A . Enhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands. Nat Commun. 2019; 10(1):368. PMC: 6341107. DOI: 10.1038/s41467-018-08069-x. View

Ho A . Androgen Receptor Pathway in Salivary Gland Cancer. J Clin Oncol. 2021; 39(36):4069-4072. DOI: 10.1200/JCO.21.01983. View

Shinmura K, Kato H, Kawanishi Y, Kamo T, Inoue Y, Yoshimura K . BSND is a Novel Immunohistochemical Marker for Oncocytic Salivary Gland Tumors. Pathol Oncol Res. 2017; 24(2):439-444. DOI: 10.1007/s12253-017-0248-9. View

Wolff A, Hammond M, Allison K, Harvey B, Mangu P, Bartlett J . Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018; 36(20):2105-2122. DOI: 10.1200/JCO.2018.77.8738. View

Alotaibi A, Alqarni M, Alnobi A, Tarakji B . Human Epidermal Growth Factor Receptor 2 (HER2/neu) in Salivary Gland Carcinomas: A Review of Literature. J Clin Diagn Res. 2015; 9(2):ZE04-8. PMC: 4378820. DOI: 10.7860/JCDR/2015/11289.5572. View

Skalova A, Agaimy A, Stanowska O, Baneckova M, Ptakova N, Ardighieri L . Molecular Profiling of Salivary Oncocytic Mucoepidermoid Carcinomas Helps to Resolve Differential Diagnostic Dilemma With Low-grade Oncocytic Lesions. Am J Surg Pathol. 2020; 44(12):1612-1622. DOI: 10.1097/PAS.0000000000001590. View

Takahashi H, Tada Y, Saotome T, Akazawa K, Ojiri H, Fushimi C . Phase II Trial of Trastuzumab and Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Salivary Duct Carcinoma. J Clin Oncol. 2018; 37(2):125-134. DOI: 10.1200/JCO.18.00545. View

Todorovic E, Weinreb I . Intraductal Carcinomas of the Salivary Gland. Surg Pathol Clin. 2021; 14(1):1-15. DOI: 10.1016/j.path.2020.09.003. View

Csanyi-Bastien M, Lanic M, Beaussire L, Ferric S, Francois A, Meseure D . Pan-TRK Immunohistochemistry Is Highly Correlated With NTRK3 Gene Rearrangements in Salivary Gland Tumors. Am J Surg Pathol. 2021; 45(11):1487-1498. DOI: 10.1097/PAS.0000000000001718. View

10.

Skalova A, Hyrcza M, Leivo I . Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Salivary Glands. Head Neck Pathol. 2022; 16(1):40-53. PMC: 9018948. DOI: 10.1007/s12105-022-01420-1. View

11.

Bishop J, Yonescu R, Batista D, Begum S, Eisele D, Westra W . 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(10):1982-8. PMC: 3779501. DOI: 10.1016/j.humpath.2013.03.017. View

12.

Simpson R . Salivary duct carcinoma: new developments--morphological variants including pure in situ high grade lesions; proposed molecular classification. Head Neck Pathol. 2013; 7 Suppl 1:S48-58. PMC: 3712088. DOI: 10.1007/s12105-013-0456-x. View

13.

Barasch N, Gong X, Kwei K, Varma S, Biscocho J, Qu K . Recurrent rearrangements of the Myb/SANT-like DNA-binding domain containing 3 gene (MSANTD3) in salivary gland acinic cell carcinoma. PLoS One. 2017; 12(2):e0171265. PMC: 5315303. DOI: 10.1371/journal.pone.0171265. View

14.

Can N, Lingen M, Mashek H, McElherne J, Briese R, Fitzpatrick C . Expression of Hormone Receptors and HER-2 in Benign and Malignant Salivary Gland Tumors. Head Neck Pathol. 2017; 12(1):95-104. PMC: 5873488. DOI: 10.1007/s12105-017-0833-y. View

15.

Haller F, Skalova A, Ihrler S, Markl B, Bieg M, Moskalev E . Nuclear NR4A3 Immunostaining Is a Specific and Sensitive Novel Marker for Acinic Cell Carcinoma of the Salivary Glands. Am J Surg Pathol. 2019; 43(9):1264-1272. DOI: 10.1097/PAS.0000000000001279. View

16.

Seethala R, Barnes E, Hunt J . Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract. Am J Surg Pathol. 2007; 31(1):44-57. DOI: 10.1097/01.pas.0000213314.74423.d8. View

17.

Canberk S, Onenerk M, Sayman E, Canbey Goret C, Erkan M, Atasoy T . Is DOG1 really useful in the diagnosis of salivary gland acinic cell carcinoma? - A DOG1 (clone K9) analysis in fine needle aspiration cell blocks and the review of the literature. Cytojournal. 2015; 12:18. PMC: 4564987. DOI: 10.4103/1742-6413.162774. View

18.

Weinreb I, Seethala R, Perez-Ordonez B, Chetty R, Hoschar A, Hunt J . Oncocytic mucoepidermoid carcinoma: clinicopathologic description in a series of 12 cases. Am J Surg Pathol. 2008; 33(3):409-16. DOI: 10.1097/PAS.0b013e318184b36d. View

19.

Boon E, Bel M, van Boxtel W, van der Graaf W, van Es R, Eerenstein S . A clinicopathological study and prognostic factor analysis of 177 salivary duct carcinoma patients from The Netherlands. Int J Cancer. 2018; 143(4):758-766. PMC: 6055864. DOI: 10.1002/ijc.31353. View

20.

Dalin M, Watson P, Ho A, Morris L . Androgen Receptor Signaling in Salivary Gland Cancer. Cancers (Basel). 2017; 9(2). PMC: 5332940. DOI: 10.3390/cancers9020017. View