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Secretory carcinoma (SC) of the salivary gland represents a unique diagnostic entity that often masquerades as other low-grade neoplasms. Clinicians must recognize that a definitive salivary secretory carcinoma diagnosis relies on a combination of morphological evaluation and advanced ancillary testing. Although these tumours grow slowly, their cytological features frequently overlap with mucoepidermoid carcinoma and acinic cell carcinoma. Consequently, pathologists must remain vigilant during the initial assessment of fine-needle aspiration cytology (FNAC) specimens.
A primary challenge in identifying SC is its lack of pathognomonic features on routine smears. However, researchers have identified several characteristic clues. Neoplastic cells typically display uniform, round nuclei with distinct nucleoli and abundant vacuolated cytoplasm. Furthermore, the presence of a bubbly or mucinous background often suggests the diagnosis. Pathologists should also evaluate the cellular architecture, looking specifically for papillary or microcystic growth patterns. Because other tumours exhibit similar vacuolation, evaluating the entire cytological context is essential.
To improve accuracy, the application of immunocytochemistry (ICC) on cell blocks is highly recommended. Specifically, SC usually shows strong positivity for S100 and mammaglobin, while remaining negative for DOG1. This specific profile helps distinguish it from acinic cell carcinoma. Additionally, identifying the ETV6-NTRK3 translocation remains the gold standard for confirmation. Therefore, integrating clinical findings with meticulous microscopic analysis ensures a reliable diagnosis for every patient.
Secretory carcinoma often mimics acinic cell carcinoma and low-grade mucoepidermoid carcinoma due to overlapping features such as cytoplasmic vacuolation and slow growth patterns. Careful evaluation of background secretions and ancillary testing is required for accurate differentiation.
Immunocytochemistry typically reveals that secretory carcinoma cells are positive for S100 and mammaglobin but negative for DOG1. This specific immunophenotype is crucial for distinguishing it from other salivary gland tumours during cytological examination on cell blocks.
Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or establish a doctor-patient relationship. Always consult a qualified healthcare professional for medical concerns or diagnosis. Refer to the latest local and national guidelines for clinical practice.
References
Singh M et al. A Secret Worth Telling: The Salivary Secret (Ory) Affair. Cytopathology. 2026 May 07. doi: 10.1111/cyt.70086. PMID: 42098902.
Kim YA et al. Cytopathologic Features of Secretory Carcinoma of Salivary Gland: Report of Two Cases. Journal of Pathology and Translational Medicine. 2019;53(1):70-74. doi: 10.4132/jptm.2018.11.09.
Prabhakar P et al. Oncocytic Salivary Gland Tumours: Cytological Features and Diagnostic Pitfalls. Indian Journal of Otolaryngology and Head and Neck Surgery. 2022 Dec;74(Suppl 3):6112-6118. doi: 10.1007/s12070-021-02764-w.

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