Noreen Akhtar, Aribah Atiq, Asif Loya, Usman Hassan, Mudassir Hussain, Muhammad Abu-Bakar, Sajid Mushtaq


Background: Secretory carcinoma of the salivary gland (SC) is a new entity that harbours a specific ETV6 gene rearrangement. The clinical behaviour of this tumour is not well-known as it is a relatively new entity but it is generally considered as a tumour of low malignant potential. The objective of the study was to find out the frequency of ETV6 translocation in cases diagnosed based on histology and immunohistochemistry, to study morphological features and immunohistochemical findings of our cases and to determine the survival and disease-free status of our patients. Methods: Twenty-five diagnosed cases of SC were retrieved from the archives of SKMCH and RC. Diagnosis was made primarily based on morphology and immunohistochemistry. Immunohistochemistry includes S100, p63, mammaglobin, DOG 1, GCDFP-15, TTF-1, GATA3, SMA, AMA, and AR. The diagnosis was further confirmed by molecular testing, i.e., Fluorescence in situ hybridization (FISH) studies to observe specific ETV6 gene break. Follow up of the patients was done by developing a questionnaire. Statistical analysis of the data was done using SPSS-23.0. Results: The mean age of diagnosis was 41±17.4 and the male to female ratio was 1.5:15. The mean size of the tumour was 45.48±27.35. The most common site of the tumour was parotid gland (60%). On morphology, SC showed a wide range of morphological patterns, most common being the tubular, microcystic, intraductal, and papillary. Immunohistochemical stains mammaglobin (22/22), GCDFP-15(15/15) and GATA3 (10/10) showed 100% positive result. However, all cases were negative for p63 (0/18) and DOG 1(0/11). ETV6 break was seen in 17/17 cases (100%). The mean disease-free survival was 75 months and the overall survival was 51.90±2.80 months. Conclusion: This study highlights the presence of specific molecular alteration in all cases, which were diagnosed based on morphology and immunohistochemistry.

Keywords: Secretory carcinoma of Salivary gland; ETV6

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Ska´lova´ 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 tumour entity. Am J Surg Pathol 2010;34(5):599–608.

Stevens TM, Kovalovsky AO, Velosa C, Shi Q, Dai Q, Owen RP, et al. Mammary analogue secretory carcinoma, and mimickers: a comparative study. Modern Pathol 2015;28:1084–100.

Marchio C, Irvani M, Natrajan R, Lambros MBK, Geyer FC, Savage K, et al. Mixed micropapillary-ductal carcinoma of the breast: a genomic and immunohistochemical analysis of morphologically distinct components. J Parhol 2009;218(3):301–15.

Skalova A, Vanecek T, Simpson RH, Laco J, Majewska H, Baneckova M, et al. Mammary analogue secretory carcinoma of salivary glands: molecular analysis of 25 ETV6 gene rearranged tumours with lack of detection of classical ETV6-NTRK3 fusion transcript by standard RT-PCR: report of 4 cases harboring ETV6-X gene fusion. Am J surg Pathol 2016;40(1):3–13.

Reis-Filho JS, Natrajan R, Vatcheva R, Lambros MBK, Marchio C, Mahler-Araujo B, et al. Is acinic cell carcinoma a variant of secretory carcinoma? : A FISH study using ETV6 ‘split apart’ probes. Histopathology 2008;52(7):840–6.

Bishop JA, Yonescu R, Batista D, Eisele DW, Westra WH. Most nonparotid acinic cell carcinomas represent mammary analogue secretory carcinoma. Am J Surg Pathol 2013;37(7):1053–7.

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(1):35–9.

Bissinger O, Götz C, Kolk A, Bier H, Agaimy A, Frenzel H, et al. Mammary Analogue Secretory Carcinoma of Salivary Glands: Diagnostic Pitfall with Distinct Immunohistochemical Profile and Molecular Features. Rare Tumours 2017;9(3):89–92.

Ellis G, Simpson RHW. Acinic cell carcinoma. In: Barnes EL, Eveson JW, Reichart P, editos. World Health Organization Classification of Tumours. Pathology and Genetics of Head and Neck Tumours. Lyon: IARC Press, 2005; p.216–8.

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(7):919–29.

Shah AA, Wenig BM, LeGallo RD, Mills SE, Stelow EB. Morphology in conjunction with immunohistochemistry is sufficient for the diagnosis of mammary analogue secretory carcinoma. Head Neck Pathol 2015;9(1):85–95.

Hamada T. Mucin expression in pleomorphic adenoma of salivary gland: a potential role for MUC1 as a marker to predict recurrence. J Clin Pathol 2004;57(8):813–21.

Mythily C, Vasahar A. P63 expression in pleomorphic adenoma and Mucoepidermoid carcinoma. Int J Pharm Bio Sci 2016;7(4):507–10.

Okumura Y, Miyabe S, Nakayama T, Fujiyoshi Y, Hattori H, Shimozato K, et al. Impact of CRTC1/3-MAML2 fusions on histological classification and prognosis of mucoepidermoid carcinoma. Histopathology 2011;59(1):90–7.

Nakayama T, Miyabe S, Okabe M, Sakuma H, Ijichi K, Hasegawa Y, et al. Clinicopathological significance of the CRTC3–MAML2 fusion transcript in mucoepidermoid carcinoma. Mod Pathol 2009;22(12):1575–81.

Stevens T, Parekh V. Mammary Analogue Secretory Carcinoma. Arch Pathol Lab Med 2016;140(9):997–1001.

Ni H, Zhang X, Wang X, Xia Q, Lv J, Wang X, et al. Extended immunologic and genetic lineage of mammary analogue secretory carcinoma of salivary glands. Hum Pathol 2016;58:97–104.

Khurram S, Sultan-Khan J, Atkey N, Speight P. Cytogenetic and immunohistochemical characterization of mammary analogue secretory carcinoma of salivary glands. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;122(6):731–42.

Said-Al-Naief N, Carlos R, Vance G, Miller C, Edwards P. Combined DOG1 and Mammaglobin Immunohistochemistry Is Comparable to ETV6-breakapart Analysis for Differentiating Between Papillary Cystic Variants of Acinic Cell Carcinoma and Mammary Analogue Secretory Carcinoma. Int J Surg Pathol 2016;25(2):127–40.

Bajpai M, Pardhe N. Immunohistochemical Expression of CD-117 (c-KIT), P-53 and Ki-67 in Adenoid Cystic Carcinoma of Palate. J Coll Physicians Surg Pak 2018;28(6):S130S132.

Bajpai M, Pardhe N, Chandolia B, Arora M. Central Acinic Cell Carcinoma of the Mandible Simulating as Benign Odontogenic Lesion: A Case Report. Iran J Med Sci 2018;43(2):223–6.

Boon E, Valstar M, van der Graaf W, Bloemena E, Willems S, Meeuwis C, et al. Clinicopathological characteristics and outcome of 31 patients with ETV6-NTRK3 fusion gene confirmed (mammary analogue) secretory carcinoma of salivary glands. Oral Oncol 2018;82:29–33.

BA K. Systematic review of mammary analog secretory carcinoma of salivary glands at 7 years after description. Head Neck 2017;39(6):1243–8.

Skálová A, Vanecek T, Majewska H, Laco J, Grossmann P, Simpson R, et al. Mammary Analogue Secretory Carcinoma of Salivary Glands With High-grade Transformation. Am J Surg Pathol 2014;38(1):23–33.

Skalova A. Mammary Analogue Secretory Carcinoma of Salivary Gland Origin: An Update and Expanded Morphologic and Immunohistochemical Spectrum of Recently Described Entity. Head Neck Pathol 2013;7(Suuppl 1):30–6.

Chiosea S, Griffith C, Assaad A, Seethala R. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. Histopathology 2012;61(3):387–94.

Wang B. Update molecular diagnosis and treatment on salivary gland tumours - Mammary Analog Secretory Carcinoma. Med Case Rep 2018;2018:4.


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