Sinonasal Secretory Carcinoma of Salivary Gland with High Grade Transformation: A Case Report of this Under-Recognized Diagnostic Entity with Prognostic and Therapeutic Implications
Secretory carcinoma (SC) is a recently described salivary gland carcinoma with characteristic ETV6-NTRK3 fusion. In this case report, we described a SC of the maxillary sinus that underwent high grade transformation in a 61-year-old patient. The diagnosis was confirmed by the presence of ETV6 translocation. Within the sinonasal tract, SC is an important differential diagnosis especially of sinonasal adenocarcinoma, non-intestinal type (non-ITAC), as these two entities bears histologic and immunophenotypic similarity. Distinction between these two tumors can be challenging based on the morphology alone and may require additional immunohistochemical and molecular studies. It is important to recognize that SC can occur in the sinonasal tract as correctly diagnosing SC may be prognostic relevant and may provide new targeted therapeutic avenues for these patients.
KeywordsSecretory carcinoma Sinonasal non-intestinal type adenocarcinoma High grade transformation ETV6-NTRK3 fusion
This study was funded in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Compliance with Ethical Standards
Conflict of interest
All authors declare that he/she has no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 1.El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. World Health Organization classification of tumours: pathology and genetics of head and neck tumours. 4th ed. Lyon: IARC Press; 2017.Google Scholar
- 2.Skalova 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 tumor entity. Am J Surg Pathol. 2010;34(5):599–608. doi: 10.1097/PAS.0b013e3181d9efcc.PubMedGoogle Scholar
- 11.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 tumors 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. doi: 10.1097/PAS.0000000000000537.CrossRefPubMedGoogle Scholar
- 14.Connor A, Perez-Ordonez B, Shago M, Skalova A, Weinreb I. Mammary analog secretory carcinoma of salivary gland origin with the ETV6 gene rearrangement by FISH: expanded morphologic and immunohistochemical spectrum of a recently described entity. Am J Surg Pathol. 2012;36(1):27–34. doi: 10.1097/PAS.0b013e318231542a.CrossRefPubMedGoogle Scholar
- 17.Projetti F, Lacroix-Triki M, Serrano E, Vergez S, Barres BH, Meilleroux J, et al. A comparative immunohistochemistry study of diagnostic tools in salivary gland tumors: usefulness of mammaglobin, gross cystic disease fluid protein 15, and p63 cytoplasmic staining for the diagnosis of mammary analog secretory carcinoma? J Oral Pathol Med. 2015;44(4):244–51. doi: 10.1111/jop.12226.CrossRefPubMedGoogle Scholar
- 18.Andreasen S, Skalova A, Agaimy A, Bishop JA, Laco J, Leivo I, et al. ETV6 gene rearrangements characterize a morphologically distinct subset of sinonasal low-grade non-intestinal-type adenocarcinoma: a novel translocation-associated carcinoma restricted to the sinonasal tract. Am J Surg Pathol. 2017. doi: 10.1097/PAS.0000000000000912.Google Scholar
- 22.Drilon A, Li G, Dogan S, Gounder M, Shen R, Arcila M, et al. What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC). Ann Oncol. 2016;27(5):920–6. doi: 10.1093/annonc/mdw042.CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Doebele RC, Davis LE, Vaishnavi A, Le AT, Estrada-Bernal A, Keysar S, et al. An oncogenic NTRK fusion in a patient with soft-tissue sarcoma with response to the tropomyosin-related kinase inhibitor LOXO-101. Cancer Discov. 2015;5(10):1049–57. doi: 10.1158/2159-8290.CD-15-0443.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Skalova A, Vanecek T, Majewska H, Laco J, Grossmann P, Simpson RH, et al. Mammary analogue secretory carcinoma of salivary glands with high-grade transformation: report of 3 cases with the ETV6-NTRK3 gene fusion and analysis of TP53, beta-catenin, EGFR, and CCND1 genes. Am J Surg Pathol. 2014;38(1):23–33. doi: 10.1097/PAS.0000000000000088.CrossRefPubMedGoogle Scholar
- 29.Cipriani NA, Blair EA, Finkle J, Kraninger JL, Straus CM, Villaflor VM, et al. Salivary gland secretory carcinoma with high-grade transformation, CDKN2A/B loss, distant metastasis, and lack of sustained response to crizotinib. Int J Surg Pathol. 2017. doi: 10.1177/1066896917709350.