Skip to main content

Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases


Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors’ files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1–216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6


  1. 1.

    Skalova A, Stenman G, Simpson RHW, et al. The role of molecular testing in the differential diagnosis of salivary gland carcinomas. Am J Surg Pathol. 2018;42:e11–27.

    Article  Google Scholar 

  2. 2.

    Bishop JA, Weinreb I, Swanson D, et al. Microsecretory adenocarcinoma: a novel salivary gland tumor characterized by a recurrent MEF2C-SS18 fusion. Am J Surg Pathol. 2019;43:1023–32.

    Article  Google Scholar 

  3. 3.

    Kawakami F, Nagao T, Honda Y, et al. Microsecretory adenocarcinoma of the hard palate: a case report of a recently described entity. Pathol Int. 2020;70:781–5.

    CAS  Article  Google Scholar 

  4. 4.

    Bishop JA, Gagan J, Baumhoer D, et al. Sclerosing polycystic "Adenosis" of salivary glands: a neoplasm characterized by PI3K pathway alterations more correctly named sclerosing polycystic adenoma. Head Neck Pathol. 2019.

  5. 5.

    Agaimy A, Togel L, Haller F, et al. YAP1-NUTM1 gene fusion in porocarcinoma of the external auditory canal. Head Neck Pathol. 2020;14:982–90.

    Article  Google Scholar 

  6. 6.

    Haas BJ, Dobin A, Li B, et al. Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods. Genome Biol. 2019;20:213.

    Article  Google Scholar 

  7. 7.

    Skalova A, Vanecek T, Simpson RHW, et al. Molecular advances in salivary gland pathology and their practical application. Diagn Histopathol. 2012;18:388–96.

    Article  Google Scholar 

  8. 8.

    Skalova A, Vanecek T, Sima R, 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;34:599–608.

    Article  Google Scholar 

  9. 9.

    Epivatianos A, Poulopoulos A, Dimitrakopoulos I, et al. Application of α-smooth muscle actin and c-kit in the differential diagnosis of adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma. Oral Oncol. 2007;43:67–76.

    CAS  Article  Google Scholar 

  10. 10.

    Beltran D, Faquin WC, Gallagher G, et al. Selective immunohistochemical comparison of polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma. J Oral Maxillofacial Surg. 2006;64:415–23.

    Article  Google Scholar 

  11. 11.

    Bishop JA, Koduru P, Veremis BM, et al. SS18 Break-apart fluorescence in situ hybridization is a practical and effective method for diagnosing microsecretory adenocarcinoma of salivary glands. Head Neck Pathol. 2021.

  12. 12.

    Rashidi A, Fisher SI. FISH-negative, cytogenetically cryptic acute promyelocytic leukemia. Blood Cancer J. 2015;5:e320.

    CAS  Article  Google Scholar 

  13. 13.

    Antonescu CR, Katabi N, Zhang L, et al. EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosomes Cancer. 2011;50:559–70.

    CAS  Article  Google Scholar 

  14. 14.

    Brayer KJ, Frerich CA, Kang H, et al. Recurrent fusions in MYB and MYBL1 define a common, transcription factor-driven oncogenic pathway in salivary gland adenoid cystic carcinoma. Cancer Discov. 2016;6:176–87.

    CAS  Article  Google Scholar 

  15. 15.

    Dalin MG, Desrichard A, Katabi N, et al. Comprehensive molecular characterization of salivary duct carcinoma reveals actionable targets and similarity to apocrine breast cancer. Clin Cancer Res. 2016;22:4623–33.

    CAS  Article  Google Scholar 

  16. 16.

    Mitani Y, Liu B, Rao PH, et al. Novel MYBL1 gene rearrangements with recurrent MYBL1-NFIB fusions in salivary adenoid cystic carcinomas lacking t(6;9) translocations. Clin Cancer Res. 2016;22:725–33.

    CAS  Article  Google Scholar 

  17. 17.

    Rettig EM, Talbot CC Jr, Sausen M, et al. Whole-genome sequencing of salivary gland adenoid cystic carcinoma. Cancer Prev Res. 2016;9:265–74.

    CAS  Article  Google Scholar 

  18. 18.

    Rooper LM, Mansour M, Yonescu R, et al. The decline of salivary adenocarcinoma not otherwise specified as a tumor entity: reclassification using contemporary immunohistochemical profiling and diagnostic criteria. Am J Surg Pathol. 2020.

  19. 19.

    Rooper L, Sharma R, Bishop JA. Polymorphous low grade adenocarcinoma has a consistent p63+/p40- immunophenotype that helps distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma. Head Neck Pathol. 2015;9:79–84.

    Article  Google Scholar 

  20. 20.

    Agaimy A, Mueller SK, Bumm K, et al. Intraductal papillary mucinous neoplasms of minor salivary glands with AKT1 p.Glu17Lys mutation. Am J Surg Pathol. 2018;42:1076–82.

    Article  Google Scholar 

  21. 21.

    Rooper LM, Argyris PP, Thompson LDR, et al. Salivary mucinous adenocarcinoma is a histologically diverse single entity with recurrent AKT1 E17K mutations: clinicopathologic and molecular characterization with proposal for a unified classification. Am J Surg Pathol. 2021.

  22. 22.

    Ghannoum JE, Freedman PD. Signet-ring cell (mucin-producing) adenocarcinomas of minor salivary glands. Am J Surg Pathol. 2004;28:89–93.

    Article  Google Scholar 

  23. 23.

    Bastaki JM, Purgina BM, Dacic S, et al. Secretory myoepithelial carcinoma: a histologic and molecular survey and a proposed nomenclature for mucin producing signet ring tumors. Head Neck Pathol. 2014;8:250–60.

    Article  Google Scholar 

  24. 24.

    Gnepp DR. Mucinous myoepithelioma, a recently described new myoepithelioma variant. Head Neck Pathol. 2013;7(Suppl 1):S85-89.

    Article  Google Scholar 

Download references


This study was funded by the Jane B. and Edwin P. Jenevein M.D Endowment for Pathology at UT Southwestern Medical Center. No external funding was obtained for this study.

Author information



Corresponding author

Correspondence to Justin A. Bishop.

Ethics declarations

Conflict of interest

All authors declare that he/she has no conflict of interest as it relates to this research project.

Ethical Approval

All procedures performed in this retrospective data analysis involving human participants were in accordance with the ethical standards of the institutional review board (IRB 112017–073), which did not require informed consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bishop, J.A., Sajed, D.P., Weinreb, I. et al. Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases. Head and Neck Pathol (2021).

Download citation


  • Salivary gland neoplasms
  • Adenocarcinoma not otherwise specified
  • Microsecretory adenocarcinoma
  • MEF2C-SS18