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Sclerosing Polycystic “Adenosis” of Salivary Glands: A Neoplasm Characterized by PI3K Pathway Alterations More Correctly Named Sclerosing Polycystic Adenoma

  • Justin A. BishopEmail author
  • Jeffrey Gagan
  • Daniel Baumhoer
  • Anne L. McLean-Holden
  • Bahram R. Oliai
  • Marta Couce
  • Lester D. R. Thompson
Original Paper
  • 13 Downloads

Abstract

Sclerosing polycystic adenosis (SPA) is a rare benign salivary gland lesion that usually arises from the parotid gland. SPA was originally interpreted to be a non-neoplastic alteration analogous to fibrocystic changes of the breast, but now there is uncertainty about whether it may represent a neoplasm. SPA often contains intraductal proliferations with an appearance similar to ductal neoplasia of the breast, and one study reported X-chromosome inactivation using polymorphisms of the human androgen receptor (Skalova et al., in AJSP 30:939–944, 2006). We investigated the genetics of SPA through targeted next generation sequencing (NGS). Four cases of SPA were retrieved from the authors’ consultation files. A custom, targeted NGS panel including 1425 cancer‐related genes was performed on all cases, followed by immunohistochemistry for PTEN. All four cases developed in females, ranging from 40 to 69 years (mean 52.5 years), affecting the parotid (n = 3) and submandibular glands (n = 1). All cases exhibited characteristic histologic features of SPA: well-circumscribed lesions with fibrosis and an admixture of ducts, myoepithelial cells and acinar cells, the latter containing brightly eosinophilic intracytoplasmic granules. Two cases had intraductal apocrine epithelial proliferations. By targeted NGS, loss-of-function mutations in PTEN were revealed in all 4 cases. In addition, 2 of 4 cases harbored PIK3CA mutations and 2 of 4 possessed PIK3R1 alterations; one case lacked both PIK3CA and PIK3R1 mutations. PTEN expression by immunohistochemistry was lost in the ductal and acinar elements but not the myoepithelial cells in all cases. SPA is characterized by genetic alterations in the PI3K pathway, with PTEN mutations seen most frequently. This molecular profile is similar to salivary duct carcinoma and the apocrine variant of intraductal carcinoma (i.e., salivary duct carcinoma-in situ). PI3K pathway alterations were found in cases both with and without intraductal apocrine proliferations, and PTEN immunohistochemistry suggested that the ductal and acinar cells, but not myoepithelial cells, were affected. Taken together, these findings strongly support that SPA is a neoplasm, more correctly named “sclerosing polycystic adenoma.” The salivary duct carcinoma-like genetic alterations, coupled with the fact that the surrounding myoepithelial cells appear to be non-neoplastic, suggest a close relationship between SPA and apocrine intraductal carcinoma.

Keywords

Sclerosing polycystic adenosis Sclerosing polycystic adenoma Salivary gland neoplasms Intraductal carcinoma Parotid gland Phosphatidylinositol 3-Kinases (PI3K) PTEN Oncogenes Salivary ducts 

Notes

Acknowledgements

The views expressed are those of the authors solely and do not represent endorsement from Southern California Permanente Medical Group or the University of Texas Southwestern Medical Center.

Funding

This study was funded in part by the Jane B. and Edwin P. Jenevein M.D Endowment for Pathology at UT Southwestern Medical Center.

Compliance with Ethical Standards

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 #5968), which did not require informed consent.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PathologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Bone Tumor Reference Center at the Institute of PathologyUniversity Hospital Basel and University of BaselBaselSwitzerland
  3. 3.ProPathDallasUSA
  4. 4.Department of PathologyUniversity Hospital Cleveland Medical CenterClevelandUSA
  5. 5.Southern California Permanente Medical GroupWoodland Hills Medical CenterWoodland HillsUSA

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