{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:41:10Z","timestamp":1788997270398,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Sclerosing polycystic adenoma (SPA) is a rare neoplasm occurring in the salivary glands, mainly the parotid gland. Although it was originally thought to represent a non-neoplastic process, recent genetic data have proven its monoclonality, supporting its neoplastic origin. We report a case of a 73-year-old woman who presented with left neck swelling and pain. A 3 cm hypoechoic, heterogeneous, solid mass was identified on neck ultrasonography within the left parotid gland. Fine needle aspiration revealed benign acinar cells and lymphocytes. Left partial superficial parotidectomy was performed and a diagnosis of SPA was made. Targeted next-generation sequencing (NGS) revealed three clinically significant alterations in the PIK3R1, HRAS, and AR genes. Alterations in the PIK3R1 gene have been previously reported in cases of SPA; however, this study is the first to report two novel clinically significant genomic alterations in the HRAS and AR genes. AR protein expression by immunohistochemistry was strongly and diffusely positive in the neoplastic epithelial cells compared to the adjacent normal salivary gland tissue, which was dead negative for AR. This molecular profile will enhance our understanding of the molecular pathways underlying the development of this tumor. Although this entity was initially thought to be a reactive process, evidence from our case and similar cases strongly support the notion that it is neoplastic due to the presence of specific genetic alterations linked to it.<\/jats:p>","DOI":"10.3390\/cimb45020061","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T02:52:21Z","timestamp":1674183141000},"page":"954-962","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["PIK3R1, HRAS and AR Gene Alterations Associated with Sclerosing Polycystic Adenoma of the Parotid Gland"],"prefix":"10.3390","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3799-2595","authenticated-orcid":false,"given":"Hisham F.","family":"Bahmad","sequence":"first","affiliation":[{"name":"The Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Elhammady","sequence":"additional","affiliation":[{"name":"Florida Cancer Specialists & Research Institute, Fort Myers, FL 33916, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Gass","sequence":"additional","affiliation":[{"name":"Florida Cancer Specialists & Research Institute, Fort Myers, FL 33916, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Paramo","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Mount Sinai Medical Center, Miami Beach, FL 33140, USA"},{"name":"Department of Translational Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Poppiti","sequence":"additional","affiliation":[{"name":"The Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140, USA"},{"name":"Department of Translational Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Alexis","sequence":"additional","affiliation":[{"name":"The Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140, USA"},{"name":"Department of Translational Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s12105-014-0532-x","article-title":"Salivary gland tumor \u201cwishes\u201d to add to the next WHO Tumor Classification: Sclerosing polycystic adenosis, mammary analogue secretory carcinoma, cribriform adenocarcinoma of the tongue and other sites, and mucinous variant of myoepithelioma","volume":"8","author":"Gnepp","year":"2014","journal-title":"Head Neck Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/00000478-199602000-00004","article-title":"Sclerosing polycystic adenosis of major salivary glands. A clinicopathologic analysis of nine cases","volume":"20","author":"Smith","year":"1996","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1097\/00000478-200608000-00002","article-title":"Clonal nature of sclerosing polycystic adenosis of salivary glands demonstrated by using the polymorphism of the human androgen receptor (HUMARA) locus as a marker","volume":"30","author":"Gnepp","year":"2006","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s004280100481","article-title":"Sclerosing polycystic adenosis of parotid gland with dysplasia and ductal carcinoma in situ. Report of three cases with immunohistochemical and ultrastructural examination","volume":"440","author":"Michal","year":"2002","journal-title":"Virchows Arch."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1097\/01.pas.0000186394.64840.1d","article-title":"Sclerosing polycystic adenosis of the salivary gland: A report of 16 cases","volume":"30","author":"Gnepp","year":"2006","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S97","DOI":"10.1007\/s12105-013-0465-9","article-title":"Sclerosing polycystic adenosis of salivary glands: A review with some emphasis on intraductal epithelial proliferations","volume":"7","author":"Petersson","year":"2013","journal-title":"Head Neck Pathol."},{"key":"ref_7","first-page":"982432","article-title":"Sclerosing polycystic adenosis of the retromolar pad area: A case report","volume":"2014","author":"Mokhtari","year":"2014","journal-title":"Case Rep. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1016\/j.humpath.2013.01.017","article-title":"A unique case of sclerosing polycystic adenosis of the sinonasal tract","volume":"44","author":"Su","year":"2013","journal-title":"Hum. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00428-014-1551-4","article-title":"Invasive carcinoma arising from sclerosing polycystic adenosis of the salivary gland","volume":"464","year":"2014","journal-title":"Virchows Arch."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1007\/s12105-019-01088-0","article-title":"Sclerosing Polycystic \u201cAdenosis\u201d of Salivary Glands: A Neoplasm Characterized by PI3K Pathway Alterations More Correctly Named Sclerosing Polycystic Adenoma","volume":"14","author":"Bishop","year":"2020","journal-title":"Head Neck Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1097\/PAS.0000000000000883","article-title":"Newly Described Entities in Salivary Gland Pathology","volume":"41","author":"Gnepp","year":"2017","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_12","unstructured":"El-Naggar, A.K., Chan, J.K., and Grandis, J.R. (2017). WHO Classification of Head and Neck Tumours, IARC Publications."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s12672-014-0190-1","article-title":"Androgen receptor splice variants in the era of enzalutamide and abiraterone","volume":"5","author":"Nakazawa","year":"2014","journal-title":"Horm. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1158\/0008-5472.CAN-08-2764","article-title":"Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer","volume":"69","author":"Hu","year":"2009","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16759","DOI":"10.1073\/pnas.1012443107","article-title":"Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptor","volume":"107","author":"Watson","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/jcb.20898","article-title":"Androgen axis in prostate cancer","volume":"99","author":"Culig","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1056\/NEJMoa1315815","article-title":"AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer","volume":"371","author":"Antonarakis","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_18","first-page":"1","article-title":"Resistance to Novel Antiandrogen Therapies in Metastatic Castration-Resistant Prostate Cancer","volume":"10","author":"Boudadi","year":"2016","journal-title":"Clin. Med. Insights Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6570","DOI":"10.1158\/1078-0432.CCR-14-1746","article-title":"Alterations associated with androgen receptor gene activation in salivary duct carcinoma of both sexes: Potential therapeutic ramifications","volume":"20","author":"Mitani","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Dalin, M.G., Watson, P.A., Ho, A.L., and Morris, L.G. (2017). Androgen Receptor Signaling in Salivary Gland Cancer. Cancers, 9.","DOI":"10.3390\/cancers9020017"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0092-8674(86)90495-2","article-title":"Biological and biochemical properties of human rasH genes mutated at codon 61","volume":"44","author":"Der","year":"1986","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1177\/1947601911411084","article-title":"Ras in cancer and developmental diseases","volume":"2","author":"Santos","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1158\/1535-7163.MCT-19-0660","article-title":"A Historic Perspective and Overview of H-Ras Structure, Oncogenicity, and Targeting","volume":"19","author":"Shu","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.semcancer.2018.03.001","article-title":"RAS-mediated oncogenic signaling pathways in human malignancies","volume":"54","author":"Khan","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"18224","DOI":"10.18632\/oncotarget.4015","article-title":"Targeted next generation sequencing of parotid gland cancer uncovers genetic heterogeneity","volume":"6","author":"Vollbrecht","year":"2015","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ross, R.L., Burns, J.E., Taylor, C.F., Mellor, P., Anderson, D.H., and Knowles, M.A. (2013). Identification of mutations in distinct regions of p85 alpha in urothelial cancer. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0084411"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.ccr.2009.10.016","article-title":"Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation","volume":"16","author":"Jaiswal","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ccell.2018.01.021","article-title":"Systematic Functional Annotation of Somatic Mutations in Cancer","volume":"33","author":"Ng","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/s41467-018-03867-9","article-title":"Characterization of PIK3CA and PIK3R1 somatic mutations in Chinese breast cancer patients","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.oraloncology.2012.02.021","article-title":"The PI3K\/AKT\/mTOR signalling pathway is active in salivary gland cancer and implies different functions and prognoses depending on cell localisation","volume":"48","author":"Ettl","year":"2012","journal-title":"Oral Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1002\/cncr.31600","article-title":"Frequent PTEN loss and differential HER2\/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy","volume":"124","author":"Saintigny","year":"2018","journal-title":"Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1097\/PAS.0b013e3182880d5a","article-title":"PIK3CA mutations and PTEN loss in salivary duct carcinomas","volume":"37","author":"Griffith","year":"2013","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1097\/PAS.0000000000000410","article-title":"Molecular characterization of apocrine salivary duct carcinoma","volume":"39","author":"Chiosea","year":"2015","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1097\/PAS.0000000000000952","article-title":"Recurrent RET Gene Rearrangements in Intraductal Carcinomas of Salivary Gland","volume":"42","author":"Weinreb","year":"2018","journal-title":"Am. J. Surg. Pathol."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/45\/2\/61\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:11:09Z","timestamp":1760119869000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/45\/2\/61"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,19]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["cimb45020061"],"URL":"https:\/\/doi.org\/10.3390\/cimb45020061","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,19]]}}}