{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:23:20Z","timestamp":1793039000616,"version":"4.5.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:p>Sclerosing polycystic adenoma (SPA) is a rare salivary gland neoplasm originally thought to represent a non-neoplastic lesion. Recently we have encountered an index case of apocrine intraductal carcinoma of parotid gland of 62-year-old man with invasive salivary duct carcinoma component arising from SPA, a combination of tumor entities that has never been published so far. Here, we further explore the nature of SPA by evaluating 36 cases that were identified from the authors\u2019 consultation files. The patients were 25 females and 11 males aged 11 to 79 years (mean, 47.8\u2009y). All tumors originated from the parotid gland. Their size ranged from 11 to 70\u2009mm (mean, 28\u2009mm). Histologically, all cases revealed characteristic features of SPA, such as lobulated well-circumscribed growth, focal hyalinized sclerosis, presence of large acinar cells with abundant brightly eosinophilic intracytoplasmic granules, and ductal components with variable cytomorphologic characteristics, including foamy, vacuolated, apocrine, mucous, clear\/ballooned, squamous, columnar and oncocyte-like cells. In all cases, there were foci of intraluminal solid and cribriform intercalated duct-like epithelial proliferations with variable dysplasia which were positive for S100 protein and SOX10, and fully enveloped by an intact layer of myoepithelial cells. In addition, 14\/36 cases (39%) had focal intraductal cribriform and micropapillary apocrine-type dysplastic epithelial structures composed of cells positive for androgen receptors and negative for S100\/SOX10. The intraductal proliferations of both types showed focal mild to severe dysplasia in 17 cases (17\/36; 47%). Two cases showed overt malignant morphology ranging from high-grade intraductal carcinoma to invasive carcinoma with an apocrine ductal phenotype. Next generation sequencing using ArcherDX panel targeting RNA of 36 pan-cancer-related genes and\/or a TruSight Oncology 170\/500 Kit targeting a selection of DNA from 523 genes and RNA from 55 genes was performed. Tumor tissue was available for molecular analysis in 11 cases, and 9 (9\/11; 82%) of them harbored genetic alterations in the PI3K pathway. Targeted sequencing revealed <jats:italic toggle=\"yes\">HRAS<\/jats:italic> mutations c.37G&gt;C, p.(Gly13Arg) (2 cases) and c.182A&gt;G, p.(Gln61Arg) (2 cases), and <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic> mutations c.3140A&gt;G, p.(His1047Arg) (3 cases), c.1633G&gt;A, p.(Glu545Lys) (1 case), and c.1624G&gt;A, p.(Glu542Lys) (1 case). Moreover, mutations in <jats:italic toggle=\"yes\">AKT1<\/jats:italic> c.49G&gt;A, p.(Glu17Lys) and c.51dup, p.(Tyr18ValfsTer15); c.49_50delinsAG, p.(Glu17Arg) (as a double hit) were found (2 cases). In addition, germinal and somatic mutation of <jats:italic toggle=\"yes\">PTEN<\/jats:italic> c.1003C&gt;T, p.(Arg335Ter); c.445C&gt;T, p.(Gln149Ter), respectively, were detected. Gene fusions were absent in all cases. These prevalent molecular alterations converging on one major cancer-related pathway support the notion that SPA is a true neoplasm with a significant potential to develop intraluminal epithelial proliferation with apocrine and\/or intercalated duct-like phenotype. The name SPA more correctly reflects the true neoplastic nature of this enigmatic lesion.<\/jats:p>","DOI":"10.1097\/pas.0000000000001807","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T18:00:38Z","timestamp":1631469638000},"page":"268-280","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":40,"title":["Sclerosing Polycystic Adenoma of Salivary Glands"],"prefix":"10.1097","volume":"46","author":[{"given":"Alena","family":"Sk\u00e1lov\u00e1","sequence":"first","affiliation":[{"name":"Department of Pathology, Charles University, Faculty of Medicine in Plzen"},{"name":"Bioptic Laboratory Ltd"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Ban\u011b\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pathology, Charles University, Faculty of Medicine in Plzen"},{"name":"Bioptic Laboratory Ltd"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Laco","sequence":"additional","affiliation":[{"name":"The Fingerland Department of Pathology, Charles University, Faculty of Medicine and University Hospital Hradec Kralove, Hradec Kr\u00e1lov\u00e9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Di Palma","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Division of Clinical Medicine, University of Surrey, Royal Surrey County Hospital, Guildford, Surrey, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas","family":"Agaimy","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-N\u00fcrnberg (FAU), Comprehensive Cancer Center (CCC) Erlangen-EMN, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikola","family":"Pt\u00e1kov\u00e1","sequence":"additional","affiliation":[{"name":"Molecular and Genetic Laboratory, Bioptic Laboratory Ltd, Plzen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Costes-Martineau","sequence":"additional","affiliation":[{"name":"Department of Pathology, CHU Gui de Chauliac, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt F.","family":"Petersson","sequence":"additional","affiliation":[{"name":"Department of Pathology, National University Health System, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari F.C.M.","family":"van den Hout","sequence":"additional","affiliation":[{"name":"Department of Pathology, Research Institute GROW, Maastricht University Medical Center, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisele","family":"de Rezende","sequence":"additional","affiliation":[{"name":"Department of Anatomic Histopathology and Cytogenetics, Department of Laboratory Medicine, Niguarda Cancer Center, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lie","family":"Klub\u00ed\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pathology, Charles University, Faculty of Medicine in Plzen"},{"name":"Bioptic Laboratory Ltd"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Kobl\u00ed\u017eek","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine in Prague, Prague, Charles University and Motol University Hospital, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olena","family":"Koshyk","sequence":"additional","affiliation":[{"name":"Medical Laboratory CSD, Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Vane\u010dek","sequence":"additional","affiliation":[{"name":"Molecular and Genetic Laboratory, Bioptic Laboratory Ltd, Plzen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilmo","family":"Leivo","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Pathology, University of Turku, and Turku University Hospital, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"R1-20250608","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 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