{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T11:21:38Z","timestamp":1778498498197,"version":"3.51.4"},"reference-count":14,"publisher":"BMJ","issue":"5","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2016,9,23]]},"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Hidradenoma papilliferum (HP) is a benign vulvar neoplasm that arises from anogenital mammary-like glands, and its morphology is similar to mammary intraductal papilloma. The aim of this study was to investigate oncogenic mutations involved in the tumourigenesis of HP. We focused specifically on <jats:italic>PIK3CA<\/jats:italic> and <jats:italic>AKT1<\/jats:italic> mutations, which are both reported to be detected in 33% of mammary intraductal papillomas.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In total, seven HP cases were analysed. Clinicopathological analyses and immunohistochemistry for oestrogen receptor, p63, smooth muscle actin (SMA), p53 and \u03b2-catenin were performed. Furthermore, <jats:italic>PIK3CA<\/jats:italic>, <jats:italic>AKT1, BRAF<\/jats:italic> and <jats:italic>KRAS<\/jats:italic> hot spot mutations were examined by Sanger sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Morphologically, all HPs had a papillary and tubular architecture with a biphasic pattern of epithelial and myoepithelial cells. Immunohistochemistry revealed that oestrogen receptor expression was restricted to epithelial cells, whereas p63 and SMA were exclusively expressed in myoepithelial cells. The patterns of p53 and \u03b2-catenin immunostaining suggested wild-type genotypes. Direct sequencing revealed the presence of somatic <jats:italic>PIK3CA<\/jats:italic> mutations (Ex9. c.1633G&gt;A, p.E545K and Ex20. c.3140A&gt;G, p.H1047R) in two of the HPs and an <jats:italic>AKT1<\/jats:italic> (c.49G&gt;A, p.E17K) mutation in one. <jats:italic>BRAF<\/jats:italic> and <jats:italic>KRAS<\/jats:italic> mutations were not found in any of the HP cases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                     <jats:italic>PIK3CA<\/jats:italic> and <jats:italic>AKT1<\/jats:italic> are frequently mutated in HP tumours (29% and 14%, respectively). PIK3CA\/AKT1 pathway alterations in HP further support the hypothesis that HP is the vulvar (anogenital mammary-like gland) analogue of breast intraductal papilloma.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jclinpath-2016-204003","type":"journal-article","created":{"date-parts":[[2016,10,14]],"date-time":"2016-10-14T22:30:27Z","timestamp":1476484227000},"page":"424-427","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["<i>PIK3CA<\/i> and <i>AKT1<\/i> mutations in hidradenoma papilliferum"],"prefix":"10.1136","volume":"70","author":[{"given":"Keisuke","family":"Goto","sequence":"first","affiliation":[{"name":"Department of Diagnostic Pathology, Kainan Hospital, Aichi, Japan"},{"name":"Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daichi","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukitsugu","family":"Kudo-Asabe","sequence":"additional","affiliation":[{"name":"Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Hibiya","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akimasa","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Fukayama","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiteru","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2016,10,14]]},"reference":[{"key":"2025092510130155000_70.5.424.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0303-6987.2004.00176.x"},{"key":"2025092510130155000_70.5.424.2","doi-asserted-by":"publisher","DOI":"10.1080\/00313020902884493"},{"key":"2025092510130155000_70.5.424.3","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0b013e31820e63e8"},{"key":"2025092510130155000_70.5.424.4","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2012-0434-OA"},{"key":"2025092510130155000_70.5.424.5","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000000495"},{"key":"2025092510130155000_70.5.424.6","doi-asserted-by":"publisher","DOI":"10.1097\/00004347-199404000-00009"},{"key":"2025092510130155000_70.5.424.7","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1819"},{"key":"2025092510130155000_70.5.424.8","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1106"},{"key":"2025092510130155000_70.5.424.9","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2009.142"},{"key":"2025092510130155000_70.5.424.10","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2660"},{"key":"2025092510130155000_70.5.424.11","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.197"},{"key":"2025092510130155000_70.5.424.12","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22315"},{"key":"2025092510130155000_70.5.424.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2016.04.014"},{"key":"2025092510130155000_70.5.424.14","unstructured":"O'Malley F , Visscher D , MacGrogan G , et al . Intraductal papilloma. In: Lakhani SR , Ellis LO , Schnitt SJ , et al ., eds. WHO classification of tumours of the breast. Lyon: IARC Press, 2012:100\u20132."}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jclinpath-2016-204003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T17:13:06Z","timestamp":1758820386000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2016-204003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,14]]},"references-count":14,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,4,18]]},"published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1136\/jclinpath-2016-204003"],"URL":"https:\/\/doi.org\/10.1136\/jclinpath-2016-204003","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"value":"0021-9746","type":"print"},{"value":"1472-4146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,14]]}}}