{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T22:12:13Z","timestamp":1770329533349,"version":"3.49.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives:<\/jats:title>\n                  <jats:p>PTEN hamartoma tumor syndrome (PHTS) is a hereditary disorder caused by germline inactivating mutations of the PTEN gene. PHTS includes Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. We describe how the peculiar pathologic and immunohistochemical thyroid features lead pathologists to suggest PHTS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>A 28-year-old white Spanish woman had a multinodular goiter. Total thyroidectomy was performed after fine-needle aspiration biopsy. Microscopic, immunohistochemical, and molecular analyses of the thyroid lesions were realized.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>The thyroid was multinodular, showing one papillary microcarcinoma, five follicular adenomas, three adenolipomas, 46 tiny adenomatous nodules (microadenomas), scattered foci of adipose tissue, and lymphocytic thyroiditis. Tumors were positive for thyroglobulin, thyroperoxidase, pendrin, cyclin D1, and p27 but negative for calcitonin and PTEN. A germline heterozygous deletion of one adenine at nucleotide 827 in exon 8 of the PTEN gene was confirmed. No BRAF, NRAS, or KRAS somatic mutations were detected in the papillary microcarcinoma, follicular adenoma, adenolipomas, or microadenomas. Negativity for PTEN was also found in the colonic tubulovillous adenoma and the storiform collagenoma.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>Pathologists play a crucial role in recognizing pathologic thyroid findings associated with PHTS for selecting patients for genetic testing.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1309\/ajcp84ingjuvtbme","type":"journal-article","created":{"date-parts":[[2015,7,16]],"date-time":"2015-07-16T12:48:53Z","timestamp":1437050933000},"page":"322-328","source":"Crossref","is-referenced-by-count":35,"title":["Thyroid Pathology Findings in Cowden Syndrome"],"prefix":"10.1093","volume":"144","author":[{"given":"Jos\u00e9","family":"Cameselle-Teijeiro","sequence":"first","affiliation":[{"name":"Department of Anatomic Pathology, Clinical University Hospital, Health Research Institute of Santiago de Compostela, SERGAS, Santiago de Compostela, Spain"},{"name":"Department of Anatomic Pathology, Medical Faculty, University of Santiago de Compostela, Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Fachal","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Hospital do Meixoeiro, SERGAS, Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M.","family":"Cabezas-Agr\u00edcola","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Clinical University Hospital, Health Research Institute of Santiago de Compostela, SERGAS, Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natividad","family":"Alfons\u00edn-Barreiro","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Hospital do Meixoeiro, SERGAS, Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ihab","family":"Abdulkader","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Clinical University Hospital, Health Research Institute of Santiago de Compostela, SERGAS, Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Vega-Gliemmo","sequence":"additional","affiliation":[{"name":"Galician Public Foundation of Genomic Medicine (FPGMX), Clinical University Hospital, Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Antonio","family":"Hermo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital do Meixoeiro, SERGAS, Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,8,1]]},"reference":[{"key":"2021052713505254300_b1-1440322","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1093\/jnci\/djt277","article-title":"Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria","volume":"105","author":"Pilarski","year":"2013","journal-title":"J Natl Cancer Inst"},{"key":"2021052713505254300_b2-1440322","doi-asserted-by":"crossref","first-page":"5387","DOI":"10.1038\/onc.2008.237","article-title":"Genetic and phenotypic heterogeneity in the PTEN hamartoma tumour syndrome","volume":"27","author":"Orloff","year":"2008","journal-title":"Oncogene"},{"key":"2021052713505254300_b3-1440322","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1158\/1078-0432.CCR-11-2283","article-title":"Lifetime cancer risks in individuals with germline PTEN mutations","volume":"18","author":"Tan","year":"2012","journal-title":"Clin Cancer Res"},{"key":"2021052713505254300_b4-1440322","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/S0190-9622(83)70081-2","article-title":"Cowden\u2019s disease (multiple hamartoma and neoplasia syndrome): a case report and review of the English literature","volume":"8","author":"Salem","year":"1983","journal-title":"J Am Acad Dermatol"},{"key":"2021052713505254300_b5-1440322","unstructured":"National Comprehensive Cancer Network I\n          . The NCCN guidelines genetic\/familial high-risk assessment: breast and ovarian. http:\/\/www.nccn.org. Accessed September 12, 2013."},{"key":"2021052713505254300_b6-1440322","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S1092-9134(99)80011-2","article-title":"Thyroid pathologic findings in patients with Cowden disease","volume":"3","author":"Harach","year":"1999","journal-title":"Ann Diagn Pathol"},{"key":"2021052713505254300_b7-1440322","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1089\/thy.2010.0226","article-title":"Thyroid pathology in PTEN-hamartoma tumor syndrome: characteristic findings of a distinct entity","volume":"21","author":"Laury","year":"2011","journal-title":"Thyroid"},{"key":"2021052713505254300_b8-1440322","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1210\/jc.2010-1315","article-title":"Thyroid nodules and cancer in children with PTEN hamartoma tumor syndrome","volume":"96","author":"Smith","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2021052713505254300_b9-1440322","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1097\/PAS.0b013e31822fbc7d","article-title":"Immunohistochemical staining of thyroidectomy specimens for PTEN can aid in the identification of patients with Cowden syndrome","volume":"35","author":"Barletta","year":"2011","journal-title":"Am J Surg Pathol"},{"key":"2021052713505254300_b10-1440322","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1097\/PAS.0b013e31824dd86c","article-title":"PTEN hamartoma of soft tissue: a distinctive lesion in PTEN syndromes","volume":"36","author":"Kurek","year":"2012","journal-title":"Am J Surg Pathol"},{"key":"2021052713505254300_b11-1440322","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1399-0004.2009.01309.x","article-title":"Beyond BRCA1 and BRCA2 wild-type breast and\/or ovarian cancer families: germline mutations in TP53 and PTEN","volume":"77","author":"Blanco","year":"2010","journal-title":"Clin Genet"},{"key":"2021052713505254300_b12-1440322","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajhg.2012.10.021","article-title":"Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes","volume":"92","author":"Orloff","year":"2013","journal-title":"Am J Hum Genet"},{"key":"2021052713505254300_b13-1440322","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1210\/jc.2010-1315","article-title":"Thyroid nodules and cancer in children with PTEN hamartoma tumor syndrome","volume":"96","author":"Smith","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2021052713505254300_b14-1440322","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ajhg.2008.07.011","article-title":"Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes","volume":"83","author":"Ni","year":"2008","journal-title":"Am J Hum Genet"},{"key":"2021052713505254300_b15-1440322","doi-asserted-by":"crossref","first-page":"E2063","DOI":"10.1210\/jc.2011-1616","article-title":"Incidence and clinical characteristics of thyroid cancer in prospective series of individuals with Cowden and Cowden-like syndrome characterized by germline PTEN, SDH, or KLLN alterations","volume":"96","author":"Ngeow","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2021052713505254300_b16-1440322","doi-asserted-by":"crossref","first-page":"261","DOI":"10.4274\/Jcrpe.984","article-title":"Thyroid involvement in two patients with Bannayan-Riley-Ruvalcaba syndrome","volume":"5","author":"Peiretti","year":"2013","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"2021052713505254300_b17-1440322","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1089\/thy.2010.0365","article-title":"Frequency of germline PTEN mutations in differentiated thyroid cancer","volume":"21","author":"Nagy","year":"2011","journal-title":"Thyroid"},{"key":"2021052713505254300_b18-1440322","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.surg.2012.08.055","article-title":"Should patients with Cowden syndrome undergo prophylactic thyroidectomy?","volume":"152","author":"Milas","year":"2012","journal-title":"Surgery"},{"key":"2021052713505254300_b19-1440322","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nrc3431","article-title":"Molecular pathogenesis and mechanisms of thyroid cancer","volume":"13","author":"Xing","year":"2013","journal-title":"Nat Rev Cancer"},{"key":"2021052713505254300_b20-1440322","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1136\/jmedgenet-2011-100152","article-title":"Two distinct thyroid tumours in a patient with Cowden syndrome carrying both a 10q23 and a mitochondrial DNA germline deletion","volume":"48","author":"Pradella","year":"2011","journal-title":"J Med Genet"},{"issue":"suppl","key":"2021052713505254300_b21-1440322","doi-asserted-by":"crossref","first-page":"194S","DOI":"10.1177\/1066896910370883","article-title":"The pathologist\u2019s role in familial nonmedullary thyroid tumors","volume":"18","author":"Cameselle-Teijeiro","year":"2010","journal-title":"Int J Surg Pathol"},{"key":"2021052713505254300_b22-1440322","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1309\/AJCP7ULS0VSISBEB","article-title":"Cribriform-morular variant of papillary thyroid carcinoma: molecular characterization of a case with neuroendocrine differentiation and aggressive behavior","volume":"131","author":"Cameselle-Teijeiro","year":"2009","journal-title":"Am J Clin Pathol"},{"key":"2021052713505254300_b23-1440322","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1038\/ctg.2011.4","article-title":"Upper and lower gastrointestinal findings in PTEN mutation-positive Cowden syndrome patients participating in an active surveillance program","volume":"2","author":"Levi","year":"2011","journal-title":"Clin Transl Gastroenterol"},{"key":"2021052713505254300_b24-1440322","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.humpath.2011.06.022","article-title":"Colonic ganglioneuromatous polyposis and metastatic adenocarcinoma in the setting of Cowden syndrome: a case report and literature review","volume":"43","author":"Trufant","year":"2012","journal-title":"Hum Pathol"},{"key":"2021052713505254300_b25-1440322","doi-asserted-by":"crossref","first-page":"861","DOI":"10.3748\/wjg.v18.i8.861","article-title":"A case of Cowden syndrome diagnosed from multiple gastric polyposis","volume":"18","author":"Ha","year":"2012","journal-title":"World J Gastroenterol"},{"key":"2021052713505254300_b26-1440322","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.3748\/wjg.v20.i7.1833","article-title":"Colonic manifestations of PTEN hamartoma tumor syndrome: case series and systematic review","volume":"20","author":"Stanich","year":"2014","journal-title":"World J Gastroenterol"}],"container-title":["American Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ajcp\/article-pdf\/144\/2\/322\/38276177\/ajcpath144-0322.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ajcp\/article-pdf\/144\/2\/322\/38276177\/ajcpath144-0322.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T01:33:41Z","timestamp":1622165621000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajcp\/article\/144\/2\/322\/1767218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,1]]},"references-count":26,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,8,1]]},"published-print":{"date-parts":[[2015,8,1]]}},"URL":"https:\/\/doi.org\/10.1309\/ajcp84ingjuvtbme","relation":{},"ISSN":["1943-7722","0002-9173"],"issn-type":[{"value":"1943-7722","type":"electronic"},{"value":"0002-9173","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,8,1]]},"published":{"date-parts":[[2015,8,1]]}}}