{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:15:04Z","timestamp":1787588104587,"version":"build-2736575974"},"reference-count":23,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":3010,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Hereditary tumour predisposition syndromes may increase the risk for development of thyroid nodules at a young age. We present the case of an adolescent female with Cowden syndrome who had some atypical phenotypic features which overlapped with the DICER1 syndrome. Material and Methods: A 17-year-old female presented with a 3-month history of progressive right neck swelling. Fine needle cytology of the thyroid revealed a follicular neoplasm with features suggestive of follicular variant of papillary thyroid carcinoma and she underwent a hemithyroidectomy. Enlarging nodules in the remaining thyroid led to a completion thyroidectomy at 19 years of age. The patient\u2019s past medical history included an ovarian mixed malignant germ cell tumour, pulmonary nodules and cysts, renal cysts, mucocutaneous lesions, an arachnoid cyst, and a fibrous breast lesion. Macrocephaly was noted on physical examination. Results: Based on the patient\u2019s complex phenotype and young age, a hereditary predisposition syndrome was suspected and genetic testing of PTEN and DICER1 was undertaken. A heterozygous truncating germ-line PTEN mutation was identified, which combined with clinical findings, met criteria for the diagnosis of Cowden syndrome. Additional loss of heterozygosity of the wild-type PTEN allele was detected in the right thyroid lesion and ovarian tumour. No DICER1 mutations were identified. Conclusions: Genetic testing was crucial in elucidating this patient\u2019s predisposition to the early development of neoplastic and non-neoplastic conditions. Our report also highlights the phenotypic overlap between the Cowden and DICER1 syndromes and illustrates the importance of recognising the variable phenotypic features of hereditary syndromes in order to enable timely implementation of appropriate care.<\/jats:p>","DOI":"10.1159\/000481620","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T17:01:33Z","timestamp":1511283693000},"page":"44-50","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-17","source":"Crossref","is-referenced-by-count":5,"title":["A Case Report of Syndromic Multinodular Goitre in Adolescence: Exploring the Phenotype Overlap between Cowden and DICER1 Syndromes"],"prefix":"10.1530","volume":"7","author":[{"given":"Doroth\u00e9e","family":"Bouron-Dal\u00a0Soglio","sequence":"first","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne","family":"de\u00a0Kock","sequence":"additional","affiliation":[{"name":"2"},{"name":"3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Gauci","sequence":"additional","affiliation":[{"name":"4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Sabbaghian","sequence":"additional","affiliation":[{"name":"2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Thomas","sequence":"additional","affiliation":[{"name":"4"},{"name":"5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen\u00a0C.","family":"Atkinson","sequence":"additional","affiliation":[{"name":"6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Pachter","sequence":"additional","affiliation":[{"name":"6"},{"name":"7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Ryan","sequence":"additional","affiliation":[{"name":"8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John\u00a0P.","family":"Walsh","sequence":"additional","affiliation":[{"name":"6"},{"name":"9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.\u00a0Priyanthi","family":"Kumarasinghe","sequence":"additional","affiliation":[{"name":"10"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Carpenter","sequence":"additional","affiliation":[{"name":"11"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u00e7a","family":"Aydo\u011fan","sequence":"additional","affiliation":[{"name":"12"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin\u00a0J.R.","family":"Stewart","sequence":"additional","affiliation":[{"name":"7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William\u00a0D.","family":"Foulkes","sequence":"additional","affiliation":[{"name":"2"},{"name":"3"},{"name":"13"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine\u00a0S.","family":"Choong","sequence":"additional","affiliation":[{"name":"5"},{"name":"6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2017,11,21]]},"reference":[{"key":"2026070713084500200_ref1","doi-asserted-by":"crossref","unstructured":"Rao A, Rothman J, Nichols KE: Genetic testing and tumor surveillance for children with cancer predisposition syndromes. Curr Opin Pediatr 2008; 20: 1\u20137.10.1097\/MOP.0b013e3282f4249a18197032","DOI":"10.1097\/MOP.0b013e3282f4249a"},{"key":"2026070713084500200_ref2","doi-asserted-by":"crossref","unstructured":"Francis GL, Waguespack SG, Bauer AJ, Angelos P, Benvenga S, Cerutti JM, Dinauer CA, Hamilton J, Hay ID, Luster M, Parisi MT, Rachmiel M, Thompson GB, Yamashita S: Management guidelines for children with thyroid nodules and differentiated thyroid cancer. Thyroid 2015; 25: 716\u2013759.10.1089\/thy.2014.046025900731","DOI":"10.1089\/thy.2014.0460"},{"key":"2026070713084500200_ref3","doi-asserted-by":"crossref","unstructured":"Heravi-Moussavi A, Anglesio MS, Cheng SW, Senz J, Yang W, Prentice L, Fejes AP, Chow C, Tone A, Kalloger SE, Hamel N, Roth A, Ha G, Wan AN, Maines-Bandiera S, Salamanca C, Pasini B, Clarke BA, Lee AF, Lee CH, Zhao C, Young RH, Aparicio SA, Sorensen PH, Woo MM, Boyd N, Jones SJ, Hirst M, Marra MA, Gilks B, Shah SP, Foulkes WD, Morin GB, Huntsman DG: Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N Engl J Med 2012; 366: 234\u2013242.10.1056\/NEJMoa110290322187960","DOI":"10.1056\/NEJMoa1102903"},{"key":"2026070713084500200_ref4","doi-asserted-by":"crossref","unstructured":"Witkowski L, Mattina J, Schonberger S, Murray MJ, Choong CS, Huntsman DG, Reis-Filho JS, McCluggage WG, Nicholson JC, Coleman N, Calaminus G, Schneider DT, Arseneau J, Stewart CJ, Foulkes WD: DICER1 hotspot mutations in non-epithelial gonadal tumours. Br J Cancer 2013; 109: 2744\u20132750.10.1038\/bjc.2013.63724136150","DOI":"10.1038\/bjc.2013.637"},{"key":"2026070713084500200_ref5","doi-asserted-by":"crossref","unstructured":"de Kock L, Sabbaghian N, Soglio DB, Guillerman RP, Park BK, Chami R, Deal CL, Priest JR, Foulkes WD: Exploring the association between DICER1 mutations and differentiated thyroid carcinoma. J Clin Endocrinol Metab 2014; 99:E1072\u2013E1077.10.1210\/jc.2013-420624617712","DOI":"10.1210\/jc.2013-4206"},{"key":"2026070713084500200_ref6","doi-asserted-by":"crossref","unstructured":"Rutter MM, Jha P, Schultz KA, Sheil A, Harris AK, Bauer AJ, Field AL, Geller J, Hill DA: DICER1 mutations and differentiated thyroid carcinoma: evidence of a direct association. J Clin Endocrinol Metab 2016; 101: 1\u20135.10.1210\/jc.2015-216926555935","DOI":"10.1210\/jc.2015-2169"},{"key":"2026070713084500200_ref7","doi-asserted-by":"crossref","unstructured":"de Kock L, Sabbaghian N, Plourde F, Srivastava A, Weber E, Bouron-Dal Soglio D, Hamel N, Choi JH, Park SH, Deal CL, Kelsey MM, Dishop MK, Esbenshade A, Kuttesch JF, Jacques TS, Perry A, Leichter H, Maeder P, Brundler MA, Warner J, Neal J, Zacharin M, Korbonits M, Cole T, Traunecker H, McLean TW, Rotondo F, Lepage P, Albrecht S, Horvath E, Kovacs K, Priest JR, Foulkes WD: Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. Acta Neuropathologica 2014; 128: 111\u2013122.10.1007\/s00401-014-1285-z24839956","DOI":"10.1007\/s00401-014-1285-z"},{"key":"2026070713084500200_ref8","doi-asserted-by":"crossref","unstructured":"Sabbaghian N, Srivastava A, Hamel N, Plourde F, Gajtko-Metera M, Niedziela M, Foulkes WD: Germ-line deletion in DICER1 revealed by a novel MLPA assay using synthetic oligonucleotides. Eur J Hum Genet 2014; 22: 564\u2013567.10.1038\/ejhg.2013.21524065110","DOI":"10.1038\/ejhg.2013.215"},{"key":"2026070713084500200_ref9","doi-asserted-by":"crossref","unstructured":"Khan NE, Bauer AJ, Doros L, Schultz KA, Decastro RM, Harney LA, Kase RG, Carr AG, Harris AK, Williams GM, Dehner LP, Messinger YH, Stewart DR: Macrocephaly associated with the DICER1 syndrome. Genet Med 2017; 19: 244\u2013248.10.1038\/gim.2016.8327441995","DOI":"10.1038\/gim.2016.83"},{"key":"2026070713084500200_ref10","doi-asserted-by":"crossref","unstructured":"Orloff MS, Eng C: Genetic and phenotypic heterogeneity in the PTEN hamartoma tumour syndrome. Oncogene 2008; 27: 5387\u20135397.10.1038\/onc.2008.23718794875","DOI":"10.1038\/onc.2008.237"},{"key":"2026070713084500200_ref11","doi-asserted-by":"crossref","unstructured":"Hobert JA, Eng C: PTEN hamartoma tumor syndrome: an overview. Genet Med 2009; 11: 687\u2013694.10.1097\/GIM.0b013e3181ac9aea19668082","DOI":"10.1097\/GIM.0b013e3181ac9aea"},{"key":"2026070713084500200_ref12","doi-asserted-by":"crossref","unstructured":"Cottin V, Thomas L, Loire R, Chalabreysse L, Gindre D, Cordier JF: Mesenchymal cystic hamartoma of the lung in Cowden\u2019s disease. Respir Med 2003; 97: 188\u2013191.10.1053\/rmed.2003.144712587971","DOI":"10.1053\/rmed.2003.1447"},{"key":"2026070713084500200_ref13","doi-asserted-by":"crossref","unstructured":"Lee EJ, Jung WS, Ko JM, Park HJ: Multiorgan involvements of Cowden disease in a 50-year-old woman: a case report and literature overview. J Korean Soc Radiol 2013; 69: 251\u2013255.10.3348\/jksr.2013.69.3.251","DOI":"10.3348\/jksr.2013.69.3.251"},{"key":"2026070713084500200_ref14","doi-asserted-by":"crossref","unstructured":"Cho MY, Kim HS, Eng C, Kim DS, Kang SJ, Eom M, Yi SY, Bronner MP: First report of ovarian dysgerminoma in Cowden syndrome with germline PTEN mutation and PTEN-related 10q loss of tumor heterozygosity. Am J Surg Pathol 2008; 32: 1258\u20131264.10.1097\/PAS.0b013e31816be8b718594467","DOI":"10.1097\/PAS.0b013e31816be8b7"},{"key":"2026070713084500200_ref15","unstructured":"Neumann S: Cowden syndrome with an ovarian tumor (multiple hamartoma syndrome) (in German). Chirurg 1991; 62: 629\u2013630.1657548"},{"key":"2026070713084500200_ref16","doi-asserted-by":"crossref","unstructured":"Smpokou P, Fox VL, Tan WH: PTEN hamartoma tumour syndrome: early tumour development in children. Arch Dis Child 2015; 100: 34\u201337.10.1136\/archdischild-2014-30599725114091","DOI":"10.1136\/archdischild-2014-305997"},{"key":"2026070713084500200_ref17","doi-asserted-by":"crossref","unstructured":"Foulkes WD, Priest JR, Duchaine TF: DICER1: mutations, microRNAs and mechanisms. Nat Rev Cancer 2014; 14: 662\u2013672.10.1038\/nrc380225176334","DOI":"10.1038\/nrc3802"},{"key":"2026070713084500200_ref18","doi-asserted-by":"crossref","unstructured":"Wu MK, de Kock L, Conwell LS, Stewart CJ, King BR, Choong CS, Hussain K, Sabbaghian N, MacRae IJ, Fabian MR, Foulkes WD: Functional characterization of multiple DICER1 mutations in an adolescent. Endocr Relat Cancer 2016; 23:L1\u2013L5.10.1530\/ERC-15-046026545620","DOI":"10.1530\/ERC-15-0460"},{"key":"2026070713084500200_ref19","doi-asserted-by":"crossref","unstructured":"Foulkes WD, Gore M, McCluggage WG: Rare non-epithelial ovarian neoplasms: pathology, genetics and treatment. Gynecol Oncol 2016; 142: 190\u2013198.10.1016\/j.ygyno.2016.04.00527079213","DOI":"10.1016\/j.ygyno.2016.04.005"},{"key":"2026070713084500200_ref20","doi-asserted-by":"crossref","unstructured":"Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L: 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016; 26: 1\u2013133.10.1089\/thy.2015.002026462967","DOI":"10.1089\/thy.2015.0020"},{"key":"2026070713084500200_ref21","doi-asserted-by":"crossref","unstructured":"Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C: Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res 2012; 18: 400\u2013407.10.1158\/1078-0432.CCR-11-228322252256","DOI":"10.1158\/1078-0432.CCR-11-2283"},{"key":"2026070713084500200_ref22","doi-asserted-by":"crossref","unstructured":"Milas M, Mester J, Metzger R, Shin J, Mitchell J, Berber E, Siperstein AE, Eng C: Should patients with Cowden syndrome undergo prophylactic thyroidectomy? Surgery 2012; 152: 1201\u20131210.10.1016\/j.surg.2012.08.05523158187","DOI":"10.1016\/j.surg.2012.08.055"},{"key":"2026070713084500200_ref23","doi-asserted-by":"crossref","unstructured":"de Kock L, Druker H, Weber E, Hamel N, Traubici J, Malkin D, Arseneau J, Stewart CJ, Bouron-Dal Soglio D, Priest JR, Foulkes WD: Ovarian embryonal rhabdomyosarcoma is a rare manifestation of the DICER1 syndrome. Hum Pathol 2015; 46: 917\u2013922.10.1016\/j.humpath.2015.02.00825836323","DOI":"10.1016\/j.humpath.2015.02.008"}],"container-title":["European Thyroid Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/481620","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/7\/1\/44\/35929\/etj481620.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/7\/1\/44\/35929\/etj481620.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:48:47Z","timestamp":1783446527000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article\/7\/1\/44\/4904\/A-Case-Report-of-Syndromic-Multinodular-Goitre-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,21]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000481620","relation":{},"ISSN":["2235-0802","2235-0640"],"issn-type":[{"value":"2235-0802","type":"electronic"},{"value":"2235-0640","type":"print"}],"subject":[],"published":{"date-parts":[[2017,11,21]]}}}